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The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

RLBUHT
Trust Formulary






Oc t ober 2011

Contents (Click on heading to go to that section)

Preface

Dispensing for Discharge

Prescribing in Palliative Care

Prescribing for the Elderly

Therapeutic Concentration Monitoring

Dosage Adjustments for Medicines in Renal Impairment

Haematology and Biochemistry Reference Ranges

Gastro-intestinal System

Cardiovascular System

Respiratory System

Central Nervous System

Infections

Endocrine System

Obstretics, Gynaecology and Urinary Tract Disorders

Treatment of Malignant Disease and Immunosuppression

Medicines Affecting Nutrition and Blood

Musculoskeletal and Joint Diseases

Medicines Acting on the Eye

Medicines Acting on the Ear Nose and Throat

Medicines Acting on the Skin

Immunological Products and Vaccines

Medicines Used in Anaesthesia



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

PREFACE

This formulary has been designed to guide the prescribing of staff on all wards and
departments in this Trust.

It also contains prescribing guidelines for specific therapeutic areas, e.g. management
of alcohol withdrawal, triple therapy for ulcer healing, anticoagulation.

The format is in the style of the British National Formulary (BNF), the most recent
edition of which should be used in conjunction with this document for more detailed
prescribing information.

Technical issues/problems with the intranet version should be addressed to the
Pharmacy Directorate Information Analyst (ext. 4559).

Comments and suggestions on content may be made to the Chairman of the Medicines
Management Group (MMG) or the Assistant Director of Pharmacy Clinical services.

Restricted or Special Medicines

Certain medicines in the formulary are not available for general use. These are
indicated in the text by the symbol (s), with details of the restrictions that apply. These
restrictions only apply to the initiation of a prescription.

Non - formulary Medicines

Wherever possible, only formulary items should be prescribed. If there is a specific
need to start an individual patient on a non - formulary preparation then this can be
achieved at the request of a Consultant by the completion of a compassionate use
request form. This is then discussed with the Chair of the MMG for a decision. Please
note however, as non - formulary preparations are not generally stocked in the
pharmacy there may be a delay of 24 hours (up to four days at weekends and bank
holidays) whilst supplies are purchased.

Patients Admitted On Non - Formulary Medicines

If patients are admitted on non - formulary medicines, it is Trust policy that they are
maintained on their medication in cases where changing to a formulary preparation
would be detrimental to that patient's care. Where these factors are not important e.g.
choice of antacid, haemorrhoid preparation, etc. then the doctor should prescribe only
formulary items.

Guidance on Prescribing - For guidance on prescribing please refer to the trust
prescribing of medicines policy

Use of Unlicensed Medicines refer to Trust policy on the supply and use of
unlicensed medicines

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

New Medicine Policy

Introduction

New medicines bring valuable advantages for patients and the health service. The
use of new medicines however has to be carefully managed for several reasons:
New medicines may bring benefits but may also bring new and perhaps
unrecognised hazards; they have implications for the finances of both the Trust and
primary care. There are concerns about the education of medical and non-medical
staff in their use and sometimes with pharmacy management and stock keeping of
new medicines.
That a medicine is new is never a sufficient reason alone to introduce it to the
hospital there must be reasonable evidence that it is superior in some way to that
which is already prescribed (safety, efficacy, convenience or cost) or that it treats a
previously untreatable condition.

Process

A case for a new medicine must be made by a consultant to the Medicines
Management Group (MMG) addressing the following points:

- Clinical advantages of the new therapy
- Likely therapies to be replaced
- Likely levels of use
- Net cost to the trust
- Impact on other directorates
- Any service implications (monitoring, change in patterns of care, new patients
treated etc., in the RLBUHT and also elsewhere in the health service including
other hospitals or primary care)

The application is to be made on appropriate forms available from Pharmacy. It is
the responsibility of the consultant to present the case in person to the MMG.
Documents, which present an inadequate case, will be returned for further
submission. Submissions must be counter signed by the relevant clinical director
and also have the directorate accountants support if there are financial implications.

Decision

In making a recommendation, the MMG will use its judgement as to whether this
represents a good use of NHS resources. Any formal economic evaluations
available will be used to inform this process.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Principles for decision

1) The MMG will not approve new medicines where there are reasonable
licensed alternatives already available within the Trust.
2) No unlicensed medicines should be approved except in very exceptional
circumstances, where no licensed alternative is available.
3) A case made by several consultants within a discipline should be considered
more favourably than one made by a single consultant.
4) The views of all relevant consultants in a particular specialty about a new
medicines application may be sought.
5) Any medicine to be considered by NICE within the next 46 months will not be
considered, pending the publication of NICE guidance (this would not prohibit
use in the meantime on a named patient basis by a particular consultant).
6) All medicines with a major implication for primary care prescribing or use
outside the hospital (including shared care arrangements) will be discussed
with PCT/ primary care representatives.
7) All decisions that affect primary care will need to be ratified by the North
Mersey Area medicines Management Committee

Mechanism of working

1) Some responses can be dealt with by chairmans action alone (where change
is therapeutically sound in chairmans opinion and has no minor
service/resource implications).
2) More complex issues or where the chairman feels unable to support the
application or where there are major service/resource implications will be
referred to the MMG at its next meeting. The requesting consultant is required
to attend the meeting in person to present and discuss the case.
3) The MMG will inform the consultant responsible for submitting the application
of the decision in writing.

Time Scale

- In circumstances 1, a positive response is usually possible within two weeks.
- In 2, a response may be possible within two months.
- If there are major financial implications the response will depend on the
negotiations with Commissioners

Urgent New Medicine Requests
- To be made personally to the Chairman of the MMG via a completed
compassionate use form with justifications, or in his absence to the Clinical
Director of Pharmacy who will liaise as necessary with the Medical Director.

Appeal
- A consultant has a right of appeal against any declined request.
- The first recourse of appeal will be to the MMG. If rejected on appeal to MMG, then
appeal may be made to the Medical Director in consultation with the Chairman of the
MMG
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

"Dispensing For Discharge" Scheme and use of Patients Own
Medicines (POMs) Definition

- Dispensing For Discharge is medication supplied from the Hospital
Pharmacy labelled with full dosage instructions so that these supplies can be
used during in-patient stay and for discharge.
- The POMs scheme refers to use of patient's own medicines (dispensed in
the community) during their inpatient stay (and on discharge), if assessed as
appropriate, in accordance with set protocols.

Scope

The scheme currently operates on all wards at RLUH and several wards at
Broadgreen Hospital.

Aims/Advantages

- Minimise delay in the supply of medicines at discharge because
medication is available in sufficient quantity and is labelled with dosing
instructions on the ward.
- Meet government guidelines on best practice as outlined in "A Spoonful of
Sugar" (Audit Commission 2001) and NSFs.
- Re - deploy pharmacy staff time in a patient focused manner and speed
up the discharge process.
- Reduce medication administration errors because the nurse is only
selecting from the patients own medicines which are stored at the bedside.
- Minimise occurrences of medicines not available because the time
interval between prescribing and administration of medication may be
reduced.
- Medication charts remain on the ward because Pharmacy staff are ward
based.
- Reduce waste because the patient's own medicines ("POMs") are used rather
than destroyed. Hospital supplied medication for in-patient use is also used for
discharge.
- Medication administration rounds are quicker and timelier because
nursing staff are not limited by a single trolley and only have to search one
patient's medicine locker for the appropriate medication.
- Reduce patients confusion about medication and improve concordance
with therapy by explaining the need for changes in brand / medicine / dose /
frequency.

Pre admission

- Patients should be encouraged to bring in all their medication from home for
assessment and possible continued use in hospital.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Entry into the Scheme

- Patients will only be entered into the scheme after a medication chart (with full
medication administration details) has been completed by a doctor.

Pharmacy Element of "POMs" Scheme (Ward level)

Each ward on which the scheme operates will be assigned a Clinical Ward
Pharmacist (WP) and a Medicines Management Technician (MMT).
- The ward will be visited by the WP and MMT throughout the day during the
week. A limited service is provided to all wards over the weekend whereby a
pharmacist will visit during pharmacy opening hours to collect requisitions and
discharge prescriptions. No medication charts should be sent to the Pharmacy
dispensary. A WP and MMT provide a limited service to the Acute Medical
Admissions Unit during pharmacy opening hours on Saturday and Sunday
mornings.
- The WP will clinically check prescriptions for appropriateness of therapy as per
Trust / clinical guidelines.
- The WP will be available as a Medicines Information source at ward level, and
may be contactable via a pager.
- The MMT will be involved in various medication issues such as assessing
POMs and ordering medication from Pharmacy under the guidance of the WP.
MMTs carry a pager, they are contactable during the day to deal with stock
queries and checking of discharge prescriptions (TTOs) to speed up the
discharge process.


Use of Patients Own Medicines (POMs) and Dispensing for Discharge Scheme

Medicines Supply Process


Pat i e n t
ad m i tt e d t o
wa rd
Me d i ca t i o n
c ha rt
c o mp l e te d
b y M e di c a l
St a f f
Cl e rki n g - i n
st a f f t o
as c e rt ai n i f
a n y PO M s
bro u g h t i n t o
h o sp i t al
Me d i ca t i o n s up p l y
arra n g e d by
WP/ M MT o n ne x t
vi si t
I f m e d i c a t i o n i s
req u i re d b e f o re t hi s
vi si t , n u rsi n g s t a f f
sh o u ld onl y ord e r
th o s e m e d i ci n es
wh i c h a re n o t
av a i l a b l e a s wa rd
st o c k
Me d i ca t i o n t o b e
st o re d i n t h e b e d s i d e
me d i ci n e s c a bi n e t
(e x c ep t i n ha l e rs,
to p i c al p re pa ra t i o ns ,
me d i ci n e s re q u i r i n g
ref r ig e ra t i o n a nd
CD s )
Yes
No
M MT
a ss e s se s
PO M s
NO T
s ui t a b l e f o r
c on t i n ue d
u se
p at i e n t t o
c on s e nt f o r
re mo v a l o f
PO Ms
SUI TA BL E
f o r
c on t i n ue d
u se
ve rb a l
c on s e nt t o
u se
i nd i ca t e d
a s O wn
b y
WP/ M MT
No s u pp l y
re q u i re d
WP /M M T en d o rs es
Ph a rm ac y se c t i o n o f ch a rt
wi t h : a t i c k i n t he OW N
s e ct i o n , n u mb e r o f d ay s
s u pp l y, L / N f o r l ab e l l ed wi t h
i n st ru c t i o n s , o r n o t , d a t e of
a s se s s me n t a n d re -su p p l y
d a t e
Su p p l i e s
re q u i re d
f ro m
Ph a rm ac y
M EETS
Di sp e n si n g
f o r
Di s ch a rg e
c ri t e ri a
EXC L UDED
f ro m
Di sp e n si n g
f o r
Di s ch a rg e
2 8 d ay su p p l y i ss u e d
WP /M M T en d o rs es
P ha rm a cy s ec t i on o f ch a rt
wi t h n um b e r o f d a ys s up p l y
a n d d a t e of s u p pl y L (f o r
L a b el l e d ) a n d re -su p p l y d a te
Ap p ro p ri at e q ua n t i t y s up p l i ed
WP /M M T en d o rs es
Ph a rm ac y se c t i o n o f ch a rt
wi t h Qt y su p p l ie d ; da t e o f
s u pp l y a n d re -su p p l y d a te
N e nd o rs e me n t t o i n d i c a t e
m e d i c i ne s n o t l a be l l e d f o r
d i sc h ar ge
Ke y:
WP Wa rd Ph arm ac i st
M MT Me di ci n es Ma na g em en t Tec hn i ci an


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Discharge Procedure

- A discharge prescription must be completed, even if no medication is required
to be dispensed as a copy is sent to the patient's GP by the ward clerk.


Process of Completion of TTO

- An electronic TTO is written by a registered prescriber.
- An unauthorised copy of the TTO must be printed off and a member of the ward
pharmacy team contacted.
- Endorsement on the TTO of what requires dispensing and when there is already
quantity sufficient (QS) on the ward or at the patient's home (QSH).
- The TTO must be authorised by a pharmacist following a clinical check of the
prescription (which includes checking for transcription errors from medicine chart onto
TTO prescription).
- Completion of the dispensing procedure, either on ward using pre-packs and ward
labellers or in the dispensary (if any medication requires dispensing).
- Ward staff must print 3 copies of the completed discharge summary, one for the
patient, one for the medical notes and one to be posted to the GP.
- It is the responsibility of the discharge nurse (must be a Trust accredited registered
nurse) to check all medication against the discharge summary before handing over to
patient or carer.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Use of Patients Own Medicines (POMs) and Dispensing for Discharge

Discharge Medicines Supply Process (TTO)


Dis charge
pre script ion
creat ed and an
u n-aut hori sed
co py p rint ed of f.
Bleep WP/MMT
Cl inica l
assessmen t
and
aut orisa ti on of
prescri pt ion by
phar macist
I f disp ensing
requ ired
medi cines
ret urned t o
ward : -
Some/ all
medi cati on
req uired t o be
disp ensed
Medi cines
disp ensed
Trust
accre dit ed
and
regist ered
nurse t o p rint
au th orised
di scharge
summary and
check bef ore
issue of
di scharge
medicin es
NO med icat ion
requ ired t o b e
disp ensed
Endors ed
QS/ QSH on
t he TTO by
Pharmacy st af f
t o i ndica te
suf fi cient
quan ti ty
Pat i ent ha s at least 7 days
supp ly?
All medi cines/ dosa ges match
t hose on di scharge
pre script ion?
Remove di scont inu ed
medici nes f rom pa ti ent l ocker
Cont act ward
p harmacist (WP/ MMT)
Cont act Pha rma cy
Techn ician (WP/ MMT)
NO
NO
Pat ie nt t o be given cop y of
d ischarg e su mmar y and cop y
t o be f iled in ca se n ote s.



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


PRESCRIBING IN PALLIATIVE CARE

Contents (Click on heading to go to that section)

Pain Control
General principles
W.H.O Analgesic Ladder
Assessment and Management of Pain

W.H.O Analgesic Ladder
Step 1 Mild Pain
Step 3 Moderate Pain
Step 3 Severe Pain

Opioid Dose Conversion Ratios

Nausea and Vomiting in Palliative Care

Restlessness and Confusion

Breathlessness

Syringe Driver Therapy



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Pain Control - General Principles

- Pain is what the patient says it is and should be treated to the patient's
satisfaction.
- The perception of pain is affected by factors such as insomnia, depression,
anxiety, etc. and these should be addressed alongside the direct treatment of
pain.
- Accurately diagnose cause of pain as some forms of pain are only partially
responsive to opioids.
- 80% of patients will have more than one site of pain.
- Unless otherwise indicated, always use the oral route.
- Use REGULAR analgesia once source of pain is diagnosed. Do NOT
prescribe pain relief when required (except for breakthrough pain).
- Prescribe fast acting analgesia for breakthrough pain in addition to
maintenance therapy.
- Manage pain according to the W.H.O. analgesic ladder.
- Set realistic goals by negotiation with the patient.
- Re-assess frequently.
- Consider non-medicine treatments.
- Anticipate unwanted side effects of medication e.g. constipation , nausea and
vomiting


W.H.O. Analgesic Ladder

STEP 1 STEP 2 STEP 3
Strong opioids **
Morphine
Diamorphine
+ adjuvant*

Weak opioids **
Codeine phosphate
+ adjuvant*


Simple analgesics
Paracetamol
+ adjuvant*



*Adjuvant drugs may include co - analgesics e.g. NSAIDs, tricyclics, gabapentin or other means
of pain relief e.g. radiotherapy, intercostal block etc.
** Dose reduction required for patients with renal impairment and the elderly

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Assessment and Management of Pain
A full history and examination of the patient should be undertaken. Remember that the
patient may have more than one type of pain and their pain may not be related the main
diagnosis.
Cause of pain Management
Visceral W.H.O. analgesic ladder : see above
Headaches Non specific
- Paracetamol when required
Raised ICP
- Seek senior medical advice immediately
Gastro-intestinal pain Constipation
- Consider regular laxatives and enemas if indicated
Obstruction
- Faecal softeners e.g. docusate sodium and/or
antispasmodics
- Non-opioid analgesics
- If problem persists contact Palliative Care Team
Colic
- Hyoscine butylbromide 20mg by s.c. injection
repeated after 30 minutes if necessary.
Can be added to a syringe driver for s.c.
administration. Check compatibilities)
Muscle spasm Muscle relaxants such as baclofen (5-10mg three times a
day), diazepam (2-10mg daily) are useful
Metastatic bone pain NSAID plus morphine. Seek senior advice.
Radiotherapy may be appropriate for solitary metastases.
(Consider bisphosphonate if widespread metastases and
bone pain at multiple sites)
Nerve compression Addition of dexamethasone (8mg daily in divided doses) may
reduce the compression on a nerve.
Avoid giving dexamethasone after 2pm.
Seek senior or pain specialist advice.
Consider role of radiotherapy
Nerve pain Burning, itching, stabbing, electric shock type pain.
Treat according to W.H.O. ladder.
Co-analgesics are important for neuropathic pain as it may
respond only partially to opioids, these agents include
gabapentin, amitriptyline, pregabalin, carbamazepine and
clonazepam
Pleural pain Antibiotic if appropriate.
Intercostal block if localised (seek anaesthetic advice)
Analgesia (NSAIDS).
Incident Pain Ensure adequate background analgesia. Contact Pain
Team
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

W.H.O. Analgesic Ladder

STEP 1: MILD PAIN Simple analgesics
- Non opioid analgesics to be given regularly for mild pain.

- Medicine of choice is Paracetamol.
- Intravenous paracetamol is restricted to Anaesthetists, Palliative Care and
the Pain Team only, for use postoperatively in patients where the oral
route is inappropriate, or following the Palliative Care Teams advice. It
should be converted to the oral or rectal route as soon as possible.
- Move to Step 2 if correctly administered regular non - opioids are ineffective.


STEP 2: MODERATE PAIN Weak opioids
- Used in addition to non - opioids for mild to moderate pain
- Medicines of choice are codeine phosphate and dihydrocodeine.
- Co-codamol 8/500 or 30/500 may be more easily tolerated by patients on
multiple medications.
Even weak opioids cause side effects such as constipation and nausea.
Patients may develop tolerance to nausea and vomiting but not to
constipation, so prescribe prophylactic laxatives to patients receiving
regular doses of opioids.
- Move to Step 3 if weak opioids become ineffective.


STEP 3: SEVERE PAIN Strong opioids

- See below
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Choice of medicine Morphine is the strong opioid of choice for oral analgesia. It is contra-
indicated in renal failure. If GFR<30ml/min or if creatinine >200, seek
specialist palliative care advice.
Choice of route Oral administration is the route of choice when available. Parenteral
administration should only be considered if there is reduced
consciousness in the last few hours or days of life, vomiting or severe
dysphagia.

The preferred parenteral route is subcutaneous which is as effective
as the intramuscular route and much less painful.

Transdermal fentanyl should only be used for stable pain and should
be avoided or used with caution in elderly. It is one of the
recommended opioids for use in patients with renal impairment,
following palliative care advice. It is second line treatment.
Choice of dose and formulation The starting dose of a strong opioid should be dependent upon the
patient's previous analgesic requirements, age and general condition.
For frail and elderly patients smaller doses may be sufficient.
Seek specialist advice for patients in renal failure
Starting doses Previously on a non - opioid analgesic - Start with 2.5 to 5mg
morphine sulphate liquid orally as needed.

Previously on a weak opioid - Start with 2.5 to 5mg of morphine
sulphate liquid or short acting tablets (Sevredol) every 4 hours and
when required.


- Titrate the dose to the patient's pain. The aim is to prevent the pain returning
before the next dose. After each dose of opioid monitor response and review.

- Regular analgesic requirements can be assessed by calculating the total dose
of morphine administered in the previous 24 hours.

- Prescriptions for morphine and oxycodone must specify either "immediate" or
"sustained release" preparation. Use the brand name for the preparation used.
Initiation of oxycontin and oxynorm is restricted to Acute Pain Team and
Palliative Care Team only.

- Once pain is controlled, oral morphine liquid / immediate release tabs can be
converted to a 12 hourly - sustained release preparation using the total daily
morphine dose given (click here for approximate equivalent doses).

- Morphine liquid should always be prescribed 'when required' after conversion
to a slow release preparation to manage any breakthrough pain and calculate
further amendments to the regular dosing schedule. Prescribe one sixth of the
daily morphine dose as a `when required' dose. e.g. when a patient is on
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

12hourly sustained release morphine tablets, 120mg twice daily orally, the
correct breakthrough dose of morphine liquid (oramorph 10mg/5ml) is 1/6 of
240mg (total daily dose is 2x120mg) which equals 40mg prn PO.

- Click here for strengths of morphine sulphate preparations available.

- Fentanyl is available in a transdermal patch formulation. This can ONLY be
used in patients whose analgesic requirements are stable and where the
patients condition is stable (not patients who are deteriorating). Seek
Palliative Care Team advice if considering using fentanyl patches

- If pain remains uncontrolled despite several breakthrough doses of analgesia,
contact specialist team for advice.

- There is no maximum dose of strong opioid if the patient is in pain, and not
opioid toxic. It is possible for a patient with opioid resistant pain to become
toxic if their pain is unresponsive to opioids. The effect of each opioid dose
should be assessed. If the patient appears toxic but still in pain or is getting no
relief from their when required opioid, contact the Palliative Care team.

- Always prescribe regular combination (softener plus stimulant) laxatives for
patients on regular opioids (strong or weak).

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Summary Guidelines for Use of Strong Opioids

Always prescribe regular combination laxatives and when required anti-emetics

Oral route of choice


Previous analgesia



Regular doses of weak opioid Regular doses of non-opioids


2.5-5mg morphine sulphate 2.5-5mg Morphine sulphate liquid
liquid every 4 hours every 4 hours



Is it effective?



YES NO
Continue with same dose. Increase dose by 25-50 %
Monitor efficacy



Convert to oral slow release preparations. Calculate total opioid requirement and divide by 2.
e.g. required 4x 10mg doses of morphine liquid in previous 24 hours = 40mg oral morphine in
24 hours = 20mg of morphine SR tablets (MST) every 12 hours.


Maintain when required dose of morphine liquid for breakthrough pain (one sixth of total
daily morphine dose)


If regular SR morphine tablets are not controlling pain increase the doses according to the
total amount of when required doses used, but do not increase by more than 50% of
previous 24 hour dose (as advised above). Increase by 30-50%. Remember to increase
breakthrough doses as the SR doses go up.

If oral route not available use subcutaneous injections or 24 hour infusion instead.

NB immediate release morphine tablets also available (Sevredol)

If there is evidence of toxicity please reduce the opiate dose by 30-50% and reduce the
breakthrough doses correspondingly.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Preparations
- Paracetamol
tablets/suppositories
By mouth or rectum, 0.5 - 1g every 4 to 6 hours when
required.
Max. 4g daily
- Diclofenac By mouth or rectum, 50mg 150mg daily in divided doses
Sustained release tablet 75mg twice daily
- Codeine phosphate By mouth, 30mg tablets, 25mg/5ml syrup
30 - 60mg every 4 hours when required. Max 240mg daily.
- Co-codamol This is a combination of paracetamol and codeine phosphate
Do not co-prescribe with paracetamol.
Available in tablet and dispersible formulations,
8/500 and 30/500 strengths. Maximum 8 tablets in 24 hours
- Dihydrocodeine By mouth, 30mg tablets, 10mg/5ml syrup
30-60mg every 4 to 6 hours when required. Max. 240mg daily
- CD Morphine
sulphate
By mouth
Please prescribe all oral opioids by the dose in mg.
Prescribing by volume (e.g. ml) is not acceptable as they
come in different preparations and concentrations and
may lead to the wrong dose being given.
Short acting preparations;
- Morphine sulphate 10mg/5ml available as oral solution
- Morphine sulphate is also available as a concentrated
oral solution 20mg/1ml. For use in patients requiring
very high doses of morphine
- Morphine sulphate tablets 10mg, 20mg, 50mg
(Sevredol)

Long acting preparations (twice daily)
- Morphine sulphate s/r tablets 5mg, 10mg, 30mg,
60mg, 100mg, 200mg
- Morphine sulphate s/r sachets , 20mg, 30mg, 60mg,
100mg, 200mg.
- Morphgesic is the brand kept at RLBUHT
- There are other preparations that patients may be
admitted on including MST, Zomorph, Morcap. Please
contact, pharmacy or palliative care team if unsure of
preparation.


Extra long acting preparations (once daily)
- Morphine sulphate m/r capsules (MXL)
Palliative Care Team only, unless patient admitted on
this brand when any doctor can prescribe.

Parenteral preparations:
- Morphine sulphate injection 10mg, 15mg, 20mg, 30mg.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

- CD Diamorphine
injection
Available as 5mg, 10mg, 30mg, 100mg, 500mg vials
- CD Oxycodone By mouth
Please prescribe all oral opioids by the dose in mg.
Short acting preparations immediate release
- Oxynorm oral solution 5mg/5ml
- Oxynorm concentrated oral solution 10mg/ 1ml

Long acting preparations (twice daily)
- Oxycontin 5mg, 10mg, 20mg, 40mg, 80mg tablets

Parenteral preparations:
- Oxycodone injection 10mg/ml 2ml ampoules
- CD Fentanyl


Palliative Care / Pain Team only

Patches: mcg per hour patches: 12, 25, 50, 75, 100

Sublingual tablets (Abstral): 100mcg, 200mcg, 300mcg,
400mcg, 600mcg, 800mcg

Nasal Spray (PecFent): 100mcg, 400mcg


- CD Hydromorphone Palliative Care Team only
Oral preparations only in both immediate and modified release
forms.
- CD Alfentanil Palliative Care Team only
Subcutaneous use only, very potent and short acting. Safer in
renal failure than other opioids.



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Opioid Dose Conversion Ratios

General approach
This is a summary of selected opioid dose conversion ratios. These can be used to
calculate equivalent doses of opioids when switching from a weak opioid to
morphine, or from one strong opioid to another. Caution is always necessary.
Conversion ratios can never be more than an approximate guide because of:
- Wide inter-individual variation in opioid pharmacokinetics
- Other variables such as nutritional status and concurrent medication
- Data derived from single dose rather than chronic dose studies.
Thus, careful monitoring during conversion is necessary to avoid both under-dosing
and excessive dosing. This is particularly the case if:
- switching at high doses
- there has been a recent rapid escalation of the first opioid
- switching to methadone.
When switching at high doses (e.g. morphine or equivalent doses of 1g/24h), it is
generally good practice to prescribe a lower than calculated dose (e.g. 1/31/2
lower), and rely on p.r.n. doses to make up any deficit while re-titrating to a
satisfactory dose of the new opioid. In a comparably cautious way, when there has
been a recent rapid dose escalation of the first opioid, use the pre-escalation dose to
calculate the initial dose of the second opioid
The Tables below relate mainly to switching to or from morphine. If switching from
an opioid other than morphine to another opioid, it will be necessary to convert the
dose of the first opioid to morphine equivalents, and then use that quantity to
determine the dose of the second opioid. With any switch:
- round the calculated dose up or down to the nearest convenient dose of the
preparation concerned, e.g. tablet, TD patch, ampoule
- decide on an appropriate p.r.n. dose.
The conversion ratios are taken from the 3
rd
edition of the Palliative Care Formulary.



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Approximate dose conversion ratios: PO to PO
Conversion Ratio Calculation Example
Codeine to morphine 10:1
Divide 24h codeine dose
by 10
Codeine 240mg/24h PO
morphine 24mg/24h PO
Dihydrocodeine to morphine 10:1
Divide 24h dihydrocodeine
dose by 10
Dihydrocodeine 240mg/24h
PO morphine 24mg/24h
PO
Hydrocodone to morphine 1.5:1
Divide 24h hydrocodone
dose by 1.5
(decrease dose by 1/3)
Hydrocodone 60mg 24h PO
morphine 40mg/24h PO
Tramadol to morphine 10:1
Divide 24h tramadol dose
by 10
Tramadol 400mg/24h PO
morphine 40mg/24h PO
Morphine to hydromorphone
5:1
a


7.5:1
b

Divide 24h morphine dose
by 5


Divide 24h morphine dose
by 7.5
Morphine 60mg/24h PO
hydromorphone
12mg/24h PO

Morphine 60mg/24h PO
hydromorphone 8mg/24h
PO
Morphine to methadone Variable Contact palliative care for advice
Morphine to oxycodone
1.5:1


2:1
b

Divide 24h morphine dose
by 1.5
(decrease dose by 1/3)

Divide 24h morphine dose
by 2
Morphine 30mg/24h PO
oxycodone 20mg/24h PO


Morphine 30mg/24h PO
oxycodone 15mg/24h PO


a. for converse, some use 1:4, e.g. hydromorphone 8mg/24h POmorphine 32mg/24h PO
b. italicized entries=manufacturers recommendations.

See below for dose conversion ratios; PO to SC/IV and SC/IV to SC/IV
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Approximate dose conversion ratios; PO to SC/IV
Conversion Ratio Calculation Example
Hydromorphone to
hydromorphone
2:1
Divide 24h hydromorphone
dose by 2
Hydromorphone 32mg/24h PO
hydromorphone 16mg/24h
SC/IV
Methadone to methadone 2:1
a

Divide 24h methadone dose by
2
Methadone 30mg/24h PO
methadone 15mg/24h SC/IV
Morphine to alfentanil 3040:1
Divide 24h morphine dose by
3040
Morphine 40mg/24h PO
alfentanil 1mg/24h SC/IV
Morphine to diamorphine 3:1 Divide 24h morphine dose by 3
Morphine 30mg/24h PO
diamorphine 10mg/24h SC/IV
Morphine to hydromorphone 1015:1
Divide 24h morphine dose by
1015
Morphine 30mg/24h PO
hydromorphone 2mg/24h
SC/IV
Morphine to methadone Variable Contact palliative care for advice
Morphine to morphine 2:1 Divide 24h morphine dose by 2
Morphine 30mg/24h PO
morphine 15mg/24h SC/IV
Morphine to oxycodone 2:1 Divide 24h morphine dose by 2
Morphine 60mg/24h PO
oxycodone 30mg/24h SC/IV
Oxycodone to oxycodone
1.5:1

2:1
b

Divide 24h oxycodone dose by
1.5 (decrease dose by 1/3)

Divide 24h oxycodone dose by
2

Oxycodone 30mg/24h PO
oxycodone 20mg/24h SC/IV

Oxycodone 30mg/24h PO
oxycodone 15mg/24h SC/IV

a. because the mean oral bio-availability is 80% (range 40100%), some centres use 1:1, e.g.
methadone 30mg/24h PO methadone 30mg/24h SC/IV

b. italicized entries=manufacturers recommendations.
See below for dose conversion ratios; SC/IV to SC/IV

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Approximate dose conversion ratios; SC/IV to SC/IV
Conversion Ratio Calculation Example
Morphine to alfentanil 1520:1
Divide 24h morphine
dose by 1520
Morphine 40mg/24h SC/IV
alfentanil 2mg/24h SC/IV
Morphine to buprenorphine 3040:1
Divide 24h morphine
dose in mg by 3040
Morphine 40mg/24h SC/IV
buprenorphine 1mg /24h
SC/IV
Morphine to hydromorphone 5:1
Divide 24h morphine
dose by 5
Morphine 30mg/24h SC/IV
hydromorphone 6mg/24h
SC/IV
Morphine to methadone Variable Contact palliative care for advice
Morphine to oxycodone 1:1
Use same dose as 24h
morphine dose
Morphine 30mg/24h SC/IV
oxycodone 30mg/24h
SC/IV


Side Effects of Opioid Analgesics
Constipation: Prophylactic combination laxatives should be given routinely to
all patients receiving regular opioids. Titrate the dose to the
degree of constipation.
Nausea, vomiting Occurs in approximately 30% of patients, usually mild and self-
limiting. Approximately 1% have persistent N+V secondary to
their opioid as it usually resolves within 72hours. Prophylactic
anti - emetics should be prescribed 'when required'
Sedation and confusion Usually mild and self limiting lasting 2 - 3 days. If persistent
reassess and consider dosage, alternatives and adjuvant drugs.
Consider dose reduction or switching opiates
Respiratory depression
Tolerance
Dependence/addiction
Safe if titrated upwards gradually. If guidelines are followed
these side effects are not a problem in palliative care. For further
advice contact the palliative care team.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Co analgesics

Metastatic Bone Pain
NSAIDs are the analgesic of choice if there is an inflammatory component. All NSAIDs are
gastric irritants whichever route they are administered by and are contra-indicated in severe
renal impairment. NSAIDs and opioids are often used in combination.

- Ibuprofen tablets/syrup 400mg 3 times daily after food increased if necessary.
Maximum dose 2.4g daily.
- Diclofenac By mouth 25 - 50mg 3 times daily after food or
75mg m/r twice daily or 100mg m/r once daily.

By rectum 100mg at night.

Maximum daily dose by any route is 150mg.
- Celecoxib capsules


By mouth, 100mg - 200 mg twice daily
Consult BNF for contra-indications

Neuropathic pain

- Amitriptyline tablets Start with 10-25mg, (10mg in the elderly) taken in the early
evening to avoid hangover effect. Pain relief may begin in 1
7 days. Rate of increase depends on pain level and
degree of supervision. If tolerated dose may be increased
by about 25mg every three days to 100mg at night.

Elderly: rate of increase may need to be slower e.g. 25mg
per week.
Caution in cardiac disease as increases the risk of
tachyarrythmias
- Gabapentin capsules Initial dose 300mg at night on day 1
300mg BD on day 2
300mg TDS day 3
Maximum dose is 3600mg in divided doses

Side effects may be sedation or drowsiness and myoclonus
which can be mistaken for opioid toxicity.
- Pregabalin Second line after trying gabapentin/ amitriptyline
Initial dose 25mg BD

Gradual titration to a maximum dose of 300mg BD.
- Others including;
clonazepam, sodium
valproate,
carbamazepine
Palliative Care Team initiation only


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Constipation
This is a common problem and is often a cause of great discomfort and distress.
Prevention is the best strategy and all patients receiving opioids should receive
combination laxatives.
All patients will require a regular softener in addition to a stimulant laxative.
In cases of established constipation potentially reversible causes should be
excluded, such as bowel obstruction, hypercalcaemia, anticholinergic medications,
dehydration, etc.

Stimulant laxatives

Co-Danthramer restricted indication. Use restrictes to terminally ill patients of all
ages only. This is a combination of danthron which is a stimulant laxative and a
poloxamer which is a stool softener. Danthron is an irritant to the skin and should not
be used in incontinent patients as it may cause blistering and burns. Warn patients
about change in urine colour (dark red).


4 step method for titration of codanthramer:

Step 1: Codanthramer 25/200 suspension 10ml on or Codanthramer 25/200
capsules 2 caps on
Step 2: Codanthramer suspension 10ml bd or Codanthramer capsules 2 caps
bd

Step 3: Codanthramer (75/1000) strong suspension 5ml bd or Codanthramer
strong (37.5/500) capsules 2 caps bd

Step 4: Codanthramer strong suspension 10ml bd or Codanthramer strong
capsules 4 caps bd
- Codanthramer 25/200 caps and suspension 1-2 caps (5-10ml) at bedtime initially to
be increased to bd as needed
- Strong Codanthramer caps 37.5/500 1-2 caps at bedtime to be increased to
bd as needed
- Strong codanthramer suspension 75/1000 in
5ml
5ml 10ml at bedtime to be increased
to bd as needed
- Senna tabs/ syrup 7.5mg 2-4 tablets at bedtime
- Docusate sodium caps 100mg / oral solution
50mg/5ml
Up to 500mg daily in divided doses

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Docusate is a stool softener that has weak stimulant properties. In doses above
400mg/24h it acts as a stimulant and a softener. Avoid elixir as it tastes unpleasant.

Osmotic/ Bulk forming Laxatives
Lactulose
Movicol
Magnesium hydroxide

These work by retaining and drawing fluids into the bowel lumen and increasing stool
bulk. They are not recommended in Palliative patients as they are burdensome as
the volume of liquid taken with osmotic laxative does not contribute to hydration and
is kept within the gut, but usually limits what the patient can then tolerate orally and it
may contribute to dehydration. Extension of the gut wall causes increased peristalsis
but they are not stimulants and therefore not considered combination laxatives.
Lactulose increases wind.


Opioid induced constipation
For opioid induced constipation subcutaneous methylnaltrexone (Relistor) a
peripheral -opioid antagonist may be considered and is licensed for the induction of
prompt bowel movements when response to usual laxative therapy has been
insufficient. It comes in 12 mg/0.6 mL single-use vials for subcutaneous use every other
day, although longer intervals will be permitted, as per clinical need. It works, on
average, within 2 hours. The recommended dose is 8 mg for patients weighing between
38-62 kg or 12 mg for patients weighing 62-114 kg. Patients whose weight falls outside
of these ranges should be dosed at 0.15 mg/kg. It is not licenced for use in renal or
hepatic failure. Methylnaltrexone should only be prescribed following Palliative
Care Team advice.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Nausea and Vomiting in Palliative Care
It is very important that the cause is identified as treatment varies. Constipation,
intestinal obstruction, medicine induced and hypercalcaemia are common causes of
nausea and should be rectified by appropriate treatments.
If nausea persists for more than 48 hours gastric stasis may occur and oral medicines
will not be absorbed. Use subcutaneous route. Note the subcutaneous route is an off
licence route of administration.

Anti - emetics acting at the chemoreceptor trigger zone are useful during the first few
days of opioid therapy. The patient will become tolerant to the nauseous effect of
opioids after a few days.

Where a single agent has failed to control nausea, a combination of an agent acting at
the chemoreceptor trigger zone and one acting at the vomiting centre will often be
effective. (e.g. cyclizine and Haloperidol)

Anti - emetics acting at the Chemoreceptor Trigger Zone (CTZ)
- Haloperidol By mouth or s/c injection
1.5mg at night upto BD
- Metoclopramide By mouth, s.c* or i.m. injection
10mg 3 times daily

By s.c. infusion via syringe driver*
30 mg over 24 hours in water for injection.

*Subcutaneous route of administration is off licence
and higher doses may be recommended by the
Palliative Care Team.
- Levomepromazine Broad spectrum antiemetic with weaker effects on
CTZ than haloperidol and metoclopramide.
6.25mg 25mg by mouth, s.c. injection or infusion
over 24 hours

Metoclopramide is a gastrointestinal prokinetic and may cause colic or perforation if used in
complete bowel obstruction.

Anti - emetics acting at the Vomiting Centre
- Cyclizine
Tablets / injection
By mouth, s.c. injection 50mg 3 times daily or
subcutaneous infusion of 150mg over 24 hours

- Levomepromazine Broad spectrum antiemetic.
6.25mg 25mg by mouth, s.c. injection or infusion
over 24 hours

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Anti - emetics acting on the Gastrointestinal tract
Prokinetics

- Metoclopramide By mouth, s.c* or i.m. injection
10mg 3 times daily

By s.c. infusion via syringe driver*
30 mg over 24 hours in water for injection.

*Subcutaneous route of administration is off licence
and higher doses may be recommended by the
Palliative Care Team.
- Domperidone By mouth 10-20mg 3-4 times daily

Per rectum (30mg suppositories) 30-60mg bd


Gut chemoreceptors

- Ondansetron By mouth, s.c. or i.v. injection 4-8mg 3 times daily
By s.c. infusion via syringe driver 8-32mg over 24
hours

- Granisetron Oncologist only





The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Excessive Respiratory Secretion
Palliative Care Team use only

First Line
- Hyoscine hydrobromide

By s.c. injection, 400 - 600 micrograms every 4 8 hours

By s.c. infusion, 1200 - 2400micrograms over 24 hours
- May cause sedation / agitation
- May cause confusion at higher doses
Second line
- Glycopyrronium

By s.c. injection , 200 - 400microgram every 4-6 hours

By s.c. infusion, 1200 - 2400 micrograms over 24 hours



Restlessness and Confusion

Medicine choice depends on symptoms described, use midazolam or lorazepam if
agitated, haloperidol may be more effective if patient is hallucinating.
- Haloperidol
tablets/injections
May cause sedation
By mouth, 1.5 3mg od or prn.
(usual maximum 10mg/24hours)

By s.c. infusion*, 5mg/ml and 20mg/2ml
3-5mg over 24 hours.
- Lorazepam tablets Sublingually, 0.5 1mg as required, (maximum 4mg/24
hours)
- Midazolam injection CD By s.c. injection 2.5-5mg as required

By s.c. infusion*
Start with 5-10mg over 24 hours.
Titrate up to 30mg over 24 hours as needed. If symptoms
still uncontrolled contact the Palliative Care Team for further
advice.

* subcutaneous route of administration is off licence.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Breathlessness
Medicine choice depends on symptoms described, use midazolam or lorazepam if
agitated, haloperidol may be more effective if patient is hallucinating.

- Morphine sulphate By mouth / s.c. injection
2.5mg 5mg every 4 hours.
- Lorazepam tablets Sublingually
0.5mg 1mg as required, (maximum 4mg/24hours)


Midazolam 2.5-5mg sc when anxiety is severe

If breathlessness is still a problem refer to the Palliative Care Team.



Syringe Driver Therapy

Subcutaneous syringe driver therapy is not a panacea for symptom control. There is no
evidence that in chronic cancer pain the parenteral route is more effective. Indications
include:
- Dying phase if appropriate
- Persistent nausea and vomiting
- Severe dysphagia
- Too weak for oral route
- Poor absorption

If more than one medicine is to be administered in the syringe driver, specialist
advice should be obtained as certain medicine combinations may cause
precipitation. (Click here).

General guidelines
- Change syringe every 24 hours
- Check infusion regularly, at least every 4 hours, for local skin reactions and
the syringe for precipitation/crystals
- For advice on medicine combinations contact pharmacy or palliative care team

Calculation of diamorphine Requirements
- If patient already taking morphine or other strong opioid:

Conversion from oral morphine to subcutaneous diamorphine is 3:1
Calculate the 24 hour dose of morphine and divide this total dose by three.
E.g. 90mg of MST twice daily = 180mg morphine sulphate / 24hours
= 60mg diamorphine in the pump s.c. over 24hours.

Prescriber must state on the medication chart that the dose is
administered over 24 hours
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- If patient has pain and is not taking morphine or other strong opioid use either:

Diamorphine 2.5 - 5mg s.c. injection PRN every 4 hours
OR
Diamorphine 10mg by s.c. infusion via a syringe driver over 24 hours

- To calculate an appropriate four hourly PRN diamorphine dose for
breakthrough pain:

Divide the 24 hour dose of diamorphine in the syringe driver by six
e.g. 60mg diamorphine in the syringe driver, prescribe PRN 10mg s.c. every
four hours

- To calculate the subsequent doses of diamorphine over 24 hours:
Add the dose of diamorphine in the syringe driver to the diamorphine given
PRN in the previous 24 hours. The maximum recommended dose increase is
50% of the current 24 hour opioid dose.
E.g. 30mg in syringe driver over 24 hours and an additional 4 x 5mg prn s.c.
doses required in the last 24 hours. The new dose for the syringe driver would
work out as 30mg plus 20mg from the prns, as this is more than a 50% dose
increase in the syringe driver the maximum safe increase should be to 45mg
over 24 hours.

- Then calculate a new PRN dose (one sixth of new dose), to ensure that pain
requirements are met after increasing the syringe driver dose. In the example
above it would be 7.5mg s.c. prn. (one sixth of 45mg)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

SYRINGE DRIVER COMPATIBILITIES

Always use Water for Injection as diluent

Subcutaneous administration of medicines all listed below is off licence

Medicine Compatibility with
Diamorphine
Comments
Haloperidol Yes
Metoclopramide Yes
Cyclizine Caution To avoid precipitation keep both
Concentrations below 20mg/ml. Use water for
injections as diluent.
Levomepromazine
(methotrimeprazine)
Caution Powerful sedative
Caution with doses greater than 100mg
Glycopyrronium Yes
Midazolam Yes
Hyoscine hydrobromide Yes
Hyoscine butylbromide Yes Do not use with cyclizine - causes precipitation
Octreotide Yes
Dexamethasone Avoid May be administered as bolus subcutaneous
dose, or use a separate syringe driver

If precipitation/ crystallization is seen in the syringe stop the pump, seek pharmacy or
palliative care advice, then replace the syringe and line with maximum dilution.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Prescribing For Older People

Prescribing for older people can often prove more challenging than for the general
adult population. Adverse drug reactions are more common due to multiple pathology
and associated polytherapy. Older patients may have difficulty complying with
complex regimens involving many medicines, so mistakes are more likely.

The side effects of treatment may present atypically and are often incorrectly
attributed to the disease being treated e.g. "giddiness" caused by postural
hypotension treated as vertigo. There are also age - related changes in the
absorption, distribution, metabolism and excretion of medicines, which should be
taken into account. End - organ sensitivity to medicines may change e.g. exaggerated
central nervous system responses.

Practical Guidelines to aid prescribing

1) Make sure that the symptom you are treating is not itself due to current
medication. When an older patient is ill, especially if the symptoms are non -
specific (e.g. incontinence, confusion), the cause may be a medicine they are
taking

2) Remember that non - neurological medicines may have adverse effects on the
central nervous system e.g. digoxin which may produce a chronic confusional
state.

3) Assume that all medication may produce adverse effects. Weigh the risks
against the benefits if prescribing new medication. The prescribing of Non-
Steroidal Anti inflammatory drugs especially carries a high risk.

4) Prescribe low doses when indicated. The British National Formulary often gives
advice, but if you are uncertain, consult your ward pharmacist or Medicines
Information (ext 2096).

5) Keep the number of medicines prescribed to an absolute minimum.

6) Explain the reason for each medicine to the patient, how to take it and when to
finish the course. Seek the advice of the pharmacist where necessary for help in
ensuring compliance when the patient is discharged from hospital.

7) Be aware of any special precautions or patient monitoring which may be
necessary. Plasma level monitoring is mandatory for aminoglycosides e.g.
gentamicin, and recommended for other medications such as phenytoin,
theophylline, lithium and digoxin

8) Keep all medication under review. Do not repeat prescriptions unless there is
a good reason for continuing therapy.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Compliance Issues

Defective hearing, poor eye sight, impaired memory and confusion all contribute to
difficulties in understanding and being able to take medication as prescribed. It is
important to ascertain who will be administering medication when the patient is
discharged from hospital. The first stage in ensuring compliance rests with giving
adequate verbal explanation and instructions to the patient and/or their carers.
Please discuss any problems identified with medication with the ward pharmacist who is
able to provide medication reminder cards or other compliance aids e.g. Haleraids, etc.
Medication may be able to be provided in a dosette box/blister pack; however this is not
suitable for all patients. An assessment of suitability must be made by the ward
pharmacist and arrangements made for provision of this service on discharge. Advance
notice, preferably at least 24 hours before discharge is needed to be able to complete
this procedure and dispense medication.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
Therapeutic Concentration Monitoring

Measurement of medicine concentration may be of value in the assessment of
compliance, therapeutic control, or confirmation of clinical toxicity.

The following table gives guidance on appropriate sampling times and accepted
therapeutic ranges for those medicines in which monitoring is advisable because of
erratic or unpredictable dose response relationships or narrow therapeutic ranges.

The time to steady state indicates the appropriate interval required before blood
sampling after the initiation of therapy or dose change. Sampling before this time may
produce misleading results. Please note sampling time relative to last dose on blood
form.

If in doubt, contact your ward pharmacist or Medicines Information (ext. 2096). Advice
may also be sought from Microbiology for antibiotic concentration monitoring or from
Clinical Biochemistry for other medicines.

Note: The medicine interactions listed in the table below are common examples
of interactions where plasma drug concentrations are affected. It is not a
comprehensive list. Other medicines may interact without affecting plasma
concentrations. Refer to the BNF, your ward pharmacist or Medicines Information
(ext. 2096) for further information.



MEDICINE PHARMACOKINETIC
PARAMETERS
TIME TO
STEADY
STATE
IDEAL
SAMPLING
TIME
ACCEPTED
THERAPEUTIC
RANGE
COMMENTS
Aminophylline see
Theophylline
Carbamazepine T
50
= 12 17 hours

F (tablet) = 70-79%
F (liquid) = 96%

Vd = 0.8 to 2L/kg
2 - 4
weeks
after
starting
therapy
or 2 - 6
days
after
dose
change.
Trough level.
Take
immediately
before next
oral dose.
4 10 mg/L Metabolism is
self induced
initially (increase
dose over 2 - 4
weeks).
Carbamazepine
has an active
metabolite.
Levels |d by:
Erythromycin,
Clarithromycin,
Cimetidine.
Ciclosporin
CyAMS
measures
parent
ciclosporin only.

CyAMS total
parent medicine
and major
metabolites
T
50
= 19 hours (10-27
hours).

F (tablet) = 10-89%

Vd = 3.9 to 4.5L/kg
3-5 days Trough level.
Take
immediately
before next
dose
Renal
Transplant:
150 - 275g/L
CyAMS
(post-transplant)
100 - 200g/L
CyAMS
(stable graft
conditions)

Bone Marrow
Transplant:
200 - 300g/L
CyAMS

Auto-immune
disease:
100 - 150g/L
CyAMS
For further
information see
the Laboratory
Handbook.
In dual therapy
for renal
transplant levels
may be lower.

Levels |d by:
Allopurinol,
Erythromycin,
Clarithromycin,
Ciprofloxacin,
hormones,
Cimetidine,
Fluconazole

Levels +d by:
Enzyme
inducing
antiepileptics,
Rifampicin, St.
Johns Wort.

Toxic
concentration
CyAMS >
350g/L.
Toxicity is
sometimes
manifested by
raising serum
creatinine.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINE PHARMACOKINETIC
PARAMETERS
TIME TO
STEADY
IDEAL ACCEPTED COMMENTS
STATE
SAMPLING THERAPEUTIC
TIME RANGE
Digoxin
T
50
= 36 to 48 hours

F (tablet) = 70%
F (liquid) = 80%

Vd = 4-7L/kg (IBW)
5 - 7
days
At least 6 - 8
hrs after last
dose (oral or
iv) or
immediately
pre dose
1 - 2 g/L Dose reduction
may be
necessary in
elderly or renally
impaired.
Levels |d by:
Amiodarone,
Calcium Channel
Blockers,
Quinine and
Quinidine.
Lithium
T
50
= 14-24 hours (up
to 36 hours in elderly.
Also increased in
patients on long term
therapy, up to 48
hours).

F = 100%

Vd = 0.7-1.4L/kg
3 - 7
days
Trough level.
Take
immediately
before next
oral dose
(doses
usually 12 -
24hrly)
0.4 - 1 mmol/L Levels |d by:
ACE inhibitors,
NSAIDs,
diuretics,
dehydration and
renal
impairment.
Antipsychotics
and SSRIs may
| neurological
toxicities due to
lithium.
Phenobarbital T
50
= 36 hours - 5
days

F = 80-100%

Vd = 0.5-1L/kg
10 - 25
days
Trough level.
Take
immediately
before next
oral dose
10 30 mg/L Has a long half
life, up to 5 days.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINE PHARMACOKINETIC
PARAMETERS
TIME TO
STEADY
IDEAL ACCEPTED COMMENTS
STATE
SAMPLING THERAPEUTIC
TIME RANGE
Phenytoin T
50
= 7-42 hours

F = 70-100%

Vd = 0.65L/kg
7 - 35
days
Immediately
before next
oral dose. (2
4 hrs after
IV dose)
8 15 mg/L The rate of
phenytoin
metabolism
reaches
maximum at
therapeutic
concentrations.
Half life | with |
dose (i.e. a small
| in the
maintenance
dose can lead to
a
disproportionate
| in plasma
concentration).

Levels+d by
Carbamazepine.
Levels may be |
or + by Sodium
valproate.

Levels |d by:
Cimetidine,
Omeprazole,
Metronidazole,
Fluconazole.
Sodium
valproate
(valproic acid)
T
50
= 8-20 hours

F = 90-100%

Vd = 0.1-0.5L/kg
2 - 3
days
Trough level.
Take
immediately
before next
oral dose
50 100 mg/L
for epilepsy.

50-125 mg/L for
acute mania.
Monitoring only
useful to check
compliance,
therapeutic effect
may lag behind
therapeutic
plasma level.
Levels |d by
Cimetidine.
Levels +d by
Carbamazepine.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINE PHARMACOKINETIC
PARAMETERS
TIME TO
STEADY
IDEAL ACCEPTED COMMENTS
STATE
SAMPLING THERAPEUTIC
TIME RANGE
Tacrolimus T
50
= 9-12 hours
(increased in liver
dysfunction).

F = 14-32%

Vd = 0.85-1.91L/kg
2 days Trough level.
Take
Immediately
before next
oral dose
Renal
Transplant:
10 - 20g/L

Auto-immune
disease:
5 - 15g/L
Levels >20g/L
may be
associated with
nephrotoxicity
and glucose
intolerance.

Levels |d by:
Erythromycin,
Clarithromycin,
grapefruit juice,
Fluconazole.
Theophylline
Aminophylline
T
50
= 3-13 hours

F = 100%

Vd = 0.5L/kg

NB Aminophylline
salt factor is 0.8
2 - 3
days
PO -Trough
level. Take
immediately
before next
oral dose.

IV take after
patient has
been on the
infusion for at
least 2 hours.
10 20 mg/L Levels |d by:
Cimetidine,
Ciprofloxacin,
Erythromycin,
Clarithromycin.

Levels +d by:
Enzyme inducing
anticonvulsants,
Rifampicin,
smoking.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINE PHARMACOKINETIC
PARAMETERS
TIME TO
STEADY
IDEAL ACCEPTED COMMENTS
STATE
SAMPLING THERAPEUTIC
TIME RANGE
Gentamicin
and
Tobramycin (s)
T
50
= 2-3 hours in
normal renal function.
T50 is significantly
increased in patients
with renal
dysfunction, or burns.
(may be > 70 hours
in anuric patients)

F = poorly orally
absorbed, must be
given parenterally.

Vd = 0.25L/kg
24 hours Trough:
Immediately
before next
dose

Peak: 1 hr
after dose
administration
Trough:
< 1mg/L

Peak:
6 - 10mg/L for
most infections

Peak is 3-5mg/L
for subacute
endcoarditits

NB peaks are
not generally
monitored for
ONCE a day
dosing of
aminoglycosides.
See Trust
Antimicrobial
policy.

Note: CAUTION
IF CO -
ADMINISTERED
WITH OTHER
NEPHROTOXIC
MEDICINES.
- Generally
peak is
affected by
dose and the
trough
affected by
frequency.
- High
concentratio
ns of certain
penicillins
may
inactivate
aminoglycosi
des in vivo
e.g.
Piperacillin,
Ticarcillin.
Amikacin (s) T
50
= 2-3 hours in
normal renal function.
T
50
is significantly
increased in patients
with renal
dysfunction, or burns.
(may be > 70 hours
in anuric patients)

F = poorly orally
absorbed, must be
given parenterally.

Vd = 0.25L/kg
24 hours Trough:
Immediately
before next
dose

Peak: 1 hr
after dose
administration
Trough:
< 10mg/L

Peak:
20 - 30mg/L
- Levels may
be in
elderly,
dehydrated
or renally
impaired
patients.
- High
concentratio
ns of certain
penicillins
may
inactivate
aminoglycosi
des in vivo
e.g.
Piperacillin,
Ticarcillin.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINE PHARMACOKINETIC
PARAMETERS
TIME TO
STEADY
IDEAL ACCEPTED COMMENTS
STATE
SAMPLING THERAPEUTIC
TIME RANGE
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
Teicoplanin T
50
= 90-160 hours

F = poorly orally
absorbed, must be
given parenterally.

Vd = 1.13L/kg
Trough:
Immediately
before next
dose

Levels
should be
taken
BEFORE
giving the
dose on the
3rd or 4th
day.

NB always
give the dose,
DO NOT
WAIT for
levels to be
reported.

Trough:
10mg/L
and <
60mg/L.

NB for
endocarditis,
osteomyleitis
and septic
arthritis the
trough should be
> 20mg/L.


See Trust
Antimicrobial
policy


Serum
concentration
monitoring is
required in
patients who
have any of the
following:

1. present with
severe
infections such
as septicaemia
or deep seated
staphylococcal
infection
(including bone
and joint
infection)

2. are
intravenous
drug abusers

3. present with
burns

4. present with
impaired,
deteriorating, or
unstable renal
function

5. are
undergoing
renal
replacement
therapy (CRRT,
HD and PD).

Levels are not
routinely
required for
patients not
fulfilling the
above criteria.

Contact
microbiology for
advice if unsure
if levels required

MEDICINE PHARMACOKINETIC
PARAMETERS
TIME TO
STEADY
IDEAL ACCEPTED COMMENTS
STATE
SAMPLING THERAPEUTIC
TIME RANGE
Vancomycin T
50
= 4-6 hours in
normal renal function.
T
50
is significantly
increased in patients
with renal
dysfunction, (may be
> 7 days in anuric
patients)

F = poorly orally
absorbed, must be
given parenterally.

Vd = 0.2-1.5L/kg
72 hrs
for initial
therapy.

24 - 48
hrs after
dose
change.
Trough:
Immediately
before
infusion.

Peak: 1 hr
after dose
administration


Trough:
< 10mg/L

Peak:
20 - 30mg/L



VANCOMYCIN
MUST BE
INFUSED
SLOWLY.
Recommended
rate is 10mg/min
to prevent
adverse
reactions such
as hypotension,
flushing and
transient rash.
Dilute to
maximum
concentration of
5mg/ml
(10mg/ml in fluid
restricted
patients but
there is an
increased risk of
infusion-related
thrombophlebitis)

Key

T
50
= Half life.
Vd = Volume of distribution
F = Bioavailability
IBW ideal body weight

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
DOSAGE ADJUSTMENTS FOR MEDICINES IN RENAL
IMPAIRMENT

Dosage reductions are traditionally based on the degree of renal impairment
classified by three bandings of creatinine clearance. However eGFR is more usually
reported and is used in these tables, which are based on the current SPCs (available
from www.medicines.org.uk) and the current Renal Drug Handbook, copies of which
can be found on renal wards. Neither estimated creatinine clearance nor eGFR are
accurate if renal function is unstable, as the serum creatinine used to estimate them
may not reflect what is happening within the kidney.

For patients not of typical weight for their age, eGFR will diverge from creatinine
clearance unless corrected for surface area. Further guidance is available in the
BNF.

In these patients,
GFR
(Adjusted)
= eGFR x (Surface area)
1.73

For some drugs, using eGFR will not be accurate enough; these are noted in the
tables. Creatinine clearance should be estimated using the method of Cockcroft and
Gault, and the relevant SPC should be consulted. The band for CKD Stage 5 usually
covers haemodialysis and peritoneal dialysis, but not continuous filtration techniques
used in ITU.

Increasingly, SPCs, the BNF, and the Renal Drug Handbook diverge slightly in their
recommendations, and clinical judgement will be required, In particular, consideration
should always be given to:

- whether renal function is likely to improve or worsen
- the clinical condition of the patient, especially in severe
infection/immunocompromised patients
- whether a loading dose is appropriate, especially for antibiotics
- whether the medicine might itself worsen renal function (e.g. nephrotoxic
antibiotics, NSAIDs, etc)
- whether the medicine might worsen a problem associated with renal impairment
(e.g. hyperkalaemia, gastrointestinal bleeding).
- that patients with renal failure are more sensitive to the central nervous system
(CNS) side effects of medicines such as antidepressants, sedatives,
antipsychotics, antihistamines and opioid analgesics
- that the absence of a medicine from the list does not imply that standard doses
can be used.

Further information can be obtained from the Renal Drug Handbook,
www.medicines.org.uk,
Medicines Information (2096), and doctors/pharmacists experienced in nephrology.



TYPICAL
NORMAL
DOSE
CKD 3
(eGFR 30-
60mL/min)
MODERATE
(eGFR 15-30mL/min)
SEVERE
(eGFR <15mL/min)
(including ESRD)
COMMENTS
ACE inhibitors Start with low dose & adjust according to response. Monitor renal function and plasma potassium closely.
Aciclovir - oral
herpes simplex

herpes zoster

Aciclovir
intravenous
(depends on indication)

2-400mg x 5 x
day
800mg x 5 x day

5-10mg/kg TDS

Normal

Normal


5 10mg/kg BD
(TDS >50mL/min)

Normal

800mg TDS
(Normal >25mL/min)

5 - 10mg/kg OD
(BD >25mL/min)

2-400mg BD
(if <10mL/min)
800mg BD
(if <10mL/min)

2.5 5 mg/kg OD
(5-10mg/kg >10mL/min)
For other indications or in
dialysis, consult The
Renal Drug Handbook
Allopurinol 100-900mg OD
(usually 300mg)
200 300 mg OD 100 - 200mg OD 100 mg OD or
Alternate Days
In renal impairment, start
at 100mg OD & increase
if plasma and/or urinary
urate response is
unsatisfactory. Less than
100mg daily may be
required. Monitor full
blood count.
Contraindicated with
azathioprine.
Benzylpenicillin


600mg-2.4g
QDS
(can go higher)
Normal Some reduction required according
to clinical circumstances
600mg-1.2g QDS Nephrotoxic in high
doses. High doses can
cause cerebral irritation,
convulsions, coma.
Maximum dose in
severe renal failure is
4.8g per day
These doses higher
than SPC.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

TYPICAL CKD 3 MODERATE SEVERE COMMENTS
NORMAL
DOSE
(eGFR 30-
60mL/min)
(eGFR 15-30mL/min) (eGFR <15mL/min)
(including ESRD)
Cefalexin 250mg QDS-
500mg TDS
Normal Normal 250-500mg BD-TDS
Cefotaxime 1-2g TDS
(can go higher)
Normal Normal Half dose but not
frequency below
5mL/min

Cefradine (oral) 250-500mg
QDS
Normal Normal 250mg QDS should
suffice

Ceftazidime 1g TDS (can go
higher)
1g BD
(Normal > 50mL/min)
1g OD 500mg OD
(1g OD has been
used)
High doses can lead to
neurological
complications including
encephalopathy,
convulsions & coma. On
dialysis-see Renal Drug
Handbook.
Ceftriaxone 1-4g OD Normal

Normal

Maximum 2g OD
Cefuroxime (IV) 750mg 1.5g
TDS-QDS
(can go higher)
750mg 1.5g TDS 750mg 1.5g BD
(Normal > 20mL/min)
750mg 1.5g OD
(BD>10mL/min)

Ciclosporin No adjustment needed Nephrotoxic. Monitoring
mandatory.
Ciprofloxacin 250-750mg BD
(oral)
100-400mg BD
(IV)
250mg-500mg BD 50-100% of normal dose BD 50% of normal dose
BD
Dialysis patients: See
Renal Drug Guide
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

TYPICAL CKD 3 MODERATE SEVERE COMMENTS
NORMAL
DOSE
(eGFR 30-
60mL/min)
(eGFR 15-30mL/min) (eGFR <15mL/min)
(including ESRD)
Clarithromycin 250mg-500mg
BD (oral)
500mg BD (IV)
Normal 250-500mg BD
(SPC says 250mg BD)
250mg BD
Co-amoxiclav (IV)


Co-amoxiclav
(oral)
1.2g TDS


375-625mg TDS
Normal


Normal
1.2 g BD
(SPC says 600mg BD)

375mg-625mg BD
IV = 600 1.2g BD


375mg BD

Renal Handbook allows
higher oral doses
Co-trimoxazole
(PCP)
120mg/kg/day in
2-4 doses
Normal

30mg/kg BD from day 4 onwards 30mg/kg BD IV needs to be well
diluted- see Renal Drug
Handbook
Dalteparin 2500-5000u
(Prophylaxis)
200iu/kg/OD
(VTE treatment)
Normal Prophylaxis: use normal dose.
Treatment below 20-30mL/min: can accumulate and cause fatal haemorrhage: monitor
antifactor Xa levels for duration of treatment (RLUH does Tuesdays and Fridays, take 6
hrs after dose given). May be appropriate to use reduced dose but evidence weak:
consult Haematology. Enoxaparin (Clexane) has a licensed dose.
Digoxin
(maintenance)
62.5-
250microgram
OD
125-250 microgram
daily
125-250 microgram daily
(Levels required)
62.5 microgram daily
or alternate days
In haemodialysis, give
after session, especially if
alternate day regimes
used
Enoxaparin (ACS) 1mg/kg BD 1mg/kg BD 1mg/kg OD 1mg/kg OD See notes for dalteparin,
above
Ertapenem 1g OD 1g OD 0.5-1g OD
(Unlicensed)
0.5g OD
(or 1g 3 x week)
(Unlicensed)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

TYPICAL CKD 3 MODERATE SEVERE COMMENTS
NORMAL
DOSE
(eGFR 30-
60mL/min)
(eGFR 15-30mL/min) (eGFR <15mL/min)
(including ESRD)
Erythromycin 250mg-500mg
QDS
Normal Normal

50-75% of normal
Max 1.5g daily
(<10mL/min)

Flucloxacillin 250mg-2g QDS Normal Normal

Usual Max 4g Nephrotoxic in high
doses
Fluconazole 50-400mg OD Normal Normal

50% dose
Haemodialysis patients - can
dose at normal dose
3 x week after HD
SPC suggests half dose
after first day whenever
CrCl < 50mL/min

Gabapentin 300mg OD, then
BD, then TDS
Start lower than normal, increase according to response
See Severe for <15mL/min
<15mL/min; Initially
100mg OD, or
300mg alternate
days, and titrate
carefully
Further information on
SPC at
www.medicines.org.uk
Ganciclovir -
intravenous
(Treatment of
CMV)
5mg/kg/BD

Considerable reductions needed after first dose. Consult Renal Drug Guide, or
SPC at www.medicines.org.uk

Gentamicin IV Varies Considerable reductions needed after first dose. Consult Renal Drug Guide. Daily gentamicin levels required.
For high levels - consider reducing frequency rather than dosage. Use other medicines where possible.
Consult Microbiologist / Medicines Information
Imipenem/cilastatin
(Primaxin)
(As imipenem)
1g-2g daily in
divided doses
500mg TDS-QDS

500mg BD-TDS
(>20mL/min)
250mg BD
Max 3.5mg/kg BD

Risk of convulsions. More
information at:
www.medicines.org.uk
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

TYPICAL CKD 3 MODERATE SEVERE COMMENTS
NORMAL
DOSE
(eGFR 30-
60mL/min)
(eGFR 15-30mL/min) (eGFR <15mL/min)
(including ESRD)
Meropenem

0.5-1g TDS (can
go higher)
500mg-2g BD 500mg-1g BD 500mg-1g OD
Metformin Max 2g/day 25-50% normal Avoid Avoid Causes lactic acidosis in
renal impairment

Methotrexate Up to 20-25mg
weekly
50-100% normal 50% normal Avoid
Metronidazole 400mg TDS
(oral)
500mg TDS (IV)
Normal Normal Normal Slight difference with
SPC
Morphine Varies 75% normal Metabolites are more potent than morphine & accumulate in renal impairment with the
potential to cause marked respiratory depression & cerebral sensitivity. Extreme caution
is required for self - administration regimens. Consult Renal Drug handbook or
Medicines Information for advice.
Pamidronate
(Hypercalcaemia
15-90mg Normal Normal Serum Calcium > 4
Give 60 mg
Serum Calcium < 4
Give 30mg


Tazocin 4.5g TDS Normal

4.5g TDS

4.5g BD
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
TYPICAL
NORMAL
DOSE
CKD 3
(eGFR 30-
60mL/min)
MODERATE
(eGFR 15-30mL/min)
SEVERE
(eGFR <15mL/min)
(including ESRD)
COMMENTS
Teicoplanin 800mg OD Normal
(SPC says half dose)
Load for 4 days as normal, then
200mg-400mg every 24-48 hours, or,
as per Med Micro
Load for 4 days as
normal, then 200mg-
400mg every 48-72
hours, or, as per
Med Micro


See Renal Drug
Handbook or SPC at
www.medicines.org.uk
Tranexamic acid
oral

intravenous

1-1.5g BD-TDS

0.5-1g TDS
(Depends on
weight and
indication)

25mg/kg BD

10mg/kg BD

25mg/kg OD-BD

10mg/kg OD-BD

12.5mg/kg OD-BD

5mg/kg OD-BD
See Renal Drug
Handbook or SPC at
www.medicines.org.uk
Valganciclovir
(CMV)
900mg BD
(treat) or
900mg OD
(prevent)
Considerable reductions needed after first dose. Consult Renal Drug Guide,
Medicines Information, or SPC at www.medicines.org.uk
EXTREME CARE:
CHECK IF DOSE IS FOR
TREATMENT OR
PROPHYLAXIS
Vancomycin IV

1g BD Use with Caution Contact Medicines Information on 2096 or see Renal Drug
Handbook
ORAL NEEDS NO
REDUCTION



Haematology and Biochemistry Reference Ranges

Haematology Normal values Units
Haemoglobin 13.0 - 16.7 (male) 11.8 - 14.8 (female) g / dL
White Cell Count 3.5 - 11.0 10
9
/ L
Haematocrit 39 - 50 (male) 36 - 44 (female) %
Platelets 150 - 400 10
9
/ L
Neutrophils 2.0 - 7.5 10
9
/ L
Coagulation Normal values Units
Prothrombin time * 9.0 - 13.0 secs.
APTT 25.0 - 36.0 (heparin treatment range 1.8 - 3.3
times normal control )
secs.
Fibrinogen 1.5 - 3.5 g / L
D Dimer < 500 nanogram/ml
Biochemistry Normal values Units
Sodium 135 -145 mmol / l
Potassium 3.5 - 5.3 mmol / l
Chloride 99 - 109 mmol / l
Bicarbonate 22 - 33 mmol / l
Urea 2.5 - 7.0 mmol / l
Creatinine 50 - 130 micromol / l
Calcium 2.2 - 2.6 mmol / l
Calcium (adjusted) 2.2 - 2.6 mmol / l
Phosphate 0.7 - 1.4 mmol / l
Magnesium 0.75 - 1.00 mmol / l
Anion gap 6 - 16 mmol / l
Glucose 3.5 - 6 mmol / l
Lactate 0.5 - 2.2 mmol / l
Protein Normal values Units
Total protein 60 - 80 g / L
Albumin 35 - 50 g / L
Bilirubin 2 - 17 micromol / L
ALT 0 - 35 iu / L
Alk. phos. 35 - 125 iu / L
Amylase < 150 iu / L
GGT < 50 (male) < 35 (female) iu / L
CR protein (CRP) < 5 mg / L
Troponin T ** < 14 nanogram / L
Creatine kinase 33 - 194 (male) 35 - 143 (female) iu / L

* Range varies according to condition.
** Sample at least 6 hours post chest pain.



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

GASTRO - INTESTINAL SYSTEM

Contents (Click on heading to go to that section)

Dyspepsia and gastro-oesophageal reflux disease
Antacids and dimethicone

Antispasmodics and Other Medicines Altering Gut Motility
Antimuscarinics
Other Antispasmodics
Motility Stimulants

Ulcer - Healing Regimens
Intravenous Acid Suppression
Acute Healing

Acute diarrhoea

Chronic bowel disorders
Inflammatory Bowel Disease (IBD)

Laxatives
Management of Constipation
Management of Impacted Faeces
Bulk - forming Laxatives
Stimulant Laxatives
Faecal Softeners
Osmotic Laxatives
Bowel Cleansing Solutions
Guidelines for Pre-op Bowel Preparation of patients

Local preparations for anal and rectal disorders
Soothing haemorrhoidal preparations
Compound haemorrhoidal preparations with corticosteroids
Preparations for treating Anal Fissures
Rectal Sclerosants

Stoma Care

Medicines affecting intestinal secretions
Medicines affecting biliary composition and flow
Pancreatin

Management of Patients with Chronic Liver Disease

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Dyspepsia and gastro-oesophageal reflux disease

Antacids and dimethicone

For 'simple indigestion', compound preparations have no clear advantage over simpler
preparations and tend to be more expensive. Magnesium containing antacids tend to
have a laxative effect. Liquid preparations are more effective than tablets.

Simple Antacids
- Magnesium trisilicate
mixture
10mL (mixed in water) 3 times daily or as required.
Max. 60mL a day before review.


Dimethicone
- Infacol liquid (s) Gastroenterologists only.
For use as an antifoaming agent during gastroscopy.
Unlicensed use

Alginates
- Gaviscon Advance liquid
(sugar free)
5 10ml after meals and at bedtime.
(Note: Each 10ml contains 4.6mmol of sodium)

- Gaviscon Advance Tablets 1 2 tablets after meals and at bedtime
(Note: Two tablets contains 4.5mmol of sodium)


Antispasmodics and Other Medicines Altering Gut Motility

Antimuscarinics
- Hyoscine butylbromide Acute spasm: By i/v or i/m injection 20mg, repeated after
30mins if necessary. (maximum of 100mg in 24 hours)

Note: Hyoscine butylbromide tablets are poorly absorbed
therefore are of little use for acute spasm.
- Hyoscine butylbromide (s)
tablets
Chronic disorders only.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
Other Antispasmodics
- Alverine citrate
capsules
60-120mg TDS
- Mebeverine 135mg 3 times daily, preferably 20 minutes before meals.

- Peppermint water 10mL when required

- Peppermint oil e/c
capsules
(s) Gastroenterologists and Surgeons only.

Motility Stimulants

Metoclopramide and domperidone are dopamine antagonists that stimulate gastric
emptying and small intestinal transit, and enhance the strength of oesophageal
sphincter contraction. Domperidone is preferred for patients under 20 years of age
since metoclopramide may occasionally induce an acute dystonic reaction.
Domperidone is also preferred for long term use where possible since it is less likely to
cause dystonic reactions.
For disorders such as gastroparesis, erythromycin may be added (unlicensed
indication) if standard motility stimulants are unsuccessful. The usual dose is 125mg
QDS (increased to 250 mg QDS if necessary).


Ulcer - Healing Regimens

Intravenous Acid Suppression

Intravenous H
2
antagonists are ineffective for the treatment of an acute bleed. There
is some evidence that an intravenous proton pump inhibitor (PPIs) may reduce re -
bleeding from known ulcers, (to only be initiated after a review by either a consultant
gastroenterologist or gastro SPR).

There is no evidence to support the use of STAT doses of IV PPls in acute situations
before the patient has had an endoscopy.
- Ranitidine injection For prophylaxis only when oral route not available:
50mg diluted to 20mL and given i.v. over at least 2 mins 3 times
daily
- Omeprazole injection See algorithm on the next page
- Pantoprazole injection See algorithm on the next page


Algorithm to Aid Decisions Regarding the Prescribing of IV PPIs

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Acute Healing

Helicobacter pylori Positive Ulcers (Eradication Therapy)

Studies have demonstrated that in one week regimens that include a proton
pump inhibitor and clarithromycin with either metronidazole or amoxicillin, H.
pylori eradication is achieved in 90% or more patients.
The combination of amoxicillin and clarithromycin is preferred first line. If
amoxicillin cannot be used because of true penicillin allergy, clarithromycin
and metronidazole can be used instead. Remind patients to avoid alcohol if
taking metronidazole.

Choice of eradication regimen should depend on:
Known allergies
Known resistance or exposure within last two years to metronidazole / tinidazole
- avoid metronidazole containing regimens.
If the patient has had a previous course of eradication therapy a C
13
-urea breath
test should be performed before considering a second course of treatment using
a different combination of antibiotics. If in doubt consult a gastroenterologist.


Triple Therapy
Regimen 1
- Omeprazole
capsules
20mg twice daily for 1 week
OR
- Lansoprazole
capsules
30mg twice daily for 1 week
PLUS
- Amoxicillin
capsules
1g twice daily for 1 week
PLUS
- Clarithromycin
tablets
500mg twice daily for 1 week

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Or for penicillin allergic patients
- Omeprazole
capsules
20mg twice daily for 1 week
OR
- Lansoprazole
capsules
30mg twice daily for 1 week
PLUS
- Clarithromycin
tablets
250mg twice daily for 1 week
PLUS
- Metronidazole
tablets
400mg twice daily for 1 week



If clarithromycin cannot be used regimen 2 can be followed.

Regimen 2
- Omeprazole
capsules
20mg twice daily for 1 week
OR
- Lansoprazole
capsules
30mg twice daily for 1 week
PLUS
- Amoxicillin
capsules
1g twice daily for 1 week
PLUS
- Metronidazole
tablets
400mg twice daily for 1 week

Helicobacter pylori Negative Ulcers

Duodenal Ulcer Healing
- Omeprazole
capsules
20mg 40mg daily for 4 weeks

OR
- Lansoprazole
capsules
30mg daily for 4 weeks.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Gastric Ulcer Healing
- Omeprazole
capsules
20mg 40mg daily for 8 weeks

OR
- Lansoprazole
capsules
30mg daily for 8 weeks.


All patients with gastric ulcers should be re-scoped and biopsied on completion
of the course. Subsequent relapses should be referred to a gastroenterologist.

H
2
antagonists should not be prescribed `when required'. These agents should
be reserved for patients who cannot tolerate PPIs, since PPIs are the first line
choice for ulcer healing.
- Ranitidine
tablets/dispersible tablets
300mg at night or 150mg twice daily for 4 8 weeks


Maintenance Therapy

For complicated ulcer, frequent relapses or co - incidental disease.
- Ranitidine tablets 150mg at night.

- Omeprazole
capsules
20mg daily


NSAID Ulcer Prevention

In patients requiring long - term NSAID therapy who are at risk of developing
GI bleeding and ulceration lansoprazole or omeprazole may be used to
prevent NSAID - associated ulcers. H
2
antagonists have not been shown to
be effective for this purpose.

Combination products of misoprostol and NSAIDs (e.g.Arthrotec) are not
available in the Trust. The components should be prescribed separately when
required.

Prophylaxis of NSAID - induced Gastric or Duodenal Ulcer
- Omeprazole
capsules
20mg once daily

OR
- Lansoprazole
capsules
15 - 30mg once daily


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Treatment of NSAID Related Duodenal / Gastric Ulcer

Patients on NSAID treatment who develop a gastric or duodenal ulcer can be
treated with a proton pump inhibitor. Upon healing of the ulcer, the proton
pump inhibitor dose may be reduced to a maintenance dose.
- Lansoprazole
capsules
15 - 30mg once daily for 4 weeks, continued for further 4
weeks if not fully healed.

- Omeprazole
capsules
20mg once daily for 4 weeks, continued for further 4
weeks if not fully healed






























The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Flow Chart for Management of Patients with Gastro-oesophageal reflux
disease (GORD) (Adapted from NICE Guidelines 2004: Dyspepsia
Management of adults with dyspepsia in primary care)
GORD
Endoscopy result?
Oesophagitis Endoscopic negative
reflux disease
Omperazole
40mg OD for
1-2 months
Omeprazole
20mg OD for
1 month
Response
No response
or relapse
Esomeprazole
40mg OD OR
Omperazole
40mg BD
(unlicensed
dose) for 1
month
No response
No response
Ranitidine
300mg ON or
Domperidone
10mg TDS for
1 month
Ranitidine
300mg ON or
Domperidone
10mg TDS for
1 month
Low dose
treatment
as required
No response
REVIEW
No response
Return to
self care
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Flow Chart for the Management of Patients With non-ulcer Dyspepsia
(Adapted from NICE guidelines 2004: Dyspepsia Management of adults with
dyspepsia in primary care)




The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Flow Chart for the Management of Patients with Uninvestigated
Dyspepsia (NICE Guidelines 2004: Dyspepsia Management of adults with
dyspepsia in primary care)



- Sucralfate liquid For refractory GORD or patients with banded varices
Dose 1g QDS, max. 8g daily.
Note: Separate administration of other medicines by
2 hours and enteral feeds by 1 hour from sucralfate
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Hypersecretory Syndromes

e.g. Zollinger - Ellison syndrome

- Omeprazole
capsules
initially 60mg once daily up to 120mg daily (above 80mg in 2
divided doses)
- Lansoprazole
capsules
Initially 60mg once daily adjusted according to response
up to 120mg or more in two divided doses


Acid Aspiration Prophylaxis during General Anaesthesia
In the above guidance lansoprazole oro-dispersible tablets may be substituted for
capsules only IF the patient has swallowing problems
- Omeprazole
capsules
40mg on the preceding evening, then 40mg 2 - 6 hours
before surgery





Acute diarrhoea

The first line of treatment is the prevention or treatment of fluid and electrolyte
depletion with intravenous fluids or oral rehydration sachets e.g. Dioralyte. Anti-
diarrhoeal agents should be avoided if an infective cause is suspected, since
they may prolong the illness.
- Loperamide
tablets/syrup
Acute diarrhoea: 4mg initially followed by 2mg after each
loose stool for up to 5 days; max. 16mg daily.

- Codeine
phosphate
tablets/syrup
30mg 3 - 4 times daily; max. 240mg daily.

- Colestyramine (S) Gastroenterologists only: 12 - 24g (3-6 sachets) daily
mixed with water, in single or divided doses, subsequently
adjusted as required; max. 36g daily
Note: Take all other medicines at least 1 hour before
or 4 6 hours after dose of Colestyramine.









The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Chronic Bowel Disorders
Inflammatory Bowel Disease (IBD)

Treatment of Acute Ulcerative Colitis

Acute mild to moderate disease affecting the rectum or recto - sigmoid is
treated initially with local application of an aminosalicylate or corticosteroid.

- Sulfasalazine
Suppositories/enemas
(s) Gastroenterologists only
- Mesalazine
suppositories/enema/rectal
foam
(s) Gastroenterologists and Surgeons only
- Hydrocortisone foam enemas (s) Gastroenterologists and Surgeons only
- Prednisolone enema/foam
/suppositories
(s) Gastroenterologists and Surgeons only

Extensive IBD or disease that does not respond to local therapy requires oral
treatment, together with topical therapy.

Mild disease affecting the colon may be treated with an aminosalicylate alone
but refractory or moderate disease usually requires an oral corticosteroid e.g.
prednisolone for 8 weeks. IBD patients are more susceptible to osteoporosis
and Calcichew D3 forte 2 OD should be prescribed if these patients are
started on steroids. IBD patients over 65 on steroids should additionally also
be on a bisphosphonate (see BSG guidelines -
http://www.bsg.org.uk/images/stories/clinical/ost_coe_ibd.pdf)

If mesalazine is prescribed the brand should be specified due to differences in
release profiles/bioavailability. There is little evidence that high doses are
more effective in inducing remission therefore standard doses of 2.4g
mesalazine (or equivalent) are usually adequate.


- Balsalazide capsules (s) Gastroenterologists only
- Mesalazine e/c tablets
(Asacol/ Mesren)

- Mesalazine e/c tablets (s)
(Mezavant)
Ulcerative Colitis and Crohns Disease
800mg to 1200mg 3 times daily

Gastroenterologists only
2.4g to 4.8 g once daily

- Mesalazine s/r tablets (s)
(Pentasa)
Gastroenterologists and Surgeons only
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

- Mesalazine e/c tablets (s)
(Salofalk)
Gastroenterologists only
- Olsalazine capsules (s) Gastroenterologists only
reserve for proven left-sided disease only
- Sulfasalazine[sulphasalazine ]
tablets (s)
Gastroenterologists only


Guidelines for the management of Acute Severe Ulcerative Colitis (UC)
Truelove and Witts Criteria define severe Ulcerative Colitis as:
Bowels open > 6 times per 24 hours plus any one or more of the following
systemic manifestations
- Haemoglobin < 10g/dl.
- Pulse rate > 90 bpm
- Temperature > 37.5C
The differential diagnosis includes bacterial infection (Clostridium difficile,
Campylobacter, Salmonella, Shigella, Escherichia coli 0157), viral infection if
immuno-compromised (CMV), amoeba especially if travel history, Crohns
colitis and ischaemia. Diverticulitis can occasionally mimic symptoms of acute
severe UC.

Monitor/record DAILY
- Temperature and pulse 6 hourly
- Stool chart
Frequency
Colour / blood content
Estimate of volume (record even if only passed blood or mucus)
- Abdominal examination findings: tenderness, bowel sounds

Note increasing pulse/temperature/abdominal pain or tenderness may
indicate deterioration or frank perforation and requires appropriate urgent
investigation and discussion with consultant.

Investigations
The aim is to confirm the diagnosis, assess severity and extent of disease,
and identify / predict complications early.

- On admission
Stool culture + Clostridium difficile x 1 (as a minimum)
Sigmoidoscopy and rectal biopsy should be done within 48 hours
admission
Bloods
o FBC, UEC, CRP, LFT (albumin), Mg , Glucose, Cholesterol
o Blood cultures if temp > 37.5
Abdominal X-ray: look for stool-free colon (indicates extent involved);
severe disease indicated by mucosal oedema (thickened wall),
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

mucosal islands, dilated small bowel loops, colonic dilatation (diameter
> 4.5cm)

- Daily (unless consultant requests otherwise)
- Bloods
FBC, UEC, (particularly note potassium), LFT
CRP (a vital prognostic guide)
- Abdominal X-ray for severe extensive colitis (any of fever,
tachycardia, tenderness, dilatation on initial films) in absence of
these criteria less frequent AXR is OK

Results must be reviewed the same day (especially potassium).


Management

- Approximately 25 30% of patients admitted with severe acute UC
will come to colectomy during the same admission. The colorectal
surgical team should thus be informed of all patients admitted with
acute severe colitis within 24 hours; any patient admitted with acute
colitis who is not settling by day 3 should be reviewed by the
colorectal team. It is vital that surgeons, stoma therapy team etc are
involved to give sufficient time for planning and also allow the
patient to come to terms with possible / probable colectomy.

- Malnourished patients should be considered for early calorie
supplementation, either orally or naso-gastrically. They should be
weighed and reviewed by the dietician. Patients with severe disease are
often nauseated and anorectic for the first day or two: they are allowed to
eat normally.

- IV fluids to correct dehydration, with at least 60 mmol potassium per day
(eg. Two bags of either one litre glucose 5% or sodium chloride 0.9% one
containing 40mmol of KCL and the other 20mmol of KCL)
Patients are highly prone to hypokalaemia due to the diarrhoea and
steroid therapy and this requires close attention particularly if
anaesthesia for colectomy is imminent.
- Low molecular weight heparin dalteparin 5,000 units od for all patients
who have no contraindications admitted with inflammatory bowel disease
regardless of whether mobile or not

- Antibiotics, oral metronidazole 400 mg tds, + oral ciprofloxacin 500 mg bd
Used in patients with toxic dilatation or febrile with a temperature >
37.8, preferably after stool and blood cultures have been sent or for
patients with a first attack of undiagnosed bloody diarrhoea.
For UC in the absence of these features antibiotics are not routinely
indicated.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

- Oral 5-aminosalicylates can be withheld whilst on intravenous therapy
(there is no evidence that they have a role in acute severe colitis), but
restart this on discharge.

- Avoid anti-diarrhoeals, opiates etc., and avoid NSAIDs if at all possible. If
the patient is experiencing severe pain discuss with consultant.

- The steroid regime is IV hydrocortisone 100 mg qds + 5-ASA enemas
(e.g. Salofalk 2g nocte)

- Bone protection should be co-prescribed with high dose steroids:
low risk - Calcichew D3 Forte 2 daily.
high risk (>65yr, known osteoporosis/osteopaenia) - Calcichew D3 Forte
2 daily and alendronate 70mg once a week.

- 50% of patients with acute severe colitis will make a good response to the
above regime, 25% will require colectomy, and 25% will make a partial
response, requiring careful assessment and discussion re increased
immunosuppression vs surgery

- Definition of failure of steroids: after three days on intravenous
steroids in the context of severe colitis with systemic manifestations as
defined above, the presence of
Either
Stool frequency > 8 times per 24 hours
or
Stool frequency > 3 times per 24 hours AND CRP > 45

This gives an 85% likelihood of requiring colectomy. For patients with
resistant proctitis these criteria do not generally apply. If patients fail
steroids on the above criteria then the choice is between ciclosporin,
infliximab and surgery.

Ciclosporin regime (see ciclosporin protocol for full detail)
- The patient must give oral informed consent
- The following contra-indications must be excluded:
Known hypersensitivity to ciclosporin
Concurrent tacrolimus use
Known hypersensitivity to polyethoxylated castor oils
Uncontrolled hypertension
A serum cholesterol <3mmol/L (increased risk of seizures)
A serum magnesium <0.50mmol/L (increased risk of seizures)
Concurrent rosuvastatin use (convert to alternative statin)
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Dose and administration
The recommended dose is 2mg/kg daily administered as a continuous
infusion. IV ciclosporin is available as 50mg/ml ampoules. The dose should be
diluted to a concentration of 50mg in 50ml of either glucose 5% or sodium
chloride 0.9%. The infusion should be administered in a 50ml syringe using a
syringe driver. The infusion fluids should not be added to PVC containing
bags, to avoid the risk of leaching of plastic into the infusion. The rate of
infusion should be calculated as follows:

- The dose should be prescribed in the IV therapy section of the drug chart
and expressed as Ciclosporin 50mg in 50ml glucose 5% (or sodium
chloride 0.9%), run at xml/hour
- The hourly rate (x) = 2 x weight
------------------
24(hrs)
Infusions should be replaced on a continuous basis.
- Any dose remaining after 24 hours should be discarded and a new
infusion prepared.

Recommendations for Other Medication

- Corticosteroids: Continue treatment whilst IV ciclosporin is being given. If
remission is achieved, convert to oral prednisolone 40mg OD for 2 weeks,
then 30mg OD for 2 weeks, then 20mg OD for 2 weeks, then reduce by
5mg/week to zero thereafter
- PCP (Pneumocystis carinii pneumonia) prophylaxis: there is at
present no recommendation for the use of PCP prophylaxis . The available
evidence suggests that the incidence of PCP is low in patients with UC
who receive ciclosporin.
- Common interactions: Drugs which may increase ciclosporin levels:
macrolides, ciprofloxacin, allopurinol, fluconazole. Drugs which may
reduce ciclosporin levels: St Johns Wort, rifampicin, carbamazepine

If the patient is receiving other medicines, pharmacy should be contacted
(either via the ward pharmacist or medicines information on ext 2096).
Patients should avoid grapefruit and grapefruit juice whilst they are receiving
IV ciclosporin since it may increase levels.

Monitoring
Before administration the following base-line tests should be carried out:
- Potassium (Range 3.5 5.3 mmol/L) Ciclosporin can cause
hyperkalaemia.
- Urea and creatinine Ciclosporin can impair renal function in a dose
related manner. If renal function deteriorates either reduce the dose or
cease therapy. If the serum creatinine rises by more than 30% from the
baseline value the dose of ciclosporin should be halved
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

- Magnesium (range 0.75 1.0 mmol/L) Ciclosporin enhances the
clearance of magnesium; hypomagnesaemia can increase the risk of
seizures. Low levels should be corrected before starting therapy
- Cholesterol Hypocholesterolaemia increases the risk of seizures.
- Liver function tests Ciclosporin can interfere with hepatic function in a
dose related manner. If liver enzymes or bilirubin become significantly
affected (twice the upper limit), reduce dose or stop therapy
- Blood pressure (must be <150/90) Ciclosporin can cause hypertension.

During treatment the following monitoring is required:
- Monitor the patient for the first 30 minutes of the first infusion since the
polyethoxylated castor oil can cause anaphylactic reactions
- Potassium, magnesium, creatinine, urea, cholesterol and LFTs should be
checked daily
- BP should be checked four times a day daily
- Ciclosporin levels should be checked on the third day of treatment. The
recommended trough level is 150-250ng/ml

Phone Clinical Chemistry on
the day ciclosporin is started to inform that a ciclosporin level is
needed on day 3.
Results should be recorded in the monitoring table provided these will be
available from ward 5y or Pharmacy.

Duration of Intravenous therapy and Follow Up
If during therapy there are clinical signs of worsening of colitis (significant
increase in stool frequency or CRP, radiological evidence of toxic colon)
ciclosporin should be discontinued and colectomy performed. If the patient is
responding to IV ciclosporin it is continued for 7 days before converting to oral
therapy 5mg/kg/day in 2 divided doses

(aiming for a pre-dose ciclosporin level
of 100-200ng/ml) for 3-6 months.
Since ciclosporin has not been proven to be beneficial in maintaining
remission in UC, all patients should be commenced on either azathioprine or
mercaptopurine if they were not taking it previously. Patients should be
followed up initially on a weekly basis for the first month and thereafter at 2-4
week intervals until ciclsporin is discontinued and established on a thiopurine.
Approximately 50% will respond to ciclosporin, of whom 50% will relapse
when ciclosporin is stopped. Even in relapsers the time bought can be useful
to allow adjustment to the idea of colectomy and its implications.

Infliximab
Although used, NICE has not approved the routine use of infliximab for rescue
therapy in acute severe colitis. However infliximab is recommended as an
option for the treatment of acute exacerbations of severely active ulcerative
colitis only in patients in whom ciclosporin is contraindicated or clinically
inappropriate, based on a careful assessment of the risks and benefits of
treatment in the individual patient (NICE technology appraisal guidance 163
December 2008)
There are ongoing trials to compare ciclosporin versus infliximab in acute UC
(CONSTRUCT trial). We are a participating centre in this trial.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Follow up after discharge
Patients should be reviewed two weeks after discharge in the out-patient
clinic.

Indications for colectomy
- Toxic dilatation of the colon: if present on admission, 24-48 hours of
intensive medical therapy is warranted provided the patient is sufficiently
stable. Failure to respond by 48 hours, or the development of dilatation
during medical therapy mandates colectomy.
- Perforation
- Massive bleed
- All patients who are failing to improve on Day 3 should be discussed with
the colorectal surgeons such that the patient is monitored closely by both
medical and surgical teams and if colectomy is required this happens in a
planned manner on or soon after day 5. Stoma Therapy, etc will then have
had a chance to review the patient, provide explanation and information
etc. Few patients who have not made a good response to medical therapy
by day 5-7 will subsequently respond, and the risks of surgery escalate
with increasing delay
- Deterioration at any stage during admission may also necessitate urgent
colectomy.




















The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Care Pathway for Management of Acute Severe Colitis
Addressograph Date of admission: _ / _ / _
Referred to Gastro: _ / _
Previous A: UC / Crohns / indeter / nil
Length of flare: wks
On steroids: Y / N
Mandatory observations / investigations: Record in table
Day 1 Day 3 Day 5 Day 7
Temp
No. of
stools/24hrs

CRP
Albumin
Hb
Plts

Stool culture Sent: 1) _ / _ (date sent)
Result: 1)
CDT Sent: 1) _ / _ (date sent)
Result: 1)
Sigmoidoscopy: _ / _ Macroscopic:
Microscopic:
AXR: 1) _ / _ 2) _ / _ 3) _ / _
Treatment
- iv steroids: _ / _
- rectal 5-ASAs _ / _
- bone protection _ / _
- dalteparin _ / _
- Ciclosporin: _ / _ level on day 3 ---------------
Management
IBD Nurse Referral: review
Dietician referral: review
Surgical referral: _ / _
Colectomy: _ / _
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Management of acute Crohns disease

Management of these patients requires a consideration of both the location
and severity of disease.
Oral Mesalazine may be considered for mild ileocolonic disease, though the
evidence is very weak
Metronidazole 400mg TDS and ciprofloxacin 500mg BD may be used for
perianal disease
Steroids may be required in severe active disease, although there is a
tendency to try to avoid them in ileocolonic disease if possible
In addition, patients must stop smoking
All patients should be prescribed dalteparin 5000units OD to reduce the risk of
thromboembolism following completion of the VTE risk assessment.

- Infliximab 100mg
Injection (s)
Consultant Gastroenterologists only

Infliximab inhibits the activity of tumour necrosis
factor.

Indicated for
Treatment of severe, active Crohns disease in
patients who have not responded despite full and
adequate course of therapy with a corticosteroid and
an immunosuppressant or who are intolerant of / have
medical contra-indication to such therapy
Or
Treatment of fistulising, active Crohns disease in
patients who have not responded despite a full and
adequate course of therapy with conventional
treatment, (including antibiotics, drainage and
immunosuppressive therapy).

Dose: 5mg/kg IV administered in 250mL sodium
chloride 0.9% over 2 hours.
- Adalimumab (s)


Consultant Gastroenterologists only

For use in patients with Crohn's disease who fail to
respond to infliximab or develop an attenuated
response to it.
Before biological therapy is initiated infection must be excluded. A chest x-ray must
also be performed to exclude tuberculosis (TB). If there is an abnormal chest x-ray or
patient has a history of TB a respiratory consultant should be consulted.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Maintenance of Remission of Acute Ulcerative Colitis
- Aminosalicylates e.g. Mesalazine tablets. 1.2 2.4g daily in divided
doses. Continued use may reduce risk of colon
cancer. Avoid lactulose since this will lower stool pH
and may prevent the release of mesalazine.
Note: CSM warning in BNF regarding aminosalicylates and the risk of blood
dyscrasias/interstitial nephritis.

- Azathioprine Unlicensed use
If treatment with aminosalicylates fails consider
adding Azathioprine: Initially 25- 50 mg OD, increased
to max. 2-2.5mg/kg/day

Maintenance of Crohns disease
- Azathioprine Unlicensed use consultant gastroenterologists only
Initially 25-50 mg OD, increased to max. 2-2.5
mg/kg/day
- Methotrexate Unlicensed use consultant gastroenterologists only
15-25mg WEEKLY by the oral or intramuscular route.
Used if patient cannot tolerate azathioprine or
azathioprine ineffective

Before patients are initiated on azathioprine they should be tested for TPMT
(thiopurine methyl transferase) activity. Low activity warrants starting
azathioprine at half dose.
All patients receiving azathioprine or methotrexate should have FBC & LFTs
monitored every 2 weeks until dose stable, then every 3 months.






















The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Laxatives

Management of Constipation

First line treatment includes increasing dietary fibre, mobility and fluid intake,
and removing possible medication causes.
Identify possible causes of constipation e.g. medicine induced, underlying
disease, mechanical obstruction, pregnancy, dehydration, immobility.
If first choice treatment is not tolerated or ineffective, the table below indicates
alternative management approaches.

First line treatment Second line
treatment
Third line
treatment
CHRONIC
CONSTIPATION
Ispaghula
preparations (e.g.
Fybogel)
Senna tablets (i.e. in
slow gut transit)
Docusate sodium
capsules
MEDICINE -
INDUCED
CONSTIPATION
Avoid causative
agent if possible
Senna tablets
DIET -
INDUCED
CONSTIPATION
High fibre diet with
adequate hydration
Ispaghula preparations
(e.g. Fybogel)


Additional Factors to Consider

Elderly Bulking agents may not be suitable for fragile or immobile
elderly patients. Short-term use of a stimulant laxative
(e.g. senna) with or without a stool softener is more
appropriate.
Cardiac failure Defaecation must be free of strain in these patients,
hence a stool softener is most appropriate.
Malignancy The cause of constipation should be diagnosed and
treated accordingly
Haemorrhoidectomy
patients
A bulk forming laxative (Fybogel) and osmotic laxative
(Lactulose) are often given together post - operatively to
facilitate passing a soft and effective stool.
Psychiatric Constipation arising from depression is resistant to
treatment unless the depression is being treated.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Management of Impacted Faeces
Faecal incontinence/
discomfort
NO Faecal
incontinence/
discomfort
Hard stools:
Lactulose senna
Soft stools:
senna
If no effect then:
Daily enema until bowel clear:
sodium citrate enema
phosphate enema
Arachis oil enema (for hard stools)
If no effect then:
Soft stools:
sodium
picosulphate
sachet (Picolax)
Hard stools:
(manual evacuation)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Bulk - forming Laxatives
- Ispaghula husk
(Fybogel)
1 to 2 sachets once or twice daily.
Should be taken with at least one glass of water and
should not be taken immediately before going to bed.
Onset of action up to 48 hours.
Useful in colostomy/ileostomy patients, but contra -
indicated in faecal impaction or existing bowel
obstruction.


Stimulant Laxatives
- Senna tablets/syrup 2 to 4 tablets or 10 - 20mL at night.
Initial dose should be low then gradually increased.
Action seen within 12 hours.
Usually reserved for short-term use as prolonged use
can precipitate the onset of atonic colon and
hypokalaemia.
May cause abdominal cramps and contra - indicated
in bowel obstruction.

- Bisacodyl tablets/
suppositories
By mouth, 5 - 10mg at night. Acts in 10 - 12 hours
By rectum, 10mg in the morning. Acts within 20 - 60
minutes

- Co - danthramer
capsules/suspension/
strong suspension
1 - 2 capsules or 5 10mL at night.
Acts within 6 - 12 hours
May colour urine and skin red.
Note: Only licensed for constipation in terminally
ill patients of all ages


Faecal Softeners
- Arachis oil enema To soften impacted faeces: One enema daily until
bowel clear. Warm the enema to body temperature
before use.

- Docusate sodium
capsules/solution
Up to 500mg daily in divided doses.
Acts within 1 - 2 days. Also has a mild stimulant
effect.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Osmotic Laxatives
- Lactulose 15mL twice daily. Should only be used when other
laxatives have failed to produce an effect. Must be
taken regularly for 2 - 3 days before an effect is seen
therefore not suitable for short term or 'when required'
use. Main indication is hepatic encephalopathy when
higher doses are used.

- Macrogol sachets Used for chronic constipation and faecal impaction.
- Sodium citrate
enema
One or two daily when required

- Phosphate One enema when required. Warm the enema to body
temperature before use

- Magnesium sulphate
enema
(s) Gastroenterologists and Surgeons only
Note: Specially manufactured by pharmacy, for use in
hepatic encephalopathy only

Bowel Cleansing Solutions

The bowel prep of choice for patients undergoing colonoscopies in the Trust is
Moviprep.

Patients eligible for Moviprep undergoing colonscopies

Since Moviprep induces minimal electrolyte shifts it can be used in patients
with renal failure. However, dialysis patients must first be reviewed by a
renal consultant to determine if these patients need to be admitted into
hospital for close fluid balance monitoring.

The following contraindications are to be excluded before commencing
therapy:

- Gastrointestinal obstruction or perforation, ileus, gastric retention,
acute intestinal or gastric ulceration or toxic megacolon
- Severe acute inflammatory bowel disease
- Congestive cardiac failure (NYHA grade 3 or 4)
- Difficulty swallowing
- Reduced levels of consciousness
- Hypersensitivity to any of the ingredients
- Known Glucose- 6 -phosphate dehydrogenase deficiency
- Known Phenylketonuria

Schedule and administration instructions for Moviprep
A course of treatment consists of two litres of Moviprep. A litre of Moviprep
consists of one 'Sachet A' and one 'Sachet B' dissolved together in one litre of
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

water. This reconstituted solution should be drunk over a period of one to two
hours. This should be repeated with a second litre of Moviprep. In addition, at
least one litre of clear fluid must be consumed in the period taking the bowel
prep

Time of colonscopy Times to take reconstituted solution
Morning list 14:00 and 18:00 the day before the test

Afternoon list 18:00 day before test
08:00 day of the test
Evening list 07:00 day of the test
13:00 day of the test


Dietary advice

2 Days before the Test

Two days before the test the patient may have only low residual food.
Foods from the following list are acceptable: boiled or steamed white
fish, boiled chicken, potato without skin, egg, cheese, white bread,
butter/ margarine, seedless jam, marmite, honey, rich tea biscuits,
chocolate, yoghurt, jelly (not red) and ice-cream
Red meat, fruit, vegetables, nuts, pulses or cereals in any form are not to
be consumed

1 Day before the Test
- Morning Appointment: After a light breakfast (cereal) the day before
the test (morning list) patient should eat NO further solid food
until after the investigation. Patients with diabetes should replace
each mealtime with one Ensure drink.

Clear fluids intake is strongly encouraged (as much as possible) as
advised in the relevant sections and can be taken up to 2 hours before
the test. Clear fluids include fruit juices (without pulp), fizzy drinks or tea
and coffee(without milk). Bovril and clear soup and sugary drinks such
as Lucozade are also acceptable.

- Afternoon Appointment: After a light lunch soup without bread-
day before the test (morning list) patient should eat NO further
solid food until after the investigation. Patients with diabetes
should replace each mealtime with one Ensure drink.

Clear fluids intake is strongly encouraged (as much as possible) as
advised in the relevant sections and can be taken up to 2 hours before
the test. Clear fluids include fruit juices (without pulp), fizzy drinks or tea
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

and coffee(without milk). Bovril and clear soup and sugary drinks such
as lucozade are also acceptable.
- Evening Appointment. After a light evening meal the day before the
test (morning list) patient should NO further solid food until after
the investigation. Patients with diabetes should replace each
mealtime with one ensure drink.

Clear fluids intake is strongly encouraged (as much as possible) as
advised in the relevant sections and can be taken up to 2 hours before
the test. Clear fluids include fruit juices (without pulp), fizzy drinks or tea
and coffee(without milk). Bovril and clear soup and sugary drinks such
as Lucozade are also acceptable.
Nothing should be consumed from 2 hours before the test

Patients regular medicines

Iron and constipating medicines i.e. loperamide, codeine phosphate should
be stopped five days before the test.

The patients other regular oral medication should be continued as normal but
taken at least one hour before administration of bowel cleansing agents.

On the day of the test patients with diabetes should omit their diabetic
medication.

If patients are on the contraceptive pill they must be advised to take additional
precautions for up to 7 days after taking bowel cleansing agents

The decision whether to withhold oral anticoagulants or clopidogrel is based
on the risk of the patient bleeding as a result of the procedure/intervention
against the risk of a thromboembolic event as a result of interrupting
anticoagulation/clopidogrel therapy. Aspirin and dipyridamole therapy can be
continued as normal. Current advice is based on the BSG guidelines,
Guidelines for the management of patients on warfarin or clopidogrel
undergoing endoscopic procedures updated 2008
http://www.bsg.org.uk/pdf_word_docs/anticoagulant_08.pdf












The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
Other available bowel cleansing agents

- Sodium picosulfate
sachet (Picolax)
One sachet dissolved in water and taken before 8am
and second sachet the afternoon of the day before the
operation/investigation.
Maintain high fluid intake, and monitor sodium closely

Note: Should not be used for patients with obstructive
or nearly obstructive lesions of the colon.

- Fleet Phospho Soda Bowel prep only. Dilute one bottle (45ml) in half a
glass of water (120ml) and drink this followed by at
least one glass (240ml) of water. The second bottle
should be taken 12 hours later.
Not suitable for use by patients with renal
impairment.
- Gastric lavage
solution (Klean Prep)
Bowel prep only. Reconstitute one sachet in 1 litre of
water and drink 250mL every 10 - 15mins until rectal
effluent is clear or 4 litre dose consumed.

Note: Ensure high fluid intake is maintained to
prevent volume depletion.

May be alternative for patients with renal failure.


Guidelines for Pre-op Bowel Preparation of Patients
Electrolyte management 1) Check recent potassium. If less than 4.0 mmol/l give
two tablets of Sando K (Each tablet contains 12 mmol
of K
+
).
2) Patients with a positive cardiac history (angina, CCF,
LVF, hypertension or cardiac medicines) and
potassium is less than 4.0 mmol/l give 500 ml 0.9%
sodium chloride with 20 mmol potassium by i.v.
infusion over 4 hours for each picolax sachet.
3) Check potassium on morning of operation. If less
than 3.5 mmol/l inform anaesthetist.
For all resections except TEMS (Trans Endoscopic Micro Surgery)
Patients below 70 years
of age;
1) Picolax one sachet orally before 8 a.m. one day pre-
op + 500 ml of oral fluids.
2) Picolax one sachet orally between 2 and 4 p.m. one
day pre-op + 500 ml of oral fluids.
3) If effluent not clear contact medical staff for advice.
4) Clear fluids for 24 hours pre-op.
5) Nil by mouth for 4 hours pre-op.
Patients aged 70 years and
above;
1) Picolax one sachet orally before 8 a.m. one day pre-
op + 500 ml Hartmanns by i.v. infusion over 4 hours.
2) Picolax one sachet orally between 2 and 4 p.m. one
day pre-op + 500 ml Hartmanns by i.v. infusion over
4 hours.
3) If effluent not clear contact medical staff for advice.
4) Clear fluids for 24 hours pre-op.
5) Nil by mouth for 4 hours pre-op.
TEMS or Severe constipation
Patients below 70 years of
age
1) Picolax one sachet orally before 8 a.m. two days pre-
op + 500 ml of oral fluids.
2) Picolax one sachet orally between 2 and 4 p.m. two
days pre-op + 500 ml of oral fluids.
3) Repeat (1) and (2) one day pre-op.
4) If effluent not clear contact medical staff for advice.
5) Clear fluids for 48 hours pre-op.
6) Nil by mouth for 4 hours pre-op.
Patients aged 70 and above; 1) Picolax one sachet orally before 8 a.m. two days pre-
op + 500 ml Hartmanns by i.v. infusion over 4 hours.
2) Picolax one sachet orally at 12 midday two days pre-
op + 500 ml Hartmanns by i.v. infusion over 4 hours.
3) Repeat (1) and (2) one day pre-op.
4) If effluent not clear contact medical staff.
5) Clear fluids for 48 hours pre-op.
6) Nil by mouth for 4 hours pre-op.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Local preparations for anal and rectal disorders

Anal and perianal pruritus, soreness and excoriation are best treated by application
of bland ointments and suppositories. Careful local toilet as well as adjustment of diet
to avoid hard stools is also helpful.
Good evidence is lacking for use of preparations containing local anaesthetics for
relief of pain associated with haemorrhoids and pruritus ani.
- They may cause more irritation.
- Prolonged use should be avoided.
- Lidocaine [lignocaine] ointment may be used before emptying the bowel to
relieve the pain associated with anal fissure.

Soothing haemorrhoidal preparations
- Anusol
cream/ointment/supposit
ory
One suppository or application of cream/ointment night and
morning and after defaecation.

- Lidocaine [lignocaine]
5% ointment/ 2% gel
Apply to anal fissure before bowel emptying.

- Hydrocortisone 1%
cream /ointment
Apply twice daily.



Compound haemorrhoidal preparations with corticosteroids
- Anusol HC
ointment/suppositories
Use night and morning and after bowel movement.

- Proctosedyl
ointment/suppository
(s) Surgeons only.
- Perinal spray (s) Surgeons only.

Preparations for treating Anal Fissures
- Glyceryl trinitrate 0.2%
ointment
(s) Unlicensed product.
Used two to three times daily.
- Diltiazem 2% cream (s) Unlicensed product.
Used twice daily for 8 12 weeks. Store tube in a fridge.

Rectal Sclerosants
- Oily phenol injection (s) Consultants only.

Stoma Care
- Stoma Care Nurse RLUH Bleep 4266 and 4269
BGH Bleep 4052

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Medicines affecting intestinal secretions

Medicines affecting biliary composition and flow
- Ursodeoxycholic acid
tablets
(s) Consultants only.
Dose for primary Biliary Cirrhosis: 10-15mg/kg/day in 2-4
divided doses.

Pancreatin
All pancreatin preparations are for consultant use only.

























The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Management of Patients with Chronic Liver Disease

Introduction

Liver disease is a complex area; the involvement of a Hepatologist is strongly
advisable. The management of patients presenting with chronic liver disease requires
consideration of the following:
- Does the patient have acute or chronic disease? Have biliary obstruction and
haemolysis been excluded?
- Consideration of the underlying cause removal or treatment of the underlying
cause (e.g. alcohol excess, autoimmune hepatitis) can halt or prevent the
progression of liver damage
- Treatment of the symptoms/complications present - jaundice, ascites, portal
hypertension (with or without varices) and encephalopathy
- Consideration of altered medicine handling and the need for dosage reduction
of medicines in patients with liver disease


Ascites
Aims of treatment are to remove fluid with minimal disturbance of electrolytes and
without precipitating renal failure. Treatment consists of:
- Ensure patients are put on a salt free diet
- Diuretic therapy:
- Spironolactone (a specific aldosterone antagonist): Start at 100mg daily,
increase the dose every 3-5 days, max. dose 400mg daily
- Furosemide: Use if spironolactone alone ineffective or patient also has
peripheral oedema. Start at 40mg daily (max. 160mg daily)
- Monitor weight on a daily basis aim to lose a maximum of 1kg per day (a
loss of 0.5-0.75kg/day is adequate in a non-oedematous patient)
- Monitor U&Es three times a week initially. Daily U&Es are required for
difficult cases.
- Stop if Cr> 150mmol/L or Na<125mmol/L or K>5.5mmol/L
(spironolactone only)
- Fluid restriction to 1-1.5L per day if hyponatraemic

- Paracentesis: for tense ascites or diuretic-resistant cases of ascites. Consider
if patient receiving in excess of spironolactone 400mg daily. Cover with 100ml
20% albumin solution for every 2-3 litres drained. Stop diuretics the day before
and on the day of paracentesis to reduce risk of renal impairment. Never leave
a paracentesis catheter in place for more than 12 hours spontaneous
bacterial peritonitis is often not spontaneous.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Spontaneous Bacterial Peritonitis (SBP)
Bacterial peritonitis is a specialist subject; advice from a Hepatologist should be
sought at the earliest possibility. The decision to treat bacterial peritonitis is based on
a neutrophil count in the ascitic fluid > 250 cells/mm
3
, a positive gram stain culture or
both. Signs that the patient may be developing SBP include: sudden abdominal pain,
raised temperature, and development of encephalopathy. Patients who have had
paracentesis in the last 48 hours have a low threshold for treatment SBP is often
not spontaneous.
- A Cochrane review concluded that there is no convincing evidence regarding
which antibiotic should be used first line and that treatment of SBP is based on
clinical experience.
1
Initial treatment for confirmed cases according to the
hospital antibiotic formulary is piperacillin/ tazobactam IV 4.5g TDS for 5 days.
- Secondary prophylaxis Patients who have had a proven episode of SBP and
it has been treated should be given prophylactic ciprofloxacin 500mg OD long
term
2

- There is evidence to support the use of salt poor albumin to reduce the
incidence renal impairment and mortality in these patients
3
. Patients in the
study were given 1.5g/kg body weight at the time of diagnosis followed by
1g/kg on day 3.
- There is evidence for primary prophylaxis with an ascitic protein count < 10g/l.
Under hepatology advice may be started on ciprofloxacin 500mg OD long
term.

Variceal Bleed
Acute variceal bleeds are associated with a mortality of approximately 30%.
Treatment aims to stop bleeding and prevent further bleeds. All patients who are
suspected to have experienced an upper GI bleed require urgent endoscopy to
diagnose and treat the bleed. Medical management consists of:
- Prompt resuscitation using colloids, blood, platelets
- IV vitamin K 10mg OD for 3 days if prothrombin time is raised
- Terlipressin 2mg 4 hourly (given as a slow IV bolus) for up to 72 hours or until
bleeding stops. This has been shown to decrease mortality.
- Octreotide may be considered for patients with severe vascular disease. The
dosage regime is 1mg made up to 60ml with sodium chloride 0.9% which is
then administered over 20 hours a maximum of 1 infusion per day may be
used
- Prophylactic antibiotics Initially piperacillin/ tazobactam IV 4.5g TDS whilst
nil by mouth, converting to ciprofloxacin 500mg BD orally when the patient is
allowed to eat and drink continued until the patient has received a total of 5
days treatment (IV and oral combined). Antibiotics have been shown to reduce
rates of bleeding since it is thought that bacterial translocation may contribute
to re-bleeding
4

- Propranolol should be prescribed for secondary prevention of bleeding varices
(and primary prevention of varices identified during routine OGD). Treatment is
contra-indicated in patients with asthma. Start at 20mg BD and titrate
according to pulse and BP. (Alternative is carvedilol starting at 3.125 6.25mg
OD)Aim for a resting pulse of 60bpm or a 25% reduction from baseline.
Ensure systolic BP remains above 100mmHg
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Isosorbide mononitrate is no longer recommended for prophylaxis against
variceal bleeds since an increase in mortality has been associated with its use.

Encephalopathy
When a patient presents with hepatic encephalopathy, it is important to consider if
there are any precipitating causes present. Common precipitants include:
- Decompensated liver disease
- Administration of sedative medicines
- Infection
- Electrolyte disturbances
- Constipation (which may be medicine-induced)
- Upper GI bleed

The treatment of hepatic encephalopathy involves:
- Remove or treat any precipitating factors
- Lactulose 30-50ml TDS. Aim to produce 2-3 soft motions per day without
causing diarrhoea
- If patient is NBM or still constipated despite lactulose, prescribe phosphate
enemas BD
- In resistant cases consider neomycin (gastroenterologist use only). Initially 1g
BD but may be increased to a maximum of 1g QDS. Although absorption is
usually minimal, renal function should be monitored along with signs of
ototoxicity.

Hepato-renal Syndrome
Hepato-renal syndrome is a specialist subject; referral of these patients to a
hepatologist is imperative. When a patient develops renal failure secondary to liver
disease, it is called hepato-renal syndrome. There are two types:
- Type 1: When renal function deteriorates rapidly
- Type 2: When renal function slowly deteriorates. Type 2 hepato-renal
syndrome may evolve into Type 1 hepato-renal syndrome at any time.
In many cases the cause of hepato-renal syndrome is not found, but common
precipitants include:
- Over-diuresis
- Infection
- Major GI bleed
- Decompensated liver disease
If a patients liver disease is corrected, their renal function will return to normal. The
treatment of hepato-renal syndrome involves the following:
- Stop diuretic therapy (if prescribed)
- Rehydrate as necessary unless advised otherwise by gastroenterologists
avoid intravenous sodium chloride
- Start terlipressin 0.5-2mg QDS with 100ml albumin 20% per day.
- Monitor renal function daily, stop terlipressin once renal function has
recovered.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Medicine Use in Liver Disease

When faced with treating a patient who has liver disease for other conditions, two
questions are often raised
- Is medicine X safe to use in liver disease?
- Does medicine X require a dosage reduction?

Medicine dosing in liver disease

Medicine dosing in liver disease is not as easy to predict as that for renal disease.
Consideration should be paid to how the medicine is eliminated (hepatic versus
renal) and how it is distributed (e.g. binding to albumin). The general rule is to use
the lowest effective dose at the longest interval possible and titrate according to
clinical response.
For further advice regarding medicine choice and dosing in liver disease contact
either your ward pharmacist or medicines information (ext: 2096).
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Medicine Choice in Chronic Liver Disease
The table below discusses the use of medicines for specific indications in patients with liver
disease. Please note that this list is NOT exhaustive.
Indication Medicine of choice
Analgesia - Paracetamol may be used, but use half the dose
- Small doses of opiates (e.g. codeine 30mg BD-TDS) may be
added (providing the patient is not encephalopathic). Ensure the
patient does not become constipated (prescribe prophylactic
senna and lactulose during treatment with such medicines)
- Avoid NSAIDs if patient is jaundiced or has liver disease
Infection - Avoid flucloxacillin and co-amoxiclav if the patient has previously
experienced cholestatic jaundice/hepatic dysfunction to either one
of these
- Erythromycin may worsen hepatic function monitor LFTs closely
if used in patients with liver disease
Hypertension Most agents are considered safe:
- ACE inhibitors and angiotensin receptor antagonists may be used,
but monitor potassium closely if concurrently prescribed
spironolactone since patient could become hyperkalaemic
- Beta blockers atenolol may be preferable (unless the patient
has varices) since it is renally cleared
- If the patient is receiving loop diuretic therapy, it may be prudent
to avoid thiazide diuretics since this combination can result in a
profound diuresis
Depression - Paroxetine is preferred owing to its shorter half-life
Epilepsy - Phenytoin A lower dose may be needed due to reduced hepatic
metabolism and lower serum albumin levels
- Avoid sodium valproate
Diabetes - Insulin
- Sulphonylureas may cause hepatotoxicity
- Thiazolidinediones (pioglitazone and rosiglitazone) should be
avoided in liver disease
Anxiety - Oxazepam (short-acting, not extensively metabolised by the liver)
Psychosis - Haloperidol not generally associated with liver toxicity, but use
with caution since it may precipitate coma. Dose should be
reduced


References
1. Soares-Weiser K, Brezis M, Leibovici L. Antibiotics for spontaneous bacterial peritonitis in
cirrhotics (Review). The Cochrane Collaboration 2005
2. Moore KP and Aithal GP. Guidelines in the management of ascites in cirrhosis. British Society
of Gastroenterology Guidelines. Gut 2006;55;1-12
3. Sort P, Navasa M, Arroyo V et al. Effect of intravenous albumin on renal impairment and
mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med 1999;
341:403-9
4. Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici L. Antibiotic prophylaxis for cirrhotic
patients with gastrointestinal bleeding (Review). The Cochrane Collaboration 2005-08-17

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


CARDIOVASCULAR SYSTEM

Contents (Click on heading to go to that section)

Positive Inotropic medicines
Cardiac glycosides
Phosphodiesterase Inhibitors

Diuretics
Thiazide Diuretics
Loop Diuretics
Potassium Sparing Diuretics
Potassium sparing diuretics with other diuretics
Osmotic Diuretics

Anti - arrhythmic Medicines
Management of Arrhythmias
Atrial Fibrillation
Atrial Flutter
Ventricular Tachycardia
Supraventricular and Ventricular Arrhythmias
Ventricular Arrhythmias
Bradycardias

Beta - adrenoreceptor Blockers

Medicines affecting the renin-angiotensin system and some other
antihypertensive medicines
Management of Hypertension
Hypertensive crisis
Use of Antihypertensive Medicines in Patients With Co - existing Disease
Vasodilator antihypertensive medicines
Alpha - adrenoreceptor blocking medicines
Management of Heart Failure
Medicines affecting the Renin-Angiotensin system

Nitrates, calcium-channel blockers, and potassium channel activators
Nitrates
Calcium - channel Blocking Medicines
Peripheral and Cerebral Vasodilators

Sympathomimetics
Inotropic Sympathomimetics
Vasoconstrictor Sympathomimetics
Cardiopulmonary resuscitation

Anticoagulants and protamine
Prophylaxis of Venous Thromboembolism
Treatment of Venous Thromboembolism
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Guidelines for the Management of Pulmonary Embolism and Deep Vein
Thrombosis
Parenteral anticoagulants
How to Use Intravenous Heparin in Adults
Oral Anticoagulants
Management of over - anticoagulation With Warfarin
Anticoagulant Clinic/ Long Term Anticoagulation
Protamine sulphate

Antiplatelet Medicines

Myocardial Infarction and fibrinolysis
Primary Prevention of Myocardial Infarction
Secondary Prevention of Myocardial Infarction
Non ST Elevation Acute Coronary Syndromes ( NSTEACS ) Guideline
Pathway from diagnosis to coronary angiogram
Fibrinolytic Medicines

Antifibrinolytic Medicines and Haemostatics

Lipid - regulating Medicines

Local Sclerosants













The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Positive Inotropic Medicines

Cardiac glycosides
- Digoxin
tablets/syrup/injection
Used for supraventricular arrhythmias and in the
management of heart failure

Supraventricular arrhythmias
Loading doses are sometimes omitted depending on the
clinical status of the patient.

Oral digitalisation: Digoxin 500micrograms stat followed by
250micrograms every 8 hours for 3 further doses if
required

Intravenous digitalisation: By i.v. infusion, 750 1000
micrograms in 50mL sodium chloride 0.9% or glucose 5%
over at least two hours (maintenance dose to be started
the following day)

Or

250micrograms in 50mL sodium chloride 0.9% or glucose
5% over 30mins.
Give a further 250micrograms 1 hour later. Repeat after 2
hours if necessary.

Maintenance oral dose: 62.5 - 500micrograms daily
according to age and renal function.

Heart failure
Used in heart failure as digoxin is a positive inotrope.
There is no need for a loading dose.
Maintenance oral dose: 62.5 - 250micrograms daily
according to age and renal function. Patients may still
benefit even if level is less than the recommended
therapeutic range

Click here for therapeutic level monitoring.


Phosphodiesterase Inhibitors
- Enoximone injection (s) Cardiologists (CCU) and Anaesthetists only.




The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Diuretics

Thiazide Diuretics
- Bendroflumethiazide
tablets
Hypertension: 2.5mg each morning

- Indapamide tablets
(thiazide like diuretic)
Hypertension (in preference to bendroflumethiazide as initial
treatment of primary hypertension): 2.5mg each morning
- Metolazone tablets Added into loop diuretics treatment (synergistic effect) to
treat persisting oedema.
(Dose range 2.5mg alternate days - 5mg od)

Note: Profound diuresis may occur in combination with
loop diuretics. Review use before patient is discharged.
Monitor plasma electrolytes and weight regularly.
Loop Diuretics
- Furosemide [frusemide]
tablets/liquid/injection
Oedema: By mouth, initially 40mg in the morning,
increasing to 80 - 160mg once or twice daily.
Do not give dose after 6pm unless patient is catheterised.

Oliguria: By mouth, initially 250mg daily increasing in steps
of 250mg every 4 - 6 hours to max. dose of 1.5g in 24
hours.

250mg by injection can be considered approximately
equivalent to 500mg orally. Therefore do not prescribe as
po/iv because the formulations are not bioequivalent

By i.v. injection, initially give 20 - 50mg slowly at max.
recommended rate of 4mg/min.
The risk of ototoxicity is related to the rate of
administration.

By i.v. infusion, 250 - 500mg. May be diluted in
50 - 100mL sodium chloride 0.9% (not glucose) for
infusion. Max. rate 4mg/min.
Sometimes a continuous infusion is given eg.250mg in
50ml given at 2ml/hr via syringe pump.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Bumetanide
tablets/liquid/injection
Note: furosemide [frusemide] 40-60mg orally is
approximately equivalent to bumetanide 1mg orally.

Oedema: By mouth, 1mg in the morning increasing to 2 -
4mg once or twice daily. In elderly patients 500micrograms
daily may be sufficient.

Bumetanide injection is only indicated if patient is intolerant
to Furosemide.

By i.v. injection, 1 - 2mg given over 1 -2 minutes repeated
after 20mins if necessary.

By i.v. infusion, 2 - 5mg diluted in 50 to 100mL glucose 5%
or sodium chloride 0.9%. 3mg given over 30mins, 4mg
over 45mins and 5mg over 60mins

Potassium Sparing Diuretics and Aldosterone antagonists

The diuretic effects of potassium sparing diuretics are additive to those of thiazide
and loop diuretics. They cause retention of potassium and are used as an alternative
to giving regular potassium supplements with thiazide or loop diuretics.
The retention of potassium is more effective than potassium supplementation.

Potassium sparing diuretics are not usually required alongside the treatment of
hypertension with thiazide diuretics unless hypokalaemia occurs.

- Amiloride tablets/liquid With other diuretics: 5 - 10mg daily.
Alone: 10mg daily Max. 20mg daily.

- Spironolactone tablets Low doses of spironolactone (usually 25 - 50mg daily) may
be considered for patients with severe heart failure (severe
LVSD) who are already receiving an ACE inhibitor.


- Eplerenone tablets (s) Licenced for heart failure (LVEF< 40% and clinical signs)
post myocardial infarction. To be started within 3- 14 days
of the event.
Starting dose 25mg daily titrated up to 50mg daily.

Restricted to cardiology use only







The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Potassium sparing diuretics with other diuretics

Combination products should be reserved for patients who have a problem with
compliance.

It is preferable to administer potassium sparing diuretics (or indeed potassium
supplements) separately if needed unless treatment is unlikely to change.
- Co - amilozide tablets (Amiloride hydrochloride 2.5mg or 5mg plus
hydrochlorothiazide 25mg or 50mg)

Hypertension: 1 - 4 tablets in the morning of 2.5/25
strength or 1 - 2 tablets of 5/50 strength increased if
necessary to a max. of 4 daily of 5/50 strength.

- Co - amilofruse 5/40
tablets
(Amiloride 5mg plus furosemide [frusemide] 40mg)
1 2 tablets daily
Please specify strength of tablet as also available as 2.5/20

Osmotic Diuretics
- Mannitol Injection (s) Consultants only.


Anti - arrhythmic Medicines

Management of Arrhythmias

Note: Medicine treatment for SVT or VT is not appropriate if marked hypotension is
present (systolic BP < 90mmHg) with cardiac failure or poor peripheral, renal or
cerebral perfusion. DC conversion is treatment of choice in these circumstances.

See entry under individual medicines for more details on dosage and administration.













The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Initial Treatment of Acute Arrhythmias
Supraventricular
Tachycardias (SVT)
1) Adenosine 3mg by rapid i.v. bolus (inject over less than
2 seconds into a large vein with cardiac monitoring)
followed by 6mg after 1 - 2 minutes if necessary
and then by 12mg after a further 1 - 2 minutes
Do not use in asthmatic patients

(If given through an iv line rather than a cannula it should be
followed by a sodium chloride 0.9% flush)

2) Verapamil 2.5 - 10mg by slow iv injection (inject slowly
over 2 mins with ECG monitoring).
Do not use with / after beta - blockers or in possible
ventricular tachycardia or atrial fibrillation with pre-
excitation e.g. Wolff Parkinson White syndrome. Do not
use in broad complex tachycardia unless under the
direct supervision of a consultant cardiologist.
Atrial Fibrillation 1) Beta-blockers
2) Digoxin
3) Amiodarone (click here for administration policy)
4) Dronedarone- this is not yet approved for use but is
under review by the medicines management team

Patients should also be anticoagulated if not contraindicated
once rhythm has been confirmed.
Click here for further details on management.
Ventricular Tachycardia If sustained and patient is haemodynamically compromised use
DC shock.

If unsustained or patient is haemodynamically stable or there is
a delay to DC shock use
1) Amiodarone
2) Lidocaine [lignocaine] i.v. (ready diluted infusion bags
4mg/ml are available for use)
Consider use of intravenous magnesium sulphate especially if
Torsades de pointes present, (click here for dosage).
Chronic and Recurrent
Supraventricular
Arrhythmias
1) Digoxin
2) Verapamil or beta - blockers if LV function is good
3) Flecainide
4) Amiodarone
Paroxysmal Atrial
Fibrillation and SVT
Good LV function:
1) Sotalol
2) Flecainide
3) Disopyramide
Impaired LV function:
1) Amiodarone
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Recurrent Symptomatic
Ventricular Arrhythmias
1) Sotalol
2) Amiodarone
3) Flecainide
4) Propafenone



Atrial Fibrillation
Options are rate control or rhythm control.

Rhythm control
NB Only for patients who have been in atrial fibrillation for less than 48 hours. If not
seek specialist advice regarding TOE guided cardioversion
Options:
1) DC shock
2) Betablockers (including sotalol)
3) Amiodarone
4) Flecainide (contraindicated if known or suspected structural heart disease
/IHD/ previous MI)
5) Dronedarone non formulary- requests by consultant cardiologists will be
considered on an individual patient basis due to concerns over side effect
profile.

Rate control
Options:
1) Betablockers (not sotalol)
2) Rate limiting calcium channel blockers (verapamil or diltiazem- as alternative
to betablockers)
3) Digoxin
4) Amiodarone

Warfarin should be considered for patients at high risk of developing stroke unless
contra indicated and is required for patients prior to DC cardioversion if AF
persistent for greater than 48 hours.

For immedicate anticoagulation for AF, dalteparin at a dose of 200units/kg daily can
be given. See here for algorithm of dalteparin doses.

See also NICE guidance on the treatment of AF.
http://www.nice.org.uk/nicemedia/live/10982/30055/30055.pdf


Pill in the pocket approach with flecainide may be suitable for some patients
(Consultant cardiologist prescribing only).



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Atrial Flutter

Medications as for atrial fibrillation as above.
NB- more likely to respond to DC cardioversion than chemical cardioversion. Patients
also need to be considered for anticoagulation as for Atrial Fibrillation.


Management of Known or Strongly Suspected Digoxin Overdose
- Digibind injection (s) Consultants only.

After advice from Poisons Information Service.
For use where measures beyond withdrawal of cardiac
glycoside; correction of electrolytes and fluid balance are
also necessary.

Ventricular Tachycardia
- Magnesium sulphate
50% injection
2mmol magnesium/mL (1g in 2mL).

This schedule is for treatment of serious arryhthmias
including torsades de pointes.

By i.v. Infusion, Give 8mmol (4ml of 50% injection) over 10
- 15mins.
CCU protocol: Add 20mmol (10ml of 50% injection) to
250ml glucose 5% and infuse intravenously over 30 mins























The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Medicines for Supraventricular and Ventricular Arrhythmias

- Amiodarone
tablets/injection
By mouth: Loading regimen, 200mg 3 times daily for 7
days, reduced to 200mg twice daily for a further seven
days before the maintenance dose.

Unlicensed loading regimes (only to be prescribed by
consultant cardiologists) may be used e.g. 400mg bd until
patient has received 10g, then reduced to 200mg daily

Maintenance dose: 200mg daily or minimum required to
control arrhythmia. Significant toxicity may develop when
doses above 200mg a day are used for maintenance.

Guidelines for iv administration of amiodarone

Initial dose 300mg followed by 900mg infusion if required
(Maximum 1.2g in maximum volume of 500ml in 24 hours)

300mg: Given as slow iv injection over 3 minutes (in
extreme emergency) as per cardiac arrest protocol with
ECG monitoring (minijet pre- filled syringe) into large ante
cubital vein
Or
iv infusion in 250ml glucose 5% over 30 minutes preferably
via central line

900mg: iv infusion in 500ml glucose 5% over 23.5 hours
via central line or long line

The decision to give via a peripheral line must be
discussed with the consultant for that patient or the on
call consultant.
The reasons for this decision should be documented
in the patients medical notes.
Notes: Patients should be advised of the potential side effects of amiodarone

Many patients taking amiodarone develop corneal deposits (reversible on
discontinuation). There is a rare risk of optic neuritis and blindness.
Warn drivers that car headlights may dazzle them at night.
- Amiodarone may cause phototoxic reactions.
- Advise patients to use a total sunblock that blocks both UVA and UVB light when
exposed to the sun, e.g. Uvistat 30.
- Amiodarone can cause disorders of thyroid function.
- Laboratory tests should be performed before prescribing, (or as soon as possible
after initiation) and at least every 6 months.
- Patients must be counselled about the risk of irreversible pulmonary fibrosis. This
should be documented in the patient's notes.
- Pneumonitis should be considered if new or progressive shortness of breath or
cough develops in patients taking amiodarone.
- Liver function should be monitored pre - treatment and at 6 monthly intervals
thereafter.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Disopyramide capsules/
m/r tablets/injection
By mouth, 300 - 800mg daily in divided doses.
Slow release tablets 250 - 375mg twice daily.

By i.v. injection, 2 mg/kg over at least 5 mins (max. rate
30mg/min) to max. 150 mg, with ECG monitoring,
followed immediately
by either 200mg orally then 200mg every 8 hours for 24
hours
or
400micrograms/kg/hr by intravenous infusion in sodium
chloride 0.9%, or glucose 5% (max 800mg in 24 hours)

Max. 300mg in first hour, and 800mg daily.

- Flecainide (s)
tablets/injection
Cardiologists only.
By mouth: 50-100mg bd (max 300mg daily)

By injection: 2mg/kg (to max 150mg) iv infusion over 30
mins via syringe pump (may be diluted with glucose 5%).
If continuous infusion is needed afterwards please see
product information.
- Oral beta-blockers See beta-blocker section of formulary here

- Rate limiting calcium
channel blockers
Click here for iv and here for oral treatments
- Propranolol injection (s) Cardiologists and Anaesthetists only.

- Atenolol injection (s) Cardiologists and Anaesthetists only or as part of
myocardial infarction pathway

- Metoprolol injection (s) Cardiologists and Anaesthetists only.

- Quinidine bisulphate s/r
tablets (s)
Cardiologists only.
- Sotalol tablets (s) Cardiologists and Consultants only.

- Esmolol injection (s) Cardiologists and Anaesthetists only. Protocol for
administration for arrhythmias available in CCU

- Procainamide (s)
tablets/injection
Cardiologists and Anaesthetists only.
Unlicensed treatment available only from special import
companies and requires a consultant responsibility form

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Ajmaline injection (s) Cardiologists only for diagnosis of Brugada's syndrome
Unlicensed treatment available only from special import
companies and requires a consultant responsibility form


Ventricular Arrhythmias
- Amiodarone See here
- Propafenone tablets (s) Cardiologists only.
- Lidocaine [lignocaine]
Injection
DO NOT give if any form of heart block is present.

In patients without gross circulatory impairment:
By slow i.v. injection, 100mg over a few minutes followed
by infusion 4mg/minute for 30 minutes, 2mg/minute for 2
hours then 1mg/minute. Further reduce if infusion lasts
beyond 24 hours


Available as a pre-filled bag, 0.4% lidocaine in 500ml dextrose 5% (equivalent to
4mg /ml)
REQUIRED DOSE RATE OF INFUSION
1 mg/min 15ml/hr
2mg/min 30ml/hr
3mg/min 45ml/hr
4mg/min 60ml/hr


Bradycardias

Discontinue any medicines that may worsen or precipitate bradycardia

- Atropine sulphate
injection
For management of bradycardias especially if complicated
by hypotension:
By IV injection, initial dose 300 micrograms, followed by
100 microgram increments (up to max 600 micrograms in 1
dose) at 3-5 minute intervals as required.
Total dose should not exceed 0.03mg/kg (2mg) in patients
with mild bradycardia or 0.04mg/kg (3mg) in patients with
severe bradycardia as this dose generally results in complete
vagal blockade
- Isoprenaline (S) For the support of the heart rate in those awaiting definative
management of bradycardia and in the treatment of
Torsades de Pointes.
Only to be used by consultant cardiologists


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Beta - adrenoreceptor Blockers

All beta - blockers are contra - indicated in patients with
A) Asthma
B) Uncontrolled heart failure
C) Sick sinus syndrome
D) Second or third degree heart block
E) Cardiogenic shock

Beta - blockers should be used with caution in patients with
A) History of obstructive airways disease (consider reversibility testing prior to initiation
of a cardioselective betablocker)
B) Peripheral vascular disease
C) Diabetes


NB. Beta-blockers are no longer recommended first line for hypertension (NICE guidance)

In heart failure patients, beta-blockers licensed for heart failure should only be
initiated when patients are stable and not in acute heart failure. They should be
initiated by specialists in heart failure and should be started at a low dose and titrated
up very gradually over a number of weeks to the target (or maximum tolerated) dose.

Beta-Blocker
(Alphabetical Order)
Licenced Indication Doses
Angina Tablets: 50-100mg daily
Arrhythmias Tablets: 50-100mg daily

Atenolol tabs/liquid
(injection consultant
only or as part of the
MI pathway)
Immediately post MI Injection: iv bolus 2.5- 5mg as
single dose injected over 5 minutes
Angina and post MI

Max 10mg daily Bisoprolol tabs
(cardioselective)
Stable moderate to severe
heart failure
Start at 1.25mg daily and titrate up
gradually to 10mg daily
Angina Start at 12.5mg bd and increase if
tolerated to 25mg bd
Carvedilol tabs
(non-cardioselective)
Heart failure Start at 3.125mg bd and titrate
gradually to max 25mg bd (50mg
bd if >85kg)

Arrhythmias

Esmolol injection
(cardiologists and
anaesthetists only)
Hypertension
Continuous infusion
Protocol available on CCU/ HEC
for administration
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Beta-Blocker Licenced Indication Doses
(Alphabetical Order)
Hypertensive crisis Labetolol injection
(consultants and
anaesthetists only)
Aortic dissection

See ITU protocol and product
information
Nebivolol tabs
Cardiologists only
(very cardioselective)
Heart failure (but bisoprolol and
carvedilol are first line for heart
failure regional protocol)

1.25mg daily titrated gradually up
to max 10mg daily
Portal hypertension 40mg bd increased as necessary to
max 160mg bd
SR preparations may be used once
daily.
Arrhythmias

10-40mg tds
Propranolol tabs/ SR
caps
Anxiety (palpitations/sweating)

40mg od increased to tds as
necessary

Ventricular arrhythmias

Sotalol tabs
Prophylaxis of paroxysmal
SVTs
Initially with ECG monitoring, and
checking of QTc interval
80mg od (or 40mg bd) increased
as necessary
max usually 160mg bd

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Medicines affecting the renin-angiotensin system and some other
antihypertensive medicines

Management of Hypertension
The choice of initial agent should be decided according to age and ethnicity and co-
existing disease states.

The table below taken from NICE guidance August 2011 on hypertension
(http://www.nice.org.uk/nicemedia/live/13561/56015/56015.pdf) summarises the
initial treatment of primary hypertension (not including patients with Type 2 diabetes
or Chronic Kidney Disease).




The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Further advice on the management of hypertension, based on the NICE guidelines,
can be found in section 2.5 of the current B.N.F or use the link above.

Antihypertensive agents:

- Thiazide Diuretics (click here)
- Calcium - channel blockers (click here)
- Angiotensin converting enzyme (ACE) inhibitors (click here)
- Angiotension II receptor blockers (ARBs) (click here)
- Alpha blockers (click here)
- Beta blockers (click here)
- Other Vasodilators (click here)

The optimal treatment targets are:
- systolic blood pressure < 140mmHg and diastolic blood pressure < 90mmHg

The targets for patients with diabetes, chronic renal disease or established
atherosclerotic cardiovascular disease are:
- systolic blood pressure < 130mmHg and diastolic blood pressure < 80mmHg

In all hypertensive patients non - pharmacological measures should also be
employed e.g. reducing sodium intake, stopping smoking and reducing stress.

The table below (click here) summarises the main indications and contraindications
for the different classes of antihypertensive medicines. Sub-maximal doses of two
medicines result in larger reductions in blood pressure and fewer side effects than
maximal doses of a single medicine.
In more severe hypertension, medicines may be added in a stepwise manner as per
NICE recommendations until the blood pressure is controlled. If blood pressure falls
below the optimal levels, treatment can be stepped down accordingly.

Aspirin 75mg daily is recommended for secondary prevention of cardiovascular
events.

For primary prevention in patients over the age of 50, cardiovascular risk prediction
charts (at the back of the BNF) can be used to assess a patients risk of
cardiovascular disease over the next 10 years. Any patient with a risk score >20%
should be assessed as to whether they need aspirin 75mg daily for primary
prevention (unlicensed use) This decision should be made on an individual patient
basis taking into account all the risks and benefits.

Hypertensive patients with hypercholesterolaemia who have a high risk of coronary
heart disease may benefit from a statin (click here)


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Hypertensive crisis

Seek specialist advice
Medication options include iv Labetalol
iv Esmolol
iv Sodium nitroprusside


Use of Antihypertensive Medicines in Patients With Co - existing Disease

Indication Contraindications
Class of
medicine
Compelling Possible Possible Compelling
Thiazides - Secondary
prevention of
stroke
- - - Gout
Beta - blockers - Post MI
- Angina
- Some Tachy-
Arrhythmias
- Heart failure
1
- Heart failure
1

- Peripheral
vascular
disease
(caution only)
- COPD (caution
only)
- Asthma
- Heart block
Calcium
channel
blockers (rate
limiting)
- Angina - Myocardial
infarction
- Combination
with beta -
blockers
- Heart block
- Heart failure
ACE inhibitors - Heart failure
- Left ventricular
dysfunction
- Post MI
- Established CHD
- Diabetic
nephropathy
- Secondary
prevention of
stroke
- Chronic renal
disease
2

- Renal
impairment
2

- Peripheral
vascular
disease
4

- ACE Inhibitor
induced dry
cough
3

- Pregnancy
- Bilateral
renal artery
stenosis
Alpha - blockers - Prostatism - Postural
hypotension
- Heart failure
- Urinary
incontinence

Adapted from: British Hypertension Society Guidelines 2004
Journal of Human Hypertension (2004) 18: 139-185

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Notes:
1) Beta - blockers may worsen heart failure, but may be used by specialists to
treat heart failure, (bisoprolol, carvedilol and nebivolol only).
2) ACE inhibitors may be beneficial in chronic renal failure but should be used
with caution. Close supervision and specialist advice are needed when there
is established and significant renal impairment.
3) ACE Inhibitor induced dry cough: an angiotensin II receptor antagonist
may be tried.
4) Peripheral vascular disease: Use ACE inhibitors and angiotensin II receptor
antagonists with caution in peripheral vascular disease due to the possibility of
undiagnosed or clinically silent reno-vascular disease.
5) Alpha blockers: should not be used as monotherapy in the absence of
another clear indication for use.

Vasodilator antihypertensive medicines
- Sodium nitroprusside
Injection (s)
Cardiologists and Anaesthetists only.
Protocol available on CCU. ITU and other HDU areas have
their own protocol according to consultant anaesthetist
guidance

- Hydralazine Used in combination with nitrates for the treatment of heart
failure as per NICE guidance (CG108 August 2010)
Usual starting dose 25mg bd- tds titrated up to max 75mg
qds with concurrent nitrate therapy (usually isosorbide
mononitrate tablets)
Cardiologists only



Alpha - adrenoreceptor blocking medicines
- Doxazosin tablets / MR
tablets
Hypertension: 1mg daily, increased after 1 2 weeks to 2mg
daily, and thereafter to 4mg daily.
Max. 16mg daily.

Doxazosin XL (modified release tablets) : Starting dose
4mg od increase to max 8mg daily after 4 weeks if
necessary
- Tamsulosin MR See urology section of the formulary
- Alfuzosin tablets/ MR
tablets
See urology section of the formulary
- Phenoxybenzamine (s)
capsules/injection
Consultants and Anaesthetists only.
- Phentolamine Injection
(s)
Anaesthetists only.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Management of Heart Failure

Chronic Heart Failure
Preparations
Diuretics (click here)
ACE inhibitors (click here)
Beta blockers (click here)
Aldosterone antagonists (click here)
Digoxin (click here)
Hydralazine and nitrates (click here)
Angiotension II receptor
antagonists (ARBs)
(click here)

See also NICE guidelines for Chronic Heart Failure CG108
(http://www.nice.org.uk/nicemedia/live/13099/50526/50526.pdf)


Acute Heart Failure
Preparations
Diuretics (click here)
Intravenous Nitrates (click here)
Inotropic sympathomimetics (click here)


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Medicines affecting the Renin-Angiotensin system
Angiotensin Converting Enzyme (ACE) Inhibitors
- In volume depleted patients any diuretic should be discontinued or the dose
reduced significantly, 2 - 3 days before initiation of an ACE inhibitor.
This may not be desirable however in heart failure patients.

- A small initial dose of an ACE inhibitor may be used as a test dose usually
given in the evening. However this isnt always necessary. Medical supervision
is recommended for at least 2 hours after the first ACE inhibitor dose has been
given or until the patients blood pressure has stabilised.

- ACE inhibitors are contraindicated in patients with bilateral renal artery
stenosis as they are likely to cause acute renal failure.

- ACE inhibitors may cause progressive impairment of renal function and
hyperkalaemia. Therefore monitor renal function closely and titrate dose
carefully in all patients particularly those with renal impairment.

- Do not give with potassium sparing diuretics unless potassium levels are
monitored closely.

- ACE inhibitors are recommended first line for all patients with heart failure due
to left ventricular systolic dysfunction (LVSD).

- Other indications are hypertension, diabetic nephropathy and secondary
prevention of CVD.

- In hospital, ACE inhibitors are often titrated up more quickly than
recommended in the BNF (shown above) however it is important for all
patients to have their BP and renal function monitored closely especially
before and after any dose change.

- If tolerated ACE inhibitors should be titrated up to the maximum recommended
dose for heart failure, secondary prevention and nephropathy.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Perindopril erbumine
(tert butylamine) tablets
Hypertension: initially 4mg daily (elderly 2mg daily)
max 8mg daily
Heart failure: 2mg daily increasing to 4mg daily

There are also perindopril arginine tablets with doses of
2.5mg and 5mg but RLBUHT doesnt stock these.
- Ramipril
tablets/capsules
Hypertension: Initially 1.25mg daily increased at intervals
of 1 - 2 weeks. Max. 10mg daily

Heart failure: Initially 1.25mg daily increased at intervals of
1 2 weeks. Max 10mg daily

Prophylaxis of cardiovascular events or stroke:
Initially 2.5mg daily increased after 1 week to 5mg daily,
increased after 3 weeks to max 10mg daily.

Prophylaxis after myocardial infarction: (started 48 hours
after MI), initially 2.5mg twice daily, increased after 2 days
to max 5mg twice daily.

Nephropathy: initially 1.25mg daily increased after 2 weeks
to 2.5mg daily then increased after a further 2 weeks to
5mg daily.



Angiotensin II - receptor Antagonists (ARBs)

There is some evidence to show that this group of medicines are effective treatments
for hypertension however they are recommended only when patients are unable
tolerate ACE inhibitors due to side effects (e.g. a problematic cough) or in preference
to an ACE inhibitor in person of African or Caribbean family origin (as per NICE
Hypertension guidelines August 2011).

There are also 3 angiotensin II receptor antagonists licenced for heart failure,
candesartan, valsartan (post MI) and losartan but again ACE inhibitors would be first
line treatment unless patient is intolerant.

The combination of an ACE inhibitor and an angiotensin II receptor antagonist has
been shown to be effective in some clinical trials for heart failure caused by left
ventricular systolic dysfunction, but should only be initiated by a specialist in that area
(i.e. consultant) and is a second line treatment. The use of ACE inhibitor and ARB
together for hypertension is not recommended.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Candesartan tablets

RLBUHT formulary choice
ARB for heart failure
Licenced for Heart Failure with impaired LV function /
hypertension

Hypertension : Initially 4- 8mg once daily (2mg in hepatic
impairment) adjusted according to response to max 32mg
daily. Usual maintenance 8mg once daily.

Heart failure: Initially 4mg daily titrated to target dose
(max) 32mg daily

Contraindicated in cholestasis

- Valsartan capsules

Only recommended by
RLBUHT for heart failure
post MI or post MI if
intolerant of ACE inhibitors


Left ventricular systolic dysfunction post MI

Heart failure: initially 40mg bd increased at intervals up to
max 160mg bd

For post MI 20mg BD increasing to 160mg BD
- Losartan tablets Licenced for hypertension / diabetic nephropathy in
Type 2 DM/ heart failure
Used in RLBUHT for hypertension and nephropathy
Hypertension and nephropathy: 50mg once daily (25mg
initially for elderly and those with severe renal impairment)
increased if necessary to max 100mg daily

- Irbesartan tablets Licenced for hypertension

Dose: 150mg once daily, increased if necessary to 300mg
once daily (in haemodialysis or patients over 75 years, an
initial dose of 75mg may be used).


It is important to remember that Angiotensin II receptor antagonists have many of the
same cautions and contraindications as ACE inhibitors and therefore it is important to
closely monitor renal function, potassium and BP especially before and after any
dose change.












The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Nitrates, calcium-channel blockers, and potassium channel
activators

Management of Angina

In addition to aspirin, statins and ACE inhibitors for patients with known ischaemic
heart disease there are also anti-anginal agents available. They should be added in a
stepwise manner.

1st line anti-anginals rate controlling

- Betablockers (click here)
- Rate limiting calcium channel blockers eg diltiazem (click here)


2nd line antianginals if 1
st
line agents contraindicated or not controlling angina

- Dihydropyridine calcium channel blockers (click here)

Patients can receive a combination of up to 3 second line anti-anginals

3
rd
line antianginals only to be prescribed by cardiologists if 1
st
and 2
nd
line agents
are contraindicated or not controlling angina

- Nitrates (click here)
- Nicorandil (click here)

4
th
line antianginals only to be prescribed by cardiologists and if 1
st
/ 2
nd
and 3
rd

line agents are contraindicated or not controlling angina

- Ivabradine (S) (click here)
- Ranolazine (S) (click here)



Management of Acute Coronary Syndrome

(click here)


Nitrates

Glyceryl trinitrate

Some form of sublingual GTN should be prescribed when required for all patients
presenting with suspected angina if no contraindications.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Sublingual tablets: 300 - 500micrograms `when required'

- Sublingual Spray: 1 - 2 sprays (400 microgram per spray) `when required'

- Buccal tablets: Can be prescribed when sublingual GTN isnt strong
enough to relieve anginal pain and can be considered
as an alternative to IV nitrates.

They are not routinely prescribed as discharge
medication unless the patient has refractory angina and
it has been specified by consultant cardiologist

The tablet should be placed between upper lip and
gum (not sublingually) and left to release the medicine.

Angina: 2 - 3mg BUCCALLY `when required'.

Left ventricular failure: 5mg 3 times daily as alternative
to IV infusion of nitrates. May be increased to 10mg 3
times daily in severe biventricular failure. Requires
close BP monitoring.


Isosorbide mononitrate

It is important to remember that patients require a nitrate free period (6-8 hours)
when taking regular nitrates as prophylaxis of angina. Therefore immediate release
isosorbide mononitrate/ dinitrate should be prescribed morning and afternoon. MR
preparations should only be prescribed once daily.

- Isosorbide mononitrate
tablets / MR tablets,
capsules
For angina and adjunct in congestive heart failure
Initially 20 - 40mg twice daily (10mg twice daily in those
who have not previously received nitrates). Increased to
max 40mg tds with last dose no later than 6pm.

Modified release preparations are only given once daily.
Usual starting dose 30mg MR once daily. Increased to
max 120mg once daily


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Isosorbide dinitrate
infusion 0.05%
Angina: By IV infusion, 2 - 10mg/hr (up to 20mg/hr). Start
at 2mg/hr and increase according to response.
There is a nurse monitoring sheet available for
documentation of dose changes and instructions on
titration rate.

Left ventricular failure: By IV infusion, 2 - 10mg/hr (up to
20mg/hr). Start at 2mg/hr and increase according to
response.

NB Formulary may change to GTN infusion instead of
isosorbide dinitrate infusion in the future.



Preparation of isosorbide dinitrate for infusion:

- Maximum concentration for peripheral administration is
500micrograms/mL (0.05%) which may be administered without further
dilution via a syringe pump.
- If there is no 0.05% available dilute 30mL of 0.1% (1000 micrograms/mL) to
60mL with glucose 5% or sodium chloride 0.9% to create a 0.05% solution and
administer via a syringe pump.
- Higher concentrations 1000 micrograms/ml (0.1%) may be given via a
central IV line only.
Isosorbide dinitrate infusion is incompatible with PVC administration sets.


Potassium Channel Activators

Nicorandil Angina: 10mg twice daily, can be increased up to a
maximum of 30mg twice daily.



Calcium - channel Blocking Medicines

Used for hypertension, angina and post MI (diltiazem). Nimodipine is used for the
treatment of subarachnoid haemorrhage.

Rate limiting calcium channel blockers
Should be avoided in heart failure due to negative inotropic effects

- Diltiazem tablets/ m/r
tablets/capsules
Brand of tablets should be specified as the different
preparations have different bioavailabilities
Start at lowest dose and titrate up as required.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


FORMULARY CHOICE BRAND DOSE AND FREQUENCY
Twice daily
modified release preparations
Tildiem Retard *

90 - 180mg twice daily
(max dose for angina 240mg bd)
Once daily
modified release preparations
Tildiem LA *

200 - 300mg once daily
(max dose 400- 500mg daily)

- Verapamil tablets/ m/r
tablets/liquid
Verapamil should not be used in conjunction with beta
blockers

Angina: 80 - 120mg 3 times daily.
Supraventricular arrhythmias: 40 - 120mg 3 times daily
Hypertension: 240 - 480mg daily in 2 - 3 divided doses.


Modified release preparations (should be prescribed by
brand where possible):
Half Securon SR 120mg daily. New patients to start on this
dose then may be changed to Securon SR Max. 2 tablets
twice a day.
Securon SR 240mg daily, increased to 1 tablet twice a
day.

Modified release preparations are not licenced for
supraventricular arrhythmias
Dihydropyridine calcium channel blockers

- Amlodipine tablets Has less negative inotropic activity therefore preferred
choice in presence of heart failure.
Hypertension and Angina: Initially 5mg once daily.
Max. 10mg once daily.


- Felodipine tablets Hypertension and Angina: Initially 5mg once daily
increased if necessary to 10mg once daily.


- Nifedipine Immediate release nifedipine is no longer recommended
as they are associated with large variations in blood
pressure and reflex tachycardia.

Hypertension: Adalat LA- 20mg-30mg once daily
increased if necessary to max 90mg once daily

Not usually used for angina prophylaxis- amlodipine or
felodipine preferred.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Management of Subarachnoid Haemorrhage
- Nimodipine injection (10mg/50mL) For treatment (iv infusion):

Must be administered via syringe pump connected via
a Y-site connection into a running drip (40mL/hr) of
either sodium chloride 0.9% or glucose 5% as a co-
infusion into central IV line. Must be non- PVC.
Infusion should be protected from light.

Nimodipine must not be added to the infusion fluid or
mixed with any other medicines. Blood pressure must
be closely monitored.

If central IV line administration is not possible, double
the rate of the co - administered infusion fluid to
80mL/hr (N.B. this is an unlicensed method of
administration).

Dose: For patients > 70kg and with stable blood
pressure

1mg/hr (5mL/hr) initially, increased after 2 hours to
2mg/hr (10mL/hr) providing the patient is not
hypotensive

For patients < 70kg or with unstable blood pressure

Start at 500micrograms/hr (2.5mL/hr) initially and
increase if
possible.

Continue for at least five days up to a max. of 14 days.
(If surgical intervention is required during treatment
continue for 5 days after surgery)

- Nimodipine tablets 30mg For prophylactic use or to complete a course
following iv administration:

By mouth, 60mg every 4 hours starting within 4 days
of haemorrhage and continuing for 21 days.










The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


4
th
line anti-anginal medicines

- Ivabradine (S) Cardiology only
Affects heart rate but not blood pressure.
Dose: initially 5mg twice daily (elderly patients 2.5mg twice
daily) titrated after 3 -4 weeks to 7.5mg twice daily.
Caution when used with beta-blockers or rate limiting
calcium channel blockers.


- Ranolazine (S) Consultant cardiologist only.
Unlike other anti-anginals should not affect heart rate or
blood pressure.
Dose: Initially 375mg twice daily increased to 500mg twice
daily after 2-4 weeks. May be increased if necessary after
that to max 750mg twice daily.



Peripheral and Cerebral Vasodilators
- Naftidrofuryl Capsules (s) Vascular surgeons only.
Note: capsules must not be opened for patients with
swallowing difficulties unless an N/G tube is in place.
Contents have a strong local anaesthetic action and
potentially can be aspirated.
PVD dose: 100-200mg three times daily


Sympathomimetics

These medicines should not be used outside the ITU / POCCU and CCU
environments.

Inotropic Sympathomimetics
Dobutamine infusion 2.5 - 10micrograms/kg/min adjusted according to
response.
Rarely up to 40micrograms/kg/min have been needed.
Occasionally patients have responded to
0.5micrograms/kg/min. The dose should be gradually
decreased rather than stopped abruptly.
Concentrations less than 5mg/ml can be administered via
a large peripheral line with monitoring for phlebitis

Infusion chart below
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Infusion rate mL/hr for Dobutamine 500mg in 500mL (i.e. 1mg/ml) glucose 5% or sodium
chloride 0.9%
Weight Micrograms/kg/min
2.5 5 7.5 10 12.5 15 17.5 20
40kg 6 12 18 24 30 36 42 48
50kg 7 15 22 30 37 45 52 60
60kg 9 18 27 36 45 54 63 72
50kg 10 21 31 42 52 63 73 84
80kg 12 24 36 48 60 72 84 96
90kg 13 27 40 54 67 81 94 108
100kg 15 30 45 60 75 90 105 120
110kg 16 33 49 66 82 99 115 132


- Adrenaline (epinephrine)
injection
Contact Anaesthetist for advice on use of adrenaline
infusion as an inotropic agent.
- Isoprenaline injection (s) Cardiologists and Anaesthetists only


Vasoconstrictor Sympathomimetics
- Ephedrine injection (s) Anaesthetists only
- Metaraminol injection (s) Anaesthetists only
- Noradrenaline (s)
(norepinephrine) injection
Anaesthetists only.
- Phenylephrine (s)
injection
Anaesthetists only.


Cardiopulmonary resuscitation

Refer to Advanced Cardiac Life Support Guidelines issued by European Resuscitation
Council and Resuscitation Council (UK).
- Adrenaline (epinephrine)
injection
1 in 10,000 (1mg/10mL).
Cardiac Arrest:
1mg (10mL) stat dose during resuscitation loop.
Repeated every 3- 5mins if necessary during alternate
cycles of CPR.



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Anticoagulants and protamine


Prophylaxis of Venous Thromboembolism

Prophylaxis of venous thromboembolism should be considered for all hospital in-
patients. An assessment form should be completed for the notes and on ICE.

Please see Hospital Policy on Prevention of Venous Thromboembolism (2010)
for assessment criteria and recommended treatments.

Available on the intranet under Policies and procedures/ General policies/ Trust
clinical policies/ pharmacy/ Prevention of thromboembolism.

For those patients already taking warfarin prior to a procedure Click here

In case of difficulty, please contact the Haematology Department for advice regarding
specific patients.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Treatment of Venous Thromboembolism
Treatment
Proven Deep Vein
Thrombosis (DVT)
Pulmonary Embolism (PE)
Dalteparin
Warfarin
Contact Medicines Information (Ext. 2096) or the Haematology Department
IV heparin stat
5000units then
IV heparin or
subcutaneous
Dalteparin
Warfarin

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Guidelines for the Management of Pulmonary Embolism and Deep
Vein Thrombosis

Decision to Use Anticoagulants

The potentially serious outcome associated with thromboembolic disease of the leg
veins and lungs means that anticoagulant treatment with heparin should be started
as soon as possible. Ideally, treatment with heparin should follow a robust clinical
diagnosis, confirmed by a senior doctor of Registrar grade or above. However, if the
suspicion of DVT or PE is high, heparin should not be withheld simply because a senior
member of the medical staff is not immediately available.

The diagnosis must be confirmed by imaging compression ultrasound, isotope
venography, ventilation perfusion scanning or pulmonary angiography within 24 hours
whenever possible.

Subsequent therapy with warfarin should not be introduced until the clinical diagnosis is
confirmed by an appropriate imaging study and pregnancy has been excluded.

The principles of treatment with anticoagulants are outlined below, followed by more
specific details of management.

Patients with acute venous thrombosis and a history of current intravenous medicine
use should be referred to the Lead Clinician for the Anticoagulant Service who will
arrange an individual management plan.

Principles of Treatment

NOTE: Subcutaneous administration of heparins (unfractionated and Low Molecular
Weight) should only be by injection into the abdomen or lateral part of the thigh.

1. Establish baseline full blood count, clotting screen and renal function. If age less
than 45 years, perform thrombophilia screen (before heparin therapy).

2. Arrange confirmatory imaging tests immediately, requesting urgent testing for results
within 24 hours.

3. For treatment of deep vein thrombosis, use subcutaneous low molecular weight
heparin (Dalteparin once daily). Monitoring is not required except in renal
impairment. In such an event, liaise with Haematologists.

4. For treatment of pulmonary embolism, use intravenous, unfractionated Heparin or
subcutaneous once daily Dalteparin.
- Monitor intravenous unfractionated heparin treatment with APTT after 6 to 8
hours aiming for a therapeutic ratio of 1.8 - 3.3. This should be reached within
24 hours of commencing heparin.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Low molecular weight heparin does not require monitoring except in renal failure
or the critical care situation. If the patient is haemodynamically compromised,
consider emergency THROMBOLYTIC THERAPY providing there are no contra
- indications. Fibrinolytics licenced for the treatment of PE are alteplase and
streptokinase.

5. Initiate warfarin once diagnosis is confirmed by imaging. Monitor INR daily. Continue
warfarin, and discontinue heparin after at least five days and once INR is in the
appropriate therapeutic range for 48 hours (whichever is the longer).

6. If on heparin for longer than 5 days, monitor platelet count daily against initial pre -
treatment result.

Parenteral anticoagulants

NOTE: Subcutaneous administration of heparins (Low Molecular Weight Heparins)
should only be by injection into the abdomen or lateral part of the thigh.

Heparins

Low Molecular Weight Heparins

Weight must be recorded on inpatient drug chart.

Units should be written out in full not abbreviated to iu or u.
Haemoglobin, platelets and plasma sodium should be checked every 3 4 days for
patients receiving low molecular weight heparins (LMWH). Renal function should be
checked prior to dosing. NB. This should not delay treatment, if unavailable prior to
1
st
dose every effort should be made to ensure results available to guide dosing for
subsequent doses.
Patients with impaired renal function receiving LMWH need their antifactor Xa levels
to be monitored to ensure appropriate dosing (levels are taken 4 hours after the dose
of dalteparin and testing is done on Mondays and Fridays).


They are all administered by subcutaneous injection.
Indication (for this hospital) Available as Dose
Dalteparin PE/ DVT treatment and
prophylaxis
Ampoules/ pre-filled
syringes
Click here and see
VTE prophylaxis
guidelines on the
intranet.
Enoxaparin NSTEACS Pre-filled syringes See NSTEACS
pathway Click here

For patients requiring immediate anticoagulation for AF, dalteparin given at a
treatment dose of 200 units/kg once a day can be used.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Patients requiring long term anticoagulation with LMWH (i.e. not suitable for warfarin
treatment) should be referred to haematology for advice on doses, monitoring and
osteoporosis prevention. Only 2 weeks treatment will be supplied as discharge
medication to ensure that the patient has some follow-up monitoring.
Patients requiring a long of prophylactic low molecular weight heparin e.g. after
orthopaedic surgery, will be given the full course on discharge.

How to Use Low Molecular Weight Heparin (Dalteparin) for Treatment of Deep
Vein Thrombosis

Calculate total dose based on body weight according to the table below.
The dose is 200 units/kg. The maximum daily dose is 18,000 units/day. Administer
subcutaneously once daily in the trunk or thigh only.

In patients at high risk of bleeding, for example post surgery, 100 units/kg twice
daily subcutaneously is recommended.

Note: The dose of Dalteparin is the same for the treatment of both deep vein
thrombosis and pulmonary embolism.
1. APTT monitoring is not required.
2. Patients with renal impairment require special monitoring and may need
dosage reduction. Please contact Haematologists for advice about appropriate
investigations (anti Xa levels).
3. Dalteparin should be continued for a minimum of 5 days and until the INR is in
range for 2 consecutive days (whichever is the longer).
4. The dose should be written in both units and millilitres to provide a check on the
dose for administration.

DVT treatment dosage with Dalteparin (based on 200 units per kg body weight)
Body weight (kg) units/daily Volume of pre - filled syringe
46 - 56 10,000 0.4ml
57 - 68 12,500 0.5ml
69 - 82 15,000 0.6ml
Over 83 18,000 0.72ml

How to Use Low Molecular Weight Heparin (Dalteparin) in the Treatment of
Pulmonary Embolism
1. First give a loading dose of unfractionated heparin 5,000 units over 5 minutes
intravenously.

2. Calculate the total dose as for the treatment for deep vein thrombosis (table
above).

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Other anticoagulants

- Epoprostenol injection (s) Consultants only.
- Taurolock injection (s) Consultant Nephrologists only
- Unfractionated heparin Click here

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Intravenous Unfractionated Heparin

Continuous unfractionated heparin infusion is not used routinely but is an option for
some patients particularly around the time of some surgery or if they have a high
bleeding risk.

How to Use Intravenous Unfractionated Heparin in Adults*

1. Establish baseline full blood count, clotting screen and renal function.
2. Give a bolus - loading dose of 5,000 units by intravenous injection.
3. Establish an infusion of heparin 1000units/mL (40mL containing 40,000units). Set
infusion to run at 1.3mL per hour (approximately 30,000 units over 24 hours).
4. Check APTT 6 to 8 hours after starting infusion.
5. Change the infusion rate to achieve the therapeutic APTT range of 1.8 to 3.3 by 24
hours (see table below).

For Adjusting the Dosage of Intravenous Heparin 1000 units/mL
APTT Ratio Infusion rate change
> 7.2 Stop for 60 minutes.
At restart, reduce rate by 1mL/hr.
5.7 - 7.1 Reduce by 0.3mL/hr.
3.4 - 5.6 Reduce by 0.1mL/hr.
1.8 - 3.3 No change.
1.4 - 1.7 Increase by 0.2mL/hr.
< 1.4 Increase by 0.4mL/hr.
Repeat APTT ratio 6 - 8 hours after each alteration in rate, unless APTT ratio is > 7.2 when
measurements should be made more frequently.

*Modified from Fennerty et al. British Medical Journal 1988; 297: 1285-8

6. Replace heparin infusion (syringe) at least every 24 hours and repeat APTT daily.
7. If heparin continues for more than 5 days, check platelet count daily.

Once prescribed by the doctor, nurses with the relevant expanded role, training and
following satisfactory assessment may administer the above according to guidelines set
out by individual directorates within the Trust.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Management of Bleeding Due to Intravenous (Unfractionated) Heparin and Low
Molecular Weight Heparin (Dalteparin):

REMEMBER: - The Haematologist on - call is available for advice.

a) Intravenous (Unfractionated) Heparin

1. Stop heparin and send sample for APTT ratio. Because the half - life of heparin
is short, stopping the infusion is usually sufficient.

2. If bleeding is severe/life threatening give protamine sulphate by slow
intravenous injection at a dose of 1mg for every 100 units heparin infused over
the previous hour (maximum dose of protamine is 50mg).
Following administration of protamine, repeat APTT ratio.

3. If bleeding continues after heparin has been stopped for 1 hour or despite giving
protamine, call Haematologist for advice.

b) Subcutaneous Low Molecular Weight Heparin (Dalteparin)

1. Check platelet count and send clotting sample to coagulation laboratory.

2. Consult haematologist regarding advice on management.

Note: Fresh frozen plasma is NOT helpful in the reversal of heparin overdose.

Oral Anticoagulants

Warfarin is the first choice oral anticoagulant. However if patient is allergic or
intolerant to warfarin then there are 2 other options available (acenocoumarol and
phenindione). If either of these alternatives are to be prescribed please contact
haematology/ Roald Dahl anticoagulation clinic for advice on starting doses and
monitoring.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Warfarin Treatment Guidelines
How to Start Warfarin Treatment*
INR should be measured daily when initiating warfarin treatment. The INR is not accurate if the
APTT ratio is > 5.0
A baseline INR should always be checked prior to initiation of warfarin.

Inpatients should be loaded with warfarin as shown on the table below with an INR taken each
day and the dose adjusted accordingly.
INR
(in morning)
Warfarin dose (mg)
(in evening)
Day 1. < 1.4 10
< 1.8 10
1.8 - 2.0 1
Day 2.
> 2.0 0
< 2.0 10
2.0 - 2.2 5
2.3 - 2.5 4
2.6 - 2.9 3
3.0 - 3.2 2
3.3 - 3.5 1
Day 3.
> 3.5 0
< 1.4 > 8
1.4 - 1.5 8
1.6 - 1.7 7
1.8 - 1.9 6
2.0 - 2.3 5
2.4 - 3.0 4
3.1 - 4.0 3
Day 4.
Predicted maintenance dose.
Predicted maintenance dose may be
unreliable if patient has been given
less than 10mg on days 1 or 2.
> 4.0 Omit dose until INR < 3
After day 4 Use clinical judgement
*Modified from Fennerty et al. BMJ 1988; 297: 1285 - 8

Outpatients are usually initiated on warfarin by giving an initial 3 day loading dose of 10mg,
10mg, 5mg or 10mg, 5mg, 5mg (depending on the size and age of the patient) with a
compulsory INR check on the 4
th
day.

(Where coumarin treatment has only been stopped temporarily in patients whose INR has
been stable it is reasonable to reintroduce warfarin at the previous dose provided that other
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


medication has not changed significantly and there is no need for heparin cover whilst off
warfarin).

Note: Many medicines interact with warfarin, especially amiodarone, omeprazole, antibiotics,
antiepileptics, NSAIDs and alcohol. Consult the BNF and/or Medicines Information (ext 2096)
for a detailed list.


Recommended Target Ranges for INR

Recommended Therapeutic Range for Oral Anticoagulation
Condition
Target INR (Range)
Prophylaxis/Treatment venous thrombosis
Treatment : pulmonary embolism
Prevention : systemic embolism
Atrial fibrillation
Valvular heart disease
Tissue heart valves
Post myocardial infarction (Includes aneurysm and dilatation)
Transient ischaemic attacks
2.5 (2.0 3.0)
Mechanical prosthetic valve
Anti - phospholipid syndrome
Recurrence of venous thromboembolism whilst on oral
anticoagulation
3.5 (3.0 4.0)
Atrial fibrillation awaiting DC cardioversion
2.75 (2.2 3.2)

Ref: Haemostasis and Thrombosis Task Force for the British Committee for Standards in
Haematology.
Guidelines on Oral Anticoagulation: Third Edition. Br J Haematol. (1998) 101:374,387

(The guidance for atrial fibrillation awaiting DC cardioversion is a hospital policy due to
underanticoagulation causing delays in treatments)

NB: Optimal range may require individual assessment according to clinical condition
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Table: Recommended Duration of Oral Anticoagulant Therapy
Short Term
Post - operative venous thrombosis in calf* 6 weeks
D - C cardioversion 8 weeks (4 weeks before; 4 weeks after)
Mural thrombus (post myocardial infarction) 12 weeks
Tissue valve prosthesis 12 weeks
Pulmonary embolism* 26 weeks (6 months)
Proximal deep venous thrombosis* 26 weeks (6 months)
*Recurrence whilst on therapy requires increased target INR. Recurrence after anticoagulant
discontinued requires further therapy
Long Term
Recurrent venous thromboembolism
Vena caval filters
Anti - phospholipid syndrome
Cardiomyopathy
Mechanical valve prosthesis
Atrial fibrillation

Ref: Haemostasis and Thrombosis Task Force for the British Committee for Standards in
Haematology.
Guidelines on Oral Anticoagulation: Third Edition. Br J Haematol. (1998) 101:374,387

Management of Oral Anticoagulation in the Peri Operative Period

Management depends upon the surgical risk of bleeding and the indication for
anticoagulation
Please see Hospital Policy Management of Oral Anticoagulation in the Peri
Operative Period (requiring urgent surgery) for guidance and recommended
treatment options.
Available on the intranet under Policies and procedures/ General policies/ Division of
Surgery/ Anaesthesia and Theatres

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Management of over - anticoagulation With Warfarin/ other oral
anticoagulants

Note: Headache may be a symptom of haemorrhage

1. Life - threatening haemorrhage (including intra - cerebral bleeds)
- Resuscitate as necessary.
- Stop warfarin.
- Send samples for INR, FBC, group and save plasma/cross match.
- Give vitamin K (phytomenadione - Konakion MM) at a dose of 5mg by slow IV
injection over 2 minutes. Alternatively vitamin K injection can be diluted in 50mL
minibag of glucose 5% and run over 10 minutes.
- Prothrombin complex concentrate is the product of choice in intracerebral
haemorrhage transfuse prothrombin complex concentrate 50 units/Kg or
fresh frozen plasma 15ml/Kg.
- Contact on - call Haematologist URGENTLY who will advise on the use of
factor concentrates.

2. Less severe haemorrhage such as haematuria, epistaxis or headache
- Withhold warfarin and check INR

- Refer to Clinical Haematologist

- If INR > 8 consider giving vitamin K (phytomenadione- Konakion MM) at a
dose of 0.5 - 2mg by slow I.V. injection over 2 minutes. Alternatively vitamin K
injection can be diluted in 50mL minibag of glucose 5% and run over 10
minutes.

- Review after 48 hours.

3. High INR without haemorrhage or headache
- INR > 4.5: Stop warfarin for 1 or 2 days then review after 24 hours.

- INR > 8 and other risk factors for bleeding are present: Stop warfarin for 1 to 2
days and add vitamin K (phytomenadione) 2.5mg orally as a single dose
(Konakion MM Paediatric injection can be given orally).

4. Unexpected bleeding or headache at therapeutic levels of INR
- Cause of bleeding should be investigated as for patients who are not taking
warfarin.

- Modify warfarin dose as appropriate.

- If cerebral haemorrhage is suspected INR should be reversed to normal as
soon as possible as in part 1 above.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Anticoagulant Clinic/ Long Term Anticoagulation

There are clinics at both Royal Liverpool and Broadgreen hospitals. Patients are
accepted only after the proper referral forms are fully completed and received by the
clinic before the appointment dates.

The decision to keep patients on long - term anticoagulant therapy should be reviewed
regularly.

The length of time for which the patient is anticoagulated is decided by the referring
clinician, and not by the anticoagulant clinic.

The Anticoagulant clinic must be informed of changes in the patient's clinical status and
medicines and any planned procedures, so that the appropriate adjustment of
anticoagulant therapy can be made.

All patients taking warfarin should have an anticoagulant referral made when they are
discharged.

New patients will only be seen on Monday and Thursday clinics at Roald Dahl clinic
in the Royal Liverpool Hospital. This should be taken into consideration when starting
warfarin in both in patients and outpatients so that they can still have a day 4 INR
check.


Protamine sulphate

- Protamine sulphate
injection
10mg/ml (Click here)

Antiplatelet Medicines

- Aspirin dispersible
tablets
Prophylaxis of cerebrovascular disease or myocardial
infarction:
75 - 300mg daily
Low doses are also given post by - pass surgery.


-Aspirin e/c is considerably more expensive than the dispersible form with little
evidence of any advantage.
-Patients who are newly prescribed low - dose aspirin e/c will routinely have
dispersible aspirin substituted by pharmacy.
-Patients who are admitted on aspirin e/c will have this therapy continued.

The standard dose for low dose Aspirin is 75mg daily and doses of 150 - 300mg
should be reviewed, with the following exception:
In the acute phase of ischaemic stroke where the dose should be 300mg
daily for 14 days and then reduced to 75mg daily.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Clopidogrel tablets Dose: 75mg once daily
Reserved for patients with aspirin hypersensitivity or true
aspirin intolerance (contraindicated in active bleeding and
little evidence of less adverse GI events over aspirin)

Also used post stent insertion and for patients with high
risk Acute Coronary Syndrome (ACS) as per RLBUHT
management of patients with suspected ACS pathway
available in A&E and HEC.

- Dipyridamole tablets Consultants only.
Only licensed for use as an adjunct to oral anticoagulation
for prophylaxis of thromboembolism associated with
prosthetic heart valves.
Dose: 300 - 600mg in 3 - 4 divided doses before food.

- Dipyridamole M/R
capsules
Licensed for secondary prevention of ischaemic stroke and
transient ischaemic attack, alone or in combination with
aspirin (in addition to the above). To be commenced once
aspirin has reduced to 75mg daily
Dose: 200mg MR BD, preferably with food.

Note: For patients with swallowing difficulties the capsules
may be opened and the granules passed down a large
bore N/G tube or swallowed in yoghurt/thickening agents.

- Prasugrel tablets (s) Dose: 10mg daily (60mg loading dose)
If under 60kg or in elderly patients 5mg daily.
Only to be initiated in this trust prior to transfer to Liverpool
Heart and Chest Hospital for Primary PCI in patients with
STEMI- see ACS pathway in A&E and HEC.
Patients may be admitted on this following PCI and if so it
is to be continued.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Myocardial Infarction and fibrinolysis

Primary Prevention of Myocardial Infarction
Consult cardiovascular risk prediction tables in BNF (back pages) and hypertension
section (click here)

Secondary Prevention of Myocardial Infarction
- All post - MI patients should be prescribed aspirin (loading dose of 300mg followed by
75mg daily indefinitely), provided there are no contra - indications.

- Clopidogrel (300mg loading dose followed by 75mg daily) as an alternative to
aspirin should be reserved for those patients in whom aspirin is contra
indicated.

- The use of clopidogrel in combination with aspirin is indicated for those
patients who have had a STEMI, NSTEMI or high risk Acute Coronary
Syndrome as per suspected ACS guidelines. It is given for a fixed period
depending on the indication which should be documented on the drug chart
and on the discharge prescription
i) STEMI - 1 month clopidogrel
ii) NSTEMI and high risk ACS- 12 months

- All post - MI patients should be prescribed a beta blocker and ACE inhibitor,
provided there are no contra - indications.
i) Bisoprolol is the most usually prescribed betablocker post MI
ii) Ramipril is the most usually prescribed ACE inhibitor

- All post - MI patients should be prescribed a statin initiated in hospital
regardless of initial total cholesterol level (if chol< 3.5 then decision for starting
a statin should be made on an individual patient basis).

- In this hospital patients post MI receive simvastatin 40mg daily or atorvastatin
80mg daily (if high risk). Atorvatatin 80mg daily should be reviewed at 6
months and this should be documented on the drug chart and discharge
prescription. Click here for further guidance on statin treatment.

- Calcium channel blockers should not be used routinely post - MI. However,
they may be suitable for patients without heart failure who have continuing
angina, where beta - blockers are poorly tolerated or are contra - indicated.
Only rate limiting calcium channel blockers such as diltiazem and verapamil
have moderate evidence of decreasing mortality if used in place of beta-
blockers.

- The Joint British Societies guidelines on prevention of cardiovascular disease
in clinical practice (Dec 2005) recommend:

7) All patients should be prescribed a GTN spray as part of their discharge
medication in case of angina post-MI.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Guidelines for the Management of Patients with Acute Coronary
Syndrome

This trust has adopted the guidelines for management of non- ST elevation acute
coronary syndrome produced by the Cheshire and Merseyside Cardiac and Stroke
Network (CMCSN) and this has been incorporated into a pathway available in A&E
and HEC. Please refer to this for further management.

Acute Coronary Syndrome (ACS) covers a spectrum of conditions including:
- Unstable angina [UA]
- Non-ST segment elevation myocardial infarction [NSTEMI]
- Acute ST segment elevation myocardial infarction [STEMI]

The term Non - ST Elevation Acute Coronary Syndrome (NSTEACS) is often used to
cover both UA and NSTEMI.
The treatment of NSTEACS is different from STEMI although there is a common
patho-physiology and presentation.

All STEMI patients should be considered for transfer to Liverpool Heart and Chest
Hospital for Primary PCI instead of thrombolysis. They are given loading doses of
antiplatelet medication prior to transfer (see pathway for details).

Patients suspected of ACS should have a Troponin T level checked 6 hours after
their chest pain started (or was most severe). RLBUHT now measures High
sensitivity Troponin T and should be interpreted as below:


Interpret all HS Troponin T results in conjunction with clinical symptoms and
ECG
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Pharmacological treatments for suspected Acute Coronary Syndrome
Aspirin Administer as soon as NSTEACS suspected:
300mg stat dose to all patients, followed by 75mg
daily. Exceptions are:
- Patients with hypersensitivity to aspirin
- Aspirin intolerance due to previous GI
bleed
- Active or recent gastric ulcer
- Known significant aspirin - induced
dyspepsia despite gastroprotection.

Patients with quiescent, old or operated peptic
ulcer; mild dyspepsia; hiatus hernia or indigestion
should receive aspirin.
Fondaparinux 2.5mg once daily subcutaneously
For all NSTEACS patients if no contraindications
and without high risk of bleeding as per ACS
pathway. For patients with eGFR < 20ml/min use
enoxaparin once daily instead.
Low molecular
weight Heparin
Enoxaparin
(Clexane)
Used if fondaparinux contraindicated or patient
requires full anticoagulation whilst being treated
for ACS eg has a valve replacement, PE or DVT
or has AF with high risk of cardiac
thromboembolism.

Enoxaparin 1mg/ kg twice daily subcutaneously
for a minimum of 48 hours. (For renal patients with
CrCl (eGFR)<30ml/min the dose is 1mg/kg once a
day).
Continue for 24 hours after patient is pain free or
until revascularisation (if planned imminently).

Anti-thrombotic
agents


Patients already
taking warfarin
should have the
need for anti-
thrombotic
medications
discussed with
senior medical staff
Clopidogrel Not all patients benefit from the addition of
clopidogrel to aspirin.
In view of this and the large cost of clopidogrel, it
is only recommended:
- Instead of aspirin for those NSTEACS truly
sensitive to or intolerant of aspirin
- In addition to aspirin for high risk
patients (ACS risk score>6 as per
pathway)
Dosage: 300mg initial dose followed by 75mg
daily for either 1 month of STEMI and 12 months if
NSTEACS.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Glycoprotein IIb
/ IIIa inhibitors
These medicines should be considered for all
high risk NSTEACS patients with continuing or
recurrent pain especially if are planned to undergo
early PCI
- Tirofiban is the product selected for use in
this Trust. A protocol for administration is
available for use on CCU and HEC.
- Enoxaparin should be administered
concomitantly with tirofiban
Prasugrel Administered as a single loading dose prior to
transfer for primary PCI in STEMI patients (see
pathway).
Nitrates

Click here
Nitrates have no benefit with respect to event rate
or mortality however can be used to relieve angina
pain or prevent attacks of angina

To relieve ischaemic pain/ angina administer
Nitrates either IV; buccally or sub-lingually as
appropriate. Oral nitrates can be used for patients
continuing to have angina attacks despite current
medications

All patients should be prescribed sublingual GTN
spray or tablets as an inpatient and on discharge.

Anti- ischaemic
agents
Beta
adrenoreceptor
blocking
medicines

Click here
Administer orally to relieve pain and
ischaemia. They may improve prognosis therefore
should be given to all patients without
contra-indication.
Usually bisoprolol is the beta-blocker of choice
post
ACS.
Contra indications include:
1. Heart failure
2. Hypotension (systolic BP < 100 mmHg)
3. Bradycardia ( < 60 beats per minute).
4. Asthma

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Calcium
channel
blocking
medicines

Click here
Non rate limiting calcium channel blockers
should be used in addition to beta
adrenoreceptor blocking medicines
- If further angina or ischaemia occurs
OR
- If hypertension persists

Rate limiting calcium channel blockers should
be used if beta-blockers are contraindicated (i.e.
Diltiazem) providing :
- There is no clinical heart failure
- No likelihood of significant left ventricular
impairment (check ECHO)
- Initial heart rate is >= 60 bpm.
- There is no hypotension (systolic BP < 100
mmHg)

Potassium
channel
openers
Nicorandil 20mg twice daily has been shown to
significantly reduce transient ischaemia, SVT and
VT compared to placebo when added to standard
therapy
Can be added to nitrates, beta adrenoreceptor
blockers and calcium channel blockers if there is
recurrent ischaemia or angina (unstable angina is
an unlicensed indication)

Statins

Click here
There is evidence that intensive treatment
with statins may have benefits in ACS
therefore atorvastatin 80mg daily should be
prescribed for patients with high risk ACS
otherwise simvastatin 40mg at night is
recommended.

Other
medicines
post ACS
Angiotensin
converting enzyme
inhibitors

Click here
They are of proven benefit post myocardial
Infarction especially where the infarction is
large, anterior or has resulted in moderate
to severe left ventricular dysfunction or heart
failure.

However due to evidence of benefit as
secondary prevention they are
recommended for all NSTEACS patients
if not contra-indicated.





The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Fibrinolytic Medicines.

These medicines may be used for patients with a diagnosis of ST elevation MI
although Primary PCI is now first line treatment. See pathway available in A&E, HEC
& CCU.

Alteplase is also licensed for the treatment of life threatening Pulmonary Embolism
and these are available in the Emergency Medicines Store and A&E majors.
- Tenecteplase Injection For acute myocardial infarction if not suitable for Primary
PCI as per ACS pathway - see product information for
dosing.
It should not be administered via a line containing dextrose

- Alteplase injection For life threatening pulmonary embolism- see product
information for dosing

Used in stroke patients only if recommended by stroke
specialist nurse or consultant as per pathway during
working hours.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Management of side effects of thrombolytic therapy

Arryhthmia
Common side-effect.
Specific treatment rarely needed unless pulseless VT or VF.
Check plasma potassium and correct if less than 4.0 mmol/L


Other Fibrinolytic Medicines
- Urokinase Injection (s) Radiologists and Consultants only.
Unlicensed medicinal product in the UK.
Used in this trust for unblocking the lumens of central lines
please speak to the specialist iv access nurse before
urokinase is prescribed.

Antifibrinolytic Medicines and Haemostatics
- Aprotinin injection (s) Anaesthetists only
- Tranexamic acid
tablets/injection
By mouth, 1 - 1.5g 2 - 4 times daily.
By slow i.v. injection, 0.5 - 1g 3 times daily.
- Drotecogin alfa injection
(recombinant activated
protein C)
(s) ITU only

Lipid - regulating Medicines

Secondary causes of hyperlipidaemia include hypothyroidism, poorly controlled
diabetes, obesity, excessive alcohol intake, beta - blockers, thiazide diuretics or
oestrogens. Correction of secondary causes and/or dietary measures may be sufficient
to reduce levels.

HMG Co - A Reductase Inhibitors ('Statins')
All patients prescribed a statin should have baseline liver function tests checked.

Patients are also advised to report any unexplained muscle pain or weakness, since
statins are associated with myalgia, myositis and myopathy.
Note: Discontinue if myopathy diagnosed.

Statins should also be discontinued in active liver disease or if there is unexplained
persistent elevation of serum transaminases

The hospital has adopted the Cheshire and Merseyside Cardiac Network guidelines for
statins which is the same as the current NICE recommendations (CG67 lipid
modification March 2010).

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Statins for primary prevention

Statin therapy is recommended as part of the management strategy for the primary
prevention of CVD for adults who have a 20% or greater 10-year risk of developing
CVD (see charts at the back of the BNF). If the decision is taken to start a statin after
discussion about risks and benefits with the patient then simvastatin 40mg at night
should be prescribed. There are no specific lipid targets for primary prevention.

Statins for secondary prevention

All patients who require a statin for secondary prevention should have a baseline lipid
level checked (although for ACS patients there is no need to wait for the result before
starting a statin).

Patients should be started on a statin of low acquisition cost (simvastatin 40mg at
night) and then lipid levels monitored and the dose titrated (maximum 80mg at night)
to reach target cholesterol levels (total chol <4mmol/L and LDL chol <2mmol/L).
- Simvastatin tablets Usual starting dose range 20-40mg at night.
If cholesterol targets not achieved after 6 weeks consider
increasing dose up to maximum 80mg at night.

Caution in using high dose simvastatin in renal patients
and those on interacting medications which can increase
risk of myopathy and myositis (see BNF for interactions).

Maximum dose 20mg at night if patient is on concomitant
amiodarone or verapamil.
- Atorvastatin tablets Reserved for use in this trust as the high potency statin for
patients with high risk Acute Coronary Syndrome
Dose: 80mg once daily

Lower doses (ie 10 and 20mg daily) should not be used for
secondary prevention unless patient has a contraindication
to simvastatin.
- Rosuvastatin tablets (s) Lipid clinics only

Important interactions involving "statins"

- Simvastatin may enhance the effect of warfarin.
- Other lipid lowering medicines, macrolide antibiotics (erythromycin and
clarithromycin), and ciclosporin may increase the risk of myositis with statins.
Patients taking simvastatin should have their treatment withheld for the
duration of macrolide antibiotic treatment.
- Imidazole antifungal medicines (effect of statins may be enhanced)
- Maximum dose 20mg at night if patient is on concomitant amiodarone or
verapamil.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Anion - exchange Resins
Due to poor compliance and tolerance these are generally now only used as add on
therapy for resistant hyperlipidaemia.

- Colestyramine Light
sachets
8 - 24g daily in water in single or up to 4 divided doses.
Other medicines should be taken at least 1 hour before or
4 6 hours after colestyramine to reduce possible
interference with absorption.

- Ezetimibe (inhibits
absorption of
cholesterol) (s)
Consultant use only



Fibrates

Note: All fibrates can cause a myositis - like syndrome, especially in patients with
impaired renal function and when used in combination with statins
- Fenofibrate tablets (s)
(micronised)
Consultants only


Nicotinic Acid group
- Niaspan (s) Consultants only



Fish oils
- Omega3acid ethyl
esters capsules
(Omacor ) (s)
Consultant Cardiologists only following Cheshire and
Merseyside Cardiac and Stroke Network guidelines.
Secondary prevention following myocardial infarction.
Dose: 1 capsule (1g) daily with food




Local Sclerosants
- Ethanolamine injection(s) Surgeons only.
- Sodium tetradecyl (s)
sulphate injection
Surgeons only.
Note: also known as STD injection



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


RESPIRATORY SYSTEM

Contents (Click on heading to go to that section)

Management of Chronic Persistent Asthma in Adults
Asthma management - general notes
Management of an Acute Asthmatic Attack
Notes for Asthma Management during Recovery in Hospital

Nebulisation Guidelines
Special Considerations
Nebulisation Volume
Driving Gas
Flow Rate
Care of the Nebuliser Chamber
Use of Nebulisers in Chronic Disease
Peak Flow Meters
Solutions for Nebulisation

Bronchodilators
Adrenoreceptor agonists
Long Acting Beta2 agonists
Antimuscarinic bronchodilators
Theophylline

Inhaled Corticosteroids (ICS)
Compound bronchodilator preparations

Antihistamines, hyposensitisation and allergic emergencies
Antihistamines

Respiratory stimulants

Oxygen therapy

Mucolytics

Cough preparations

Systemic nasal decongestants
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Management of Chronic Persistent Asthma in Adults

(Based on BTS/SIGN Guideline on Management of Asthma 2008, updated 2009)

The inhaled corticosteroid doses given below refer to beclometasone (BDP) given via
CFC-MDI. Dose adjustments have to be made for some CFC-free aerosols, other
devices and other corticosteroid molecules. If unsure please check with pharmacy.

STEP SYMPTOMS/PROBLEMS MANAGEMENT
1
Infrequent symptoms.
Normal lung function
Salbutamol or other short acting beta
2
- agonist
inhaled `as required'.
2
- Short acting beta
2
- agonist
used 3 times/week OR
- Night time symptoms 1/week
OR
- Exacerbation in past 2 years
OR
- Symptomatic 3 times/week
Add inhaled corticosteroid (ICS)
e.g. beclometasone proprionate (BDP) 100 -
400mcg b.d. or equivalent.
Start at steroid dose appropriate to disease
severity. An appropriate starting dose for many
patients is 200 mcg bd (BDP or equivalent)
If still poorly controlled As above
PLUS
- Long acting beta
2
agonist (LABA) e.g.
salmeterol 50 mcg b.d.
If no response - Stop LABA
- increase dose of ICS to upper end of dose
range (up to 400 mcg b.d BDP or equivalent)
3
If control still poor - Continue LABA
- Increase dose of ICS up to 400 mcg b.d.
(BDP or equivalent)
4
If patient remains poorly controlled - All of the above
PLUS
6 weeks sequential therapeutic trial of one or
more of:
- Increase ICS up to 1000 mcg b.d. BDP or
equivalent
- Leukotriene antagonist.
- Theophylline MR preparation
- Salbutamol MR .

5
Still not controlled Refer to Chest Physician.
Note : Always check compliance and inhaler technique before moving up a step

In asthma treatment, long acting beta 2 agonists should NEVER be used without
concomitant ICS.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Combination inhalers in asthma- The SMART regime
In selected adult patients at step 3 who are poorly controlled or in selected adult
patients at step 2 (above BDP 400mcg/day who are poorly controlled) the use of
budesonide/formoterol in a single inhaler as rescue medication instead of a short acting
beta-2 agonist, in addition to its regular use as controller therapy has been shown to be
an effective treatment regimen. Patients taking rescue budesonide/formoterol once a
day or more should have their treatment reviewed. Careful education of patients about
the specific issues around this management strategy is required and any patient who is
thought to be suitable must be reviewed and assessed by the asthma specialist nurse.

Asthma management - general notes
START at step most appropriate to initial severity.

RESCUE COURSE of oral prednisolone can be given at any step.

Give 30 - 40mg daily in the morning (up to 60mg if already on oral steroids) for
3 - 7 days.

The following guidelines may be followed when stopping a course of oral
corticosteroid:

Abrupt withdrawal is appropriate if the course of systemic corticosteroid has
continued for up to 3 weeks at a dose of up to 40mg daily.

Doses of systemic corticosteroids should be reduced gradually in all patients
who have:
o had courses lasting more than 3 weeks.
o had courses lasting 3 weeks or less AND
have received repeated courses of a systemic corticosteroid OR
received a short course of a systemic corticosteroid within one
year of cessation of long - term therapy OR
may have other reasons for adrenocortical insufficiency OR
have repeatedly taken doses of corticosteroid in the evening

REVIEW regularly.

STEP DOWN treatment in well controlled patients who have been stabilised
for at least three months, (decrease inhaled corticosteroid dose by 25 50%).

TERBUTALINE may be preferable for patients who experience tremor with
salbutamol.

THEOPHYLLINE preparations should ALWAYS be prescribed by BRAND name due
to the differing release characteristics between preparations.

CHECK inhaler technique. Refer to Asthma Nurse or your ward pharmacist if
necessary.

PEAK FLOW METER should be prescribed if patient is not already using one and
advice given regarding response to changes in PEFR and symptoms.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Management of an Acute Asthmatic Attack

(Based on British Thoracic Society / SIGN Guidelines 2008, updated 2009)

SIGNS/SYMPTOMS MANAGEMENT
Uncontrolled asthma:
- Speech normal
- Pulse < 110 beats/min


- Respiratory rate < 25 breaths/min


- Peak flow > 50 - 75% of predicted or
best

- Record PEFR
- Nebulised salbutamol 5mg or multiple
actuations (15 - 20) of metered dose inhaler
via large volume spacer. Monitor response
after 15 - 30 mins.
- If PEFR 50 - 75% of normal start oral
prednisolone 30 - 60mg and step up usual
treatment.
- If PEFR > 75% of normal step up usual
treatment.
Acute severe asthma:
- Cannot complete sentences.
- HR 110 beats/min.

- Respiratory rate > 25 breaths/min.


- Peak flow 33-50% of predicted or best.

- Oxygen 40 - 60% (aim SpO2 94-98%)
- Nebulised salbutamol 5mg 4 - 6 hourly
using oxygen as the driving gas.
- If poor response, give nebulised ipratropium
500 micrograms 6 hourly using oxygen as
driving gas
- Prednisolone 30 - 60mg stat. and daily in
the morning or Hydrocortisone 100mg i.v.
stat. and q.d.s. if oral route is not available.
- Magnesium sulphate IV 1.2-2g in 100ml
0.9% sodium chloride over 20 minutes
- Monitor response after 15 - 30 mins.
Life threatening asthma:
- Silent chest
- Drowsiness
- Hypotension
- Cyanosis
- Arrhythmia
- Exhaustion
- SpO2 < 92%
- PaO2 <8 kPa
- Peak flow < 33% of predicted/ best

- Discuss with senior clinician / ITU

- Oral prednisolone / IV hydrocortisone as
above
- Continuous oxygen as above
- Nebulised salbutamol 5mg every 15 30
minutes and ipratropium bromide
500microgram 6 hourly driven by oxygen
- Magnesium sulphate IV 1.2 2g in 100ml
0.9% sodium chloride over 20 minutes.
- Aminophylline 5mg/kg (250 - 500mg) i.v. in
250 ml glucose 5% or sodium chloride 0.9%
over 20mins (omit if already taking oral
theophylline and check level)
Followed by 0.5mg/kg/hr adjusted according
to plasma theophylline conc. OR
- salbutamol 250microgram i.v. in glucose 5%
over10 mins,then 3 - 20microgram/min
according to response and heart rate.
See infusion table further in chapter.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Notes for Asthma Management During Recovery in Hospital

- Patients should be managed, where possible, in specialist rather than general
wards
- Inhaled corticosteroids (ICS) should not be stopped on admission. For patients
previously on inhaled steroids, the dose should be stepped up.
- ICS and oral steroids should be administered concomitantly in the acute phase
- Standard inhalers should replace nebulisers 24 - 48 hours before discharge.
Change over should not take place until PEFR is at least 75% of the predicted
value.
- Check inhaler technique and change inhaler device if appropriate.
- Oral steroids may be discontinued prior to discharge, if appropriate.
Alternatively a short course may be prescribed to complete at home- a definite
course length should be specified.
- All patients admitted with an asthma exacerbation should be referred to the
asthma specialist nurse for review whilst an inpatient.
- On discharge, patients should be followed up by clinicians with expertise in
asthma management, preferably within 30 days of discharge.


Nebulisation Guidelines

The main indications for the use of a nebuliser are:
- To deliver salbutamol or ipratropium to a patient with an acute exacerbation of
asthma or airways obstruction i.e. the patient is too ill or unable to use hand
held inhalers.
- To deliver salbutamol or ipratropium on a regular basis to a patient with
asthma or airways obstruction who has been shown to benefit from regular
treatment with higher doses.
- To deliver prophylactic treatment e.g. a corticosteroid or antibiotics, to a
patient unable to use other inhalation devices.


Special Considerations

Nebulised steroids should only be initiated on the advice of a consultant chest
physician. A special nebuliser with a mouthpiece instead of a face mask is
recommended to minimise the incidence of side effects and produce the optimal droplet
size. Contact the Asthma Nurse for details.

If ipratropium bromide is being nebulised for any length of time, a mouth piece
nebuliser should be used. This is to reduce the incidence of conjunctival irritation or
precipitation of glaucoma in susceptible individuals. If this is a particular problem the
patient should wear glasses or be advised to close their eyes for the duration of
nebulisation. Alternatively, contact the Asthma Nurse for further advice.




The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Nebulisation Volume
The recommended volume for the nebuliser chamber is 2mL. This is because there is a
fixed residual volume left in the nebuliser. This may account for as much as 20% of the
dose if nebulisation volumes are too small. Different makes of nebuliser chamber
require different fill volumes for optimal medicine delivery.
If the volume of the medicine(s) to be nebulised is < 2ml, dilute to 2ml using sodium
chloride 0.9%. This will give a nebulisation time of approximately 3 - 4 mins.

Driving Gas
Oxygen
*
should be the driving gas in asthmatic patients. For patients who have COPD
AND evidence of carbon dioxide retention, air should be the driving gas. (NOTE this is
not true for all COPD patients)

Flow Rate
A flow rate of 6L - 8L/minute will deliver the correct size of droplet required for medicine
penetration into distal airway.

Care of the Nebuliser Chamber
The nebuliser should be rinsed daily with sterile water, wiped dry with a paper towel and
the inner tube cleaned using compressed air or oxygen. Cleaning is important in order
to reduce the risk of bacterial contamination and prevent the build up of crystallised
medicine in the nebuliser. The nebuliser should be replaced every 3 to 4 days. It should
also be replaced if the medicine(s) crystallise or if the nebuliser fails to function.

Use of Nebulisers in Chronic Disease
Before prescribing nebulisers for patients at home, the patient should be referred to
the respiratory team for a nebuliser trial.
If a nebuliser is prescribed for home use, patients should be instructed not to treat
acute attacks at home without seeking medical assistance and they must be given
clear instructions on the use of the nebuliser e.g. method and frequency of use;
servicing etc. Instructions on peak flow monitoring and action to take in the event of
worsening asthma should also be given.

Peak Flow Meters
A pre and post nebulisation peak flow should be taken for all asthmatic patients. The
post nebulisation peak flow should be taken 20 - 30 minutes after nebulisation. This is
especially important if ipratropium bromide is being nebulised as it takes at least 30 - 40
minutes for this medicine to produce maximal bronchodilation.

The patient should preferably be standing when a PEFR measurement is taken. If the
patient is unable to stand they should be in an upright sitting position.

When PEFR is > = 75% of the predicted value, nebulised bronchodilators can usually
be stopped and replaced by conventional hand held inhalers, (via a large volume
spacer if appropriate).

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Solutions for Nebulisation

MEDICINE/ STRENGTH DOSE COMMENTS
Bronchodilators
Salbutamol
2.5mg/2.5mL
5mg/2.5mL
2.5 5mg
4 - 6 hourly
5mg dose can cause tachycardia and/or tremor
in some patients which can be resolved by
using the 2.5mg dose.
Terbutaline Respules
5mg/2mL
5 - 10mg
4 - 6 hourly
Only used in patients intolerant of salbutamol
Ipratropium bromide
250microgram/mL
250 - 500
microgram
6 hourly
Can be mixed with salbutamol or terbutaline.
Click here if eye irritation is a problem.
Mucolytics
Sodium chloride 0.9%
5mL 6 hourly Used to loosen secretions
Sodium chloride 6% 4mL Can be used just as a stat. dose prior to
physiotherapy for induction of sputum for
samples. Or used regularly to loosen
secretions after sodium chloride 0.9% has
failed.
Corticosteroids
Budesonide
0.5mg/2mL
1mg/2mL

Fluticasone
0.5mg/2ml
2mg/2ml


1 - 2mg b.d.



0.5-2mg b.d

Nebulise bronchodilators first.
A special nebuliser is recommended to give
optimum particle size.
Contact the Asthma Nurse for details.

Fluticasone is twice the potency of budesonide
therefore doses are not equivalent.




Notes:
- Bronchodilators should be nebulised before physiotherapy to optimise the
clearance of bronchial secretions.
- If more than one medicine is to be nebulised, bronchodilators should be
nebulised separately first.
- If antibiotics are to be nebulised, contact Medicines Information (ext 2096) or
asthma nurse for advice if necessary.









The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Bronchodilators

Adrenoreceptor agonists

Selective beta2 agonists

Various inhaler devices are available. Ask your ward pharmacist or the Asthma Nurse for
details.
- Salbutamol inhaler/nebuliser
solution
/SR tablets/syrup/injection
Inhalation:
Aerosol dose, 100 - 200 micrograms (1 - 2 puffs)
when required in asthma, or 3 to 4 times daily in COPD.

Dry powder dose, Ventodisks; 200 - 400 micrograms.
Accuhaler; 200micrograms (one blister)

Nebulisation, 2.5 - 5mg 6 hourly (acute asthma attack up to
every 15 - 30 minutes). In severe exacerbations 2-4 hourly
initially then reduce frequency on review.

By mouth, SR tablets, 4 - 8mg twice daily.
Syrup, 4mg 3 - 4 times daily.

By s.c. or i.m. injection, 500 micrograms (8 micrograms /
Kg),
repeated every 4 hours if necessary. NB this route/method
is rarely used.

By slow i.v. injection, 250 micrograms (4microgram/kg)
repeated if necessary. To be injected slowly. The injection
can be diluted with water for injection to facilitate
administration.

By i.v. infusion, 5 microgram/min adjusted according to
response and heart rate. See infusion table on next page.

Usually in range 3 - 20 micrograms/minute. (In patients
with respiratory failure, higher doses have been used
successfully)

Recommended dilution: 5mg in 500ml of sodium
chloride 0.9% or glucose 5% (i.e. concentration
10micrograms / ml)

Salbutamol infusion rates for 5mg in 500ml infusion
Dose (micrograms / min ) Rate (ml / hour)
3 18
5 30
7.5 45
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Salbutamol infusion rates for 5mg in 500ml infusion
10 60
15 90
20 120
30 180
45 270



- Terbutaline
inhaler/ respules/injection/
syrup
Terbutaline preparations may be considered if a
patient experiences severe tremor with salbutamol.

There is a Trust policy and prescribing guidelines
document covering the Continuous Sub-cutaneous Infusion
of Terbutaline (CSIT) using a portable syringe driver. The
document details assessment procedures, pump setup and
maintenance doses. The Asthma Nurse Specialists should
be contacted for a copy of the document.


Theophylline

Theophylline is a narrow therapeutic index drug and TDM must be carried whilst on
therapy (especially IV therapy) Check with pharmacy/BNF for drug interactions and
patient factors which may affect theophylline metabolism.

Oral theophylline/aminophylline
For chronic long term management of asthma and COPD
- Theophylline SR tablets




Uniphyllin
All theophylline preparations should be prescribed
by brand name due to the differing bioavailability of SR
preparations.
The preferred brand for initiation of therapy is Uniphyllin.

Dose: starting dose, 200mg every 12 hours adjusted
according to blood levels and response.
Aminophylline SR tablets
(Phyllocontin)
Dose: starting dose, 225mg every 12 hours adjusted
according to blood levels and response.




IV aminophylline

For deteriorating acute severe asthma / severe acute exacerbation of COPD /
respiratory failure.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Loading dose (If patient is usually on oral theophylline, omit loading dose)
By IV infusion: 5mg/kg (usually 250 - 500mg) IV in 250ml sodium chloride 0.9% or
glucose 5% over at least 20-30 mins

Maintenance dose By continuous IV infusion : 0.5mg / kg / hr, (if the patient is obese
use IBW) The rate can then be adjusted according to plasma theophylline
concentration
Target plasma concentration: 10-20mg/ L
Plasma concentration should usually be checked within 12 hours of initiating IV
maintenance infusion and the infusion rate adjusted accordingly, if necessary..

Infusion fluids & dilution: 1000mg in 1L of sodium chloride 0.9% (most
stable) or glucose 5% or glucose 4% in sodium chloride 0.18%
Aminophylline infusion rates for dosage 0.5mg / Kg /hr of a 1mg / ml infusion
Body weight (Kg) 40 50 60 70 80 90
Rate (ml / Hr) 20 25 30 35 40 45


Long Acting Beta
2
agonists (LABAs)

Asthmatic patients requiring long term regular bronchodilator therapy MUST also be
receiving regular and adequate doses of inhaled corticosteroids (ICS)
These agents should not be used for the relief of an acute attack and should be added
to existing corticosteroid therapy not replace it.

- Salmeterol inhaler
(Evohaler or Accuhaler)
Dose, Asthma and COPD 50 micrograms twice daily

Note
Salmeterol Evohaler is 25mcg/puff hence dose is 2 puffs twice daily
Salmeterol Accuhaler is 50mcg/ puff hence dose is 1 puff twice daily

- Formoterol 6microgram
turbohaler
Formoterol 12microgram
turbohaler

Dose, Asthma 12 micrograms twice daily increased to
24mcg twice daily in severe disease. For short term
symptomatic relief (not acute asthma) additional doses can
be taken to max. 72mcg daily (max. single dose 36mcg)

COPD 12 micrograms twice daily
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Antimuscarinic bronchodilators
Ipratropium bromide inhaler
/nebuliser solution







Tiotropium

Handihaler and 18mcg inhalation
capsule
Respimat aerosol inhaler device
2.5mcg/inhalation
Aerosol Dose, COPD 2 puffs (40 micrograms) 4 times daily
Nebulisation Dose, 250 - 500 micrograms 4 times daily
Current national guidelines do not recommend routine use of
ipratropium for chronic asthma management (use in acute
setting only) This should be borne in mind when converting
patients from nebulisers to inhalers after an acute episode.

For COPD ONLY

Handihaler device dose 18mcg inhaled once daily
Respimat device dose 5mcg (2 puffs) inhaled once daily

Inhaled Corticosteroids (ICS)

It is recommended that all patients prescribed inhaled corticosteroids (ICS) via an MDI
device should use a spacer device to increase airway deposition and reduce
oropharyngeal deposition, which predisposes the patient to a sore mouth, hoarse voice
and oral candidiasis. Patients should also be advised to rinse their mouth out after using
their corticosteroid inhaler.

- Beclometasone, budesonide and fluticasone would appear to be equally
effective in the recommended doses.

- Fluticasone is twice the potency of CFC - containing beclometasone and
budesonide.

- QVAR doses are not equivalent to CFC- containing beclometasone doses.

- QVAR 100 micrograms is approximately equivalent to 200micrograms
beclometasone.

- QVAR should always be prescribed by brand name.

All ICS doses stated below are licensed only for use in asthma.
No ICS, as a single agent, is licensed for use in COPD

ICS in Asthma

- QVAR
MDI, easibreathe or autohaler device
Dose: 50 - 400 micrograms twice daily
depending on asthma severity.
- Budesonide
Turbohaler or easyhaler device
Dose: 200-800mcg twice daily depending
asthma severity.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Fluticasone
MDI, Accuhaler or easyhaler devices
Dose: 125-500mcg twice daily. Increased to
max. 1mg twice daily, according to asthma
severity.


ICS in COPD

Please note the only licensed ICS option in COPD is the combination of ICS WITH
LABA (i.e. Seretide 500 accuhaler or Symbicort 400/12 turbohaler, see next page for
details)

NICE 2010: In people with stable COPD who remain breathless or have
exacerbations despite use of short-acting bronchodilators as required, offer the
following as maintenance therapy:

- if forced expiratory volume in 1 second (FEV1) 50% predicted: either long-acting
beta 2 agonist (LABA) or long-acting muscarinic antagonist (LAMA) * NOT FOR
ICS YET *
- if FEV1 < 50% predicted: either LABA with an inhaled corticosteroid (ICS) in a
combination inhaler, or LAMA.
- Offer LAMA in addition to LABA + ICS combination to people with COPD who
remain breathless or have exacerbations despite taking LABA + ICS, irrespective
of their FEV1.


Compound Corticosteroid Preparations
Compound ICS and long acting bronchodilator inhalers have not been found to be
significantly more effective nor safer than the separate constituents used together
and stepping up/ down ICS doses in asthma is difficult with the compound inhalers.
However a compound device may help to improve compliance, decrease inhaler
burden and reduce the number of prescription charges payable especially when
doses will remain stable. They are also the only licensed ICS option in COPD
management.

Be aware that the strength of salmeterol per puff in the two Seretide device
differs.
Accuhaler 50micrograms/ puff
Evohaler 25micrograms/ puff

- Seretide Accuhaler
100/50 Accuhaler
250/50 Accuhaler
500/50 Accuhaler

*** FORMULARY CHOICE
Available as 100, 250 and 500 mcg (fluticasone strength).
Each product contains 50 micrograms of salmeterol.

Asthma dose, 1 puff twice daily (all strengths)

COPD dose, 1 puff twice daily (only 500mcg strength
licensed)
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


- Symbicort Turbohaler
100/6 turbohaler
200/6 turbohaler
400/12 turbohaler

*** FORMULARY CHOICE
Available as 100, 200 and 400 micrograms inhalers
(budesonide strength)

100 and 200 preparation contains 6 microgram
formoterol per puff
400 preparation contains 12 micrograms formoterol per
puff

Asthma dose 100/6 and 200/6 strength, 1 2 puffs twice
daily. Max 4 puffs twice daily.

400/12 strength, 1 puff twice daily.
Max 2 puffs twice daily.
If asthma is well controlled the dose can be decreased to
the lowest effective dose given once daily.

COPD dose
400/12 strength 1 puff twice daily

- Seretide Evohaler
50/25 Evohaler
125/25 Evohaler
250/25 Evohaler

*** NON FORMULARY
CHOICE
ONLY TO BE USED IF OTHER
DEVICES UNSUITABLE
Only licensed for use in asthma

Available as 50, 125 and 250 mcg (fluticasone
strength).
Each product contains 25 micrograms of salmeterol.

Asthma dose, 1 2 puffs twice daily (all strengths)

This device is not licensed in COPD- use accuhaler or
symbicort turbohaler as above.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Algorithm for appropriate inhaler choice

This algorithm aims to give a guide to inhaler choice when testing inhaler technique.
Patient choice is an important factor when ensuring compliance. However, where
possible, the algorithm should be used to ensure the cost effective use of the
available inhaler devices.
Dexterity
Problem ?
Inability to use:
1.Easibreathe
2.Turbohaler
3.Autohaler
?
Is spacer
acceptable ?
STANDARD
INHALER &
VOLUMATIC
OR
AEROCHAMBER
Propellant/
Taste problems
?
AUTOHALER
N
Y
Y
ACCUHALER
N
TURBOHALER
OR
ACCUHALER
If the lactose
taste
is needed for
acknowledge -
ment
of dose
N
Y
N
Technique problems?
1 Does patient needClick prompt
AND/OR
2.Does patient actuate
Easibreatheprematurely ?
EASIBREATHE
N
Y
Y
Poor
Co-ordination
?
Poor
Inspiration ?
N
Y Y
From this point onwards
please consider seeking
advice from
Your ward pharmacist or
asthma nurse specialist







The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Antihistamines

Sedating Antihistamines
- chlorphenamine
[chlorpheniramine]
tablets/syrup/injection

Choice in pregnancy and porphyria.
Symptomatic relief of pruritus and other allergy: By
mouth, 4mg every 4 - 6 hours.

Parenteral, emergency treatment of anaphylactic
reactions by slow i.v. injection, 10 - 20mg diluted with 5 -
10ml sodium chloride 0.9%and given over 1 minute.
- Hydroxyzine
tablets
Pruritus: Initially 25mg at night increased if necessary to
25mg 3 - 4 times daily.

Non - sedating Antihistamines
- Cetirizine
tablets
Recommended preparation
10mg daily.
- Fexofenadine
tablets
Symptomatic relief of seasonal allergic rhinitis
Dose: 120mg once daily

Symptomatic relief of chronic idiopathic urticaria
Dose: 180mg once daily

Respiratory stimulants
For use in patients with hypercapnic respiratory failure who are becoming drowsy /
comatose and in whom ventilatory support is contra indicated or not immediately
available.
- Doxapram infusion By infusion: See infusion table below

Frequent arterial blood gas and pH measurements are
necessary during treatment to ensure appropriate dosage.



Doxapram Intravenous infusion for acute respiratory failure
Time from start of infusion Dose Doxapram 2mg/mL in glucose 5%
infusion
0 - 15 mins 4mg/min 120mL/hr for 15 mins
15 - 30 mins 3mg/min 90mL/hr for 15 mins
30 - 60 mins 2mg/min 60mL/hr for 30 mins
60 mins onwards 1.5mg/min 45mL/hr continuously

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Oxygen therapy

There is a trust oxygen policy and prescription chart which must be followed for
oxygen prescribing and administration within the trust. Please refer to this document
which is available via the intranet.

Mucolytics

Oral mucolytics are recommended by the NICE guideline for COPD management
(2004) to trial in those patients who suffer with a chronic productive cough. A four
week trial should be given and the patient then reviewed to assess benefit. If no
benefit is gained the mucolytic should be discontinued. They are also recommended
in bronchiectasis.

- Carbocisteine
375mg capsules
250mg/5ml syrup
Dose, initially 750 mg three times daily for 4 weeks and
then review response.
If no improvement, discontinue treatment.
If noticeable improvement, continue on maintenance dose
of 750mg twice daily thereafter.

Nebulised mucolytics are given to patients having difficulty in expectorating
sputum. Bronchiectasis patients may be on these long term at home.

- Sodium chloride 0.9% For nebulisation
Dose, 5ml as required (usually QDS)
- Sodium chloride 6% For nebulisation.
Dose, 4ml as required (usually QDS)
If used for prolonged periods a mouthpiece may be
desirable due to irritation to the eyes.

Cough preparations

Cough suppressant
- Pholcodeine
linctus(5mg/5mL)


Dose, 5 - 10mL 3 - 4 times daily when required. May be
diluted in warm water and sipped.
(sugar free linctus also available)
Demulcent
- Simple linctus

Dose, 5mL 3 - 4 times daily when required.



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Systemic nasal decongestants
- Pseudoephedrine
tablets/syrup
Dose, 60mg 3 times daily for short term use only.
Avoid use in patients with hypertension, hyperthyroidism,
coronary heart disease or diabetes.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


CENTRAL NERVOUS SYSTEM

Contents (Click on heading to go to that section)

Benzodiazepine Policy
CSM advice
Initiating Therapy
Alternative Strategies
On Discharge
Patients on Long Term Therapy

Hypnotics and anxiolytics
Hypnotics
Anxiolytics

Medicines Used in Psychoses and Related Disorders
Antipsychotic medicines
Antipsychotic Depot Injections
Antimanic medicines

Antidepressant Medicines
Tricyclic and related antidepressant medicines
Selective Serotonin Re - Uptake Inhibitors

Medicines used in the treatment of obesity

Medicines Used in Nausea and Vomiting
Guidelines for Chemotherapy - induced Nausea and Vomiting
Choice of Anti - emetic For Regimens of Low, Moderate and High Risk of
Emesis
Assessing the Emetogenicity of a Regimen
Risk of Emesis with Single or Combination Cytotoxic Regimens
Guidelines for the Management of Post Operative Nausea & Vomiting

Analgesics
Management of Acute Pain
Non-opioid analgesics
Opioid analgesics
Equivalent Doses of Opioid Analgesics
Neuropathic pain
Antimigraine Medicines

Antiepileptics
Control of Epilepsy
Medicines used in Status Epilepticus in Adults


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Medicines Used in Parkinsonism and Related Disorders
Dopaminergic medicines used in parkinsonism
Antimuscarinic Medicines
Medicines used in chorea, tics and related disorders

Medicines Used in Substance Dependence
Management of Alcohol Withdrawal
Algorithm for prescription of vitamin supplementation in alcohol misusers
Administration of IV Pabrinex
Treatment of Withdrawal

Cigarette Smoking

Opioid Dependence
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Benzodiazepine Policy
BNF advice
Benzodiazepines should only be prescribed for short term (2 - 4 weeks) relief of anxiety that
is severe, disabling or subjects the individual to unacceptable distress.
They should only be used for insomnia when it is severe, disabling or causing the patient
extreme distress. If prescribed, benzodiazepines should be used in the lowest possible dose,
for the shortest possible time, they should be reviewed regularly and discontinued as soon as
possible.

Initiating Therapy
Patients not previously prescribed benzodiazepines, and those who are not taking them
on admission, should not be prescribed a benzodiazepine routinely, either as night
sedation or for the management of generalised anxiety disorder (GAD). Do not offer a
benzodiazepine for the treatment of GAD except as a short-term measure during
crises. Follow the advice in the British national formulary on the use of a
benzodiazepine in this context, see NICE Guidance CG 113 Quick Reference Guide -
Anxiety

- Routine use of night sedation should be avoided, patients should be encouraged to take
hypnotics on alternate nights and less frequently if possible
- If night sedation is required before surgery, it should be prescribed for one night only.
- Patients should be encouraged to sleep without medication; a hypnotic should not be
routinely offered
- Tolerance to hypnotics develops in 3 to 14 days
- The lowest effective dose should be prescribed
- Benzodiazepines be prescribed for a maximum of 5 days and only be on an 'as required'
basis.
- Chronic benzodiazepine users admitted to hospital should be allowed to continue
treatment; medication histories should be confirmed as soon as possible for patients
who are admitted to hospital and claim to be taking benzodiazepines,
- Abrupt withdrawal may cause confusion, toxic psychosis, convulsions or a condition
resembling delirium tremens
- Hypnotics should not be used for acute behavioural disturbances.
- Benzodiazepines should be avoided in the elderly since these patients are particularly
at risk of becoming ataxic and confused and are likely to fall as a result

When a clinical need for therapy exists, consider the following:
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Alternative Strategies
- Advise patients to avoid caffeine - containing drinks such as coffee and tea after 6pm. A
hot milky drink is often helpful in inducing sleep.
- Treat underlying medical and psychiatric problems, which may be causing anxiety and
insomnia, e.g. adequate pain relief or antidepressants.
- Psychological treatments including relaxation and CBT
- Reassurance that 5 - 6 hours sleep at night for the elderly is normal, especially if the
individual also `cat naps' during the day.

On Discharge
- Patients should not be prescribed a benzodiazepine on discharge unless they have
been medically assessed as a chronic user, or are taking them as part of terminal care
treatment.
- When a clear clinical need exists, the minimum quantity necessary should be prescribed
and no more than 14 days treatment supplied

Patients on Long Term Therapy
Benzodiazepines should be withdrawn gradually in any patient receiving them for longer
than four weeks.

When Considering Withdrawal:
- Close liaison with the GP is essential. Check that the patient is not already undergoing a
withdrawal schedule.
- Withdraw the benzodiazepine over a four week period after a short course, i.e. less than
four weeks.
- A withdrawal period of several months may be necessary for a patient who has been
taking benzodiazepines for several years. As a rough guide allow one or two months of
withdrawal per year of taking the medicine.
- Convert the patient to an equivalent daily dose of diazepam; preferably taken at night
- Reduce the dose in steps of 2 to 2.5mg every 2 to 3 weeks; complete withdrawal may
take several months

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Approximate equivalent doses of benzodiazepines:
= chlordiazepoxide 15mg
= loprazolam 0.5 - 1mg
= lorazepam 500micrograms
= lormetazepam 0.5 - 1mg
= nitrazepam 5mg
= oxazepam 15mg
- Diazepam 5mg
= temazepam 10mg

Advice should be available for patients wishing to discontinue benzodiazepines,
including information concerning support groups. (For further advice see the current
British National Formulary).

Hypnotics and anxiolytics

Hypnotics
The medicine of choice in the Trust for the short term management of severe
insomnia is Zopiclone, for further information see NICE Guidance TA77 Insomnia -
newer hypnotic drugs: Quick reference guide and Trust Night Sedation Policy

- Zopiclone Insomnia 7.5mg PRN nocte for a maximum of 5 nights
Elderly patients 3.75mg nocte for a maximum of 5 nights
- Lormetazepam tablets No longer recommended for insomnia in the Trust
treated as a Controlled Drug
- Temazepam CD
tablets/syrup
Insomnia: 10mg at bedtime. For patients already
prescribed this medication on admission only

Anxiolytics
- Diazepam By mouth, 2mg tablets/syrup 3 times daily increased if
necessary to 15 - 30mg daily in divided doses.
Elderly, half adult dose.
- Propranolol Anxiety with palpitations, sweating, tremor: 40mg
tablets/syrup once daily increased to 3 times daily if
necessary.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Medicines Used in Psychoses and Related Disorders
All antipsychotics used for psychoses are to be prescribed by psychiatrists only. The
uses of the following medicines are for conditions other than psychoses. The choice of
antipsychotic should be based on the required clinical effect e.g. sedation and side
effect profile.

Side Effect Profile of commonly prescribed antipsychotics

Medicine Anticholinergic effects Cardiac effects Extrapyramidal
effects
Sedative
effects
Chlorpromazine +++ ++ ++ +++
Levomepromazine +++ ++ ++ +++
Promazine ++ ++ + ++
Haloperidol + ++ +++ +
Amisulpiride 0 0 + 0
Sulpiride + 0 + +
Olanzapine + 0 0 ++
Quetiapine + + 0 +
Risperidone 0 0 + +


Antipsychotic medicines
Once the patient is stabilised, the long half lives of these medicines allows the total daily
dose to be given as a single night time dose in most patients. Use with caution in
epilepsy, cardiovascular disease, hepatic impairment and Parkinsonism. For further
information see NICE Guidance: CG 38 Bipolar disorder Quick reference guide

BNF Advice

Antipsychotic medicines for the elderly
- Antipsychotic medicines should not be used in elderly patients to treat mild to
moderate psychiatric symptoms
- Initial doses in elderly patients should be reduced to half the usual adult dose, or
less, taking into account the patients weight, co-morbidities and concomitant
medication
- Treatment should be reviewed regularly








The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Rapid tranquillisation

For further information see NICE Guidance: CG 25 Violence Quick reference guide

Intervention Minimum Effective
Dose
Maximum
dose per 24
hours
Additional Information
Step
1
De-escalation,
time out

Step
2
Offer Oral
Treatment
Lorazepam (tablets)
1 2mg (elderly or
debilitated half adult
dose)
4mg (elderly
or debilitated
half adult
dose)
If patient already receiving a
benzodiazepine give
antipsychotic.
Peak serum level reached in
2 hours
Haloperidol (tablets
or syrup) 5-10mg
(elderly or debilitated
initially half adult dose
30mg Risk of dystonic reactions
increased in neuroleptic
nave and young patients
(reverse with procyclidine
injection)
Olanzapine (tablets
or orodispersible
tablets) 5 10mg
20mg MHRA has advised that
olanzapine should not be
used for treating behavioural
symptoms of dementia due to
increased risk of stroke.
Peak plasma concentrations
in 5 8 hours
Step
3
Consider IM
treatment
Lorazepam IM
Injection 1 2mg
(elderly or debilitated
half adult dose)
4mg (elderly
or debilitated
half adult
dose)
Lorazepam injection must be
diluted 1: 1 with water for
injection for IM injection
Stored in refrigerator
Haloperidol IM
injection 5-10mg
(elderly or debilitated
initially half adult
dose)
18mg Risk of dystonic reactions
increased in neuroleptic
nave and young patients
(reverse with procyclidine
injection)
Step
4
Seek expert
mental health
advice


Atypical antipsychotic drugs

For initiation by specialists in mental health only

- Clozapine tablets If doses are missed for 48 hours or longer then
the dose must be re-titrated starting with
12.5mg od or bd due to the risk of collapse
from hypotension




The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Atypical antipsychotics and stroke

Olanzapine and risperidone are associated with an increased risk of stroke in elderly
patients with dementia. The MHRA has advised:
- Risperidone or olanzapine should not be used for treating behavioural
symptoms of dementia
- For acute psychotic conditions in elderly patients with dementia risperidone
should be limited to short-term use under specialist advice; olanzapine is not
licensed for acute psychoses
- The possibility of cerebrovascular events should be considered before treating
any patient with a history of stroke or TIA


Other uses of antipsychotics

Intractable hiccup:

Chlorpromazine oral 25-50mg 3-4 times daily
Haloperidol oral 1.5mg 3 times daily


Antipsychotic Depot Injections

For initiation by specialists in mental health only


Antimanic medicines

Lithium salts
- Lithium carbonate tablets/
s/r tablets
(s) Consultants only. Thyroid and therapeutic
concentration monitoring is advised. Avoid co -
administration with diuretics as sodium depletion
potentiates toxicity. Avoid co-prescription of NSAIDs
increased risk of toxicity. Prescribe by brand name only.
- Priadel s/r tablets 200mg (equivalent to 5.4mmol lithium)
400mg (equivalent to 10.8mmol lithium)
- Camcolit tablet/ s/r
tablets
250mg (equivalent to 6.8mmol lithium)
400mg (equivalent to 10.8mmol lithium)
- Lithium citrate liquid
(Priadel).
(s) Consultants only. 520mg/5mL (approx.5.4mmol
lithium/5mL)

N.B: Monitor plasma - lithium levels regularly (click here for therapeutic concentration
monitoring) especially if patient is also taking medication which may interact and
increase toxicity (see BNF appendix 1).

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Antidepressant Medicines

Patients should be reviewed every 1-2 weeks at the start of antidepressant treatment.
Treatment should be continued for at least 4 weeks before considering whether to
switch antidepressant due to lack of efficacy. Following remission antidepressants
should be continued at the same dose for at least 6 months. Patients with recurrent
depression should continue to receive maintenance treatment for at least 2 years.

Do not use antidepressants routinely to treat subthreshold depressive symptoms or
mild depression in patients with a chronic physical health problem (because the risk
benefit ratio is poor), but consider them for patients with:

a past history of moderate or severe depression or
mild depression that complicates the care of the physical health problem or
initial presentation of subthreshold depressive symptoms that have been
present for a long period (typically at least 2 years) or
subthreshold depressive symptoms or mild depression that persist(s) after
other interventions.

When an antidepressant is to be prescribed for a patient with depression and a chronic
physical health problem, take into account the following:

the presence of additional physical health disorders
the side effects of antidepressants, which may impact on the underlying
physical disease (in particular, SSRIs may result in or exacerbate
hyponatraemia, especially in older people)
that there is no evidence as yet supporting the use of specific antidepressants
for patients with particular chronic physical health problems
interactions with other medications.

For further information see NICE guidance: CG90 Depression in adults: quick reference
guide

The choice of antidepressant medicine depends mainly on the side effect profile.

Medicine Anticholinergic effects Cardiac effects Sedative
effects
Epileptogenic
effects
Amitriptyline +++ +++ +++ ++
Dosulepin
[Dothiepin]
++ ++ +++ ++
Lofepramine ++ + + 0
Citalopram /
Escitalopram
0 0 0 0
Fluoxetine 0 0 0 0
Mirtazapine 0 0 ++ ++
Venlafaxine 0 ++ + +
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Arrhythmias and heart block occasionally follow the use of tricyclic antidepressants,
especially amitriptyline and should therefore be used with extreme caution in patients
with cardiac disease. The use of tricyclic antidepressants is contra - indicated in
patients with arrhythmias or recent myocardial infarction.

BNF Advice
Hyponatraemia, (usually in the elderly) has been associated with all types of
antidepressants and should be considered in all patients who develop drowsiness,
confusion or convulsions whilst taking an antidepressant.

Tricyclic and related antidepressant medicines
- Amitriptyline tablets/
solution
Initially 75mg (elderly 30 - 75mg) daily at night increased
gradually as necessary to max. 150mg.
- Lofepramine tablets /
suspension
140 210mg daily in divided doses. Elderly patients often
respond tablets/syrup to lower doses.

Selective Serotonin Re - Uptake Inhibitors

- Fluoxetine capsules /
liquid
20mg daily in the morning.
- Citalopram tablets / oral
drops
20mg daily (8 drops liquid equivalent to 20mg tablet)



Medicines used in the treatment of obesity

Appetite Suppressants
The development of obesity is multi - factorial. Aggravating factors may be medicine
treatment, depression or other psycho - social problems. Medicines in the treatment of
obesity can play only a limited role and should never be used as the sole element of
treatment. Appetite suppressants may only be prescribed by consultants after referral to
a specialist clinic.
For further information see NICE guidance: CG 43 Obesity;

Medicines Used in Nausea and Vertigo

Symptomatic Relief from Underlying Cause

Anti - emetics should be prescribed only when the cause of nausea or vomiting is
known, as the symptomatic relief they produce may delay correct diagnosis. The choice
of medicine then depends on the aetiology of vomiting. See here for adjunctive therapy
for anti - emetic prescribing in palliative care.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Extrapyramidal side effects are seen with prochlorperazine, metoclopramide and
domperidone. Acute dystonic reactions with facial and skeletal muscle spasms and
oculogyric crises are more common in the young (especially women) and the very old.
- Prochlorperazine
tablets/syrup/ injection
By mouth, 5 - 10mg 2 - 3 times daily.
By deep i.m. injection, 12.5mg when required every 4 - 6
hours.

N.B: Always indicate route of administration when prescribing since doses are different.

Metoclopramide has a peripheral action on the gut as well as action at the
chemoreceptor trigger zone and is therefore the anti - emetic of choice for
gastroduodenal, hepatic and biliary disease. Do not use if gastrointestinal obstruction is
suspected.
N.B. in patients less than 20 years of age, use is restricted to severe intractable
vomiting due to risk of dystonic reactions..
- Metoclopramide
tablets/syrup/injection
By mouth, 10mg 3 times daily (5mg 3 times daily if less
than 20 years old).

By i.m./i.v. injection, 10mg 3 times daily.

Domperidone has a similar central and peripheral action to metoclopramide but is less
likely to cause central side effects such as sedation and dystonic reactions, since it
does not readily cross the blood brain barrier. It is therefore the anti-emetic of choice in
Parkinson's disease.
- Domperidone tablets/
suspension /
suppositories
By mouth, acute nausea and vomiting (including that
induced by levodopa) 10 - 20mg every 3-4 times daily
By rectum, 60mg twice a day

Hyoscine is the most effective medicine for motion sickness. It may also be used for
vertigo and nausea associated with Mnire's Disease and middle ear surgery.

- Hyoscine hydrobromide
tablets
(s) ENT and Consultants only. May be used sublingually.

Cyclizine is an antihistamine, which acts on the vomiting centre. It is more sedating
than other anti - emetics. It may aggravate heart failure.
- Cyclizine tablets/injection By mouth, 50mg up to 3 times daily.
By i.m. or i.v. injection, 50mg up to 3 times daily.

Vomiting during pregnancy

Recommended stepwise treatment of nausea and vomiting in pregnancy:
Step 1: (non-pharmacological management) small, high carbohydrate, low
fat, frequent meals and P6 (wrist) accupressure
Step 2: (first-line medicines) - cyclizine or promethazine
Step 3: (second-line medicines) - prochlorperazine or metoclopramide
Step 4: (treatment resistant symptoms) consider ondansetron
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Other medicines for Menieres disease

- Betahistine tablets Initially 16mg TDS with food; maintenance dose 24
48mg daily
Cost band for 28 days (16mg TDS): B


Guidelines for Chemotherapy - induced Nausea and Vomiting
1. Anti - emetics are best given regularly and before chemotherapy. Ondansetron should be
administered just before treatment, if given IV, and 1 hour before if given orally.
2. Dexamethasone may be used to prevent, but not to treat emesis. If the patient is already
taking corticosteroids, seek advice on the use of this medicine.
3. If the patient fails on current treatment, move to the next anti - emetic regimen.
4. Consider the use of oral cyclizine 50mg three times daily if necessary.
5. If delayed emesis is likely, use prophylactic anti - emetics instead of "as required" doses.
Ondansetron should not be used for this purpose.
6. If anticipatory nausea and vomiting occurs, give lorazepam 1mg the night before and on
the morning of chemotherapy.
Note: Counsel the patient on the possibility of drowsiness with this medicine.
7. Other possible oral anti - emetic agents include prochlorperazine 5mg three times daily,
haloperidol 1.5mg twice daily and levomepromazine [methotrimeprazine] 12.5mg twice
daily.


Choice of Anti - emetic for Regimens of Low, Moderate and High Risk of Emesis

Low Emetic Risk Moderate Emetic Risk High Emetic Risk
First line schedule
- Prior to chemotherapy:
- Dexamethasone 8mg iv
- +/- Metoclopramide 10mg iv

- Then
- Dexamethasone 4mg po t.d.s. with
- Metoclopramide 20mg po t.d.s. or
domperidone 20mg po t.d.s. for 3 - 5
days.

Anti - emetics should be prescribed regularly to
prevent delayed emesis.
First line schedule
- Prior to chemotherapy:
- Ondansetron 8mg iv
- +/- dexamethasone 8mg iv

- Then
- Ondansetron 8mg po b.d.
- +/- dexamethasone 4mg po t.d.s.

- Post chemotherapy switch to:
- Metoclopramide 10 - 20mg po/iv t.d.s. regularly
to prevent delayed emesis.

Exceptions to this schedule are patients receiving high
dose chemotherapy with TBI (Total Body Irradiation). Use
ondansetron 16mg iv +/- dexamethasone 4 - 12mg iv
over 24 hours if indicated (review daily).
- Regular anti - emetics may
not be routinely required.
- If necessary, give
metoclopramide 10mg iv
prior to chemotherapy.
- If symptoms develop, then:
- metoclopramide 10 -
20mg po/iv t.d.s.
- or domperidone 10 -
20mg po t.d.s.
- or domperidone 30mg
PR t.d.s.
Second line schedule
If anti - emetics fail in the acute period (i.e. first
24 hours or before chemotherapy complete)
- Next cycle, prior to chemotherapy:
- Ondansetron 8mg iv
- Then
- Ondansetron 8mg po b.d. for 3 days.
- Switch to metoclopramide 10mg po
t.d.s. or domperidone 10mg po t.d.s.
post chemotherapy for 3 days.
Second line schedule
If anti - emetics fail in the acute period (i.e. first 24 hours
or before chemotherapy complete), add lorazepam 1 -
2mg po/iv stat.
(Failure = one vomit or > 4 hours of distressing nausea).
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Assessing the Emetogenicity of a Regimen

1. A regimen containing any agent that is high risk should be classified as highly
emetogenic.
2. A regimen containing two or more moderate risk agents should be classified as
highly emetogenic.
3. A regimen containing one moderate risk agent plus any number of low risk agents
should be classified as moderately emetogenic.
4. A regimen containing one or more low risk agents should be classified as having
low emetogenicity.

Risk of Emesis with Single or Combination Cytotoxic Regimens
Low Risk:-
Regimens Containing One or More of the
Following Time to onset of symptoms (hours)
Asparaginase 1 - 3
Bleomycin 3 - 6
Bulsulphan
Chlorambucil 48 - 72
Cladribine
Fludarabine
5 Fluorouracil 3- 6
Gemcitabine
Hydroxycarbamide [hydroxyurea] 6 - 12
Melphalan (po) 6 - 12
Mercaptopurine (po) 4 - 8
Methotrexate < 50mg/m
2
4-12
Tioguanine [thioguanine ] (po) 4 - 8
Thiotepa 6 - 12
Vinblastine 4 - 8
Vincristine 4 - 8
Vindesine

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Moderate Risk:-
Regimens Containing One or More of the
Following + any Low Risk agents Time to onset of symptoms (hours)
Amsacrine
Cyclophosphamide (po)
Cyclophosphamide IV < 750mg/m
2
4 -12
Cytarabine <1g/m
2
6 12
Dactinomycin 2 - 6
Docetaxel
Daunorubicin 2 - 6
Doxorubicin 4 - 6
Epirubicin
Etoposide 3 - 8
Idarubicin
Ifosfamide <1.5g/m
2

Melphalan <100mg

Methotrexate >50mg/m
2

Mitomycin 1 - 4
Mitoxantrone
Paclitaxel
Pentostatin (deoxycoformycin)
Procarbazine (po) 24 - 27
Raltitrexed

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

High Risk:-
Regimens Containing One or More of the
Following or two or more Moderate Risk agents Time to onset of symptoms (hours)
Busulfan 40mg
Carboplatin
Carmustine (2 - 4) hours
Cisplatin (1 - 6) hours
Cyclophosphamide IV >750mg/m
2

Cytarabine >1g/m
2

Dacarbazine (1 - 3) hours
Ifosfamide>1.5g/m
2

(1 2)
Lomustine
Melphalan >100mg

Mustine (0.5 - 2)
Streptozocin (1 - 4)
- Metoclopramide
Injection
By continuous IV infusion, initially (before starting
chemotherapy) 2 - 4mg/kg in 50 - 100mL glucose
5% or sodium chloride 0.9% over 15 - 30 mins then
3 - 5mg/kg in 500mL glucose 5% or sodium chloride
0.9% over 8 - 12 hours. Max. 10mg/kg in 24 hours.
- Ondansetron
tablets/injection
Moderately emetogenic chemotherapy or radio-
therapy:
By mouth, 8mg 1 - 2 hours before treatment
or
By slow IV injection, 8mg immediately before
treatment, then 8mg orally every 12 hours for up to
5 days.
Severely emetogenic chemotherapy or radiotherapy:
By slow IV injection, 8mg immediately before
treatment, followed by 8mg at intervals of 2 - 4 hours
for 2 further doses. Then 8mg by mouth every 12
hours for up to 5 days.
- Dexamethasone
tablets/syrup/injection
Use as adjunct to metoclopramide or ondansetron:
8mg IV before chemotherapy, then 2mg orally 3
times daily post chemotherapy for 3 days or
according to unit protocols.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Guidelines for the Management of Post Operative Nausea & Vomiting

PONV Assessment Score
0 No nausea or vomiting
1 Mild nausea. No vomiting
2 Moderate nausea and\or occasional vomiting
3 Severe nausea and\or frequent vomiting

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Analgesics

(See here for assessment and management of acute pain)

Management of Acute Pain
Pain is a complex physiological and psychological sensation, which acts as a
warning sign. The pain tolerance differs between individuals and can be affected
by a number of factors. Factors that lower the pain tolerance include insomnia,
anxiety, fear, isolation, depression and boredom. Treatment of pain is
dependent on cause, type (musculoskeletal or visceral), duration (acute or
chronic) and severity. See here for management of pain in palliative care.

Principles of Pain Management
- Pain is what the patient says it is and should be treated to the patient's
satisfaction.
- Accurately diagnose cause of pain.
- Prescribe according to the W.H.O. analgesic ladder. (here)
- Use REGULAR analgesia once source of pain is diagnosed.
- Set realistic goals by negotiation with the patient.
- Re - assess frequently.
- Consider non - medicine treatment.
- Give analgesics REGULARLY before consideration is given to moving up the
analgesic ladder.

Nonopioid analgesics
Non-steroidal anti-inflammatory drugs (NSAIDs) are the analgesics of choice
for musculoskeletal pain especially if there is an inflammatory component or
bone pain.
All NSAIDs are gastric irritants regardless of the route of administration,
naproxen or ibuprofen in the lowest possible doses are associated with the
lowest risk of GI side effects.
Consider prophylaxis against gastrointestinal ulceration if administration is
likely to be chronic.
Use with extreme caution in asthmatics. The use of NSAIDs is contra -
indicated in asthmatics that have a known hypersensitivity to aspirin or other
NSAIDs. Use with caution in the elderly and in patients with renal impairment.
NSAIDs may be associated with an increased risk of thrombotic events;
assess cardiovascular risk before prescribing.

- Paracetamol Infusion
10mg/mL
For use only when the oral
route is not available

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Compound Analgesic Preparations

Co prescribing of compound analgesics with paracetamol on a when required
basis has led to overdose of paracetamol.

Opioid analgesics
- Diamorphine CD
injection
Acute pain:
By s.c. or i.m. injection, 5mg repeated every 4 hours
if necessary.
By slow i.v. injection, 1.25 2.5mg every 4 hours if
necessary.
Myocardial infarction: By slow i.v. injection,
(1mg/min), 5mg (elderly or frail patients 2.5mg)
followed by a further 2.5 5mg (elderly or frail
patients 1.25 2.5mg) if necessary.
Acute pulmonary oedema: By slow i.v. injection, 2.5
5mg.
- Morphine sulphate CD Acute pain:
By s.c. or i.m. injection, 10mg (elderly or frail
patients 5mg) every 4 hours if necessary.
By slow i.v. injection, 2.5 mg (elderly or frail patients
1.25mg) every 4 hours if necessary.
Myocardial infarction: By slow i.v. injection,
(1mg/min)
10mg (elderly or frail patients 5mg) followed by a
further 5 10mg (elderly or frail patients 2.5 5mg)
if necessary.
Acute pulmonary oedema: By slow i.v. injection, 5
10mg.
- Fentayl sublingual
tablets (Abstarl),
Pain team only
- Oxycodone CD
tablets/capsules/
injection
Pain Team and Palliative Care Team only.
- Pethidine CD
tablets/injection
Pethidine is inappropriate for routine use due to its
short action. It should be avoided in patients with
renal failure.
Accumulation of metabolites may result in
neurotoxicity

Tramadol recommendations for use
- Treatment with tramadol should be short and intermittent and only for
moderate to severe pain
- Tramadol should be used with great caution in patients with a history of
dependence
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

- Patients with epilepsy or a history of epilepsy should only be treated if
there are compelling reasons
- Tramadol should be used with caution in patients taking medication
that can lower the seizure threshold, particularly serotonin re - uptake
inhibitors and tricyclic antidepressants.

- Tramadol capsules/ s/r
capsules/ injection
50mg 100mg every 4 hour usual maximum
400mg in 24 hours
- Ketorolac
injection/tablets
(s) Anaesthetists and A&E only.



Equivalent Doses of Opioid Analgesics

Click here for opioid dose conversion ratios.


Neuropathic pain
1
st
line
- Gabapentin capsules

300mg single dose on day 1, 300mg BD on day 2,
300mg TDS on day 3. Increase according to
response to maximum 3.6g daily.
2
nd
line
- Pregabalin capsules
(s) Consultants only, pain clinic and Diabetologists


Post Herpetic Neuralgia
- Amitriptyline tablets Start with 25mg, (10mg in the elderly) taken in the
early evening to avoid hangover effect. Pain relief
may begin in 1 7 days. Rate of increase depends
on pain level and degree of supervision. If tolerated
dose may be increased by about 25mg every three
days to 75mg at night.
Elderly: rate of increase may need to be slower e.g.
25mg per week.
- Capsaicin cream
0.075% (Axsain)
(s) Consultants only.
Note: only to be used after lesions have healed.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Antimigraine Medicines

Treatment of the acute migraine attack

Analgesics
- Paracetamol
PLUS
Metoclopramide
500mg - 1g every 4 - 6 hours when required. Max
4g daily.10mg 3 times daily when required.
- Ibuprofen
PLUS
Metoclopramide
400mg 3 times daily when required.
10mg 3 times daily when required.

Note: Products combining a simple analgesic with an anti emetic, e.g.
Migraleve, have not been shown to be any more effective than the above
regimens and are considerably more expensive.

5HT
1
agonists
- Sumatriptan
tablets/injection
(s) Consultant and A & E use only.


Prophylaxis of migraine
- Propranolol tablets / m/r
capsules
Ensure no contra - indications apply e.g. asthma.
80mg daily in single or divided doses according to
preparation.
May be gradually increased to max. 240mg daily if
necessary.
- Pizotifen tablets Useful when there is a contra - indication or
unacceptable side effects to propranolol.
Note: Causes weight gain.
Dose: 1.5mg daily increasing to 3mg if necessary.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Antiepileptics
(Click here for therapeutic level monitoring)

Control of Epilepsy
Use monotherapy whenever possible, if one treatment is unsuccessful due to
seizures or adverse effects try monotherapy with another medicine. Care must
be used to build up to an adequate or tolerated dose of the second medicine
and then taper off the first medicine slowly. A neurology opinion should be
sought before initiating antiepileptic medication. For further information see
NICE Guidance: CG20 Epilepsy in adults: Quick reference guide

Maintenance doses of antiepileptic medicines should not be prescribed for
alcohol induced seizures as there is no evidence that they are effective in
preventing further seizures.

Partial Seizures Sodium valproate, Carbamazepine and Lamotrigine
can be used as monotherapy.
Generalised Seizures

- Tonic Clonic Carbamazepine, lamotrigine, sodium valproate.
- Absence seizures Sodium valproate, especially if co exists with
tonic-clonic seizures, lamotrigine.
- Myoclonic Sodium valproate
- Carbamazepine
suppositories/ tablets/
MR tablets/ liquid
By mouth, initially 100 - 200mg 1 - 2 times daily
and build up slowly in increments of 100 200mg
every 2 weeks to a usual dose of 0.8 - 1.2g daily in
divided doses.

By rectum, short term use (seven days max)
125mg approximately equivalent to 100mg by
mouth. Max. dose by rectum is 250mg 4 times daily
for up to 7 days.

Serum level monitoring is recommended.
- Lamotrigine tablets (s) Consultants only.
- Phenytoin capsules/
suspension/injection
No longer recommended as a first line antiepileptic
medicine for maintenance treatment of any seizure
type.
100mg capsules are equivalent to 90mg
(15mL) of 30mg/5ml syrup.

By i.v. injection, same dose as by oral route
administered into large peripheral vein, no faster
than 50mg/min with ECG monitoring.

Method of administration, click here
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

- Sodium valproate /
valproic acid
tablets/liquid/injection
By mouth, initially 600mg daily in divided doses
preferably after food, increasing by 200mg/day at 3
day intervals to a max. of 2.5g daily in divided
doses. Usual maintenance 1 - 2g daily.

By IV injection, by short i.v. infusion over 30
minutes for continuation of valproate treatment
when oral therapy not possible.
Give at same dose as current oral dose.
- Sodium valproate M/R Prescribe by brand name (e.g. Epilim Chrono).
By mouth, initially 600mg daily increasing by
200mg/day at 3 day intervals to a max of 2.5g daily in
divided doses. Usual maintenance 1 - 2g daily. Total
daily dose given in 1 to 2 divided doses.

Medicines used in status epilepticus
Management of Major Status Epilepticus in Adults
Initial
Management
For further information see NICE guidance Treatment of Status
Epilepticus
- Turn to lateral semi-prone position and protect airway if needed
(extend neck).
- Appropriate management of airways, breathing and circulation.
- Give oxygen 35 - 40% by face mask
- Establish IV access, if this fails consider the rectal route.
- Lorazepam 4mg I.V bolus (first choice) alternatively intravenous
diazepam (Diazemuls) at a dose of 10mg
- If no i.v. access give diazepam 10-20mg rectally (Stesolid rectal
tubes).
- Note: Risk of respiratory depression with all benzodiazepines.
- Monitor B.P
- Take blood for U&E, glucose, anti - epileptic medicine levels,
calcium, magnesium, FBC.
- Measure blood gases to assess acidosis

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Management of Major Status Epilepticus in Adults
Subsequent
Management
- Repeat Lorazepam 4mg IV after 10 minutes
- Phenytoin 15mg/kg loading dose, administered into large
peripheral vein, no faster than 50mg/min with BP and ECG
monitoring, (risk of arrhythmias)
Method of administration of phenytoin, either by syringe pump, or
direct injection, without dilution. Flush line with sodium chloride 0.9%
before and after infusion. Note: Max. rate 50mg/min.
Or:
By minibag, in100 - 250mL sodium chloride 0.9% only. Final
concentration must not exceed10mg/mL. Use an in line filter (0.22 -
0.50micron) and administer over 20-40 mins (max. rate 50mg/min) but no
longer than one hour. Flush line with sodium chloride 0.9% before and
after infusion.
N.B: Filter can be used for up to 72 hours.

- Hypoglycaemia give 250ml of 10% glucose
- History of alcohol abuse give 2 pairs ampoules IV Pabrinex

Refractory - Contact Anaesthetist on call.
- Propofol or Thiopental as on the advice of anaesthetist.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Used in Parkinsonism and Related Disorders

Dopaminergic medicines used in parkinsonism
The recommended ratio of dopa - decarboxylase inhibitor to levodopa is 1:4 in
order to achieve sufficient inhibition of extracerebral dopa - decarboxylase. Co -
careldopa 25/100 (Sinemet Plus) provides low dose levodopa (100mg) with
sufficient decarboxylase inhibitor (25mg) for initial therapy. Co - careldopa
10/100 (Sinemet - 110) and Co - careldopa 75/200 (Sinemet - 275) are NOT
appropriate preparations for initial therapy. Domperidone may be used to control
the nausea associated with levodopa therapy.

Some medicines in this section are restricted to consultant initiation only due to
the difficulty in diagnosing Parkinson's disease.

For further information see NICE guidance: CG 35 Parkinson's disease Quick
reference guide

- Apomorphine Injection (s) Lead Consultant for Parkinsons Disease only
- Co - beneldopa (Madopar)
capsules/soluble tablets/
m/r capsules

- Co - careldopa (Sinemet)
tablets/ m/r tablets

- Entacapone tablets (s) Lead Consultant for Parkinsons Disease only.
- Pramipexole tablets (s) Lead Consultant for Parkinsons Disease only
- Ropinirole tablets (s) Lead Consultant for Parkinsons Disease only
- Rotigotine patches (s) Lead Consultant for Parkinsons Disease only
- Selegiline
tablets/syrup/lyophilisate
(s) Lead Consultant for Parkinsons Disease only
Selegeline 10mg (conventional) is equivalent to
selegeline lyophilisate 1.25mg(Zelapar)
- Stalevo tablets (s) . Lead Consultant for Parkinsons Disease only
Co-careldopa with entacapone.
50/12.5/200mg; 100/25/200mg and150/37.5/200mg.
To replace entacapone plus co-careldopa
regimens with improvement in patient
compliance.
Other preparations available on consultant request.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Antimuscarinic Medicines
- Procyclidine
tablets/syrup/injection
To treat medicine induced extrapyramidal effects:
By mouth, 2.5mg 3 times daily gradually increased if
necessary to max. 30mg daily.
Acute dystonia:
By i.m or i.v.. Injection, 5 - 10mg repeated if
necessary after 20 mins. (usually effective in 5 -10
minutes but may need 30 minutes for relief)

Medicines used in chorea, tics and related disorders
- Haloperidol
tablets/liquid
Motor tics: 0.5 - 1.5mg 3 times daily adjusted
according to response.
N.B: Not for use in tremors related to Parkinson's disease







































The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Used in Substance Dependence
- Alcohol withdrawal ranges from an insignificant upset to a life - threatening
syndrome with delirium, fits and serious neurological complications.
- Withdrawal symptoms may start around 3 - 6 hours after stopping drinking and can
last 5 - 7 days, sometimes longer.
- Up to 12 hours after the last drink symptoms may include tremor, sweating,
anorexia, nausea, insomnia and anxiety.
- Between 10 and 60 hours, alcohol withdrawal seizures are a risk and may precede
or accompany delirium tremens. Predisposing factors include hypoglycaemia,
hypokalaemia, hypomagnesaemia and epilepsy.
- Patients with thiamine deficiency may develop Wernicke's encephalopathy, which is
characterised by confusion, ataxia, memory disturbance and ophthalmoplegia.
Patients may then develop Korsakoff's syndrome, where they have difficulty
acquiring new memories.
Management of Alcohol Withdrawal

General Support
Initial investigation should include estimation of blood urea and electrolytes,
glucose, amylase, calcium, magnesium, blood gases and LFTs. Blood glucose
should be monitored frequently in severe cases.

Rehydration and correction of hypoglycaemia, hypokalaemia and
hypomagnesaemia are essential.

Note: A glucose load (sweet food or IV glucose) can precipitate Wernicke's
encephalopathy in a thiamine deficient patient, so IV Pabrinex must be given to
all high risk patients as in the flow chart below.

Thiamine Deficiency
The algorithm on the next page describes the treatment of established
Wernickes encephalopathy and those deemed to be at high risk.

All patients should be prescribed:
- Thiamine tablets
100mg TDS (doses should be split in this way to
maximise absorption)
PLUS

- Multivitamin tablets
One or two daily.

Continue upon discharge only if the patients diet is inadequate

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Refer all patients who are encephalopathic to a gastroenterologist

Algorithm for prescription of vitamin supplementation in alcohol
misusers

Patients who abuse alcohol are at risk of developing Wernickes
encephalopathy as a result of poor dietary intake of thiamine. Thiamine
absorption is mediated by a saturable transport mechanism (the maximum
amount absorbed from an oral dose is approx. 8mg). Therefore oral thiamine
doses should be split patients will absorb more if they are given 100mg TDS
than if they are given 300mg OD. The algorithm below describes the vitamin
supplementation required by alcohol misusers admitted for detoxification.

Diagnosis of Wernickes/ Assessment of Risk
- Established Wernickes encephalopathy is usually characterised by confusion
ataxia, memory disturbance and ophthalmoplegia. However, in many
cases, these classical signs may not be present, and therefore, it is always
important to consider the possibility that the patient may have Wernickes
encephalopathy.
- High risk patients include:
o Those who present with significant weight loss and/or show signs of
under-nutrition
o Severe withdrawal
o Increasing memory problems/black outs
o Are in a coma or present with confusion
o Patients who present with hypoglycaemia (and are treated with IV
glucose) with evidence of chronic alcohol ingestion must be given IV
Pabrinex due to the risk of precipitating Wernickes encephalopathy.
Low Risk
Established
Wernickes /
High Risk
Give 2 pairs Pabrinex
ampoules IV three times a
day for 3 days. This may be
reduced to 1 pair daily for 3-
5 days if the patient
responds.
Give thiamine 100mg TDS and multivitamins 1 tablet daily.
Continue upon discharge only if the patients diet is inadequate.
Known/suspected alcohol misuser




































The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Administration of IV Pabrinex
Pair(s) should be added to 50-100ml of saline 0.9% or glucose 5% and infused
over 30 minutes to reduce the risk of anaphylactic reactions.
Facilities to manage anaphylaxis should be made available before the dose is
administered.
Treatment of Alcohol Withdrawal
It is important to avoid a) inadequate treatment, which may lead to Delirium
Tremens or seizures and b) over treatment, which may lead to over sedation
and respiratory depression.
Early detection and prompt initiation of treatment is crucial as untreated acute
alcohol withdrawal can progress to delirium tremens, which has been shown
to be fatal in 15-20% of untreated patients. If untreated, death may result from
respiratory and cardiovascular collapse or cardiac arrhythmias. Patients most
at risk are those with a high fever (>104F/39.9C), tachycardia, dehydration
and an associated illness (e.g. pneumonia or pancreatitis), general debility or
where the diagnosis is delayed. However, appropriate management reduces
mortality to around 1%.
In most cases this can be achieved with oral benzodiazepines, usually
chlordiazepoxide.
Because of the psychological impact of detoxification planning and
coordination with alcohol follow-up services is essential. Good nursing care in
a well lit, cool environment has been shown to reduce the impact of sensory
deprivation on the confused patient, and as such is a crucial part of the
treatment plan.
Benzodiazepines, particularly chlordiazepoxide, are central to the
management of alcohol withdrawal and have the following important
properties: Sedative, anxiolytic, anticonvulsant, cross-tolerant with alcohol,
and do not induce liver enzymes.
The Adapted Clinical Institute Withdrawal Assessment tool (CIWA-AD) will be
used by the senior doctors or ASN to provide guidance for dosage level.
Chlordiazepoxide will then be prescribed on the PRN or variable dose section
of the patient prescription/drug chart.


















The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
Oral Chlordiazepoxide Symptom Triggered Regime

The presence of jaundice, encephalopathy, ascites, bleeding, prolonged prothrombin time
>17 seconds, low serum albumin <30g/l or urea >10mmol/l should alert the clinician to
the possibility of significant or decompensated liver disease. The dose of
chlordiazepoxide should be halved in significant liver disease. Benzodiazepines should
be avoided if hepatic encephalopathy is present or if decompensation is incipient. The
Hepatology team or on-call Gastroenterology registrar on-call should be contacted
urgently.
CIWA- AD Score
Oral
Chlordiazepoxide

CIWA-AD Score
Less than 9 NIL Repeat in 1 hour
Score of 9 to 11 10 to 20mg Repeat in 1 hour
Score of 12 or greater 25 to 30 mg Repeat in 1 hour
When patient symptoms are controlled assessment can be four
hourly.
Oral Thiamine 100mg three times daily should be commenced.
OR
If confusion, ataxia, ophthalmoplegia or BMI less than 20 with recent




Tachycardia
A non - selective beta - blocker e.g. Propranolol may decrease the risk of arrhythmias
and help where tachycardia and tremor are prominent. Propranolol m/r 80mg daily,
increasing to propranolol m/r 320mg daily if required, may allow a lower dose of
sedative to be used. Care should be taken if the patient has co - existing cardiovascular
or respiratory problems.

Seizures
- Alcohol withdrawal seizures or status epilepticus should be treated with
lorazepam 4mg I.V bolus (first choice) alternatively intravenous diazepam
(Diazemuls) at a dose of 10mg
- If no i.v. access give diazepam 10-20mg rectally (Stesolid rectal tubes).
Maintenance antiepileptic medication should not be prescribed as there is no
evidence that it reduces the incidence of alcohol withdrawal seizures.

Psychiatric Syndromes
A variety of psychiatric syndromes may manifest once a patient has recovered
from the acute withdrawal state, e.g. paranoid psychosis, memory difficulties,
and affective disorders. A psychiatric consultation is advisable when persistent
auditory hallucinations and/or delusions are noted, or when an affective disorder
is suspected.

Home Detoxification Programmes
The management of acute alcohol withdrawal in the community setting can
reduce a patients length of stay in hospital and may even prevent them being
admitted into hospital.

Patients eligible for home treatment
To be suitable for home detoxification, the patient must satisfy the following
criteria:
- They must be medically fit for discharge (as determined by a doctor).
- They must be assessed by an alcohol specialist nurse regarding their
suitability for home detoxification. The result of this assessment will be
documented in the case notes.
- They must have support at home from either friends or relatives.
Patients who live alone are not suitable.
- Patients may only be discharged on days between Monday and
Thursday.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Prescribing chlordiazepoxide on discharge prescriptions (TTO)
If a patient is deemed suitable for home detoxification, chlordiazepoxide can
be prescribed on their TTO.
- Due to the nature of the reducing regimes, it is often difficult to put clear
dosing instructions onto the pharmacy-dispensing label. Therefore, a
patient information sheet (available from the alcohol specialist nurses)
detailing the doses to be taken must be completed by the prescriber
and sent to pharmacy with the TTO and medicine card for a pharmacist
to clinically check. A copy of this sheet is also sent to the patients GP.
- A maximum of 200mg of chlordiazepoxide can be
prescribed/dispensed for an individual patient. Patients who require
more than 200mg of chlordiazepoxide to complete their reducing
regime need to have a prescription written by their GP for the
remaining amount. The alcohol specialist nurses will liaise with the
patients GP to arrange this.

For further information see Trust Policy: Managing Acute Alcohol Withdrawal
and Delirium Tremens (available via intranet).





Cigarette Smoking
Smoking cessation products such as patches, chewing gum etc. should only be
used as an adjunct to counselling.
The Trust smoking cessation adviser can be contacted on 706 2332 and will
come to the ward to advise patients.

- Varenicline tablets
Dr Burhan, smoking cessation specialist advice only

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Opioid Dependence
- Opioid withdrawal symptoms are unpleasant but not life threatening.
In contrast
- Methadone overdose, or its administration to opioid - naive patients, can be
fatal.
- Opioid withdrawal is not a medical emergency, so methadone does not
routinely need to be prescribed in the Accident and Emergency Department
(unless there is objective evidence of opioid withdrawal symptoms).
- In pregnancy, opioid or benzodiazepine withdrawal can precipitate serious
foetal outcomes. Rapid stabilisation of symptoms is essential. For pregnant
patients, please liaise urgently with the on - call obstetrics registrar at the
Liverpool Womens Hospital.
- Doctors do not need a special licence to prescribe methadone in the
management of drug dependence. However, a special licence issued by the
Home Secretary is needed to prescribe, administer or supply diamorphine,
dipipanone or cocaine in the treatment of drug dependence.
- Doctors may still prescribe diamorphine, dipipanone or cocaine for patients,
including addicts, for relief of pain due to organic disease or injury, without a
special licence.

Opioid Withdrawal Symptoms

Occur
When an opioid - dependant individual is without their usual source of opioid
for a period of time.

Severity
Is variable and depends on:
1. The amount of opioid usually taken.
2. Route of administration - usually more severe in intravenous users.
3. Psychological factors, e.g. coping strategies/anxiety.

Time of Onset
Depends on the opioid used.
Short - acting opioids: 6 - 8 hours after last use e.g. Heroin, morphine, and
dihydrocodeine.
Long - acting opioids: 16 - 24 hours after last use e.g. Methadone

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Symptoms
Subjective:
- Craving for opioids.
- Anxiety symptoms.
- Pains and cramps in muscles, particularly stomach, back and legs.
- Unable to sleep.
- Feeling hot and cold.
Objective:
- Cold, sweating, clammy and goose flesh.
- Yawning.
- Nausea, vomiting and diarrhoea.
- Restlessness and insomnia.
- Tremor.
- Lachrymation and rhinorrhea.
- Raised BP and tachycardia.
Note:
1. These symptoms may occur in other medical conditions or co - exist with
other conditions.
2. Seizures or fits do not occur in pure opioid withdrawal.
3. Drowsiness, sedation, disorientation or confusional states do not occur in
pure opioid withdrawal.
4. Pyrexia is not a symptom of opioid withdrawal.
5. Opioid withdrawal may be masked or attenuated by other medicines or
substances, e.g. benzodiazepines, barbiturates, alcohol, phenothiazines.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Managing Patients on Street Heroin or Unconfirmed
Prescribed Methadone Dose.

(Click here for methadone algorithm)

Take a urine sample and send to clinical chemistry for opiates and
methadone.
Do not start methadone unless there is objective evidence of withdrawal
symptoms.
Prescribe a single dose of methadone 10mg on the once only part of the
prescription chart.
A second dose of methadone 10mg may be prescribed and given no sooner
than four hours after the first dose.
The patient should not receive more than 20mg of methadone in the first
twelve hours.
After this initial twelve hours, methadone may be prescribed as 20mg twice
daily - maximum dose 40mg in 24 hours.
Write the dose in both words and figures to prevent unauthorised alterations
Do not prescribe on a when required basis.
Endorse the prescription do not give if drowsy.
Do not give if patient is drowsy, sedated, ataxic, has slurred speech or is
asleep.
Never wake a patient to give them methadone.
Methadone doses should be prescribed in words and figures to prevent
patients from altering their prescriptions.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

General Points Regarding Methadone Prescribing.

- Oral methadone liquid should be prescribed, i.e. methadone mixture 1mg/ml.
- If the parenteral route is unavoidable, methadone should be given IM. IV
administration is unlicensed.
- In those patients with true methadone intolerance, dihydrocodeine may be
used. However, this is an unlicensed indication.
- A patients usual dose of methadone must be confirmed with the clinic, GP or
community pharmacy before prescribing, details of the confirmation must be
documented in the case notes.
- If patients have missed 72 hours or more of their usual dose of methadone
the clinic should be contacted for advice regarding an appropriate dose. If it is
not possible to contact the clinic e.g. at a weekend the follow the guidance
above.
- Dosing interval
When in the community patients usually take their daily methadone as a
single dose. Therefore there it is not necessary to have a minimum specified
time interval between doses when the daily dose is divided into two and given
twice daily while in hospital. However if the patient is showing signs of toxicity
e.g. drowsiness, confusion further doses should be with held and senior
medical advice sought.
- Discharge issues:
- Patients with a history of IV drug abuse who are not registered on a
programme should not receive methadone on discharge.
- For patients registered on a methadone programme, the GP/clinic needs
to be informed at least 24 hours in advance of a patients discharge so
they can arrange a further prescription.
- Prescribe and administer a STAT dose of methadone (to make up the
patients usual total daily dose) on the ward before discharge.
- If a patient is discharged during a weekend, a TTO for up to 48 hours (72
hours in the case of a bank holiday) supply may be written.
- All liaisons with the GP/clinic must be documented in the case notes.
- Analgesia prescriptions:
- Additional opioids should be avoided where possible due to potential for
abuse
- Regular paracetamol should be tried first line
- If the patient is still in pain despite this, dihydrocodeine may be used.
- Requests for benzodiazepines:
- Patients prescribed methadone should not be prescribed benzodiazepines
or zopiclone for night sedation (due to the abuse potential associated with
these drugs).
- Chlordiazepoxide may be used to treat acute alcohol withdrawal owing to
the potential seriousness of this syndrome.

The majority of patients admitted will be registered with one of the clinics below or their
GP. The clinic should be notified (office hours only) and the prescription suspended at
the appropriate community pharmacy to prevent dispensing of duplicate supplies.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Liverpool Drug Dependency
Clinic (Hope Street)
0151 709 0516
Brook Place (Tuebrook) 0151 330 8260
Liverpool Drug Rehabilitation
Requirement Team (Criminal
justice system users)
0151 234 5800
St. Helens Lifestyles Team 01744 458364
Addaction (Huyton) 0151 489 3005

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Flow Chart for Prescribing Methadone in Patients Admitted for an
Unrelated Medical/Surgical Reason





The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines for Dementia

Alzheimers disease must be diagnosed in a specialist clinic and treatment may only
be initiated by physicians specialising in the care of patients with dementia. For
further information see NICE guidance: TA217 Donepezil, galantamine, rivastigmine
and memantine for the treatment of Alzheimers disease


- Rivastigmine Symptomatic treatment of mild to moderately severe
dementia in patients with idiopathic Parkinson's
disease.
(s) Lead Consultant for Parkinsons Disease only

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

ENDOCRINE SYSTEM

Contents (Click on heading to go to that section)


Trust Clinical Policy for the Management of Diabetic Keto-acidosis
(DKA)
Diagnosis
Investigations
Management
Management of Cerebral Oedema
Conversion to Conventional Insulin

Management of Hyperosmolar Hyperglycaemic State (HHS)
Diagnosis
Treatment

Management of insulin treated diabetic patients and non insulin
treated diabetic patients in the peri-operative period

Trust Clinical Policy for Glucose, Potassium and Insulin Infusion
(GLIK/Alberti Regimen) for all Patient Groups
Criteria
Procedure
Blood Glucose Monitoring
Plasma Potassium Monitoring

Trust Policy For Intravenous Insulin Therapy Regimen (IVIT)
Suitable Patients
Cautions
Initiation
Adjustment
Sodium Requirements
Hypoglycaemia

Trust Policy For Intravenous Insulin Therapy Regimen (IVIT) For Diabetic
Patients With Renal Impairment (CKD stage 4 and 5 eGFR < 30ml/min)

Trust policy for the management of hypoglycaemia
Diagnosis
Action
Following a Hypoglycaemic Episode

Medicines Used in Diabetes
Insulins
Insulin Regimens
Oral Antidiabetic Medicines

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Diabetes Treatments, Liver & Renal Impairments and selected other
cautions

Thyroid and Antithyroid Medicines
Thyroid Hormones
Antithyroid Medicines

Corticosteroids
Mineralocorticoids
Glucocorticoids

Sex Hormones
Female Sex Hormones
For Women With a Uterus
For Women Without a Uterus

Male Sex Hormones and Antagonists
Anti-Androgens
Anabolic Steroids

Hypothalamic and Anterior Pituitary Hormones and AntiOestrogens
Anterior Pituitary Hormones
Posterior pituitary hormones and antagonists

Medicines Affecting Bone Metabolism
Calcitonin
Bisphosphonates

Other Endocrine Medicines
Bromocriptine and Other Dopaminerergic Medicines
Medicines Affecting Gonadotrophins
Metyrapone

Diagnostic Agents for Endocrine Disorders
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Trust Clinical Policy for the Management of Diabetic
Ketoacidosis (DKA)

- Diabetic Keto-Acidosis (DKA) is a potentially life threatening condition.
- Discuss difficult cases with on-call Specialist Registrar/Consultant.
- Consider HDU/ITU referral sooner rather than later.
- Commence treatment immediately if DKA is suspected.

Diagnosis

- Laboratory plasma glucose >11 mmol/l (most cases) or known diabetes
- Plasma ketones positive AND/OR urine ketones >++.
- Arterial pH <7.2 AND/OR plasma Bicarbonate <15 mmol/l.
- Blood glucose level >11 mmol/l, urine ketones ++, pH 7.2-7.4 and plasma
bicarbonate of 15-20 mmol/l may suggest early DKA

Investigations
Urgent:
- Laboratory blood glucose and ketones (near patient testing strips e.g.
Advantage II; Medisense Precision Plus, are not reliable in the presence of
ketones).
- Arterial Blood Gases.
- U+Es.
- Urine for ketones, glucose, protein,
- Blood culture MSU.
U+E and Laboratory Blood Glucose:
- Check
every 3 hours for 6 hours,
then
6 hourly for 12 hours,
then
every 12 hours for 1 day,
then daily.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Search for a Cause:
- Screen for infection.
- Antibiotics are only required in the presence of infection moderate
leucocytosis is a common feature of DKA
- Screen for MI in high risk groups.


Consider
- CVP measurement in cardiac/renal failure.
- ECG monitoring in hyper or hypokalaemia.
- Urinary catheter if comatose or anuric for >4 hours.
- Prophylactic subcutaneous Dalteparin 2500 - 5000 units daily in severely ill
patients.
- NG tube if persistent vomiting or unconscious.
- Plasma expanders in shock.

Management

Fluids
- Usually 4-8 litres are needed during the first 24 hours
- Start IV Sodium Chloride 0.9% as soon as the diagnosis is suspected and
adjust infusion rate according to severity of dehydration.
e.g.
1 litre over 1hour, then
1 litre over 2 hours, then
1 litre over 4 hours, then
1 litre every 6-8 hours.
- If elderly, in cardiac or renal failure; reduce fluid infusion rate and consider
CVP measurement.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Potassium
- plasma levels usually initially high but concentration falls quickly.
- When U&Es available, use premixed IV bags containing potassium as below:
plasma potassium > 5.0 mmol/l
Use Sodium Chloride 0.9% 1 litre without potassium
plasma potassium 3.5 - 5.0 mmol/l
Use Sodium Chloride 0.9% 1 litre + 20 mmol potassium/litre bag
plasma potassium < 3.5 mmol/l
Use Sodium Chloride 0.9% 1 litre + 40 mmol potassium/litre bag.

Insulin
Do Not Stop Insulin. Treat any hypoglycaemia as per policy and inform medical
staff of hypoglycaemia / hyperglycaemia or difficulties in achieving stable
control of blood glucose.


- Patients on long acting analogue insulins Insulin Glargine (Lantus) or Insulin
Detemir (Levemir) should have them continued whilst they are being treated
for DKA.
- Use the same starting rate of insulin below whether continuing long acting
insulin or not and adjust as per blood glucose



- Administer as an intravenous infusion via a syringe driver.
1. Add 50 units of soluble insulin (Humulin S) to 50 mls Sodium Chloride
0.9% (i.e. 1unit/ml).
2. Start at 6 ml/hour (6 units per hour).
3. A fresh solution should be prepared every eight hours for immediate use.
- Monitor blood glucose hourly and act on results.
- Rapid correction of hyperglycaemia is not advisable.
- Aim to decrease blood glucose levels by 5-10% per hour.
- After 1 hour, if glucose does not fall by 3-5 mmol/l, increase insulin infusion rate
to 12 units/hour.
- When blood glucose is <15 mmol/l change IV fluid to 5% Glucose.
- Thereafter, aim at maintaining blood glucose at 5 - 12 mmol/l by adjusting
insulin infusion rate: (see below)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Blood Glucose <5 mmol/l and not rising:
decrease rate by 0.5 1unit / hour to a minimum rate of 0.5 units / hour.
Blood Glucose 5 - 12 mmol/l:
continue at present rate.
Blood Glucose >12 mmol/l and not falling:
increase rate by 0.5 1unit / hour.


Bicarbonate

- Avoid administration unless pH is < 6.9.
- If indicated, give 250 - 500ml of 1.4% sodium bicarbonate over 30 - 60
minutes and assess response.

Management of Cerebral Oedema

- Occurs more often in extremes of age especially if hyperglycaemia is rapidly
corrected.
- Presents with headache, confusion with/without papilloedema.

Investigation
- Urgent brain CT scan.


Management

- avoid fluid overload.
- mannitol by rapid IV infusion - administer (weight (Kg) x 5) ml of 20% solution
over 15 minutes
OR
- dexamethasone 8.8 mg IV stat then 4.4 mg IM 6 hourly as required for 2-10
days .

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Conversion to Conventional Insulin
- Patients can eat and drink as soon as they feel able.
- Continue IV insulin until acidosis is corrected i.e. 24 hours after clearance of
ketonuria and/or plasma bicarbonate >20 mmol/L.
- Refer to Specialist Nurse for Diabetes.
- If normally on subcutaneous insulin, restart the patient's usual regimen prior
to their next meal (e.g. if on insulin analogue give it just before or with the
meal or if on other insulins give 30 minutes before their meal) and stop IV
insulin 60 minutes later.
- If the patient has not had insulin prior to this episode, contact Specialist
Registrar for Diabetes for advice.


Management of Hyperosmolar Hyperglycaemic State (HHS)
(formerly known as HONK)

- HHS is a potentially life threatening condition.
- Discuss difficult cases with on-call SpR/Consultant.
- Consider HDU/ITU referral sooner rather than later.

Diagnosis
- Plasma osmolality (2x|Na
+
+ K
+
] + urea+ blood glucose) >350 mmol/l
- Lab glucose >30 mmol/l, no significant ketones or acidosis.
- Severe dehydration and hypovolaemia.
- Confirm diagnosis, seek cause, full CVS/CNS assessment.

Clinical Investigations
- Arterial blood gases
- Full blood count
- U+E (2 - 4 hourly), glucose, HbA1c, urinalysis (check for urinary ketones
also), blood and urine culture, CXR, ECG, coagulation and troponin.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Treatment
General
- Anticoagulate with treatment dose of Dalteparin (HHS has a high mortality
due to thrombotic complications e.g. MI, CVA, PE).
- Give broad spectrum antibiotics Piperacillin/tazobactam 4.5g tds. If penicillin
allergic please refer to med micro for advice
- Consider need for NG tube, urinary catheter and CVP line.

Fluids
- Use Sodium Chloride 0.9% 1litre over 2 hours then 1litre over 4 hours, then
1litre 8 hourly thereafter.
- Avoid hypotonic solutions. Give colloid (e.g. gelofusin) if required to raise
blood pressure.
- Caution ( monitor CVP) in elderly, cardiac or renal disease patients.
- If Na+ not declining after 4hrs then consider using hypotonic saline or
dextrose with insulin - refer to Diabetes SpR

Potassium
Only pre-mixed preparations are available.
- Serum potassium>5.0
mmol/l
Use Sodium Chloride 0.9% 1 litre without potassium
- Serum potassium 3.5-5.0
mmol/l
Use Sodium Chloride 0.9% with20 mmol potassium
chloride, 1 litre bag.
- Serum potassium <3.5 Use Sodium Chloride 0.9% with 40 mmol potassium
chloride 1 litre bag.

Insulin

- Patients on long acting analogue insulins Insulin Glargine (Lantus) or Insulin
Detemir (Levemir ) should have them continued whilst they are being treated
for HHS.

- Use the same starting rate of insulin below whether continuing long acting
insulin or not and adjust as per blood glucose

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

- Set up a syringe driver with 50 units of soluble insulin Humulin S in 50 mls Sodium
Chloride 0.9% (i.e. 1unit/ml )
- Start the infusion rate at 2 mls/hr (i.e. 2 units/hr).
- The starting rate and incremental increases and decreases will need to be greater in
overweight patients with insulin resistance
- A fresh insulin solution should be prepared every 8 hours for immediate use.
- Monitor BMs hourly and act on your findings aiming to decrease blood
glucose no more than 10% per hour. Adjust the insulin infusion rate as
follows:

Blood glucose above 12 mmol/l and not decreasing increase the
insulin rate by 0.5 units (0.5 ml) per hour.

Blood glucose within target range of 5-12 mmol/l leave the
insulin running at the present rate.

Blood glucose below 5 mmol/l and not increasing decrease the
insulin rate by 1 unit (1 ml) per hour to a minimum of 0.5 units (0.5 ml)
per hour.

- Inform medical staff of hypo or hyperglycaemia or difficulties in achieving
stable control of blood glucose.
- When patient eating and drinking normally convert back to usual treatment
regimen.
- If the patient was not previously known to have diabetes refer to the Diabetes
SpR for advice.


Management of insulin treated diabetic patients and non
insulin treated diabetic patients in the peri-operative period
(Guidelines for anaesthetists and house officers)

For type 2 patients on oral hypoglycaemics/ GLP1 ONLY who are well controlled eg
have HbA1c <69mmol and there is a short starvation time and morning surgery
you should just omit oral hypoglycaemics on the morning of surgery.

If afternoon surgery then they can have (as long as they can eat in the morning)
metformin as long as no contrast media is involved but oral agents such as long
acting sulphonylureas, DPP4 inhibitors and GLP1 should be omitted

GKI is needed (see below) if:
- The starvation period is longer than 1 meal
- The patient has poor diabetes control eg HbA1c> 69mmol
- The patient is on insulin
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Guidelines for the management of these patients undergoing elective surgery.
Pre operative
assessment
Note the presence or absence of complications
e.g. retinopathy, nephropathy, hypertension, ischaemic
heart disease, neuropathy (peripheral and autonomic),
foot problems (vascular or neuropathic).
Investigations - Urinary protein ECG
- U & E profile HbA1C
General
recommendations
- Admit at least 24 to 48 hours prior to surgery.
- Operation should be in the morning and preferably
not on a Friday.
- Do not give lactate containing infusions e.g.
Hartmann's
Take special care of the heels and malleoli (either
side of the ankle joint) in patients with neuropathic
feet.
- Take the opportunity to assess the patient's skills
in injection technique, use of blood glucose
monitoring (BM) sticks, use of urine testing
sticks etc. and re - educate if problems are
identified.
The diagnosis of type 2 diabetes on admission to
the surgical ward need not necessitate
cancellation of the operation.
Morning of operation - Omit breakfast.
- Omit s.c. insulin if the patient uses insulin.
Check blood glucose and urinalysis at least 1 hour
pre - op.
- If ketonuria present and/or
blood glucose > 17mmol/L, contact anaesthetist.
- Set up GKI (Alberti) regimen as below. Continue
the GKI regimen until the first post - operative
meal. Then restart on full recovery the usual
insulin or tablet regimen.
- If normally on subcutaneous insulin, restart the
patient's usual regimen prior to their next meal
(e.g. if on insulin analogue give it just before or
with the meal or if on soluble insulins give 30
minutes before their meal) and stop GKI 60
minutes later.
- If an afternoon operation is unavoidable, the
patient should have a light breakfast, but no s.c.
insulin and the GKI infusion should be set up as
described below

Diabetic patients undergoing emergency surgery may have special requirements. Please discuss
the management with anaesthetists and the diabetes team. When in doubt, ask. The above
guidelines are for the management of diabetic patients undergoing elective surgery.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Trust Clinical Policy for Glucose, Potassium and Insulin
Infusion (GKI/Alberti Regimen) for all Patient Groups

Criteria
- If the patient remains NBM after 48 hours consider changing to an
intravenous insulin therapy regimen (IVIT).
- For surgical patients with renal impairment (plasma creatinine >
150micromol/l) consult the anaesthetist.

Blood glucose must be checked hourly intra-operatively.

Procedure
Set up as follows:

- Pre-mixed bags of 500 ml of Glucose 10% with 10 mmol potassium
chloride are available. These can be ordered from pharmacy.
- Stock levels and usage must be recorded in the Controlled Drugs book as this
is an unlicensed product.

1. Add 10 units of soluble insulin Humulin S to the bag and mix well.
2. Run off 50 ml to prevent insulin being adsorbed to the plastic of giving set
and start infusion rate at 100 ml/hour.
Patients with Body Mass Index >30:
- consider a higher content of insulin e.g. 16 units.
Patients with Body Mass Index <20, or those who usually require
less than 20 units of insulin per day:
- consider a lower content of insulin e.g. 6 - 8 units.

NB If patients are on long acting insulin analogue- insulin glargine (Lantus) or insulin
detemir (Levemir) then this should be continued and consider halving the number of
units of Humulin S that are added to the bag
Pre printed orange prescription sheets are available for prescribing GKI

Blood Glucose Monitoring
Do not stop insulin. Treat any hypoglycaemia as per policy and inform medical
staff of hypoglycaemia / hyperglycaemia or difficulties in achieving stable control
of blood glucose
- Check blood glucose hourly and adjust as below
blood glucose <5 mmol/l
change infusion bag and reduce insulin content by 4 units.
blood glucose 5-12 mmol/l
continue with current infusion bag insulin content.
blood glucose > 12 mmol/l
change infusion bag and increase content insulin by 4 units.

Patients requiring larger doses of insulin need larger adjustments of doses e.g. if on
a GKI containing 40 units of insulin and BM 14mmol/l, increase insulin by 6-8 units.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Plasma Potassium Monitoring

- Check at 4 hours, 8 hours and if stable; every 24 hours
- Adjust the infusion as follows:

Plasma potassium >5 mmol/l
change infusion bag to Glucose 10% without potassium
Plasma potassium 3.5-5 mmol/l
continue with current regimen;
Plasma potassium <3.5 mmol/l
change infusion bag to Glucose 10% with 20 mmol potassium
(500ml pre-mixed bag).


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Trust Policy for Intravenous Insulin Therapy Regimen (IVIT)

[For IVIT For diabetic patients with renal impairment (CKD stage 4 and 5 eGFR
<30ml/min) click here]

Background

Fixed insulin infusion rates for a given blood glucose level, (i.e. sliding
scales) produce erratic blood glucose readings and therefore should not be
used.

- insulin sensitivity varies from patient to patient. Even for a given patient, this
can change during the course of, and recovery from, an illness.

Suitable Patients
- Those patients who are NBM for a prolonged period e.g. post CVA or have
severe diarrhoea and vomiting etc.

Cautions
- Patients with renal impairment (CKD stage 4 and 5 eGFR <30ml/min) click
here
- This regime should not be confused with the ITU Insulin Infusion Protocol
which aims to give very tight blood glucose control in a critical care setting.

Never stop IV insulin in patients with Type 1 diabetes as diabetic ketoacidosis
can develop quickly.

Patients on long acting analogue insulins Insulin Glargine (Lantus) or Insulin
Detemir (Levemir ) should have them continued whilst they are on IVIT


Initiation

- Determine the appropriate concentration and rate of the glucose (with added
potassium) infusion in the clinical circumstances.

1. The concentration and rate of the glucose infusion should be kept constant.
Examples:
- 5% Glucose containing 20 mmol potassium/litre at 125 ml/hr,
or
- 10% Glucose containing 40mmol potassium/litre at 62ml/hr
2. Set up a syringe driver with 50 units of soluble insulin Humulin S in 50 mls
Sodium Chloride 0.9%, i.e. 1unit per ml.
3. Start the infusion at 2 units (2 mls) per hour.
4. The starting rate and incremental increases and decreases will need to be greater
in overweight patients with insulin resistance; as much as 5 units (5 mls) per hour
in some cases.
5. A fresh insulin solution should be prepared every 8 hours for immediate use.
6. Measure and chart blood glucose hourly and act on your findings as below

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Adjustment
- Adjust the insulin infusion rate as follows:

Blood Glucose below 5 mmol/l and not rising
decrease rate by 1 unit (1 ml) per hour to a minimum of 0.5 units (0.5 mls) per
hour.

Blood Glucose within target range of 5-12 mmol/l
leave the insulin running at the present rate.

Blood Glucose above 12 mmol/l and not falling
increase the rate by 0.5 units (0.5 mls) per hour.

Sodium Requirements

If an IVIT is continued for more than 24 hours, consider adding sodium chloride 0.9%
via another line running concurrently with the glucose infusion to avoid
hyponatraemia.


Hypoglycaemia

Do Not Stop Insulin. Treat any hypoglycaemia as per policy and inform medical
staff of hypoglycaemia / hyperglycaemia or difficulties in achieving stable
control of blood glucose.

















The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Trust Policy for Intravenous Insulin Therapy Regimen (IVIT)
For Diabetic Patients With Renal Impairment (CKD stage 4 and
5 eGFR < 30ml/min)

Background

Patients with renal impairment may be unable to tolerate the high fluid volumes and
potassium load used in Alberti/GKI regimens and the standard IVIT regime used at
RLBUHT. The following regimen is recommended for these patients who are
undergoing surgery or procedures where the patient will be NBM.
This regime should NOT be confused with the standard IVIT policy or the ITU Insulin
Infusion protocol which aims to give very tight blood glucose control in a critical care
setting. This is also NOT to be used to treat DKA (Diabetic Ketoacidosis) or HHS
(Hyperosmolar Hyperglycaemic Syndrome)


Never stop IV insulin in patients with Type 1 diabetes as diabetic ketoacidosis
can develop quickly.
Also never have insulin running without glucose infusion running at the same
time

Initiation

1. Use 500ml Glucose 10% and run it at 42ml/ hour. No need to routinely add
potassium to these bags but if patient is on this regime for > 24hrs please
check potassium daily.

2. Set up a syringe driver with 50 units of soluble insulin Humulin S in 50 mls
Sodium Chloride 0.9%, i.e. 1unit per ml.
The starting rate is 1 unit (1ml) per hour and adjusted as below.

In overweight patients or patients on high regular insulin doses as much as 5 units (5
mls) per hour may be needed


A fresh insulin solution should be prepared every 8 hours for immediate use.
Measure and chart blood glucose hourly and act on your findings as below

Adjustment of insulin rate

Adjust the insulin infusion rate as follows:

Blood Glucose below 5 mmol/l and not rising
decrease rate by 0.5 units (0.5 ml) per hour to a minimum of 0.5 units (0.5 ml) per
hour.

Blood Glucose within target range of 5-12 mmol/l
leave the insulin running at the present rate.

Blood Glucose above 12 mmol/l and not falling
increase the rate by 0.5 units (0.5 ml) per hour.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Patients who are NBM for a prolonged period, or those who continue to pass
significant volumes of urine may require addition fluids. These patients should be
reviewed by a nephrology / transplant consultant or SpR.


Hypoglycaemia

Do Not Stop Insulin. Treat any hypoglycaemia as per policy and inform medical
staff of hypoglycaemia / hyperglycaemia or difficulties in achieving stable
control of blood glucose.

For patients who are fluid restricted and nil by mouth give IV 100ml Glucose 20%
over 10-15 minutes centrally if possible or via a large vein peripherally to reduce the
risk of thrombophlebitis


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Trust Policy for the Management of Hypoglycaemia

Diagnosis

Capillary blood glucose level below 4 mmol/l.

Action
For those able to swallow
- Give a sugar containing product immediately:
e.g. 3 Dextrose tablets ("Dextro energy" or "Lucozade")
OR
100 ml of Lucozade (available from NHS supplies)
OR
200 ml of full sugar pop (not diet)

- This must be followed immediately by a starch containing food: -
e.g. the patients next meal if due or a bowl of plain cereal
OR
2 plain biscuits (Digestives)
OR
a sandwich or 2 pieces of toast.

NB Check blood glucose every 10 minutes until BM 4mmol/l

For those unable to swallow/ unconscious
- 200 ml of Glucose 10% IV via peripheral intravenous line over 15-20 minutes
- For fluid restricted patients give 100 ml of Glucose 20% over 15 minutes,
centrally if possible or via a large vein peripherally to reduce the risk of
thrombophlebitis.
OR
- Glucagon 1 mg sc/im/iv as prescribed. If no response within 10 minutes,
intravenous glucose must be given.

NB Check blood glucose every 10 minutes until BM 4mmol/l


Following a Hypoglycaemic Episode
- Insulin and/or oral hypoglycaemic agents must not be omitted;
- Once the hypoglycaemic episode has been treated as above and blood
glucose is >4 mmol/l, the usual medication should be administered when due.
- Record all hypoglycaemic episodes and treatment given on the blood glucose
monitoring chart.
Try to identify the cause. If recurrent refer to the Diabetes Specialist Nurses for
review / advice
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

.





The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Medicines Used in Diabetes


Insulins - the main types of insulin preparations available are:

1. Rapid Acting analogue insulins (R)
2. Short acting or Soluble Insulin (S)
3. Intermediate acting or Isophane Insulin (I)
4. Long acting analogue Insulins (L)


Insulin Regimens

1.Basal Bolus
Pre - Breakfast Pre - Lunch Pre - evening
meal
Pre - Bedtime
S or R S or R S or R
I or L


2. Twice daily - these are usually fixed biphasic mixtures see below e.g. Humulin M3
Pre - Breakfast Pre - evening
meal
S or R S or R
I I



3. Once daily - In patients with type 2 diabetes long acting insulin analogues (e.g.
Glargine (Lantus)) can be given once daily with or without oral hypoglycaemic agents














The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Rapid and Short Acting Insulin

Preparation Species Form Onset
(approx.)
Duration
of Action
(approx.)
Rapid Acting Insulins
Apidra (insulin
glulisine)
Analogue Vial
Disp pen
3ml cart
10-20 mins 1.5-4 hours
Humalog
(insulin lispro*)
Analogue Vial
Disp pen,
3ml cart
15 mins 2-5 hours
NovoRapid
(insulin aspart)
Analogue Vial
Disp pen
3ml cart
10-20 mins 3-5 hours
Short acting insulins
Insuman Rapid Human Disp pen <30 mins 7-9 hours
Humulin S Human Vial
3ml cart
30 mins-1h 6- 12 hours

Intermediate- and Long-Acting Insulins

Preparation Form Onset
(approx.)
Duration
of Action
(approx.)
Intermediate acting insulins
Insulatard Vial, 3ml Cart <1.5 hours 24 hours
Humulin I Vial , 3ml cart
Disp pen
30- 60 mins 22 hours
Long-Acting Insulins
Lantus (insulin glargine) Vial 3ml cart
Disp pen
2.5 hours 24 hours
Levemir (insulin detemir) 3ml cart, Disp
pen
2.5 hours 24 hours

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Biphasic Insulin Preparations
Usually given twice daily

Preparation Form Onset
(approx.)
Duration
of Action
(approx.)
Humalog Mix25 3ml cart Disp pen 15 mins 22 hours
Humalog Mix50 Disp pen 15 mins 22 hours
Humulin M3 Vial ,3ml cart, Disp
pen
30 mins-1h 22 hours
Insuman Combi
25
Vial, 3ml cart, Disp
pen
30mins-1h 12-19 hours
Insuman Combi
50
3ml Cart, Disp pen <30 mins 12-16 hours
NovoMix 30 3ml cart, Disp pen <10-20 mins 24 hours
Vial- 10ml vial Disp pen- Disposable pen device 3ml cart- 3ml cartridge (non
disposable pen)

Table for insulin preparations adapted from www.emims.net

Patients may be admitted on insulin other than those listed above. Please contact
pharmacy concerning availability. Contact the Diabetes Specialist Nurse bleep 4041
(RLH) for further advice


Continuous Subcutaneous Insulin Infusion (CSII)
(Known as insulin pump therapy)

Insulin pumps just require a rapid acting analogue such as Humalog, Novorapid or
Apidra. A patient using an insulin pump must be allowed to self manage both their
pump and insulin requirements. Dose adjustment for these patients can only be
made by a member of the insulin pump management team and named individuals as
identified by the team.

If glycaemic targets are not achieved or the patient appears too unwell to effectively
manage their insulin pump then in the first instance the insulin pump management
team should be contacted for advice, if this is not possible then the patient should be
converted onto either injection therapy or IV insulin depending on the clinical
situation.

All patients admitted to hospital who are managed with CSII should be referred via
the ICE system for DSN support. For further information please review the hospital
policy on insulin pump therapy.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Oral Antidiabetic Medicines


First line

Biguanides
- Metformin tablets 500mg once a day gradually increased up to 3 times a day
with meals up to a Max 3g daily
Alterantively can use 850mg twice daily.

MR tablets.
Only to be used in patients unable to tolerate ordinary
metformin. More expensive.
Initially 500mg once daily increased every 10-15 days, max
2g once daily with evening meal.

Renal impairment
In patients with a eGFR <45ml/min minute then metformin
should be reviewed. NICE 2009 recommends stopping if
Serum Cr>150micromol/L or eGFR <30ml/min/1.73m2



Second line

Sulphonylureas


- Gliclazide tablets Short acting, choice for elderly and renally impaired.
Initially 40 - 80mg daily, adjusted according to response, up
to 160mg as a single dose with breakfast.
Max. 320mg daily in divided doses.

MR tablets: (s) Consultant diabetologists only.
Initially 30mg daily with breakfast, adjusted according to
response every four weeks. Max 120mg daily
NOTE: gliclazide mr 30mg may be considered to be
approximately equivalent in therapeutic effect to 80mg of the
standard formulation.
- Glimepiride tablets Initially 1mg daily adjusted according to response in 1mg
steps at 1 - 2 week intervals.
Usual max. 4mg (exceptionally, up to 6mg) taken shortly
before or with first main meal.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Other Antidiabetic drugs
- Pioglitazone
tablets
Used alone or in combination with metformin or a sulphonylurea or
with both or with insulin.

Dose 15 30mg once daily increased to 45mg according to
response.

Important Notes
(1) Rosiglitazone has been withdrawn and should be stopped. If it
is appropriate you can switch to Pioglitazone,

(2) Pioglitazone appears to be associated with an increased risk
of bladder cancer which should be taken into consideration when
choosing this drug. It should not be used in un-investigated
macroscopic haematuria and should be used with care in those at
increased risk of bladder cancer. Patients should be monitored at
3-6 months and regularly thereafter
Glitpins

- Sitagliptin

For use in patients with type 2 diabetes in combination with
metformin or a glitazone or with a sulphonylurea or with metformin
and a sulphonylurea
To be initiated only by diabetes SpRs and Consultants
GLP-1 Analogues







- Exenatide (
injection)




- Liraglutide (
injection)









Liraglutide or Exenatide may be useful in some (BMI > 30-35)
type 2 patients.

Combination with insulin is off-licence and not recommended by
NICE

Only to be initiated by diabetes SpRs and Consultants

Use in combination with metformin or sulphonylurea or both when
metformin or sulphonylurea or both inadequate

Initially 5 microgram twice daily by s.c. injection. Increased if
necessary after at least 1 month to 10 microgram twice daily
Use in combination with: Metformin or a sulphonylurea, in
patients with insufficient glycaemic control despite maximal
tolerated dose of monotherapy with metformin or sulphonylurea
Or in combination with: Metformin and a sulphonylurea or
metformin and a thiazolidinedione in patients with insufficient
glycaemic control despite dual therapy.
Initially 0.6mg daily by s.c injection, increased if needed after at
least 1 week to 1.2mg daily maximum







The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
Diabetes Treatments, Liver & Renal Impairments and selected other cautions

This is not a comprehensive list of cautions & contraindications for this you must consult the BNF or a pharmacist.
We recommend you consult the latest version of the British National Formulary (BNF) or a pharmacist if in doubt.
In any patient the decision to use or not to use a treatment is based on a host of factors including a carefully considered risk-benefit analysis
agreed with the patient. The table below is a guide:


Creat=Serum creatinine in micromole/litre; eGFR=MDRD value; ALT=alanine aminotransferase; ULN=upper limit of normal; CCF=congestive heart
failure; Mod LV=moderate LV impairment on ECHO or angiography; CK=creatinine kinase; Rx=treatment; and Dose=consider dose reduction.
Fibrate=fenofibrate. OK=no explicit contraindication or caution.







Adapted from Mersey Health and Community Diabetes guidelines 2011-2013

Thyroid and Antithyroid Medicines


Thyroid Hormones
- Levothyroxine sodium
(thyroxine) tablets
Initially 50 100 micrograms daily, before breakfast, (50
micrograms for those over 50 years). Adjust in steps of 50
micrograms every 3 4 weeks until normal metabolism
maintained.
Usual maintenance dose 100 - 200 micrograms daily. Where
cardiac disease is present, 25 micrograms daily OR 50
micrograms on alternate days, adjusted in steps of 25
micrograms.
Exclude cortisol deficiency either clinically or by measuring
cortisol as indicated before commencing thyroxine
replacement for the first time.
- Liothyronine
tablets/injection
(s) Consultants only.
By mouth: 10 20 micrograms daily gradually increased to
60 micrograms daily in 2 - 3 divided doses.
By slow i.v injection: hypothyroid coma: 5 20 micrograms
repeated every 12 hours or more frequently. Alternatively, 50
micrograms initially then 25 micrograms every 8 hours
reducing to 25 micrograms daily.

Administration details: Add 2ml water for injection to the
ampoule to dissolve powder.
Draw up the dose and give as a slow i.v. bolus (over 4
minutes).

`Block and Replace Therapy' for thyrotoxicosis

Carbimazole 40mg daily is given for 4 to 6 weeks then when T
4
is in normal range ADD
levothyroxine sodium [ thyroxine ] 100micrograms daily.

Thereafter adjust the levothyroxine sodium [thyroxine] dose to maintain T
4
in normal
range. Therapy is usually given for 18 months.

The `block and replace' regimen has been shown to produce lower relapse rates.
It is preferable, because doses do not need to be adjusted once the thyroid tests are in
normal range.

This regimen should not be used in pregnant women.

If Carbimazole is not toletrated consider using Propylthiouracil 200mg bd (need to do
LFTs)







The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Thyrotoxicosis in Pregnancy

In pregnant women use propylthiouracil (PTU) if possible. Maximum dose
200mg bd. Wean down rapidly and do monthly Thyroid function tests

Breast feeding-
Propylthiouracil first choice as it crosses the placenta and into breast milk
twentyfold less than carbimazole. If the patient is unable to tolerate PTU use
the lowest dose carbimazole possible. Patients taking less than 15mg
carbimazole or 150mg PTU can safely breastfeed without TFT monitoring of the
baby.
Patients should be referred and discussed with Dr Purewal at The Joint Endocrine
Disorders of Pregnancy Clinic.

Hypothyroidism in pregnancy

Thyroid binding globulins increase in pregnancy under hormone stimulation. Patients
need more regular TFT monitoring usually 6-8 weekly. Patients should be referred and
discussed with Dr Purewal at The Joint Endocrine Disorders of Pregnancy Clinic.
Levothyroxine and liothyronine can both be used safely.

Thyroid Crisis

This is an emergency requiring specialist management. Discuss with an Endocrine
Consultant.


Please note - Propylthiouracil and Carbamazepine can both cause reversible
neutropaenia, and patients should be counselled to stop them and have urgent FBC
if they develop a sore throat or high temperature. The drugs are to only be restarted
when FBC is shown to be normal.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Antithyroid Medicines
CSM warning for Carbimazole
Advise patients to report symptoms suggestive of bone marrow depression
especially sore throat or mouth ulcers. In such cases treatment should be
stopped
- Carbimazole tablets For patients not on "block and replace" therapy.
Initially, 15 - 40mg daily until the patient becomes
euthyroid (usually 4 - 8 weeks). The dose should then
be progressively reduced to maintenance of 5 - 15mg
daily. Therapy is usually given for 18 months.

- Aqueous iodine
(Lugols) oral solution
(s) Consultants only.
Dose: 0.1 - 0.3ml three times daily. Well diluted with
milk or water.
- Propylthiouracil tablets (s) Consultants only.




Adjuncts to Antithyroid Medicine Therapy
- Propranolol tablets Thyrotoxicosis (adjunct): 10 - 40mg 3 - 4 times daily.

Parathyroid Surgery
- Methylthioninium
Chloride (Methylene
Blue) injection
(s) Consultants only. To stain and identify the
parathyroid glands. Unlicensed use.
Dose: 5mg/Kg body weight in 500mL glucose 5% or
Sodium Chloride 0.9% (maximum concentration
350mg in 500ml) over 1 hour.
Maximum staining occurs 1 hour after infusion and
lasts for about 20minutes.












The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Corticosteroids
All patients receiving long - term therapy should be advised to carry a steroid card.


Mineralocorticoids
- Fludrocortisone tablets Mineralo-corticosteroid replacement in
adrenocortical insufficiency: 50-300 micrograms
daily.


Glucocorticoids
- Prednisolone tablets
1mg, 5mg, 25mg
- e/c tablets 5mg
- soluble tablets 5mg
By mouth, initially (depending on condition), 5-
20mg daily (severe disease up to 60mg daily) in the
morning. Doses may vary depending on a
individual basis
Note: Enteric coated are not generally recommended
and reserved for those patients on doses greater
than 60mg.
- Dexamethasone
tablets/injection
By mouth, usual range 0.5 - 10mg daily.
By i.m. or slow i.v. injection, initially 0.5 17.6mg
daily.
- Hydrocortisone
tablets/injection
Replacement therapy: By mouth, 10 - 30mg daily in
divided doses. Give a higher dose in the morning to
mimic diurnal variation e.g. 15mg dose split as 10mg
am, 5mg teatime. Some patients do split doses so a
20mg dose may be prescribed as 10mg mane, 5mg
midday and 5mg pm
Patients should be advised to increase the dose of
replacement steroids during periods of stress.

By intramuscular, slow i.v. Injection or infusion, 100 -
500mg 3 - 4 times daily.
- Methylprednisolone
Injection
(s) Consultants only.


Equivalent anti-inflammatory doses of corticosteroids

NB This table takes no account of mineralocorticoid effects, nor does it take account of
variations in duration of action



Prednisolone 5mg equivalent to
- Betamethasone 750 micrograms
- Cortisone acetate 25mg
- Deflazacort 6mg
- Dexamethasone 750 micrograms
- Hydrocortisone 20mg
- Methylprednisolone 4mg
- Triamcinolone 4mg
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Sex Hormones - See here for agents used in the treatment of malignant
disease.

Female Sex Hormones
By Consultant prescription only

Oestrogens for Hormone Replacement Therapy
- Women with a uterus need oestrogen plus progesterone. Women who have
had a hysterectomy require oestrogen only. There is some evidence that
transdermal oestrogen is safer than oral oestrogen with reduced risk of venous
thromboembolism and gallstones.

For Women with a Uterus - Combined Therapy
1. Sequential Therapy (i.e. Withdrawal Bleeds)
First choice
- Estraderm MX 50 patches plus cyclical
progesterone



Second choice:
- Femoston 1/10 and 2/10,

2. Patients > 1 Year PostMenopause
- Tridestra

3. Continuous Therapy (i.e. No Withdrawal Bleeds)
- Tibolone
- Premique

Low dose oestrogen contains equine derived
oestrogens

For Women without a Uterus - Oestrogen Therapy
- Estraderm MX patch
25, 50, 75, 100
micrograms

- Progynova 1mg, 2mg
- Premarin 0.625mg,
1.25mg

Contains equine derived oestrogens
- Hormonin
- FemSeven patch One patch to be applied weekly.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Progestogens
- Norethisterone tablets (s) Consultants only.
In conjunction with chemotherapy regimens, the
dose used is 5mg tds.



Male Sex Hormones and Antagonists
- Testosterone
implant/injection
(s) Consultants only.
- Testosterone patch
(Andropatch)
(s) Consultants only.
- Testosterone gel (s) Consultants only.

Anti-Androgens

- Cyproterone tablets (s) Consultants only.
Cyproterone Acetate
- Finasteride tablets (s) Urologists only.
- Dutasteride capsules (s) Urologists only
Dutasteride and Finasteride

Anabolic Steroids
- Nandrolone injection (s) Nephrologists only.


Hypothalamic and Anterior Pituitary Hormones and Anti
Oestrogens

Anterior Pituitary Hormones
- Tetracosactride
(tetracosactrin)
Injection (synacthen
test)
(s) Consultants only.
- Thyrotrophin injection
900mg
(s) Consultants only


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Posterior pituitary hormones and antagonists
- Desmopressin
intranasal
spray/tablets/injection
(s) Consultants only.
- Desmopressin nasal
spray/ injection
(Octim)
(s) Consultant Haematologists only
- Terlipressin injection (s) Gastroenterologists only.
- Vasopressin injection (s) Consultants only.

Antidiuretic Hormone Antagonists
- Demeclocycline
capsules
(s) Consultants only.
Dose: Initially 0.9 1.2g daily in divided doses,
reduced to 600 900mg daily for maintenance.
Discontinue if plasma urea rises above the normal
range.
- Tolvaptan (s) Consultants endocrinologists only.
Dose: 15mg once daily for hyponatraemia secondary
to SIADH

Medicines Affecting Bone Metabolism

Calcitonin

- Calcitonin (salmon)
[salcatonin] injection
Prior to starting treatment, give a test dose of 10units
sc to exclude hypersensitivity.
Hypercalcaemia of malignancy, Calcitonin 100units tid
sc for 5 days.
For analgesic effect in acute vertebral fracture,
Calcitonin 100units sc daily for up to 6 weeks.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Bisphosphonates
- Alendronate tablets 70 mg once weekly
Prescribers should clearly strike through the days on
in-patient prescription charts when doses are not to be
taken
Must be taken 30 minutes before breakfast with at
least a glassful of tap water only. The patient should
remain upright for 30 minutes after taking
Alendronate.
- Risedronate tablets 35mg weekly. See alendronate above for prescribing
advice.
Pagets disease 30mg: daily for 2 months may be
repeated if necessary after at least 2 months
Must be taken 30 minutes before breakfast with at
least a glassful of tap water only.The patient should
remain upright for 30 minutes after taking
Risedronate.


- Ibandronate 150 mg
once a month
Must be taken an hour before breakfast with at least
400ml of tap water only. The patient should remain
upright for one hour after taking Ibandronate.
- Ibandronate (Bonviva)
3mg IV every three
months
For patients with gastrointestinal intolerance to oral
bisphosphonates
Clinical Biochemistry only
- Zoledronate (Aclasta)
IV 5mg yearly
For patients with gastrointestinal intolerance to oral
bisphosphonates
Clinical Biochemistry only
- Zoledronate 4mg IV
(Zometa)
Pagets disease of bone. Hypercalcaemia of
malignancy.
Clinical Biochemistry only
- Strontium Ranelate
sachets
One 2g sachet daily on an empty stomach eg an
hour before breakfast or at least two hours after
food.


Other Endocrine Medicines

Bromocriptine and Other Dopaminerergic Medicines
- Bromocriptine tablets (s) Consultants only.
- Cabergoline tablets (s) Consultants only.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
Medicines Affecting Gonadotrophins
- Danazol capsules (s) Consultants only.

Metyrapone
- Metyrapone capsules (s) Consultants only.

Diagnostic Agents for Endocrine Disorders

- Corticotropin injection (s) Dermatologists and Gastroenterologists only.
Unlicensed.
- Protirelin (TRH)
injection (unlicensed)
(s) Consultants only.
- Gonadorelin (LH RH)
injection (unlicensed)
(s) Consultants only.

OBSTETRICS, GYNAECOLOGY AND URINARY TRACT
DISORDERS

Contents (Click on heading to go to that section)


Medicines Used in Obstetrics

Prostaglandins and Oxytocics

Common Sexually Transmitted Infections


Contraceptives

Emergency Contraception
Combined Oral Contraceptives
Pregersterone Only Contraceptives

Medicines for Genito-Urinary Disorders

Medicines for Urinary Retention
Medicines for Urinary Frequency, Enuresis and Incontinence
Medicines Used in Urological Pain
Bladder Instillations and Urological Surgery
Medicines for Erectile Dysfunction

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Medicines Used in Obstetrics

Prostaglandins and Oxytocics
Oxytocin injection In A & E and theatres.
Ergometrine Injection In A & E and theatres.
Ergometrine with oxytocin
injection (Syntometrine)
In theatres.

Common Sexually Transmitted Infections

All suspected and confirmed STIs should be referred to GUM / discussed with GUM on call
(via switchboard) to enable appropriate investigation, treatment, follow up and partner
notification wherever possible.

See section 5 (click here) - GENITOURINARY & SEXUALLY TRANSMITTED
INFECTIONS

Contraceptives

To be prescribed by G.U.M. only.

Emergency Contraception

Up to 72 hours after coitus:
- Levonelle 1500mg (levonorgestrel): 1.5 mg as a single dose as soon as possible
after coitus (preferably within 12 hours but no later than after 72 hours)

Between 72 hours and 120 hours after coitus:
- ellaOne (ulipristal): 30 mg as a single dose as soon as possible but no later than
after 120 hours

Combined oral contraceptive

e.g. Yasmin, Mercilon, Microgynon

Note: The following oral contraceptive preparations should ONLY be prescribed for
women intolerant of other combined oral contraceptives and who are prepared to accept
an increased risk of thrombosis:
Marvelon, Femodene, Femodene ED, Minulet, Triadene, Tri - minulet, Mercilon, Femodette.

Progesterone Only Pill - Cerazette

Other services available in GUM long acting reversible contraceptives
Implanon insertion / removal
IUS (Mirena ) /IUD fitting / removal


The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Missed Pill Algorithm


Advice for women missing combined oral contraceptives
(30-35microgram and 20microgram ethinylestradiol formulations)



If one or two
30-35mcg ethinylestradiol pills
have been missed at anytime
OR
One 20mcg ethinylestradiol pill is
missed


If three or more
30-35mcg ethinylestradiol pills have
been missed at anytime
OR
Two or more 20mcg ethinylestradiol
pills are missed



She should take the most recent missed
pill as soon as she remembers

She should continue taking the remaining
pills daily at her usual time*

She does not require additional
contraceptive protection

She does not require emergency
contraception



She should take the most recent missed as
soon as she remembers

She should continue taking the remaining pills
daily at her usual time*

She should be advised to use condoms or
abstain from sex until she has taken pills for
7days in a row

In Addition
(because extending the pill-free
interval is risky)




If pills are missed in week
1(Days 1-7)as the pill free
interval has been extended



If pills are missed in week 3
(days 15-21) to avoid
extending the pill free interval


Emergency Contraception
should be considered if she had
unprotected sex in the pill free
interval or in week 1



She should finish the pills in
her current pack and start a
new pack the next day thus
omitting the pill free interval


*Depending on when she remembers her missed pill she may take two pills on the same day
(one at the moment of rememberingand the other at the regular time)
or even at the same time







The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Medicines for Genito-Urinary Disorders

A) Medicines for Urinary Retention
- Acute retention is painful and is managed by catheterisation.
- Chronic retention is often painless.

Alpha Blockers

After the cause has been established and treated, medicines may be used to increase
detrusor muscle tone.

Note: Initiate treatment at night time if postural hypotension is a problem.

- 1
st
line
Alfuzosin XL Tablets
(Alpha 1a selective
inhibitor)



- 2
nd
line
Tamsulosin MR
Tablets/Capsules
(Alpha 1a selective
inhibitor)

- Doxazosin Tablets


Short/Long term use - (s) Urologists only
Dosing details:
10mg once daily
2.5mg three times a day (immediate release tablets) if
patient has a stoma / severe diarrhoea



Short/Long term use - (s) Urologists only
Dosing details:
400micrograms once daily



(s) Urologists only
For Renal patients with BPH/AUR
Dosing details:
Initially 1mg once daily, increased according to response to
a maximum of 8mg once daily [immediate release tablets
should be given in divided doses (twice daily)]
Note: Doxazosin has moderate to severe effect on Blood
Pressure (Monitor BP)

Note: Anticholinergics may be used for short-term while patients are catheterized to
relieve bladder spasms


B) Medicines for Benign Prostatic Hyperplasia

Alpha Blockers
- relaxes the smooth muscles of the prostate hence helps free flow of urine through the
prostatic urethra

See section above



The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

5-Alpha Reductase Inhibitors (5-ARI)

- 5-ARIs inhibits the conversion of testosterone to the more potent Dihydro Testosterone
(DHT) and hence helps to reduce the prostate size in BPH

- 1
st
line
Finasteride tablets



- 2
nd
line
Dutasteride tablets (only
for patients not suitable
for surgery)

(s) Urologists only
Dosing details:
5mg once daily


(s) Urologists only
Dosing details:
500micrograms once daily

Note: Pregnant women or women likely to become pregnant
must wear hand gloves while handling these tablets
Advice patients that children should not handle these tablets

C) Medicines for Transrectal Ultrasound guided Biopsy of Prostate
(TRUB) procedure

Pre-TRUB:

- *Ciprofloxacin tablets oral 750mg stat dose (1-hour pre procedure)
- Gentamicin 3-5mg/kg body weight (up to a maximum dose of 240mg) will be given by
intravenous infusion (in sodium chloride 0.9% 100ml) over 20 minutes Only for
patients allergic to ciprofloxacin (Note: Dose should be prescribed in the TRUB
prescription by the doctor in charge of the patient)

Post-TRUB:

*At the end of the procedure patients will be administered a stat dose of Metronidazole 1g
suppository rectally. For patients allergic to metronidazole, an alternative antibiotic will be
administered at the clinicians discretion (discuss with med-micro).

Take home Pre-packs
- *Ciprofloxacin 500mg every 12hours from the evening of the procedure for 5 doses.
Patients will receive a 10-tablet pack of Ciprofloxacin 250mg with directions to take.
- *Patients allergic to ciprofloxacin will be discharged with Co-amoxiclav 625mg every
8hours from 8hours post-procedure for 8 doses. Patients receive a 100ml bottle of Co-
amoxiclav 250/62.5 suspension with directions to take.

* As per PGD







The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

D) Medicines for Stent removal procedure

- Ciprofloxacin tablets oral 500mg to 750mg (dependent on size of patient) stat dose (1-
hour pre procedure)
- Gentamicin 80mg IM for patients below 80Kg and 160mg IM for patients above 80Kg
Only for patients allergic to ciprofloxacin

For patients who have had recent joint replacement (<3 months) or cardiac valve
replacement or on immunosuppressants please contact Medical Micro-biology for advise
regarding additional Antibiotics cover. Risk will be assessed based on individual patients
medical history.


E) Medicines for Stone Management

Alkalinisation of Urine
- Potassium citrate
mixture
(s) Urologists only.
Dosing details:
10ml three times a day - Take well diluted with
water
- Sodium Bicarbonate
capsules (500mg)
(s) Urologists only.
Dosing details:
Variable according to individual patient requirements (up to
Maximum 10g daily)

Acidification of Urine
- Ascorbic acid
Tablets

Up to 4g daily in divided doses

Alpha Blockers (Unlicensed use)

Alpha blockers relax the smooth muscles of Bladder neck and hence used to help pass
stones after fragmentation of stones (used in both male and female)
- 1
st
line
Alfuzosin XL Tablets



- 2
nd
line
Tamsulosin MR
tablets/capsules

Short term use only - (s) Urologists only
Dosing details:
10mg once daily
2.5mg three times a day (immediate release tablets)

Short term use only - (s) Urologists only
Dosing details:
400micrograms once daily



The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

F) Medicines for Lithotripsy Procedure
Pre-Lithotripsy:

- *Diclofenac suppositories PR 100mg stat dose (or) Diclofenac tablets oral 50mg stat
dose (Maximum daily dose 150mg)
- *Cyclizine tablets oral 50mg stat dose
- *Oramorph liquid oral 10 20mg or Fentanyl Lozenges 200 400micrograms Stat
dose
- *Ciprofloxacin tablets oral 500mg stat dose
- *Gentamicin injection Intramuscular 120mg stat dose Only for patients allergic to
ciprofloxacin

Note:
2
nd
choice anti-emetic Ondansetron Melts 4mg stat dose to be prescribed by doctor
2
nd
choice analgesia Alfentanil (Rapifen
R
) IV dose as required or Pethidine 50mg IM;
this is to be prescribed as per CD prescription regulations

Post-Lithotripsy:
- Diclofenac tablets oral 50mg three times a day for 3days
- Co-codamol tablets oral 8/500 1-2 tablets four times a day for 3 days Only for
patients allergic to diclofenac
- Trimethoprim tablets oral 200mg twice daily for 3days only for patients at moderate
to high risk of UTI (to be prescribed at Doctors discretion)
- Co-amoxiclav tablets oral 375mg three times a day for 3days (for patients allergic to
trimethoprim) only for patients at moderate to high risk of UTI (to be prescribed at
Doctors discretion)

Medicines for Urinary Fre
quency and Incontinence

Algorithm for use of Anticholinergics in the management of
Urinary Frequency & Incontinence


1
st
Line
2
nd
Line 3
rd
Line
Oxybutynin XL
tablets
5mg 20mg once daily
Initial dose 5mg, then
titrate
Tolterodine XL
capsules
4mg once daily
Oxybutynin Patch
(9mg/24hrs)
1 patch twice weekly
Solifenacin tablets
5mg 10mg once daily
Initial dose 5mg, then
titrate
Trospium SR
tablets
60mg once a day
Symptoms uncontrolled with 1
st
line agents
Symptoms uncontrolled with
1
st
& 2
nd
line agents
- Symptoms controlled but
unable to tolerate side-
effects
- Patients NBM or unable to
take oral medicines for
longer periods
Tolterodine tablets
1mg twice daily
(Maximum)
for patients with hepatic impairment
or renal impairment (Crcl <30ml/min)
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011


1
st
Line
Oxybutynin immediate-
release tablets





Oxybutynin XL tablets






Oxybutynin (Kentara
R
)
36mg Patch

For short-term use only
Dosing details:
5mg 2 - 3 times daily increased if necessary to maximum
5mg 4 times daily.
Elderly 2.5 - 3mg twice daily, increased to 5 mg twice daily
according to response and tolerance.

For long-term use only - (s) Urologists only
Dosing details:
Start with 5mg Once daily and titrate according to
response up to a Maximum daily dose of 20mg OD
Note: Increased risk of side-effects with higher dose
especially in elderly patients
Only for the following patient group (s) Urologists only:
- For patients already stabilised on Oxybutynin tabs but
cant tolerate the side-effects trial with the patches
and continue if preferred by patient
- For patients who cant take tablets or liquids orally for
longer durations
Dosing details:
Apply 1 patch twice weekly
1
st
Line
- Tolterodine
XL capsules 4mg
(Detrusitol
R
XL)

For short-term or long-term use - (s) Urologists only.
Dosing details:
4mg OD

Note: For patients with Hepatic impairment or Renal
impairment (Crcl <30ml/min) the maximum daily dose
must not exceed 1mg twice daily (Use immediate release
tablets)
2
nd
Line
- Solifenacin Tablets
(Vesicare
R
)

- (s) Urologist only
For patients unable to tolerate 1
st
line agents or whose
symptoms persisted with 1
st
line agents
Dosing details:
Initial dose 5mg OD, titrated up to a maximum of 10mg OD
Note: Increased risk of side-effects with 10mg dose
3
rd
Line
- Trospium SR (Regurin
R
)
tablets

- (s) Urologist only
Dosing details:
60mg once a day
- Desmopressin (s) Consultant Urologists only.
- Amitriptyline or
Imipramine
Nocturnal enuresis
Dosing details:
10-25mg at night

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Analgesics used to relieve Urological Pain
- Diclofenac
suppositories/injection
Maximum daily dose by any route is 150mg.
By rectum, 100mg stat.
By deep Intramuscular injection, 75mg into GLUTEAL
muscle ONLY.
Dose may be repeated after 30 minutes if necessary.
Maximum duration of treatment 48 hours (i.e. 4 x 75mg
injections).
- Pethidine CD
injection
By Intramuscular injection, 50 - 100mg.
- Lidocaine [lignocaine]
2%,chlorhexidine 0.25%
(Instillagel)
To relieve discomfort of catheterisation. Male patients 11mL,
female patients 6mL
- Oxybutynin To relieve bladder spasms associated with Catheterisation
Dose 2.5mg TDS when required (Maximum daily dose
20mg)


Medicines used in Prostate Cancer management

Gonadotropin Releasing Hormone (GnRH)/Lutenising Hormone Releasing Hormone
(LHRH) Agonists
1
st
Line
Decapeptyl (Triptorelin) SR 3mg by Intramuscular injection every 4 weeks

Decapeptyl (Triptorelin) SR 11.25mg by Intramuscular injection every 3 months

Note: Always use 4-weekly injection while initiating on GnRH agonist therapy, then
change to 3-monthly injection thereafter.

2
nd
Line

Zoladex
R
(Goserelin) 3.6mg by sub-cutaneous injection into anterior abdominal wall
every 28 days

Zoladex
R
(Goserelin) LA 10.8mg by sub-cutaneous injection into anterior abdominal wall
every 12 weeks

Note: Always use 28-day injection while initiating on GnRH agonist therapy, then change
to 12-weekly injection thereafter.

Antiandrogens
- Flare with initial GnRH therapy:
Cyperoterone acetate tablets oral 100mg three times a day (may be reduced to
100mg twice daily) or
Bicalutamide tablets oral 50mg once daily
Monitoring: LFTs before initiation of treatment and during treatment
- When surgical or other medical intervention (GnRH) inappropriate
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Cyperoterone acetate tablets oral 100mg three times a day (may be reduced to
100mg twice daily) or
Bicalutamide tablets oral 150mg once daily
Monitoring: LFTs before initiation of treatment and during treatment


Gonadotropin Releasing Hormone (GnRH) Antagonist

Degarelix (Firmagon
R
)
MMG have approved the use of degarelix restricted only to those patients in whom LHRH
agonist plus a short course of anti-androgen is not suitable (patients with risk of spinal
cord compression on diagnosis).

First dose 240mg (administered as 2 injections of 120mg) subcutaneous into the
abdominal region
Subsequent doses 80mg subcutaneous into the abdominal region every 28 days

Fl ow -c har t f or c hoi c e of Gonadot r ophi n Rel easi ng Hor mone (GnRH) agoni st s /
ant agoni st


Pat i ent s di agnosed w i t h Pr ost at e Canc er i ni t i at ed on Hor monal Tr eat ment
Does Patient have Painful Bony Metastases on Diagnosis?
No Yes
If No
Start on GnRH Agonists
I f Yes
Start on GnRH Ant agoni st s
1
st
Choice:
Triptorelin^ (Decapeptyl

)
2
nd
Choice:
Goserelin ^^ (Zoladex

)


Note: No new patients will be started on Leuprorelin (Prostap) as from 1st October 2011. The
current patients on Leuprorelin will continue to receive it until there treatment is completed.
+ +
Cyproterone acetate 100mg BD or
100mg TDS for three weeks
or
Bicalutamide 50mg OD for three
weeks
Degarelix (Firmagon

)
1
st
Dose:
Cyproterone acetate 100mg BD or
100mg TDS for three weeks
or
Bicalutamide 50mg OD for three
weeks
240mg as STAT dose by
Sub-cutaneous injection

From 2
nd
dose onwards:
80mg by Sub-cutaneous
injection every 28 days
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011


Medicines used in Bladder Cancer Management

Mitomycin Bladder Instillation 40mg in 40ml Water for Injections (prepared by
pharmacy LMCU ext: 3787/3788) (use designated Yellow Mitomycin Cytotoxic prescription
chart)

Post-TURBT (for suitable patients only):

Stat dose of Mitomycin intravesical instillation 40mg in 40ml Water for Injection should
be administered within 6 48 hours to get maximum benefit in reducing recurrence
Note: Ensure bleeding has stopped post-op before administration of Mitomycin
intravesical instillation

Induction regime (administration performed at BGH Urology Centre)

Induction schedule: Weekly for 6 weeks
Dosing details: 40mg in 40ml WFI
Shelf-life of the reconstituted solution: 4 days
Duration of treatment: 1-hour (to obtain complete covering of the bladder, patients
should be advised to stay for 15minutes on each of the following lying positions; Left-
side, on stomach, right-side and backside)
Route of administration: Intravesical instillation

Maintenance Regime (administration performed at BGH Urology Centre)

Maintenance regime should be started after the induction regime is completed, and a
further 6-week drug free period is observed

Maintenance schedule: Monthly thereafter until clinically needed for individual patients
Dosing details: 40mg in 40ml WFI
Shelf-life of the reconstituted solution: 4 days
Duration of treatment: 1-hour (to obtain complete covering of the bladder patients
should be advised to stay for 15minutes on each of the following lying positions; Left-
side, on stomach, right-side and backside)
Route of administration: Intravesical instillation

BCG Bladder Instillation ImmuCyst
R
81mg (prepared by specialist nurses before
administration at BGH-UC) (use designated Green BCG prescription chart)

BCG bladder instillation contains live vaccine of BCG hence
- Must not be administered to patients until after 2 weeks Post-TURBT.
- Must not be administered to patients with infection, wait until the patient is infection
free for at least 1 week

Induction regime (administration performed at BGH Urology Centre)

Induction schedule: Weekly for 6 weeks
Dosing details: 81mg (1.8 15.9 x 10
8
cfu) in sodium chloride 0.9% 50ml
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Shelf-life of the reconstituted solution: must be used within 8hours
Duration of treatment: 1-hour (to obtain complete covering of the bladder patients
should be advised to stay for 15minutes on each of the following lying positions; Left-
side, on stomach, right-side and backside)
Route of administration: Intravesical instillation


Maintenance Regime (administration performed at BGH Urology Centre)

Maintenance regime should be started after the induction regime is completed, and a
further 6-week drug free period is observed

Maintenance schedule: Weeks 1, 2 & 3 at 3months, then weeks 1, 2 & 3 at 6-month
intervals (i.e. 6
th
month, 12
th
month, 18
th
month etc.) until clinically needed for individual
patients
Dosing details: 81mg (1.8 15.9 x 10
8
cfu) in sodium chloride 0.9% 50ml
Shelf-life of the reconstituted solution: must be used within 8hours
Duration of treatment: 1-hour (to obtain complete covering of the bladder patients
should be advised to stay for 15minutes on each of the following lying positions; Left-
side, on stomach, right-side and backside)
Route of administration: Intravesical instillation

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Commonly used Bladder Instillations in Urology
- Sodium chloride 0.9% Preferred bladder irrigation for indwelling catheters.
- Chlorhexidine gluconate
0.02% (1 in 5,000)
(s) Consultant Urologists only
Note: May irritate mucosa and cause burning and
haematuria. Discontinue use if this is a problem.
- Water, sterile For irrigation
- Glycine (s) Urologists only.
- DMSO bladder
instillation (Prepared by
Pharmacy Aseptic
Production Unit)
-
(s) Consultant Urologists only
Contains dimethylsulphoxide, hydrocortisone,
Sodium bicarbonate and Pentosan polysulphate.
Unlicensed preparation for the management of Interstitial
Cystitis (IC).
(use designated white DMSO prescription chart)
- Noxyflex bladder
washout
(s) Consultant Urologists only.
- Oxybutynin bladder
instillation
(s) Consultant Urologists only.
Unlicensed preparation (5mg/30ml) for the management of
Interstitial Cystitis
- Sodium hyaluronidate
bladder instillation
(Cystistat
R
)
(s) Consultant Urologists Only
40mg in 50ml for the management of Interstitial Cystitis (IC)
(use designated white Cystistat prescription chart)
- Tranexamic acid
bladder instillation
(s) Consultant Urologists Only
Unlicensed Preparation (1g in 1000ml) for the management
of Refractory Haematuria
- Potash Alum 1%
bladder instillation
(s) Consultant Urologists Only
Unlicensed Preparation (10g in 1000ml) for the
management of Refractory Haematuria

(Try oral Tranexamic acid and or Tranexamic acid bladder
instillation before potash alum is considered)
Note: Risk of Aluminium toxicity
- Tromethamine (THAM)
7% bladder irrigation
(s) Consultant Urologists Only
Unlicensed Preparation (to dissove acetyl cysteine stones,
staghorn calculi not dissolved by any other means) its use is
restricted by cost and complexity of the regime. The proposed regime
is 60mls per hour for the first 6-7 hours then 30mls per hour
continuously for 30 days. The cost per patient for the complete course
is approximately 9500 - 18000.

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Medicines for Erectile Dysfunction

- 5-Phosphodiesterase (5-
PDE) inhibitors
Sildenafil/ tadalafil/Vardenafil
(s) Consultant Urologists only.
- Alprostadil Intracavernosal
Injection
Caverject
R
, Caverject
R
Dual-
chamber
(s) Consultant Urologists only.
- Alprostadil Urethral
Application MUSE
R

(s) Consultant Urologists only.


The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

TREATMENT OF MALIGNANT DISEASE AND
IMMUNOSUPPRESSION

Contents (Click on heading to go to that section)

Cytotoxic Medicines
Medicines for Chemotherapy induced side effects
Prevention of Urothelial Toxicity

Management of Extravasation Injury
Medicines Affecting the Immune Response
Antiproliferative Immunosuppressants
Corticosteroids and Other Immunosuppressants
Other immunomodulating Medicines

Sex Hormones and Antagonists in Malignant Disease

Progestogens
Hormone Antagonists
Symptom Control in Palliative Care

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011



All items in this section are prescribable by Consultants and Senior Registrars
only unless indicated otherwise.

Cytotoxic Medicines

Cytotoxic injections are prepared in the Chemotherapy Linda McCartney Centre Unit (Ext.
3787/ 3788/ 3789). Special prescriptions must be used for ordering parenteral cytotoxic
regimens (available by contacting the Chemotherapy Unit). Please allow adequate time
for preparation of dose/s 24hrs notice should be given.

Oral Chemotherapy on admission to hospital

If oral chemotherapy is continued following admission to hospital patients may receive more than
the planned dose of chemotherapy which can lead to serious consequences including death.
Moreover patients who are admitted to hospital are likely to be ill and are at greater risk of toxicity
and should have the chemotherapy discontinued even if the prescribed course has not been
completed.

Please take the following action when patients are admitted to hospital on oral chemotherapy:

Merseyside & Cheshire Cancer Network policy is that any oral chemotherapy should be stopped
upon admission to hospital.
It should be restarted only after consultation with the relevant specialist.
All patients receiving oral chemotherapy should be in receipt of an alert card which clearly
outlines the treatment plan including the duration of any oral chemotherapy treatment.
Patients must be encouraged to carry the card with them and present it to health care
professionals.
The MCCN alert card fulfils these requirements.

The simple rule is therefore to stop any oral chemotherapy if a patient is admitted to
hospital and to seek the advice of the relevant specialist team e.g. Haematology or Acute
Oncology

If patients are admitted to hospital taking oral anti-cancer medicines for non-cancer indications
then a risk assessment must be undertaken and the above guidance applied as appropriate.

NPSA Rapid Response Report 2008_RRR001
Risks of incorrect dosing of oral anti-cancer medicines

In January 2009 the National Patient Safety Agency (NPSA) alerted all healthcare staff
involved in the use of oral anti-cancer medicines of potentially fatal outcomes if incorrect
doses of these medicines are used. These oral anti-cancer medicines are increasingly
being used in hospitals and in the community. Risks are increased if non-specialist
practitioners prescribe, dispense or administer these oral medicines and bypass the
normal safeguards used for injectable anti-cancer medicines.

Doctors, nurses, pharmacists and their staff must be made aware that the prescribing,
dispensing and administering of oral anti-cancer medicines should be carried out and
monitored to the same standard as injected therapy. This requires that:
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011


Healthcare organisations should prepare local policies and procedures that
describe the safe use of these oral medicines.
Treatment should be initiated by a cancer specialist.
All oral anti-cancer medicines should be prescribed only in the context of a written
protocol and treatment plan.
Non-specialists who prescribe or administer on-going oral anti-cancer medication
should have ready access to appropriate written protocols and treatment plans
including guidance on monitoring and treatment of toxicity.
Staff dispensing oral anti-cancer medicines should be able to confirm that the
prescribed dose is appropriate for the patient, and that the patient is aware of the
required monitoring arrangements, by having access to information in the written
protocol and treatment plan from the hospital where treatment is initiated and
advice from a pharmacist with experience in cancer treatment in that hospital.
Patients should be fully informed and receive verbal and up-to-date written
information about their oral anticancer therapy from the initiating hospital. This
information should include contact details for specialist advice, which can be shared
with non-specialist practitioners. Written information, including details of the
intended oral anti-cancer regimen, treatment plan and arrangements for monitoring,
taken from the original protocol should be given to the patient. When shared with
pharmacists and dispensing staff, this would enable the above dispensing
requirements to be satisfied.
Full use should also be made of NHS cancer centre web sites to provide
information for healthcare staff, patients and carers to ensure the safe use of oral
anti-cancer medicines.

The above guidance is primarily intended to promote the safe use of the medicines listed
to treat cancer. Where the use of these medicines is for non-cancer treatment, a risk
assessment should be undertaken and the guidance applied as appropriate.









The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Medicines for Chemotherapy induced side effects

Methotrexate Induced Mucositis and Myelosuppression ("Folate Rescue")
Folinic acid tablets/injection For use with methotrexate. Consult individual treatment
protocols for dosage regimes of folinic acid.

Prevention of Urothelial Toxicity
Mesna injection/tablets For use with cyclophosphamide and ifosfamide. Consult
individual treatment protocols for dosage regimes of mesna.

Management of Extravasation Injury
Stop the infusion and disconnect the drip. Do not remove Cannula. For the management
of a suspected extravasation then seek experienced assistance from Senior Haematology
Medical, Pharmacy and Nursing staff. Extravasation kits are kept on 7Y, 7YDW and 10Z.

Vinca Alkaloids

NPSA Rapid Response Report 2008_RRR004
Using Vinca Alkaloid Minibags (Adult/Adolescent Units)

There have been further reports of fatal and serious incidents from hospitals outside the
UK in which doses of vinca alkaloids intended for intravenous administration have been
administered by the intrathecal (spinal) route in error. These include three cases where
doses of vincristine had been diluted to 10ml and 20ml in syringes. The World Health
Organisation (WHO) has issued guidance (see supporting information) recommending that
doses of vinca alkaloids should be prepared and administered in intravenous minibags to
further minimise the risk of wrong route errors.

When vinca alkaloids are prescribed, dispensed or administered in adult and adolescent
units:
Doses in syringes should no longer be used.
The prescribed dose should be supplied from the hospital pharmacy ready to
administer in a 50ml minibag of sodium chloride 0.9% (for some brands of
vinorelbine glucose 5% solution for injection may be used instead of sodium
chloride 0.9%).
The following warning should be prominently displayed on the label of ALL vinca
alkaloid doses For Intravenous Use Only Fatal If Administered by Other Routes.
There should be judicious use of colour and design on the label, outer packaging
and delivery bags to further differentiate minibags containing vinca alkaloids from
other minibag infusions.
The vinca minibag should be infused intravenously over 5 - 10 minutes and the
patient closely monitored for signs of extravasation. Incidents of extravasation
should be reported and shared via the National Extravasation Information Service
(www.extravasation.org.uk).
Chemotherapy policies and procedures should be amended to reflect these
requirements.
Staff should be alerted and trained to follow the new practice.
Practice should be audited to ensure compliance with the revised safety procedure.
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Intrathecal Chemotherapy

The circular HSC 2008/001 covers the updated national guidance on the safe
administration of intrathecal chemotherapy and has been implemented across this Trust.
For further information contact Senior Haematology Medical and Pharmacy staff.


Merseyside and Cheshire Cancer Network (MCCN)

The MCCN was formed in 2000 and links together the organisations that provide care for
people with cancer across Merseyside and Cheshire. They work closely with patients,
carers, health professionals and managers to help implement the NHS Cancer Reform
Strategy and North West Cancer Plan for the people of Merseyside & Cheshire.
The Network covers a population of 2.3 million people and encompasses one Strategic
Health Authority, seven Primary Care Trusts, twelve Hospital Trusts, ten Hospices and a
number of voluntary organisations.
The purpose of the Network is broadly to organise and oversee the local implementation of
the NHS Cancer Plan which sets out a programme of investment and reform. The Plan
also includes a number of ambitious targets with the overall aim to save more lives and to
improve the patients experience by ensuring that people with cancer have access to the
right professional support and access to the best treatment throughout their period of care.
Health professionals can access network documents including local and national policies,
guidelines, treatment protocols and referral forms through their website
(www.mccn.nhs.uk).


Medicines Affecting the Immune Response

Antiproliferative Immunosuppressants
Azathioprine tablets/injection Avoid concurrent use with allopurinol.
Mycophenolate Mofetil
capsules/tablets/suspension/injection

Mycophenolate acid e/c tablets
(Myfortic)
(s) Consultant Nephrologists only. For patients intolerant of
mycophenolate mofetil

Corticosteroids and Other Immunosuppressants
Basiliximab injection (s)Prophylaxis of acute rejection in allogenic renal injection
transplantation
Ciclosporin (Sandimmun
capsules/liquid/injection or
Neoral)
Note: Prescribe by brand name only to avoid confusion
between preparations which have different bioavailabilities.
All new patients should be commenced on the Neoral brand.
Sirolimus liquid Surgeons. (s) Approved for use by Renal Transplant
Tacrolimus. Capsules (s) Renal transplant Consultant surgeons
Thalidomide tablets (s) Consultant only refer to the Thalidomide Pharmion
Pregnancy Prevention Programme
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011


Other immunomodulating Medicines

Interferons
Interferon alfa injection
(Intron A, Roferon A, Viraferon)
(s) Consultants in Rhematology; and Infectious Diseases
and Haematology
Interferon beta (s) Consultant Neurologist use only.

BCG Bladder Instillation
BCG bladder instillation
recurrent
Licensed for the treatment of primary or carcinoma and
prevention of recurrence following transurethral resection



Sex Hormones and Antagonists in Malignant Disease

Progestogens
Megestrol tablets
Medroxyprogesterone tablets

Hormone Antagonists

Breast cancer
Aminoglutethimide tablets
Anastrozole tablets (s) Consultants only.
Formestane injection (s) Consultants only
Fulvestrant injection (s) Consultant breast surgeons only
Letrozole tablets (s) Consultants only.
Tamoxifen tablets

Prostate cancer and gonaderelin analogues
Bicalutamide (s) Urologists only
Buserelin nasal spray
Cyproterone tablets (s) Urologists and Endocrinologists only.
Flutamide tablets/injection (s) Urologists only.
Goserelin injection (s) Urologists only.
Leuprorelin injection (s) Urologists only.
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011


Somatostatin analogues
Octreotide injection See BNF 8.3.4 for range of licensed doses.
Unlicensed use: Bleeding oesophageal varices.
Administration details: 1mg of octreotide made up to
total volume 60ml with sodium chloride 0.9%, the
infusion is run at 3ml/hr,
i.e. 50micrograms/hour for 20 hours each day (only one
infusion a day).

Symptom Control in Palliative Care

For advice and support, contact the Palliative Care Team Ext 2274, Bleep 4191.

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

MEDICINES AFFECTING NUTRITION AND BLOOD

Contents (Click on heading to go to that section)

Anaemias and Other Blood Disorders
Iron Deficiency Anaemias
Medicines used in megaloblastic anaemias
Medicines used in hypoplastic, haemolytic and renal anaemias
Medicines used in neutropenia

Fluids and Electrolytes
Potassium
Management of Hypokalaemia
Prevention of Hypokalaemia
Established Potassium Depletion
SUMMARY OF POTASSIUM CONTAINING INTRAVENOUS INFUSIONS
Parenteral Preparations for Fluid and Electrolyte Imbalance

Subcutaneous Administration of Fluids
Bicarbonate and lactate

Intravenous Nutrition
Total Parenteral Nutrition (TPN)

Oral Nutrition
Enteral Nutrition

Minerals
Calcium and magnesium
Phosphorus
Fluoride
Zinc

Vitamins
Vitamin B Group
Vitamin C
Vitamin D
Vitamin E
Vitamin K
Multivitamins

Metabolic Disorders
Medicines for the Treatment of Acute Porphyrias
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Anaemias and Other Blood Disorders

Iron Deficiency Anaemias
Iron preparations can cause altered bowel habit (constipation or diarrhoea) and should be
used with care especially in older patients and those with intestinal strictures or diverticular
disease. They are best absorbed on an empty stomach but may be given after food to reduce
gastro - intestinal side effects, particularly nausea. Timing of dose in relation to other
medicines is important as oral iron can reduce the absorption of levothyroxine, alendronate,
mycophenolate and some anbibiotics. The absorption of iron is itself reduced by
administering with antacids, calcium or zinc preparations.
Patients on intravenous iron supplements will not require oral supplements.

Therapeutic Response
The haemoglobin concentration should rise by 2g/100ml over 3 - 4 weeks.
After the haemoglobin has risen to normal, treatment should be continued for a further three
months in an attempt to replenish iron stores.

There is no justification for the inclusion of other ingredients, such as vitamins (except folic
acid for pregnant women or confirmed folic acid deficiency) with iron in compound
preparations.

Modified and Slow Release Iron Preparations
These preparations are likely to carry the iron past the area of iron absorption in the
gut. The lower incidence of side effects is probably due to the smaller amounts of iron
being absorbed. They therefore have no therapeutic advantage over plain
preparations.

Oral Iron
Ferrous sulphate 200mg
tablets
Therapeutic dose: 200mg 3 times daily (equivalent to 180mg
elemental iron daily).
Prophylactic dose: 200mg daily (equivalent to 60mg
elemental iron daily).

Note: There is no liquid preparation of ferrous sulphate
available but patients unable to swallow tablets can be
converted to another salt (maintain similar daily
elemental iron dose)
Ferrous fumarate
140mg/5mL syrup
(Fersamal)
10-20mL twice daily (10mL twice daily equivalent to
180mg elemental iron daily)
Note: this product requires considerable effort to re-
suspend the ferrous fumarate and must be shaken well
before dose administration.


The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Parenteral Iron Preparations
For use in patients with proven iron deficiency. Do not start oral iron until 5 days after last
injection.
For use when oral therapy unsuccessful due to malabsorption or inability to tolerate oral
iron.
Parenteral iron does not produce a faster haemoglobin response than oral iron except in
patients with chronic kidney disease receiving haemodialysis

These product carry the risk of anaphylaxis and require test dose administration

Iron Dextran
(CosmoFer)injection
50mg/mL
Consult product literature for details of dosage and
administration. Consultants use only for total dose infusion.

Iron Sucrose (Venofer)
injection 100mg/5ml
Consult product literature for details of dosage and
administration. Used for management of anaemia in CKD
(see Trust Nephrology policy)
I.V. Administration only.

Medicines used in megaloblastic anaemias
If megaloblastic anaemia is diagnosed it is essential to establish which deficiency, either
vitamin B
12
or folate, is present.
If there is doubt and where delay may be dangerous then both vitamin B
12
and folic acid
should be administered. Monitor and treat as for both B
12
and folate deficiency. This will
prevent precipitation of peripheral neuropathy.

Monitor plasma potassium during treatment as hypokalaemia may be precipitated due to an
increase in cell turnover when B
12
and folic acid are utilised.
Hydroxocobalamin (B
12
)
injection
By i.m. injection, initially, 1mg on alternate days for 1 - 2
weeks.
Maintenance, 1mg every 3 months.
Folic acid tablets/liquid 5mg daily. Higher doses up to 15mg may be required in
patients with malabsorption.

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Medicines used in hypoplastic, haemolytic and renal anaemias
Darbepoietin Injection
(Aranesp )
(s) Nephrologist use only.
Pre-filled syringes

Epoietin beta injection (Neo
Recormon )
(s) Nephrologist / Haematologist use only.
(To increase yields of autologous blood in predonation
programme in moderate anaemia)

Iron Overload
Desferrioxamine injection (s) Consultant use only seek specialist advice (UK
National Poison Service)
Deferasirox tablets (Exjade) (s) Consultant use only chronic iron overload

Medicines used in neutropenia
Filgrastim (Zarzio) injection (s) Haematologist use only.
Pegfilgrastim (Neulasta)
injection
(s) Haematologist use only.
Lenograstim (Granocyte)
injection
(s) Haematologist use only.

Fluids and Electrolytes

Potassium

Management of Hypokalaemia
Compensation for potassium loss is necessary for those patients who:

1) are taking medication which predisposes to hypokalaemia e.g diuretics, especially if co-
prescribed medication such as digoxin or anti - arrhythmic medicines, where potassium
depletion may induce arrhythmias
2) have excessive potassium loss e.g. chronic diarrhoea, fistulae.

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Prevention of Hypokalaemia
Consider dietetic advice regarding potassium - rich food.
Compliance with oral potassium salts is often poor due to nausea and vomiting
resulting from inadequate dilution. Therefore, if possible, consider the use of
potassium sparing diuretics.
Potassium chloride 25 - 50mmol daily by mouth is suitable for patients taking a normal
diet.
Potassium supplements are seldom necessary when low dose diuretics are given for
hypertension.
When larger doses of diuretics are used to treat oedema, potassium - sparing diuretics
are preferable to chronic administration of potassium salts.
Reduce the dose of potassium supplements in renal failure or the elderly.

Established Potassium Depletion
Plasma potassium
(2.5 - 3.5mmol/L)
Oral doses of 70 - 100mmol/day may be required over a
number of days.
It is preferable to give potassium salts as liquid or well diluted
soluble tablets rather than slow release preparations, which
are large and may cause oesophageal ulceration if not
swallowed with plenty of water.
Severe depletion i.e.
plasma potassium <
2.5mmol/L
Consider IV therapy using pre-mixed bags of IV fluids
containing potassium chloride
Peripheral infusion rate not to exceed 10mmol / hour
(20mmol/hour by central infusion in critical care setting
only where cardiac monitoring available)

Oral Potassium
Potassium chloride
effervescent tablets
(Sando K)
12mmol potassium per tablet.
Two tablets in 200mL water 3 times daily (72mmol/day) until
plasma potassium is in required range (usually 3 - 4 days).
Do not give at bed - time: risk of oesophageal ulceration.
Potassium chloride syrup
7.5% (1mmol/ml)
(Kay - Cee L)
20mL 3 times daily (60mmol/day) until plasma potassium is
in required range.
The taste of this product is poorly tolerated by many
patients.
Potassium chloride m/r
tablets (Slow K)
8mmol potassium per tablet.
Two tablets 3 times daily (48mmol/day) until plasma
potassium is in required range.
Tablets should be swallowed whole with plenty of fluid,
during meals whilst standing or sitting up straight. Care is
required where patients have oesophageal stricture; hiatus
hernia and peptic ulcer disease as could cause ulceration.

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Intravenous Potassium
The intravenous administration of solutions containing potassium chloride to prevent or
correct hypokalaemia is associated with a risk of potentially fatal cardiac effects resulting
from the following:

Improper preparation of infusions at ward level using ampoules of very
concentrated potassium chloride (e.g. Strong Potassium Chloride injection
15%).
Inadequate mixing of locally prepared infusions resulting in "pockets" of highly
concentrated potassium chloride.
(At RLBUHT these risks are reduced following the removal of concentrated potassium
chloride/acid phosphate ampoules from all clinical areas. All intravenous potassium is
provided as ready mixed infusion bags in various concentrations)

High concentration solutions causing local thrombophlebitis, tissue necrosis and/or
loss of IV access.
Excessive rate of infusion.
Inappropriately prolonged use of the IV route.

Prior to initiating intravenous therapy, the following require careful consideration:
Urgency of potassium replacement, e.g. presence of cardiac arrhythmia, need for
early surgery, very low plasma potassium (<3mmol/L).
Co-morbidity (e.g. fluid restriction, renal function) and co-prescription, notably
digoxin or antiarrhythmics.
Patient location, i.e. general ward or ITU/POCCU/HDU/CCU.
The most appropriate infusion solution in terms of volume and potassium
concentration.
The rate of administration and mechanism of rate control (e.g. using IVAC type
infusion pump).
The anticipated potassium needs of the patient for the following 24-48 hours. This
should be discussed with a Clinical Biochemist where necessary.

Where there remains a clear clinical need for a patient to be treated with intravenous
potassium infusions, all staff involved must ensure that this treatment is delivered in a way
that minimises all of the known risks and hazards. To this end, the Trust Intravenous
Potassium Administration Policy has been prepared.

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

Trust Intravenous Potassium Administration Policy statements
Intravenous treatment of hypokalaemia must only be instigated when the oral/ enteral
route is unavailable or will not achieve the required elevation of plasma potassium
within a clinically acceptable time.
All prescribing of potassium must be expressed in terms of millimoles of potassium and
must include the rate of infusion and duration of treatment.
A treatment programme considering the patient's potassium needs for the following 24 -
48 hours should be prepared, with assistance from Clinical Biochemisty if necessary.
All ampoules of potassium containing solutions have been removed from, and will not be
available to, any ward or clinical area under any circumstances.
Only pre-prepared potassium containing infusions must be used. These are available in
the following strengths & presentations:
20mmol in 1000mL of 0.9% sodium chloride or 5% glucose (dextrose) infusion.
(Equivalent to 0.15% potassium chloride)
40mmol in 1000mL of 0.9% sodium chloride or 5% glucose (dextrose) infusion.
(Equivalent to 0.3% potassium chloride)
40mmol in 500mL 0.9% sodium chloride or 5% glucose (dextrose) infusion.
(Equivalent to 0.6% potassium chloride) *
40mmol in 100mL 0.9% sodium chloride infusion. (Equivalent to 3% potassium
chloride) * #

* This solution is not commercially available and is purchased as an unlicensed "special" and will be
treated as a Controlled Drug within the Trust

# This solution is for ITU/POCCU/HDU/CCU use only and must be administered via a central IV line
with continuous ECG monitoring of rate & rhythm.

All potassium containing infusions must be administered via a suitable infusion pump to
control the infusion rate and volume.
All patients being treated with intravenous potassium are to have at least once daily
measurement of plasma potassium until levels are shown to be satisfactory.

Phosphate supplementation: see Section 9
Alberti-GKI. Regimens: see Section 6

The suggested infusion rates according to urgency and degree of hypokalaemia are:

Plasma Potassium
level (mmol/L)
Patients with NORMAL Renal Function and NO fluid restriction (Where
renal function and/ or fluid intake is compromised, seek senior advice)
Fluid Route Infuse over
Prophylaxis against
Hypokalaemia
(Normal = 3.5 5.3)
20mmol in 1000mL of
0.9% sodium chloride
OR
20mmol in 1000mL 5%
glucose infusion
peripherally

OR

Centrally
over at least 8 hours as
part of a normal fluids
regimen
The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011
Plasma Potassium
level (mmol/L)
Patients with NORMAL Renal Function and NO fluid restriction (Where
renal function and/ or fluid intake is compromised, seek senior advice)
Fluid Route Infuse over
Mild Hypokalaemia
(3.0 3.4 or non-
urgent)
40mmol in 1000mL of
0.9% sodium chloride
OR
40mmol in 1000mL 5%
glucose infusion
peripherally

OR

Centrally
over at least 6-8 hours
40mmol in 500mL 0.9%
sodium chloride
OR
40mmol in 500mL 5%
glucose infusion
peripherally

OR

centrally
over at least 4 hours Severe
Hypokalaemia
<3 or very urgent
40mmol in 100mL 0.9%
sodium chloride infusion
administered in
ITU/POCCU/HDU/CCU
central line with
continuous ECG
monitoring of rate &
rhythm
over at least 2 hours

Note: Overzealous potassium replacement therapy can result in life threatening hyperkalaemia.

Formula for calculating approximate potassium requirements for
replacement:
mmol potassium required = (4 - plasma potassium in mmol) x body weight (kg)


SUMMARY OF POTASSIUM CONTAINING INTRAVENOUS INFUSIONS
Millimoles per infusion 'bag'
Intravenous infusion* Na+ K+ Cl- PO43- Order / Supply
Potassium chloride 0.15% in 1000ml glucose 5% 20 20

Stock Requisition / IV 'top-up'
Potassium chloride 0.15% in 1000mL sodium chloride 0.9% 150 20 170

Stock Requisition / IV 'top-up'
Potassium chloride 0.3% in 1000mL glucose 5% 40 40

Stock Requisition / IV 'top-up'
Potassium chloride 0.3% in 1000ml sodium chloride 0.18% and
glucose 4%
30 40 30

Stock Requisition / IV top up
Potassium chloride 0.15% in 1000ml sodium chloride 0.18% and
glucose 4%
30 20 30

Stock Requisition / IV top up
Potassium chloride 0.3% in 1000mL sodium chloride 0.9% 150 40 190

Stock Requisition / IV 'top-up'
Potassium chloride 0.15% in 500 ml glucose 10% (for Gl.I.K.
Regimes)
10 10

UNLICENSED
CD requisition/ CD register record / CD issue record
Potassium chloride 0.3% in 500 ml glucose 10% (for Gl.I.K.
Regimes)
20 20

UNLICENSED
CD requisition/ CD register record / CD issue record
Potassium chloride 0.6% in 500ml glucose 5% 40 40

UNLICENSED
CD requisition/ CD register record / CD issue record
Potassium chloride 0.6% in 500ml sodium chloride 0.9% 75 40 115

UNLICENSED
CD requisition/ CD register record / CD issue record
Potassium chloride 3% in 100ml sodium chloride 15 40 55

UNLICENSED
ITU / POCCU/ HDU/CCU use only
CD requisition/ CD register record / CD issue record
Potassium Acid Phosphate 1.2% in 250ml (water) 20 20 UNLICENSED
ITU / POCCU/ HDU Others via Clinical Chemistry advice only
CD requisition/ CD register record / CD issue record

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing October 2011
* The column shows infusion names as they appear printed on the infusion bag label

Summary table notes:
Potassium Acid Phosphate 20mmol in 250ml water and potassium chloride 40mmol in 500ml 0.9% sodium chloride may be given peripherally but may cause
thrombophlebitis and loss of venous access.
All potassium-containing solutions should be stored in a separate location to other intravenous solutions.
Those solutions which require order via CD requisition do not need to be stored in a CD cupboard

Management of Hyperkalaemia
Plasma potassium Action
5.4 - 6.0mmol/L Mild Hyperkalaemia
Discontinue any inappropriate prescriptions e.g. potassium sparing
diuretics etc.
6.0 - 7.0mmol/L Moderate Hyperkalaemia

No ECG changes: Discontinue any inappropriate prescriptions e.g. potassium sparing
diuretics etc. and then
By mouth, Calcium Resonium 15g 4 times daily and/or
By rectum, Calcium Resonium enema 30g in 100mL administered by
bladder syringe and retained for 9 hours. Rectal administration results in
more rapid elimination of potassium.
Rectal route is appropriate if rapid reduction is required and will act
while the calcium resonium by the oral route is in gastro - intestinal
transit.
ECG changes: As above plus treatment as for severe hyperkalaemia
> 7mmol/L Severe Hyperkalaemia
Discontinue any inappropriate prescriptions e.g. potassium sparing
diuretics etc.
Urgently seek senior or specialist advice.
With / Without ECG
changes:
1) 10mL (equivalent to 6.8mmol of calcium) calcium chloride 10%
injection or calcium gluconate to stabilise the myocardium then
2) 10 units of soluble insulin in 250mL bag of glucose 10% given
peripherally over 60 to 120 mins.
Fluid restricted patients only:
100mls of 20% glucose with 10 units soluble insulin over 60 - 120mins
via syringe driver.
Control potassium levels with calcium resonium orally or rectally.
Monitoring:
All patients should have their blood glucose monitored for several hours
after the infusion, as the patient may become hypoglycaemic.
Consideration may be given to omitting insulin in non - diabetic patients.
Monitor calcium in susceptible individuals.
pH < 7.1 Acidotic
Seek senior or specialist advice, dialysis may be indicated.
Note: Regularly monitor plasma glucose, potassium and blood pH. The effects of
hyperkalaemia recur due to redistribution of potassium in the body.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Oral Sodium
Sodium chloride is indicated in states of sodium depletion and usually needs to be
given intravenously.

Water restriction is effective for dilutional hyponatraemia

Only in chronic conditions associated with mild or moderate degrees of sodium
depletion are oral supplements indicated. e.g. Renal disease or salt - losing bowel.

Sodium chloride 600mg (s)
m/r tablets (Slow
Sodium)
Consultants only.
10mmol each of sodium and of chloride.
Dose : 4 to 8 tablets daily in divided doses. Take doses with
a full glass of water.
Oral Rehydration Salts
Dioralyte sachets Mild to moderate diarrhoea: Reconstitute one sachet with
200mL of water and administer according to fluid loss,
usually 200 - 400mL after every loose motion.

Oral Bicarbonate
Sodium bicarbonate 500mg
capsules
(s) Nephrologists only.



Parenteral Preparations for Fluid and Electrolyte Imbalance
Intravenous Sodium
Chronic dilutional hyponatraemia should be corrected by water/fluid restriction.
Caution: hyponatraemia should be corrected slowly to avoid the risk of osmotic
demyelination syndrome.

0.9% sodium chloride can also be used to treat mild to moderate metabolic acidosis.

For further information see BNF section 9.2.2: Intravenous sodium.

SODIUM CHLORIDE INTRAVENOUS INFUSIONS
Millimoles per litre Intravenous infusion
Na
+
K
+
HCO
3
-
Cl
-
Ca
2+
Sodium chloride 0.9% 150 150
Sodium chloride 0.45% 75 75
Sodium chloride 0.18% 30 30
Sodium chloride 0.18% and
Glucose 4%
30 30
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

SODIUM CHLORIDE INTRAVENOUS INFUSIONS
Millimoles per litre Intravenous infusion
Na
+
K
+
HCO
3
-
Cl
-
Ca
2+
Compound sodium lactate
(Hartmann's)
131 5 29 111 2

Intravenous Glucose
Intravenous glucose 5% is used mainly to replace water deficits and should be given
alone when there is no significant loss of electrolytes. e.g. in fevers, hyperthyroidism,
diabetes insipidus and hypercalcaemia.

Average requirements in a healthy adult are 1.5 - 2.5 litres daily.

Sodium chloride and glucose solutions are indicated when there is combined water and
sodium depletion. Give in a 1:1 mixture i.e. alternate administration of glucose 5% with
sodium chloride 0.9%.

Glucose infusions of greater than 10% should be infused via a central i.v. line as they
are highly irritant.

Glucose infusions 5%, 10%, 20%, 50%.


Subcutaneous Administration of Fluids

When intravenous administration is not possible, large volumes (up to 2 litres per
day) of glucose 5% or sodium chloride 0.9% can be given by subcutaneous infusion.
Suitable sites for administration include intraclavicular, scapular, abdominal or thigh.

Subcutaneous administration is contra indicated in severe dehydration or shock.

Up to 20mmol potassium chloride may be added to each litre of infusion fluid and
administered over 3 -4 hours. If the patient experiences discomfort due to the build up
of fluid in the tissues around the administration site, the rate of administration should be
reduced.

Available evidence suggests that the addition of hyaluronidase to infusion bags for sub -
cutaneous administration is NOT necessary in most patients. (S.T. O'Keefe, J.N. Laven,
Gerontology1996;42:36-39).

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Bicarbonate and lactate
BICARBONATE INTRAVENOUS INFUSIONS
Millimoles per litre
Intravenous infusion
Na
+
K
+
HCO
3
-
Cl
-
Ca
2+
Sodium bicarbonate 8.4%
1000 1000
Sodium bicarbonate 1.4%
166 166
Sodium bicarbonate 1.26%
150 150

Sodium bicarbonate is used to control severe metabolic acidosis.

Caution:
Intravenous sodium bicarbonate has a high pH. Precipitation may result if it is mixed with any
medicines or infusion fluids, (including glucose).
Sodium bicarbonate infusions are likely to cause thrombophlebitis.
Risk of over treatment resulting in alkalosis.
Administer with great care in all situations. Only 1.26% and 1.4% can be infused peripherally.
Seek senior or specialist advice if in doubt.
Sodium bicarbonate 8.4% 10mL, 50ml, 250mL



Plasma Substitutes
Gelofusine infusion
Hydroxyethyl starch 6% in sodium chloride 0.6% (Volulyte 6%)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Intravenous Nutrition

Total Parenteral Nutrition (TPN)

Caution: Inappropriate administration of PN can have potentially serious
consequences. It requires a dedicated intravenous line and meticulous attention to
correct aseptic technique.

This feeding method is intended for patients when oral / enteral nutrition is not indicated
or who cannot achieve adequate nutrition by the oral or enteral route.

The duration of parenteral nutrition is determined by the return of gastrointestinal
function and may often be 2 weeks or less. For example

Delay in achieving oral/enteral nutritional requirements post-operatively
Mucositis following chemotherapy
Severe pancreatitis where nasojejunal feeding has been unsuccessful
Anastomotic leak
Bowel obstruction

Long-term PN (in some cases Home PN) is needed for patients with prolonged
episodes of intestinal failure
- Extreme short bowel syndrome of any aetiology
- Intestinal fistulae
- Gut motility disorders such as scheroderma and chronic idiopathic intestinal pseudo
obstruction syndromes

In order for the initiation of TPN to be considered, the patient concerned must be an in - patient
on the Royal Liverpool Hospital site.

Contacting the Nutrition Team

Any patient requiring parenteral nutrition should be referred, to the Nutrition
Specialist Nurses or Dietician via the ICE system for a full nutritional assessment.

It should be clearly documented in the patients case notes why a referral for TPN is being
made.

Nutrition Team members can be contacted during working hours.

Senior Dietician Bleep 4134
Consultant Nutrition Specialist
Nurse
Bleep 4595

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Nutrition Nurse Specialist Bleep 4524
Clinical Pharmacist (TPN)
(Out of normal hours, contact
on-call pharmacist via hospital
switchboard)
Bleep 4530
Duty Clinical Biochemist Bleep 4313 (including out of normal hours)

Details which must be available when contacting the Nutrition Team
- Patients full name
- Patients unit number
- Date of birth
- Ward
- Consultant
- Brief medical details and reason for referral to the Nutrition Team
- Other considerations/restrictions e.g. maximum fluid allowance

Once a patient has been assessed as a suitable candidate for parenteral nutrition, the
following must be obtained

- Current weight of the patient
- Biochemistry profile
- Sodium, Potassium, Bicarbonate
- Urea and Creatinine
- Calcium (adjusted) and Phosphate
- Magnesium
- LFTs (ALP, total Bilirubin, ALT and GGT)
- Glucose
- Triglycerides
- Trace elements (Zinc, Copper and Selenium)
- Prealbumin
- CRP

Electrolytes may need correction before parenteral nutrition (PN) can be initiated.

Full profile electrolyte monitoring will be required on a daily basis until patient is
stabilised on PN.
Trace elements, prealbumin and triglyceride levels need only be requested once a
week
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Ward Rounds Nutrition Team

Members of the Nutrition Team visit new referrals and existing PN patients, (with the
exception of ITU) each weekday morning, for assessment; recommendations and
monitoring. To avoid duplication of requests and unnecessary phlebotomy, blood
sampling request forms remain the responsibility of the patients own Consultant
team. These routine bloods are required daily during the week unless indicated
otherwise by the Nutrition Team.

Manufacture of Parenteral Nutrition (PN)
TPN bags are individualised and manufactured each morning using the previous days
blood results.

Stock PN bags are not available.
In exceptional cases it may be possible to manufacture a new bag if the initial bag is
inappropriate in the light of later results. However the TPN pharmacist must be
contacted before 12 noon for any adjustments to the PN regimen.
Contact after 12 noon will normally mean that PN will have to be omitted for that day if
the bag supplied is considered unsuitable.

Discontinuation of PN
Wards are contacted by the TPN pharmacist each weekday morning to confirm
whether a patients TPN regime is running to schedule. This is to avoid the
manufacture of excess bags when the schedule is not running to time due to
complications e.g. patient pyrexia; administration line problems etc.
Each TPN bag can costs up to 100 to produce.
Directorates are charged in full for unused bags so please contact TPN pharmacist
on bleep 4530 or Aseptic Production Unit on ext 3237 if TPN not required.

PN outside Normal Working Hours all areas except ITU
PN bags cannot be manufactured for patients referred to the Nutrition team after 12
noon on weekdays, or at weekends / Bank Holidays.
The Pharmacy Aseptic Unit does not compound PN at weekends, as weekend TPN
for patients commenced during the week is manufactured on Friday mornings.

Referrals received after 12 noon or at weekends, will be reviewed on the next
working day for suitability and appropriate intravenous access.
It is not considered an emergency to commence PN out of normal working
hours, and can be dangerous if the patient has not been fully assessed.

ITU have stock PN with and without electrolytes. These are low volume with high
osmolality and unsuitable for peripheral administration. They require separate
administration of water soluble vitamins and MUST NOT be requested / supplied for
patients outside the critical care setting.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Oral Nutrition

Enteral Nutrition

Administration of medication via enteral feeding tubes
If the oral route is unavailable an alternative medicine or route of administration
should be considered (rectal, topical, by subcutaneous or intravenous injection). Only
when this is not possible or desired, should medication be administered through an
enteral feeding tube.

There is a RLUHT nursing protocol for administration of feeds through enteral
feeding tubes available on the intranet. This gives information on checking
position of tube with pH sensitive paper before each administration of feed or
medication, flushing of tubes and other issues around their care. If a patient is unable
to receive oral medication and is fed through an enteral feeding tube, the feeding
tube can sometimes be used for administration of medicines.

Administration of medication via enteral feeding tubes is off label and can
cause problems. The bore of nasogastric, nasojejunal and gastrostomy tubes
is narrow and medicines can cause blockage of the tube and affect nutritional
support.

An example of this is acid suppression. Omeprazole MUPS and lansoprazole are
both known to cause tube blockage and should be avoided. Suitable alternatives
would be ranitidine effervescent tablets or if a PPI is required, esomeprazole is at
present the only medicine licensed for gastric tube administration as the tablet can be
dispersed in a minimum of 25ml of water.

Another problem medicine is ciprofloxacin. The suspension is oil based and will block
enteral feeding tubes whereas the tablets are easily dispersed in water.

General guidelines suggest the administration of a liquid or a dispersible tablet is
least likely to cause tube obstruction.

Not all tablets can be safely crushed and dispersed in water. If modified release
formulations are crushed they release a high dose of medicine very quickly and the
duration of action is reduced. Other controlled release formulations if crushed do not
reach the intended site of absorption in the GI tract.

Medicine/medicine and medicine/feed interactions are common. This can
compromise treatment and is especially important for anti-epileptic medicines e.g.
phenytoin and carbamazepine, antibiotics and any medicine with a narrow
therapeutic index.

For information on prescribing and administering medication through an
enteral feeding tube, and advice on appropriate formulations and timing of
doses, contact your Ward Pharmacist or Pharmacy Medicines Information
Department on extension 2096. Outside of normal pharmacy opening hours
you can contact the on-call pharmacist via the duty manager.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Minerals

Calcium and magnesium

Calcium supplements
- Calcium lactate
gluconate,
- calcium carbonate eff.
tablets (Sandocal )
Sandocal 400: 10mmol Ca
2+
/tab.
Sandocal 1000: 25mmol Ca
2+
/tab.

- Calcium Sandoz syrup 2. 2.7mmol Ca
2+
/5mL.
- Cacit effervescent
tablets
1.12.6mmol Ca
2+
/tab. (s) Clinical Chemistry only.
- Calcichew tablets 1 12.6mmol Ca
2+
/tab. (s)

Intravenous calcium may cause arrhythmias; hypotension; nausea and flushing if
administered too rapidly.

- Calcium gluconate 10%
injection
0.22 millimoles Ca
2+
/mL (1g in 10mL).

- Calcium chloride 10%
injection
0.68 millimoles Ca
2+
/mL (1g in 10mL)
Injection is hyperosmolar and irritant.



Hypercalcaemia Management

- Symptoms of moderate
hypercalcaemia:
polyuria, thirst, nausea, vomiting, anorexia, fatigue,
constipation.
- Symptoms of severe
hypercalcaemia:
Confusion, arrhythmia, coma.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

- Usual range of adjusted calcium: 2.2 2.6 mmol/L
- Always use adjusted calcium in all dosage calculations.
- hypercalcaemia of malignancy is confirmed by:
history
clinical findings
Radilological and histological findings
Suppressed parathyroid hormone (PTH) levels on a blood sample taken prior to any
treatment
- Commence rehydration with a minimum of 1 2 litres sodium chloride 0.9% over 24
hours prior to bisphosphonate therapy followed by a further 1 litre of sodium chloride
0.9% after bisphosphonate therapy, (if possible).
- zoledronic acid will normalise adjusted plasma calcium in over 90% of patients (as
compared with 75% in pamidronate treated patients).

- In some patients, the plasma adjusted calcium will increase above 2.7mmol/L two to
three weeks following initial infusion. A further infusion of 4mg zoledronic acid will
normalise the majority of these but in particularly severe hypercalaemia, an 8mg
infusion should be considered.

- In a small number of patients, the 8mg infusion has been noted to cause renal
impairment.
Cautions:
Ensure adequate hydration.
Monitor serum electrolytes, calcium, phosphate, and magnesium.
Assess renal function before each dose.
Avoid if serum creatinine above 400 micromol/litre
Cardiac disease (avoid fluid overload);

- Corticosteroids have not been shown to have any significant clinical benefits in the
management of hypercalaemia.

- Cinacalcet tablets
(s) Consultant Nephrologists only

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


CORRECTED
CALCIUM MMOL/L
ACTION
< 3.0 Asymptomatic:
Hydration regimen. Give 3 - 4 litres/day of sodium chloride 0.9%
intravenously over 24 hours and repeat calcium measurement.
Care with fluid overload and monitor potassium levels.
Only give furosemide [frusemide] in presence or anticipation of cardiac
failure.
Symptomatic:
Hydration
PLUS
Blood sample for Parathyroid hormone (PTH) BEFORE
zoledronic acid 4mg i.v. in 100mL sodium chloride 0.9% over 15 minutes.
3.0 - 4.0 Hydration as above
PLUS
Blood sample for Parathyroid hormone (PTH) BEFORE
zoledronic acid 4mg i.v. in 100mL sodium chloride 0.9% over 15 minutes.
> 4.0 Hydration as above
PLUS
Blood sample for Parathyroid hormone (PTH) BEFORE
zoledronic acid 4mg i.v. in 100mL sodium chloride 0.9% over 15 minutes.

calcitonin (salmon) [salcatonin] 100units s.c. injection 3 times daily may
be used to achieve a more rapid control of hypercalcaemia. Give a test
dose of 25units to ensure no adverse reactions take place.

Repeat plasma calcium after 6 hours. If reduced continue calcitonin
(salmon) for 48 hours or until calcium is < 4.0. If calcium is same or
increased contact Clinical Chemistry for advice.

The effects of calcitonin (salmon) are transient therefore it should be
discontinued after 5 days irrespective of plasma calcium measurements.

Notes: sample for parathyroid hormone (PTH) assessment are not required for critical care
hypercalcaemia or known lymphoma

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Magnesium

Causes of magnesium deficiency include excessive losses in diarrhoea, stoma or
fistula, alcoholism and diuretic therapy. Supplementation is usually by the intravenous
route as magnesium salts are poorly absorbed orally. Use cautiously in renal
impairment, (magnesium is renally excreted)

- Magnesium
glycerophosphate 1g
tablets
(s) Unlicensed. Nephrologists only.
4mmol magnesium / 1g tablet.
Not suitable for correcting established
magnesium deficiency.
- Magnaspartate sachets 1 sachet dissolved in 200ml of water provides 10mmol
magnesium. Use with caution in diabetics as each sachet
contains 3g sucrose.
- Magnesium sulphate
50% injection
2mmol magnesium/mL (1g in 2mL).

[This schedule is not for treatment of serious
arryhthmias including torsades de pointes.
See here for details]

By i.v. Infusion, Give 10mmol over 12 hours (Maximum
20mmol over 24 hours) in 500mL sodium chloride 0.9%.

Administration of larger daily doses than this can exceed
the renal threshold causing much of the dose to be
excreted. Blood samples for repeat plasma magnesium
should be taken several hours after infusion has been
completed to allow distribution of magnesium throughout
the body.

A total of 160mmol over 5 days may be required.
Maintenance, usually 12mmol daily.

If intravenous access is restricted and there is hypokalaemia with
hypomagnesaemia, magnesium may be added to prepared bags of potassium in saline
or glucose. The daily requirement of magnesium should be given in divided doses in
each bag of fluid.

E.g. If the 24 hour requirement is for two litres of fluid, 12mmol magnesium and 80mmol
potassium, prescribe two bags (1 litre) with 6mmol magnesium and 40mmol potassium,
each to run over 12 hours
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Phosphorus

Phosphate Supplements

- Phosphate Sandoz
soluble tablets
Contain 16.1mmol phosphate, 20.4mmol sodium,
3.1mmol potassium.
Give up to 100mmol (six tablets) of phosphate
- CD Potassium acid
phosphate 1.2% in 250ml
20mmol potassium and 20mmol phosphate in 250ml
water.
Peripheral administration: 20mmol over 24 hours.
Central venous administration: critical care areas only
20mmol over a minimum of 2 hours.
- Sodium phosphate
injection
(s) Clinical Chemistry only.
as disodium hydrogen phosphate B.P 21.49%

10mL contains 12mmol sodium and 6mmol phosphate

Phosphate Binding Agents
- Aluminium hydroxide
capsules/suspension
(Alucaps / Aludrox)

(s) Nephrologists only.
- Calcium acetate 1gram
tablets (Phosex)
(s) Nephrologists only
calcium 250mg (6.2mmol)

- Calcium carbonate tablets
(Calcichew, Titralac)
(s) Nephrologists and Clinical Chemistry only.
- Lanthanum tablets 500mg and 750mg Nephrologists - special circumstances
only.
- Sevelamer capsules
(Renagel)
(s) Nephrologists only. For use in patients who develop toxic
aluminium levels or in those for whom aluminium hydroxide
is ineffective.


Fluoride
- Sodium fluoride
drops/tablets/rinse/gel
(s) Dental Hospital only.

Zinc
- Zinc sulphate125mg
soluble tablets (Solvazinc)
(s) 45mg zinc/tablet. Consultants and Dieticians only.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Selenium

- Selenium oral solution 100mcg/2ml 6.9 ITU Consultants and Biochemistry
only


Vitamins

Vitamin B Group
- Thiamine (vitamin B
1
)
tablets
See here for use in alcohol withdrawal.
- Vitamin B and C High
Potency injection
(Pabrinex)
Mix ampoules No.1 and No. 2 in syringe and add to 50mL
glucose 5% or sodium chloride 0.9% and give over 20 30
mins. For use in management of alcohol withdrawal and
once daily for 10 days to minimise refeeding complications
in malnourished patients unable to take oral thiamine.
- Pyridoxine (vitamin B
6
)
tablets
Deficiency states, 20 - 50mg up to 3 times daily.
Prophylaxis for isoniazid neuropathy, 10mg daily.
- Nicotinamide tablets (s) Consultants only.

Oral vitamin B complex preparations
- Vitamin B Compound
Strong tablets
Nicotinamide 20mg, pyridoxine 2mg, riboflavin 2mg,
thiamine 5mg/tab
Prophylaxis, 1 - 2 tablets daily.

Vitamin C
- Ascorbic acid 200mg,
500mg tablets, 1g soluble
tablets.
Prophylactic: 25-75mg daily.
Low doses can be given as 'Ketovite tablets' see below
for details
Therapeutic: not less than 250mg daily in divided doses.
Maximum of 1.5g per week in renal patients (i.e. 200mg o.d.)
- Ascorbic acid injection (s) Nephrologists only.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Vitamin D
- Alfacalcidol capsules/oral
liquid
(s) Nephrologists and Consultants only.
- Calcitriol capsules/tablets (s) Consultants only.
- Calcium and
colecalciferol
(s) Consultants only.
o Tablet Calcichew D3 calcium carbonate 1.25g (calcium 500mg or
Ca
2+
12.6mmol) colecalciferol 5 micrograms (200 units)
Calcichew D3 Forte - calcium carbonate 1.25g (calcium
500mg or Ca
2+
12.6mmol) colecalciferol 10 micrograms (400
units)
Adcal D3 Tablets calcium carbonate 1.5g (calcium 600mg
or Ca
2+
15.1mmol), colecalciferol 10 micrograms (400 units).
o Sachet Calfovit D3 calcium phosphate 3.1g (calcium 1.2g or
Ca
2+
30mmol) colecalciferol 20 micrograms (800units)
- Calciferol injection

- Cholecalciferol

- Cholecalciferol
(s) Monitor plasma calcium at least once a week.

1000units unlicensed medicine Consultants only

20,000units unlicensed medicine Consultants only


Vitamin E
- Vitamin E
tablets/suspension
(s) Consultants only.

Vitamin K
- Menadiol sodium
phosphate tablets
Water soluble. Use where fat malabsorption is a problem
e.g. biliary obstruction or hepatic disease.
Dose: 10mg daily.

- Phytomenadione injection By slow i.v. injection - not i.m. See here for oral use of
injection in coagulation disorders.

Multivitamins
- Multivitamins tablets

Ascorbic acid 15mg, nicotinamide 7.5mg, riboflavin 0.5mg,
thiamine 1mg, vitamin A 2500u, vitamin D 300 units.
Usual dose: one tablet daily.
- Ketovite tablets 1 tablet three times daily for renal patients who need low
dose vitamin C
Ascorbic acid 16.6mg, riboflavin 1mg, thiamine 1mg,
pyridoxine 330mcg, nicotinamide 3.3mg, calcium
pantothenate 1.16mg, alfa tocopheneryl 5mg, inositol
50mg, biotin 170mcg, folic acid 250mcg,
acetomenaphthone 500mcg.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Metabolic Disorders

Medicines for the Treatment of Acute Porphyrias
- Haem arginate injection (s) Consultants only. Contact Medicines Information (Ext.
2096) for administration details.

See current BNF section 9.8.2 for a list of medicines unsafe in Acute Intermittant
Porphyria.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MUSCULOSKELETAL AND JOINT DISEASES

Contents (Click on heading to go to that section)


Medicines Used in Rheumatic Diseases and Gout
Non-Steroidal Anti - Inflammatory Medicines (NSAIDS)
Corticosteroids
Cytokine Modulators
Medicines Which Suppress the Rheumatic Disease Process
Gout and Cytotoxic Induced Hyperuricaemia

Medicines Used in Neuromuscular Disorders
Medicines Which Enhance Neuromuscular Transmission
Skeletal Muscle Relaxants

Medicines for the Relief of Soft - Tissue Inflammation
Rubefacients and Other Topical Antirheumatics
































The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Used in Rheumatic Diseases and Gout

Non Steroidal Anti - Inflammatory Medicines (NSAIDS)
NSAIDs have an analgesic potency similar to paracetamol when taken on a 'when
required' basis. They only exert an anti - inflammatory effect when a regular full dose is
given.
Differences in anti - inflammatory activity between NSAIDs are small, but there is
considerable variation in individual patient response. Therefore it is often necessary to
try several analgesic medicines before finding one to suit a particular patient. Most
NSAIDs will produce an effect within a few days.
The main difference between the NSAIDs is in the side effect profile. All those with a
higher incidence of adverse effects are restricted to specialist use only. All NSAIDs
cause gastro - intestinal irritation regardless of the route of administration since this side
effect is systemic. Therefore e/c and m/r preparations will also cause gastric irritation
and possibly bleeding. E/C and m/r preparations are unsuitable for `when required'
use.

NSAIDs should be used with caution in renal/heart failure.

- Aspirin (s) Dermatologists and Gastroenterologists only. Unlicensed.
- Ibuprofen tablets/syrup
- Ibuprofen m/r tablets (s) Consultants only
- Naproxen
tablets/suspension/
suppositories
Acute musculoskeletal disorders By mouth, 250 - 500mg twice
daily.
By rectum, 500mg at night and morning if necessary.
Acute gout: By mouth, 750mg initially then 250mg every 8
hours until attack has passed.
- Diclofenac e/c
tablets/soluble
tablets/suppositories/
injection
Max daily dose by any route is 150mg.
By mouth, 25 - 50mg 3 times daily, after food.
EC tablets are routinely used

By deep i.m. injection, into GLUTEAL MUSCLE ONLY, 75mg
once or twice daily for a max. of 2 days
By i.v. infusion, in appropriately buffered infusion fluid. Contact
Medicines Information or refer to BNF for details.
By rectum, 100mg at night. Or every 36 hours if higher dose
required.
Ureteric colic: 75mg by i.m. injection into gluteal muscle then a
further 75mg after 30 mins if necessary.
- Diclofenac s/r tablets (s) Rheumatologists and Orthopaedics only. By mouth, 75mg
once or twice daily.

In patients who require long term treatment with NSAIDs who are at risk of
developing GI bleeding and ulceration lansoprazole or misoprostol may be used. See
gastro-intestinal system section for further recommendations.
Cox-2 inhibitors are only preferable to standard NSAIDs when specifically indicated
(eg. particularly high risk of PUD, perforation or bleeding).
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

In view of evidence of increasing risk of MI, Cox-2 inhibitors are contra-indicated in
patients with a history of cardio-vascular disease (including ischaemic heart disease,
CVA and TIA). They should be used with caution in high risk groups ( BP,
cholesterol, diabetic patients and smokers).

- Celecoxib (s) Rheumatologists only. By mouth, 100mg twice daily,
increased if necessary to maximum 200mg twice daily


Corticosteroids

Local Corticosteroid Injections
- Methylprednisolone
acetate injection 40mg/ml
(Depo-medrone)
By intra-articular or intra-synovial injection 40-80 mg
according to patient size.

- Hydrocortisone acetate
injection 25mg/mL
(Hydrocortistab)
By intra-articular or intrasynovial injection, 5 10mg
according to size of the joint.

- Methylprednisolone
acetate 40mg, lidocaine
[lignocaine] 10mg/mL
(Depo-medrone with
Lidocaine)
(s) Rheumatologists and Orthopaedics only.
- Triamcinolonenacetonide
10mg/mL (Adcortyl)
(s) Intra - articular, intradermal. Dermatologists,
Rheumatologists and Orthopaedics only.
- Triamcinolone acetonide
40mg/mL (Kenalog)
(s) Intra - articular, intramuscular.
Rheumatologists and Orthopaedics only.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Which Suppress the Rheumatic Disease Process

Medicines Affecting the Immune Response

- Sodium aurothiomalate
Injection
(s) Rheumatologists only.
- Penicillamine Tablets (s) Rheumatologists only.
- Hydroxychloroquine
tablets
(s) Rheumatologists only.


- Methotrexate tablets (s) Consultant only.

Usually first line treatment.

NB this is a WEEKLY dose

Folic acid supplement is required

- Methotrexate injection
S/C
For patients who have failed to tolerate oral methotrexate

NB this is a WEEKLY dose

Folic acid supplement is required

- Sulphasalazine tablets (s) Rheumatologists only.

- Azathioprine (s) Consultants only.
- Ciclosporin
capsules/liquid/injection
(s) Consultants only.
For therapeutic level monitoring see here
- Leflunomide tablets (s) Consultant Rheumatologists only.
Note: After the washout period, the concentration of active
metabolite should be less than 20micrograms/l (measured
on 2 occasions 14 days apart) in males or females before
conception. Contact Medicines Information for further
information.

Note: There are special monitoring requirements with all DMARDs.

Contact Rheumatologist or Rheumatology Specialist Nurses for advice and to ensure
appropriate monitoring is in place. See British Society for Rheumatology updated
guidelines on monitoring requirements for DMARDs. Available at
www.rheumatology.org.uk.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Cytokine Modulators - Consultant use only

Adalimumab, Etanercept, Infliximab and Tocilizumab inhibit the activity of tumour
necrosis factor. They are indicated for moderate to severe rheumatoid arthritis when
the response to DMARDs including methotrexate has been inadequate. Rituximab is
indicated when one anti-TNF has failed.

See NICE guidance for initiation criteria.
- Adalimumab 40mg
Injection
(s) Consultant Rheumatologists only.
Alternative to etanercept and infliximab. Human
monoclonal TNF -antagonist antibody.
Given by SC injection every 2 weeks.

- Etancercept 25mg
injection
(s) Consultant Rheumatologists only

Given by SC injection of 25mg twice weekly or 50mg once
weekly
Also indicated for:
Treatment of active polyarticular juvenile chronic arthritis
where the response to methotrexate has been inadequate or
not tolerated.
Treatment of active progressive psoriatic arthritis in adults
where response to previous DMARD therapy has been
inadequate.
- Infliximab 100mg
injection

(s) Consultant Rheumatologists, Gastroenterologists. See
here for use in Crohn's Disease.
IV infusion
Administration protocol available from Medicines
Information. Should be given with methotrexate
- Tocilizumab injection (s) Consultant Rheumatologists only
Intravenous infusion every 4 weeks.
Dose: 8mg/kg (Max. 800mg)

- Rituximab 1g infusion
(Prepared by Pharmacy
Cytotoxics)
(s) Consultant Rheumatologists only
Treatment course: 1g infusion given on day 1 and repeated
on day 15.

Requires pre-treatment with an anti-pyretic, anti-histamine
and corticosteroid. This course may be repeated if
necessary every 6 -12 months.
Should be given with methotrexate


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Gout and Cytotoxic Induced Hyperuricaemia

Acute Attacks
- Naproxen
tablets/suspension
750mg initially, then 250mg every 8 hours until the attack
has passed.

- Colchicine tablets Acute gout: 1mg initially, followed by 500 micrograms every
2 - 3 hours until relief of pain is obtained or vomiting or
diarrhoea occurs, or until a total dose of 6mg has been
reached.
The course should not be repeated within 3 days.
Maintenance 1- 2 tablets daily / twice daily.
Prevention of attacks during initial treatment with allopurinol:
500micrograms 2 - 3 times daily.


If a patient suffers an acute attack of gout whilst taking allopurinol, the allopurinol should
be continued at the same dose throughout the acute attack.

If the patient is not already taking allopurinol consider commencing allopurinol 2-3
weeks AFTER the acute attack has subsided.

Long term control
Allopurinol should not be started during an acute attack; the initiation may, however,
precipitate an acute attack. To prevent this, colchicine or an NSAID should be used as
a prophylactic for at least one month after the hyperuricaemia has been corrected
(usually about 3 months of prophylaxis).

However if an acute attack develops during treatment, then the treatment should
continue at the same dosage and the acute attack treated in its own right


- Allopurinol tablets Initially, 100mg daily as a single dose, gradually increased
over 1 - 3 weeks according to plasma or urinary uric acid
concentration. Usual maintenance dose 300mg. Renal
impairment, 100mg daily and adjust according to response.
Maintenance, 200mg - 600mg daily.
Patients intolerant to allopurinol should be referred to the Rheumatologists for
alternative therapy.
- Febuxostat tablets (S) Consultant Rheumatologists use only in line with NICE
guidance (Click here)
Dose: over 18years 80mg once daily, increased to 120mg
once daily if uric acid > 6mg/100ml


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Used in Neuromuscular Disorders

Medicines Which Enhance Neuromuscular Transmission
- Edrophonium Injection
(Tensilon)
(s) Consultants only.
- Neostigmine
tablets/injection
(s) Consultants only.
- Pyridostigmine tablets (s) Consultants only.
Skeletal Muscle Relaxants
- Diazepam
tablets/syrup/injection
Muscle spasm of varied aetiology:
By mouth, 2 - 15mg daily in divided doses increased if
necessary in spastic conditions to 60mg daily according to
response.
Cost band for 28 days (2mg 3 times daily): B
By slow i.v. injection, into a large vein at a rate of not more
than 5mg/min. In acute muscle spasm, 10mg repeated if
necessary after 4 hours.
NB: Only use IM route when oral and IV routes not
possible
Tetanus: By i.v. injection, 100 - 300 microgram/kg
repeated every 1 - 4 hours, by i.v. infusion (or by naso-
duodenal tube), 3 - 10mg/kg over 24 hours adjusted
according to response.


The following medicines should only be prescribed for the relief of chronic muscle
spasm or spasticity; they are not indicated for spasm associated with minor injuries.

- Baclofen tablets/liquid 5mg 3 times daily, preferably after food, gradually
increased to max. 100mg daily.

- Quinine sulphate tablets Nocturnal leg cramps: 200mg at bedtime.
Note: If patient is also receiving digoxin, the dose of
digoxin should be halved.

- Dantrolene capsules (s) Consultants only.





The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines for the Relief of Soft - Tissue Inflammation

Rubefacients and Other Topical Antirheumatics

Topical NSAIDs
- Benzydamine cream
(Difflam)
Apply 3 - 6 times daily for up to 10 days.

- Piroxicam gel 0.5% Apply 3-4 times daily
- Ibuprofen gel 5% Apply 3 times daily

Counter Irritants
- PR spray (s) A&E only.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINES ACTING ON THE EYE
Contents (Click on heading to go to that section)

Management of Acute Ophthalmic Conditions
General Irrigation
Chemical Burns
Hypertonic Agents for Clearing Corneal Oedema
Systemic Agents

Administration of Medicines to the Eye

Control of Microbial Contamination

Anti - Infective Eye Preparations
Antibacterials
Antifungals
Antivirals

Corticosteroids and Other Anti - inflammatory Eye Preparations
Corticosteroids
Other Anti - inflammatory Preparations

Algorithm for the use of Ozurdex

Mydriatics and Cycloplegics
Antimuscarinics
Sympathomimetics

Treatment of Glaucoma
Miotics
Sympathomimetics
Beta - Blockers
Carbonic Anhydrase Inhibitors and Systemic Medicines
Prostaglandin Analogues

Local Anaesthetics

Miscellaneous Ophthalmic Preparations
Tear Deficiency, Ocular Lubricants and Astringents
Prescribing Guideline for Artificial Tears
Ocular Diagnostic and Peri-operative Preparations and Photodynamic
Treatment
Ocular Peri-operative Medicines
Ophthalmic Surgery
Viscoelastic Polymers
Subfoveal Choroidal Neovascularisation ("Age Related Macular
Degeneration")

Contact Lenses
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

All medicines annotated with (s) in this section will be restricted to Ophthalmologists
unless otherwise stated.

PF = Preservative free.

Management of Acute Ophthalmic Conditions

General Irrigation
- Sodium chloride 0.9% 150mL

Chemical Burns
- Buffered phosphate eye
lotion
(s) For irrigation.


Ascorbic acid plus citrate drops should be used together with the addition of
prednisolone 0.5% drops and chloramphenicol 1% ointment for chemical burns
according to severity.

- Ascorbic acid 10% drops (s) (Potassium ascorbate, Vitamin C)
- Citrate 6.5% drops (s) Consultant only

Depending on severity, systemic treatment with ascorbic acid tablets 1g daily and
doxycycline capsules 100mg daily can be initiated for the management of chemical
burns.

Hypertonic Agents for Clearing Corneal Oedema
- Glycerin drops (s) Consultant only
- Sodium chloride 5%
drops/ointment/PF
(s) Consultant only

Systemic Agents
- Glycerol 50% v/v in
sodium chloride 0.9%
100mL
(s) To be given orally for the short term reduction of
elevated intra-ocular pressure to treat an acute attack of
closed angle glaucoma.
- Mannitol 20% 500mL
Infusion
(s) For intravenous use. Rapid reduction of elevated intra-
ocular pressure e.g. acute attack of closed angle glaucoma.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Administration of Medicines to the Eye

Order of Administration of Ophthalmic Preparations

When two different ophthalmic preparations need to be administered at the same time
of day dilution and over flow may occur. To avoid this, a few minutes should be left
between instilling the two different preparations. The order of instillation of drops is also
important:
- First Miotics (e.g. pilocarpine) and antimuscarinics (e.g.
cyclopentolate).
- Second Sympathomimetics (e.g. adrenaline/ epinephrine), beta -
blockers.
- Third Antimicrobials, antivirals.
- Fourth Corticosteroids.

Note: Ointments always follow drops.

Control of Microbial Contamination

Eye drops and ointments should be discarded in line with the instructions or
manufacturers leaflet. Eye drops and ointments that have a 4 weeks expiry should be
discarded 2 weeks after opening when issued to in - patients except where otherwise
indicated.

Preservative free eye drops should be stored and discarded in accordance with the
manufacturers instructions.

Anti - Infective Eye Preparations

The majority of acute eye infections can be treated topically. Ulcers, keratitis,
endophthalmitis are more serious infections and require ophthalmology referral.
Subconjunctival injection or systemic administration of antimicrobials may be
necessary.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Antibacterials
Conjunctivitis

- Chloramphenicol 0.5%
drops/minims
Apply up to every two hours then reduce frequency as
infection is controlled and continue for 48 hours after healing

- Chloramphenicol 1%
ointment
Apply either at night (if eye drops used during the day) or 3 -
4 times daily if ointment used alone.

- Gentamicin 0.3%
drops/minims
Apply up to every 2 hours then reduce frequency as
infection is controlled and continue for 48 hours after
healing.

- Ciprofloxacin 0.3% drops (s) Consultant only
- Fusidic acid 1% drops
(Fucithalmic)
(s) Consultant only
- Chloramphenicol 0.5%
PF drops



(s) Consultant only

Chlamydial Conjunctivitis
Refer to department of GU medicine for investigation and systemic therapy.

Systemic tetracyclines (or erythromycin if tetracycline allergy/intolerance/contraindication)
Required

Blepharitis
- Chloramphenicol 1%
ointment
Apply 3 - 4 times daily.

- Fusidic acid 1% drops
(Fucithalmic)
(s) Consultant only
- Doxycycline capsules 50 200mg per day

.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Ulcerative Keratitis

Management should be according to protocol, including appropriate and correctly
performed sampling.
- Ciprofloxacin 0.3% drops (Ciloxan) (s)
- Ciprofloxacin 0.3% ointment (Ciloxan) (s)
- Teicoplanin 1% drops (s) Prepared by Pharmacy Aseptic
Manufacturing
- Cefuroxime 5% drops (s) Prepared by Pharmacy Aseptic
Manufacturing
- Gentamicin 1.4%, 0.3% drops (s)

Other agents as recommended by a microbiologist.

Acanthamoeba Keratitis
- Chlorhexidine digluconate 0.02% drops (s)
- Propamidine isethionate 0.1% drops (s)

Other Anti - Infective Eye Preparations
- Chlortetracycline 1% Ointment (unlicensed) (s)
- Framycetin 0.5% drops/ointment (s)
- Neomycin 3500units/g ointment (s)
- Trimethoprim 0.1% with polymyxin B 10,000
units/mdrops (Polytrim)
(s)
- Povidone Iodine eye drops (s) For surgical prophylaxis
- Benylpenicillin 20,000units/ml eye drops (s) As recommended by
microbiology.
Prepared by Pharmacy Aseptic
Manufacturing
- Vancomycin 5% eye drops (s) As recommended by
microbiology.
Prepared by Pharmacy Aseptic
Manufacturing

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Antifungals

None commercially available for topical use. Discuss with medical microbiology
- Fluconazole 0.2% drops (s) As recommended by microbiology.
Prepared by Pharmacy Aseptic Manufacturing
- Amphotericin 0.15% & 0.3% eye
drops
(s) As recommended by microbiology.
Prepared by Pharmacy Aseptic Manufacturing
- Voriconazole 1% eye drops (s) As recommended by microbiology.
Prepared by Pharmacy Aseptic Manufacturing

Antivirals

Herpetic Eye Disease
Sampling for microbiological analysis should usually be performed.
- Aciclovir 3% ointment (s) Systemic aciclovir is recommended for certain
conditions.
- Trifluorothymidine 1% (1% PF)
drops
(s)


Intra-ocular Anti - Infective Injections

Subconjunctival Injections
May be prepared by Pharmacy Aseptic Manufacturing. The optimal volume for sub-
conjunctival injections is 0.25mL (prepared with overage).

- Cefuroxime 100mg in 0.8mL (s)
- Ciprofloxacin 1mg in 0.5mL (s)
- Gentamicin 20mg in 0.2mL (s)
- Teicoplanin 10mg in 0.25mL (s)
- Amphotericin 150 microgram in 0.15mL (s)
- Amphotericin 300 microgram in 0.3mL (s)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Intra-vitreal Injections

Prepared by Pharmacy Aseptic Manufacturing. The optimal volume for intra-vitreal
injections is 0.1mL. (Prepared with overage to 0.4mL fill volume).
The usual regimen for (presumed) bacterial endophthalmitis is:

- Ciprofloxacin 0.2mg in 0.1mL (s)
- Teicoplanin 1mg in 0.1mL (s)

Others:
- Benzylpenicillin 1.2mg in 0.1mL (s)
- Cefuroxime 2.5mg in 0.1mL (s)
- Gentamicin 0.1mg in 0.1mL (s)
- Ganciclovir 2mg in 0.1ml (s)
- Foscarnet 2.4mg in 0.1ml (s)
- Amphotericin 5 microgram in 0.1mL (s)
- Amphotericin 10microgram in 0.1mL (s)
- Amphotericin 20 microgram in 0.1mL (s)

Prophylaxis against bacterial endophthalmitis in cataract and secondary lens
implantation surgery (according to protocol):
- Vancomycin 1mg in 0.1mL (s)

Intra-Cameral Injections
May be prepared by Pharmacy Aseptic Manufacturing.
- Voriconazole 1% (s)
- Voriconazole 50 microgram in 0.1ml (s)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Other Intra-ocular Injections
- Alteplase (TPA) 25 microgram in 0.1ml (s) May be prepared by Pharmacy
Aseptic Manufacturing.

- Alteplase (TPA) 50 microgram in 0.1ml (s) May be prepared by Pharmacy
Aseptic Manufacturing.

- Alteplase (TPA) 100 microgram in 0.1ml (s) May be prepared by Pharmacy
Aseptic Manufacturing.

- Triamcinolone Injection
(Commercially available off label use)
(s)

Corticosteroids and Other Anti - inflammatory Eye Preparations

Corticosteroids
Corticosteroid eye drops must be prescribed by ophthalmologists only. In certain
conditions indiscriminate use of topical corticosteroid eye drops may lead to `steroid
glaucoma' in predisposed patients. These preparations should be avoided in patients
with undiagnosed red eye, since this may be due to the herpes simplex virus, and a
corticosteroid may aggravate the condition.

General Use
- Betamethasone 0.1% drops/ointment (s)
- Dexamethasone 0.1% drops (s)
- Prednisolone 0.5% (s)
- Prednisolone 1% drops (Pred-Forte) (s)
- Hydrocortisone ointment 0.5 or 1.0%
(Martindale) once or twice daily
(s)

Special Circumstances
- Betamethasone Injection (s)
- Fluoromethalone 0.1% drops (s)
- Prednisolone 0.5% PF (including minims) (s)
- Prednisolone 0.03%, 0.05% (preserved)
drops
(s)
- Prednisolone 0.03%, 0.3%, 1% PF drops (s)



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Other Anti - inflammatory Preparations
- Antazoline sulphate 0.5%
with xylometazoline
hydrochloride
0.05%(Otrivine - Antistin)
drops
Allergic conjunctivitis: One to two drops 2 - 3 times a day.

- Azelastine 0.05% drops (s) C
- Emedastine 0.05% drops (s) Consultants and Senior Registrars only.

- Nedocromil 2% drops
(Rapitil)
(s)
- Sodium cromoglicate 2%
drops/ PF minims
Allergic conjunctivitis: One to two drops four times a day.


For post - operative inflammation and corneal pain relief:

- Diclofenac 0.1% unit
dose
(s)

- Flurbiprofen 0.03% unit
dose
(s)
- Ketorolac (Acular) eye
drops 0.5% (5mL)
(s)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Algorithm for use of Ozurdex in the treatment of macular oedema in retinal vein
occlusion.

RVO are classified as ischaemic or non-ischaemic on the basis of clinical appearance,
pupillary light response, visual acuity and fluorescein angiography plus further investigations
if required, e.g. electrophysiology.

Central Retinal Vein Occlusion (CRVO)

Non-ischaemic CRVO
For patients with visual acuity of between 6/9 and 6/60 due to macular oedema
demonstrated by optical coherence tomography (central retinal thickness greater than 250
microns), in the absence of ischaemia as demonstrated by fluorescein angiography, Ozurdex
implant is indicated.

Patients will be monitored for complications of Ozurdex and therapeutic response.
Administration of Ozurdex may be repeated at six months if visual acuity at that juncture is
not better than 6/7.5 and central retinal thickness has not been reduced to less than 250
microns.

Ischaemic CRVO
Management is aimed at treatment of the complications of ischaemia, i.e. rubeosis and
rubeotic glaucoma and retinal neovascularisation. It is not intended that ischaemic CRVO be
treated with Ozurdex implant.

Branch and Hemi-retinal Vein Occlusion (BRVO & H-RVO)

Non-ischaemic BRVO or H-RVO
For patients with visual acuity of between 6/9 and 6/60 due to macular oedema
demonstrated by optical coherence tomography (central retinal thickness greater than
250microns), in the absence of ischaemia as demonstrated by fluorescein angiography
Ozurdex implant is indicated.

Patients will be monitored for complications of Ozurdex and therapeutic response.
Administration of Ozurdex may be repeated at six months if visual acuity at that juncture is
not better than 6/7.5 and central retinal thickness has not been reduced to less than 250
microns.

Macular grid laser is a therapeutic option in branch retinal vein occlusion.

Ischaemic BRVO or H-RVO
Management is aimed at treatment of the complications of ischaemia, i.e. vitreous
haemorrhage secondary to retinal neovascularisation. It is not intended that ischaemic
BRVO/H-RVO be treated with Ozurdex implant.

The therapeutic option of intravitreal injections of Bevacizumab remains available for
treatment of macular oedema in retinal vein occlusion as an alternative to Ozurdex, for those
in whom Ozurdex is contra-indicated and for those in whom Ozurdex is not indicated.



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Mydriatics and Cycloplegics

Note: Patients should not drive for 1 - 2 hours after mydriasis.

Antimuscarinics
- Atropine 0.5% drops 1%
drops/ minims/ointment
One or two drops. Duration up to 7 days.

- Cyclopentolate 0.5%
drops/minims 1%
drops/minims
(s) One or two drops. Duration up to 24 hours

- Tropicamide 0.5%
drops/minims1%
drops/minims
(s) Ophthalmologists and A&E only.
One or two drops. Rapid action, duration 3 hours.


Sympathomimetics
- Phenylephrine 2.5%
minims
(s)
- Phenylephrine
children,10%
minims/drops
(s) More toxic than 2.5%, DO NOT use in elderly or
patients with cardiovascular disease.




The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Treatment of Glaucoma

Miotics
- Pilocarpine 0.5% drops (s)
- Pilocarpine 1%, 2%, 4%
drops/minims/3% drops
(s)
- Pilocarpine 1%, 2% PF drops (s)
- Pilocarpine 4% gel (s)

Sympathomimetics
- adrenaline / epinephrine 0.01%, 0.5%, 1%
drops
(s) For specific indications only.

- Brimonidine 0.2% Drops (Alphagan) (s)
- Brimonidine 0.2% & Timolol 0.5%) Drops
(Combigan)
(s)
- Dipivefrine 0.1% Drops (Propine) (s)
- Guanethidine (Ganda 1 + 0.2) drops (s) Only for patients previously started.

Beta - Blockers
CSM advice:
Systemic absorption may follow topical application of eye drops, therefore eye drops
containing a beta - blocker are contra - indicated in patients with bradycardia, heart
block or heart failure. Beta - blocker eye drops should not be used by patients with
asthma or a history of obstructive airways disease unless no alternative treatment is
available.
- Betaxolol 0.5% drops (Betoptic-S) (s) Patients with respiratory disease.
- Carteolol 1%, 2% drops (Teoptic) (s) Restricted usage.

- Levobunolol (Betagan) 0.5% drops/unit
dose drops
(s) First line.

- Timolol 0.25% drops/minims Timoptol LA
0.25% gel Timolol 0.1% gel (Nyogel)
(s) Only for patients already using timolol.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011


Carbonic Anhydrase Inhibitors and Systemic Medicines
- Acetazolamide 250mg s/r capsules (s) First line.
- Acetazolamide 250mg tablets (s) Second line.
- Acetazolamide 500mg injection (s)
- Brinzolamide 10mg/mL drops (Azopt) (s)
- Dorzolamide 2% drops (Trusopt) (also
available as PF)
(s)
- Dorzolamide 2% and Timolol 0.5% (Cosopt)
(also available as PF)
(s)

Prostaglandin Analogues
First Line:
- Latanoprost 0.005% drops (Xalatan)
- Latanoprost 0.005% & Timolol 0.5%
(Xalacom)
(s)
Second Line:
- Travoprost (40 mcg/ml) (Travatan)
- Travoprost 40 mcg/ml & Timolol 0.5%)
(DuoTrav)
- Bimatoprost 0.01% (100mcg /ml) (Lumigan)
- Bimatoprost 0.03% (300mcg /ml) (Lumigan)
- Bimatoprost (300mcg /ml & Timolol 0.5%)
(Ganfort)
(s)

Local Anaesthetics
- Oxybuprocaine 0.4% minims (Benoxinate) (s)

- lidocaine [lignocaine] 0.5% minims (with
fluoroscein 0.5%)
(s)
- Proxymetacaine 0.5% minims (with
fluoroscein 0.25%)
(s) first line.
- Tetracaine (amethocaine) 0.5% minims (s)


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Miscellaneous Ophthalmic Preparations


Tear Deficiency, Ocular Lubricants and Astringents


Optimum comfort for artificial tears is achieved when the pH of the product is slightly
alkaline at about pH 8.5. Solutions are buffered to maintain the pH using borates,
acetates, bicarbonates and phosphates. Most artificial tear preparations are isotonic
with normal tears.

Dry eye is much less common than thought. It is important that patients fulfil the criteria
necessary for the diagnosis of dry eye or tear deficiency. Some patients with mild tear
deficiency may be better without artificial tears. Ophthalmologists request that all
patients with suspected tear deficiency be referred for an ophthalmic opinion.



Prescribing Guideline for Artificial Tears





KNOWN SENSITIVITY TO PRESERVATIVES
















YES
STANDARD 1
ST

LINE
TREATMENTS
1
ST
LINE
PRESERVATIVE-
FREE TREATMENTS
DEVELOPS
PRESERVATIVE
SENSITIVITY
NO
FAILURE TO RESPOND:
SECOND LINE TREATMENTS
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Drops

FIRST LINE TREATMENTS
WITH PRESERVATIVES WITHOUT PRESERVATIVES


HYPROMELLOSE 0.3%


MINIMS HYPROMELLOSE

LACRILUBE OINTMENT


SNOTEARS
HYPOTEARS
LIQUIFILM


CLINTAS SOOTHE
CELLUVISC 0.5%
ARTELAC

VISCOTEARS

CELLUVISC 1%
VISCOTEARS


SYSTANE


LACRILUBE OINTMENT
SECOND LINE TREATMENTS

HYABAK
OPTIVE
SYSTANE
HYLO-FORTE


Ointments
- Lacrilube PF ointment (s)
- Simple eye ointment (s)

Gels
- Polyacrylic acid Viscotears (PF also)
Celluvisc (PF)
(s)



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Special Indications
- Acetylcysteine 5%, 10% drops (5% PF)
(pH 8.5 approx.)
(s)
- Hypromellose 2% /1% drops (s)
- Hypromellose 0.3% PF drops (s)
- Ilube drops (acetylcysteine 5%,
hypromellose 0.35%)
(s)
- Paraffin liquid drops (s)
- Polyvinyl alcohol 1.4%unit dose (s)
- Sodium chloride 0.9% drops/minims/PF (s)
PF Prepared by Pharmacy Aseptic
Manufacturing
- Collagen implants ("Shields") (s)
- Sno strips (s)



Ocular Diagnostic and Peri-operative Preparations and
Photodynamic Treatment

Ocular Diagnostic Preparations

- Fluorescein Fluorets (s) Abrasions.
- Fluorescein 2% minims (s) Leaks.

- Fluorescein 10%/20%/25%
injection
(s) Ophthalmic angiography.

- Rose bengal 1% minims (s) Diagnostic ocular surface disorders.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Ocular Peri-operative Medicines
- Apraclonidine 1% / 0.5% unit dose
drops
(s) Prevention of elevated intra-ocular pressure
after anterior segment laser surgery.

- Diclofenac 0.1% unit dose (s) For post - operative inflammation.


- Flurbiprofen 0.03% unit dose (s)
- Ketorolac eye drops 0.5%(5mL)
(Acular)
(s)

Ophthalmic Surgery
- Fluorouracil 5mg/0.2mL injection (s) Trabeculectomy, enhancement. (from
cytotoxic unit)
- Mitomycin-C 200-400mcg/ml (s) Trabeculectomy enhancement (from
pharmacy cytotoxic unit)

- Acetylcholine 1% (Miochol) intra-
ocular irrigation 2mL
(s) Miosis during surgery.

- Balanced salt solution 15mL,
250mL, 500mL
(s) Irrigation during surgery.

- Botulinum Toxin (Dysport)
injection 500 units
(s) Blepharospasm, hemifacial spasm,squint,
protective ptosis.
- Perfluorocarboninjection (s) Retinal detachment surgery not with SPU.
- Pefluorohexiloctane injection (s) Alternative to silicone oil and perfluoctane
- Silicone oil 1300cst, 5000cst,
5700cst 10mL
(s) Intra-ocular tamponade.
- Densiron (s)

Viscoelastic Polymers
- Healon (Sodium hyaluronate 0.1%,
1%, 1.4% )
(s)
- Viscoat (Sodium chondroitin sulphate
4% & Sodium hyaluronate 3%)
(s)


Enzymes
- Hyaluronidase 1500 units injection (s)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Subfoveal Choroidal Neovascularisation ("Age Related Macular
Degeneration")

Intravenous Injection:
- Verteporfin 15mg injection (Visudyne) (s)

Intra-vitreal Injection
- Bevacizumab injection (s) Unlicensed - Prepared by Pharmacy Aseptic
Manufacturing
- Pegaptanib (Macugen) (s)
- Ranibizumab (Lucentis) (s)

Contact Lenses
- Where possible, during treatment with eye drops and ointments, contact lenses should
not be worn. This is most important where an infection is present.
- Hard lenses are hydrophobic and are therefore not readily penetrated by preservatives
or medication. Benzalkonium chloride can be adsorbed onto hard lenses increasing
incidence of sensitivity.
- Soft lenses are hydrophilic and are prone to absorption and accumulation of medications
and preservatives.
- Where eye drops are prescribed and continued use of contact lenses is necessary.
Preservative free drops should be used wherever possible.
- Where preservative free drops are not available lenses should be removed prior to
instillation of drops and not replaced for at least 15 minutes.
- Benzalkonium chloride is the preservative which causes most sensitivity problems and
preparations continuing this product should not be used.

Certain preparations stain soft lenses e.g. dyes (fluorescein and rose bengal).
adrenaline (epinephrine) and dipivefrin cause brown/black discoloration.

If in doubt, consult an ophthalmologist or the Corneal Specialist Nurse.

Administration of eye treatments whilst wearing contact lenses under the supervision of
an ophthalmologist, particularly if the contact lens is a bandage contact lens is usually
necessary and appropriate.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINES ACTING ON THE EAR, NOSE AND THROAT

Contents (Click on heading to go to that section)


Medicines Acting on the Ear
Otitis Externa
Removal of Ear Wax

Medicines Acting on the Nose
Medicines Used in Nasal Allergy
Topical Nasal Decongestants

Medicines Acting on the Oropharynx
Medicines for Oral Ulceration and Inflammation
Oropharyngeal Anti - infective Agents
Treatment of Dry Mouth
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Acting on the Ear

Otitis Externa

Notes
1. Exclude underlying chronic otitis media before commencing treatment.
2. If simple measures such as syringing fail, insert a Tri - adcortyl gauze wick and refer
to aural toilet clinic.
3. If an infection is present, use topical anti - infectives for one week only as prolonged
use may result in fungal infection. Refer if fungal infection is present. (Contact M
clinic, ext 2596).
4. The CSM advises that treatment with a topical aminoglycoside antibiotic is contra -
indicated in patients who have a perforated ear drum, due to the risk of ototoxicity.
5. An acute infection may require systemic antibiotics.


Astringent Preparations
- Aluminium acetate 8% drops (s) ENT only.
- Acetic Acid 2% spray (Ear Calm) (s) ENT only.


Anti-inflammatory Preparations
- Betamethasone 0.1% drops (s) ENT only.


Anti-infective Preparations
- Gentamicin 0.3% drops (s) ENT and A&E only (see notes above).

- Ciprofloxacin 0.3% eye drops (s) ENT and A&E only
Use Eye Drops Unlicensed route
- Gentamicin tympanic injection (s) ENT Consultants only
Unlicensed indication/route
- Methylprednisolone tympanic
Injection
(s) ENT Consultants only
Unlicensed indication/route

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Antiinflammatory Preparations with Antibacterials
- Gentamicin 0.3% with Hydrocortisone 1%
drops (Gentisone HC)
(s) ENT and A&E only (see notes above)

- Neomycin 0.5% with betamethasone 0.1%
drops (Betnesol N)
(s) ENT only

- Neomycin 3250units/mL, Dexamethasone
0.1%,glacial acetic acid 2% (Otomize ear
spray)
(s) ENT only.


Anti-inflammatory Preparations with Antibacterials and Antifungals
- Dexamethasone 0.05% Framycetin 0.5%,
Gramicidin 0.005% (Sofradex ) ear drops
(s) ENT only (see notes above).


Removal of Ear Wax

Wax may be removed by syringing with warm water. If necessary, wax can be softened
with olive oil ear drops before syringing. The patient should lie with the affected ear
uppermost for 5 - 10 minutes after a generous amount of the warmed olive oil has been
introduced into the ear. If simple remedies fail, sodium bicarbonate ear drops can be
used before syringing. Contact M clinic for advice.
- Olive oil ear drops Use 1mL oil (warmed to room temp) in the ear 5 - 10mins
before syringing.

- Sodium bicarbonate
5% drops
Apply 3 - 4 drops twice daily.




The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Acting on the Nose

Medicines Used in Nasal Allergy

Antihistamines
Oral antihistamines are of value in the treatment of nasal allergies, especially hay
fever, and may be of some value in vasomotor rhinitis. They reduce rhinorrhoea and
sneezing and may be used in conjunction with systemic nasal decongestants. For
more severe symptoms topical nasal decongestants are preferred, plus eye drops
(see section above) if necessary.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Topical Nasal Decongestants
Corticosteroids
- Beclometasone aqueous
nasal spray
2 sprays into each nostril twice daily. Max. 8 sprays a day.

- Fluticasone nasal spray
(Flixonase)
(s) ENT only. 2 sprays into each nostril once daily

- Betamethasone 0.1%
nose drops
(s) ENT only. 2-3 drops into each nostril 2-3 times a day.
Discontinue after 7 days treatment if no response.

- Fluticasone Nasal Drops
(Flixonase Nasules)
(s) ENT only. 200mcg (approx 6 drops) into each nostril
once or twice daily.
Discontinue after 7 days treatment if no response.

Sodium chloride 0.9% nasal drops may relieve nasal congestion by helping to liquefy
mucous secretions. Other topical nasal decongestants for symptoms associated with
vasomotor rhinitis, nasal polyps, and the common cold may be used short term (seven
days only). Long term use may give rise to rebound congestion creating a vicious circle.
- Sodium chloride 0.9%
nasal drops
Instil 1 - 2 drops into each nostril when required.

- Xylometazoline 0.1%
nasal drops/spray
Instil 2 - 3 drops or 1 spray into each nostril 2 3 times daily
when required. Max. duration 7 days.

- Glucose 25% in glycerine
nasal drops
(s) ENT only. Specially manufactured by pharmacy.
Systemic Decongestants
Avoid in hypertension, hyperthyroidism, renal failure, diabetes mellitus and glaucoma.


Nasal Staphylococci
- Mupirocin 2% nasal
ointment (Bactroban)
MRSA eradication:
- Chlorhexidine 0.1% and
neomycin 0.5% nasal
cream (Naseptin)
Eradication of nasal carriage of Staphylococci
Apply to nostrils 4 times daily for 10 days.

Prevention of nasal carriage of Staphylococci
Apply to nostrils twice daily.

- Hydrogen peroxide
cream 1.5% (Hioxyl)
Prevention of nasal carriage of Staphylococci:
Apply to nostrils 2-3 times daily. Microbiologist
recommended alternative to Mupirocin and Chlorhexidine/
neomycin products.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Acting on the Oropharynx

Medicines for Oral Ulceration and Inflammation
Ulceration of the oral mucosa may have a number of causes e.g. recurrent aphthae,
infections, carcinoma, dermatological disorders, nutritional deficiencies, gastro -
intestinal disease, haematopietic disorders, and medicine therapy. It is important to
establish the diagnosis in each case, as the majority of lesions require specific
management in addition to local treatment.
Local treatment aims to protect ulcerated areas, relieve pain or reduce inflammation.
Secondary bacterial infection may be a feature of any mucosal ulceration.

Simple Mouthwashes
- Mouthwash tablets Dissolve in warm water. To be used at frequent intervals.


Antiseptic Mouthwashes
- Chlorhexidine gluconate
0.2%
10mL to be rinsed around the mouth for 1 minute twice
daily. Do not swallow in large amounts.


Local Analgesics and Anaesthetics
- Choline salicylate oral gel Apply gel with gentle massage up to 3 hourly.

- Benzocaine10mg,
cetylpyridinium
(Merocaine)
One lozenge sucked every 2 hours or as required.
Max. 8 lozenges daily.

- Benzocaine compound
lozenges
One lozenge sucked slowly prior to intubation

- Benzydamine oral
rinse/spray (Difflam)
Rinse or gargle, using 15mL (dilute with water if stinging
occurs), or spray 4 - 8 puffs onto affected area every 2 - 3
hours as required. Do not swallow in large amounts.

Antiseptic Lozenges
There is no convincing evidence that antiseptic lozenges have a beneficial effect and
they may irritate the oral mucosa causing a sore tongue and lips.
- Cetylpyridinium
(Merocets)
Use when required.


Mechanical Protection
- Carbenoxolone 2% oral
gel
Apply after meals and at bedtime.

- Carmellose oral
paste(Orabase)
Apply a thin layer when necessary after meals.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Local Corticosteroids
- Hydrocortisone sodium
succinate 2.5mg (Corlan
pellets)
Place one lozenge in contact with the ulcer and allow to
dissolve slowly. Use 4 times daily after food.


Severe Recurrent Aphthous Ulceration
- Chlortetracycline 2%
mouthwash
Specially prepared by the Pharmacy.
10mL to be held in the mouth for 2 - 3 minutes 3 times
daily for no longer than 3 days. Wait for 3 days (to reduce
the incidence of oral thrush) before repeating.
- Triamcinolone May be incorporated into the Chlortetracycline mouthwash
for more severe cases. At higher doses this mouthwash is
given as a substitute for oral steroids and the same
systemic side effects may occur.
Dose range: 0.25mg - 2mg per 10mL of the mouthwash to
be used 3 times daily.

Oropharyngeal Anti - infective Agents

Candidiasis
Unopposed candida albicans may cause thrush. This is sometimes precipitated by the
use of broad spectrum antibiotics, immunosuppressant medicines or inhaled steroids. If
possible withdraw the causative agent. Advise patients to rinse the mouth after inhaled
steroid use and to use a spacer device.

Local Treatment ("Artificial Saliva")
- Oral Balance Gel For a dry mouth as a result of radiotherapy or sicca
syndrome: Apply to gums and tongue as required.
- Saliva Orthana spray For a dry mouth as a result of radiotherapy: Spray 2 - 3
times onto oral and pharyngeal mucosa when required.
(N.B. porcine derivative).

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINES ACTING ON THE SKIN

Contents (Click on heading to go to that section)

Management of skin conditions
Vehicles and Diluents

Emollient and Barrier Preparations

Topical Local Anaesthetics and Antipruritic Preparations
Topical Corticosteroids
Formulation Choice
Mild Potency
Moderate Potency
Potent
Very Potent

Preparations for Eczema and Psoriasis
Vitamin D and Analogues
Coal Tar Preparations
Bath preparations

Medicines Affecting the Immune Response
Acne and Rosacea
Topical Preparations for Acne
Oral Preparations for Acne


Warts and Calluses

Sunscreens and Camouflagers

Shampoos and Other Preparations for Scalp Conditions
Corticosteroids
Coal Tar
Other Scalp Preparations

Anti - infective Skin
Antibacterial Preparations
Antifungal Preparations
Antiviral Preparations

Parasiticidal Preparations

Preparations for Minor Cuts and Abrasions

Skin Cleansers and Antiseptics

Antiperspirants
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Management of skin conditions
All items marked (s) are restricted to dermatologists only.

* Denotes items which require individual preparation in pharmacy. These have a limited shelf
life and are more difficult for patients to obtain in the community.
# Denotes preparations which may be diluted with a suitable vehicle.

Vehicles and Diluents
Aqueous cream
Cetomacrogol formula A
Emulsifying ointment
Hydrous ointment (Oily cream)
Lassar's/Hard Lassar's paste
Paraffin soft white/yellow
Unguentum M

Emollient and Barrier Preparations
- Aqueous cream
- Dermol 500 Lotion
- Diprobase
cream/ointment
- E45 cream
- Emulsifying ointment
- Epaderm
- Hydromol Ointment
- Liquid paraffin
- Liquid paraffin/WSP
50:50
- Oilatum cream
- Unguentum M

Preparations Containing Urea
- Urea cream 10%
(Nutraplus)


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Emollient Bath Additives
- Balneum bath oil
- Balneum Plus bath oil
- Emulsiderm bath additive
- Oilatum emollient bath oil.
- Oilatum Plus emollient
- Oilatum shower gel

Barrier Preparations
- Cavilon cream
- Liquid Paraffin/WSP
50:50 ointment

Topical Local Anaesthetics and Antipruritic Preparations
- Lidocaine [lignocaine]
5% ointment
Apply when required. Max. 35g in 24 hours.
- Calamine lotion Apply when required.
- Menthol 1% in aqueous
cream

- Crotamiton cream/lotion
(Eurax)
Only for use post scabies treatment.


Topical Corticosteroids
Formulation Choice

Creams are suitable for moist or weeping lesions whereas ointments are preferable for dry,
lichenified or scaly lesions or where a more occlusive effect is required.

It is important to reduce strength and frequency of applications as the condition responds.

Mild Potency
Hydrocortisone
- Hydrocortisone 0.5%, 1%
cream/ointment
Apply 2 - 4 times daily.
- Hydrocortisone2.5%
cream/ointment
(s)
- Mildison Lipocream (s)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Compound Preparations
- Alphosyl HC cream Coal tar extract 5%, allantoin, hydrocortisone 0.5%.
- Canesten HC cream With clotrimazole.
- Daktacort cream/ointment (s) With miconazole.
- Eurax HC cream (s) With crotamiton.
- Fucidin H
cream/ointment/gel
(s) With sodium fusidate.
- Nystaform HC
cream/ointment
(s) With nystatin and chlorhexidine.
- Vioform HC
cream/ointment
(s) With clioquinol. Stains clothing.

Moderate Potency
Alclometasone
- Modrasone cream/ointment (s) Cost band for 50g:

Betamethasone Valerate
- Betnovate RD cream/ointment Apply 2 - 3 times daily.

Clobetasone Butyrate
- Eumovate cream/ointment Apply up to 4 times daily.
- Trimovate cream (s) With oxytetracycline and nystatin. Stains
clothing.

Fluocinolone Acetonide
- Synalar 1 in 4 cream/ointment (s) Cost band for 50g cream:

Fludroxycortide [Flurandrenolone]
- Haelan cream/ointment/tape (s) Cost band for 60g:

Potent
Beclometasone [Beclomethasone] Dipropionate
- Propaderm
cream/ointment
(s)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Betamethasone Valerate
- Betnovate
cream/lotion/ointment*#
(s)
- Betnovate C
cream/ointment
(s With clioquinol.
- Betnovate N
cream/ointment
(s) With neomycin.
- Fucibet cream (s) With fusidic acid.

Betamethasone Dipropionate
- Diprosalic ointment (s) With salicylic acid.
- Diprosone
cream/ointment/lotion
(s)
- Lotriderm cream (s) With clotrimazole.

Diflucortolone Valerate
- Nerisone
cream/ointment/oily
cream
(s)

Fluocinolone Acetonide
- Synalar cream/ointment (s)
- Synalar C
cream/ointment
(s) With clioquinol.

Fluocinonide
- Metosyn cream/ointment (s)

Hydrocortisone - 17 - Butyrate
- Locoid cream/ointment/
lipocream
(s)
- Locoid C cream/ointment (s) With chlorquinaldol.

Mometasone Furoate
- Elocon
cream/ointment*#/lotion
(s) *# in Emulsifying ointment, WSP, LP/WSP

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Triamcinolone Acetonide
- Nystadermal cream (s) With nystatin.

Very Potent
Clobetasol Aropionate
- Dermovate cream (s)
- Dermovate ointment (s)
- Dermovate ointment* (s) (10%,25% or 50%) in white soft paraffin ointment
- Clobetasol 0.05%,
neomycin 0.5%, nystatin
100,000 IU
cream/ointment 30g
(s) (Generic version of Dermovate NN cream/ointment)


Diflucortolone Valerate
- Nerisone Forte
ointment/oily cream*
(s)

Preparations for Eczema and Psoriasis
Preparations for psoriasis
Vitamin D and Analogues
- Calcipotriol
cream/ointment
(s)
- Dovobet Ointment (s) Consultant Dermatologists only betamethasone 0.05%
(as diproprionate), calcipotriol 50micrograms / g
- Silkis Ointment
(Calcitriol) for fleural
psoriaris
(s)


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Coal Tar Preparations
Topical Preparations
- Alphosyl cream (s) Coal tar extract 5%, allantoin 2%.
- Alphosyl HC
cream/hydrocortisone
(s) Coal tar extract 5%, allantoin 2%, 0.5
- Coal tar solution 5%* in: Betnovate ointment (s)
- Coal tar solution (5% or
12%) and salicylic acid
(3%)* in:
Eumovate ointment, (s)
- Crude coal tar* : (1%, 2%, 5% or 10%) in Yellow Soft Paraffin
- Exorex Lotion (s) Coal tar 1%

Bath Preparations
Dithranol
- Dithranol (0.25%, 0.5%,
1%, 2%, 4% or 8%) and
salicylic acid 0.5%* * in:
Emulsifying ointment. (s)
- Dithranol (0.1%, 0.25%,
0.5%, 1%, 2%, 4% or
8%) in
Lassars paste ointment (s)
- Dithranol cream
(Dithrocream) 0.1%,
0.25%, 0.5%, 1%, 2%
(s)
- Dithranol 0.25% in
Haldens emulsifying base
(Dithranol pomade) (s)


Salicylic Acid
- Zinc and salicylic acid
paste (Lassar's paste)
(s)
- Salicylic acid ointment
2%
(s)
- Salicylic acid (2%, 5% or
10%)* in:
(s) Emulsifying ointment.

Oral Retinoids for Psoriasis
- Acitretin capsules (s) Consultant Dermatologists only. Hospital product
only.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Medicines Affecting the Immune Response
- Ciclosporin
capsules/liquid
(s) Consultant Dermatologists only. Note: Prescribe by
brand name (Capimune) as the different preparations have
different bio-availabilities. Start all new patients on
Capimune.
- Mycophenolate 250mg
capsules or 500mg
tablets
(s) Consultant Dermatologists only. Note: Prescribe by
brand name e.g. Myfenax. Start all new patients on
Myfenax
- Infliximab injection (s) Consultant Dermatologists only
- Etanercept injection (s) Consultant Dermatologists only
- Ustekinumab Injection (s) Consultant dermatologists only
- Methotrexate tablets (s) Consultant Dermatologists only. Note: This is a once
weekly dose.
- Tacrolimus 0.03%; 0.1%
ointment
(s) Consultant Dermatologists only "Protopic"
- Pimercrolimus1%
(Elidel) Cream
(s) Consultant Dermatologists only

Methoxalen (Psoralens) Preparations for Psoriasis
- Methoxypsoralen tablets (s) Unlicensed. Consultant Dermatologists only. 5 -
methoxypsoralen and 8 - methoxypsoralen available.
Prescriptions must state the brand to be used rather than
5 - or 8 - methoxypsoralen

Acne and Rosacea
Topical Preparations for Acne
Benzoyl Peroxide and Azelaic Acid
- Benzoyl peroxide 2.5,5,10% gel/wash (Panoxyl) (s)

Topical Antibacterials for Acne
- Clindamycin topical solution (Dalacin T) (s)
- Erythromycin topical solution with zinc (Zineryt) (s)

Topical Retinoids and Related Preparations for Acne
- Adapalene 0.1% cream/gel (Differin) (s)
- Tretinoin cream/forte cream/lotion/forte gel/gel
(Retin A) Isotretinoin gel
(s)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Oral Preparations for Acne
Hormone Treatment for Acne
- Dianette tablets (s) Consultants only.
Oral Retinoid for Acne
- Isotretinoin capsules (s) Consultant Dermatologists only. Hospital only.
Roaccutane brand 10mg and 20mg capsules or
Beacon brand 5mg and 20mg capsules

Preparations for Warts and Calluses
- Salactol paint
- Salatac gel
- Salicylic acid 40% in WSP (s)

Anogenital Warts
- Imiquimod cream (s) G.U.M. and Dermatology only
- Podophyllotoxin 0.5%topical solution (s) G.U.M. only.
- Trichloroacetic acid 50%, 90% (s) G.U.M. only.

Sunscreens
Sunscreen Preparations
- RoC sunscreen clear/tintedSPF 25 (UVA and
UVB)
(s)
- Spectraban lotionSPF 25 (UVB) (s)
- Spectraban Ultra lotionSPF 28 (UVA and UVB) (s)
- Uvistat cream SPF 20, SPF 30, lipscreen SPF
15(UVA and UVB)



The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Shampoos and Other Preparations for Scalp Conditions
Corticosteroids
- Betnovate
(Betamethasone valerate)
(s)
- Dermovate(Clobetasol) (s)
- Diprosalic
(Betamethasone, salicylic
acid)
(s)
- Diprosone(Betamethasone
dipropionate
(s)
- Elocon(Mometasone
furoate)
(s)

Coal Tar
- Alphosyl shampoo/ 2 in 1
shampoo
(s) Alcoholic coal tar extract 5%.
- Capasal shampoo Coal tar 1%, coconut oil 1% salicylic acid 0.5%.
- Cocois ointment Cost band for 100g: C
- Coconut compound
ointment
(s)
- Polytar/Polytar plus
shampoo
(s)
- SCC sal/SCC sal (scalp)
ointment
(s) Sulphur, camphor, carbolic acid, salicylic acid.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Other Scalp Preparations
- Calcipotriol scalp
lotion(Dovonex)
(s)
- Xamiol scalp gel (s) (calcipotriol & betamethasone)
- Ceanel concentrate
shampoo (cetrimide)
(s) Cost band for 150mL: B
- Ketoconazole shampoo
(Nizoral)
(s) Dermatologists and G.U.M. only. Cost band for 120mL:
C
- Selsun shampoo
(Selenium sulphide)
(s) Cost band for 150mL:B
- Stimulant lotion (s)
- Enflornithine cream
(Vaniqua)

(s) Endocrinologists


Anti - infective Skin Preparations
Antibacterial Preparations
Antibacterial Preparations Only Used Topically
- Mupirocin
ointment(Bactroban)
Treatment of MRSA infected wounds. Apply once daily to
wound for 7 days before re-screening as per MRSA policy
- Silver sulfadiazine
cream(Flamazine)

- Polymyxins (Polyfax
Ointment)


Antibacterial Preparations Also Used Systemically
- Chlortetracycline
cream/ointment
(Aureomycin)
(s)
- Fusidic acid
cream/gel(Fucidin)
(s)
- Metronidazole 0.75% gel (s)
- Metronidazole 0.8% gel For malodorous wounds.
- Metronidazole 0.5% lotion (s)
- Sodium fusidate ointment Apply 3 - 4 times daily, less often if dressings used.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Systemic Antibacterial Preparations Used in Dermatology
- Doxycycline
capsules/soluble tablets
(s) Dermatologists and G.U.M. only.
- Erythromycin tablets Acne: 250 - 500mg 4 times a day.
- Lymecycline 408mg
Caps (Tertracycline
300mg)
Acne: 408mg OD x 8 weeks.
- Minocycline tablets/sr
tablets
(s)
- Oxytetracycline tablets Acne: 250 - 500mg 4 times a day.
- Trimethoprim Tablets Acne:300mg BD (unlicensed)

Antifungal Preparations
- Clotrimazole cream/
powder/solution (for hairy
areas)
Apply 3 times daily.
- Itraconazole capsules (s) Dermatologists, GUM and Consultants only.
- Ketoconazole cream (s)
- Ketoconazole shampoo (s)
- Miconazole cream (s)
- Nystatin cream/ointment (s)
- Terbinafine tablets/cream (s) Dermatologists and Consultants only.

Antiviral Preparations
- Aciclovir
cream/dispersible tablets


Parasiticidal Preparations
Scabies
Refer to Dermatologists if possible. Itching may be
relieved with calamine lotion or oral antihistamines.
Choice:
- Permethrin dermal cream
Alternative:
- Benzyl benzoate 25%
application
(s) Irritant, may need up to 3 applications to be effective.
Prescription by Dermatology only. Under 12 years use 1/2
strength, under 2 years use 1/3 strength, diluent water.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Headlice

Choice:
- Malathion alcoholic lotion (Suleo M)
- Malathion aqueous lotion (Derbac M)

Crab (pubic) Lice

- Malathion aqueous lotion (Derbac M)

Preparations for Minor Cuts and Abrasions
- Magnesium sulphate
paste (for boils)

Skin Tissue Adhesive
- Enbucrilate (Histoacryl)

Skin Cleansers and Antiseptics
Alcohols and Saline
- Sodium chloride for
irrigation


Chlorhexidine Salts
- Chlorhexidine alcoholic solution
0.5%, aqueous solution 0.5%
pink/colourless

- Chlorhexidine 0.015%, cetrimide
0.15% sachets 25mL, 100mL

- Chlorhexidine gluconate 0.05%
sachet, skin cleaner (Hibiscrub)
spray 2.5%,0.1%,


Chlorine and Iodine
- Weak alcoholic iodine solution (s)
- Povidone iodine solution
(alcoholic, antiseptic, dry powder
spray, scalp and skin cleanser,
surgical scrub)

- Povidone iodine ointment

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Phenolics
- Triclosan (Manusept alcoholic
hand rub, Aquasept Bath
concentrate, aquasept)


Astringents, Oxidisers and Dyes
- Aluminium acetate solution* (s) Requires preparation in Pharmacy.
- Hydrogen peroxide solution
(3%, 6%), cream 1.5%
Due to its potential hazards, this product should only be
used in exceptional circumstances and must be
prescribed by a doctor of registrar grade or above. Can
be used to clean open, dirty, contaminated, traumatic
wounds and infected, sloughy and necrotic wounds.
May be used as a mechanical cleansing agent due to
its foaming action.
It is NOT recommended for clean wounds or closed or
tunnelling wounds.

- Potassium permanganate
solution/tablets
(s)
- Silver nitrate solution (0.25%,
0.5%, 5%)*/sticks
(s)

Antiperspirants
- Driclor (s)
- Glycopyrrolate 0.05%
soln.*
(s) Requires preparation in Pharmacy.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

IMMUNOLOGICAL PRODUCTS AND VACCINES

Contents (Click on heading to go to that section)


Vaccines and antisera
Immunoglobulins
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Vaccines and antisera

BCG Vaccines
- BCG freeze - dried
vaccine
(s) Occupational Health only.

BCG diagnostic agents

No licensed preparation for the Mantoux test is currently available. An unlicensed
preparation, available in 2 and 10 units of Tuberculin PPD per 0.1mL is stocked.
Please contact Medicines Information (ext 2096) for further information.

Haemophilus influenzae type B vaccine
- Haemophilus B (Hib)
vaccine
(s) Consultants only.
Conjugated polysaccharide vaccine. 0.5ml by i.m. Injection
or deep sub-cutaneous injection if there is a high risk of
bleeding. See section 1 for immunisation of splenectomy
patients.

Hepatitis vaccines
- Hepatitis A vaccine (s) Occupational Health / Infectious Diseases/ School of
Tropical Medicine / Gastroenterology / G.U.M. only.
- Hepatitis B vaccine (s) Occupational Health / Infectious Diseases/ School of
Tropical Medicine / Gastroenterology /G.U.M./
Haemodialysis patients only.
- Twinrix (Hep A&B)
vaccine
(s) For use by registrars and above in G.U.M.

Influenza vaccine
- Influenza vaccine (s) Consultants only.
See section 1 for immunisation of splenectomy patients.

Meningococcal vaccines
- Meningococcal C
conjugate
(s) Consultants only.
0.5ml by I.M. injection. May be given by deep sub-
cutaneous injection if there is a high risk of bleeding. See
section 1 for immunisation of splenectomy patients.
- Meningococcal A & C
vaccine
(s) Consultants only.


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Pneumococcal vaccine
- Pneumococcal vaccine (s) Consultants only.
Pneumovax II vaccine. 0.5ml by subcutaneous or intra-
muscular injection. See section 1 for immunisation of
splenectomy patients.

Varicella-zoster vaccine

- Varicella-zoster vaccine (s) Relevant renal transplant patients only.



Tetanus Vaccines
- On the advice of the Joint Committee on Vaccination and Immunisation (JCVI)
the Department of Health has changed the current policy for tetanus
immunisation in adult life.
- To counter the declining immunity to diphtheria seen in adults
- Adsorbed Tetanus vaccine has been discontinued.
- Adsorbed Diphtheria (low dose) Tetanus and Inactivated Poliomyelitis
Vaccine is to be used in its place.

- Adsorbed Diphtheria (low
dose) Tetanus and
Inactivated Poliomyelitis
Vaccine for adults and
adolescents
0.5mL by deep s.c or i.m. injection. See below appropriate
use and course length.

Treatment of patients with tetanus - prone wounds

The following are considered tetanus - prone wounds:

a) Any wound or burn sustained more than 6 hours before surgical treatment of the
wound or burn.
b) Any wound or burn at any interval after injury that shows one or more of the
following characteristics:
i. significant degree of de - vitalised tissue
ii. puncture type wound particularly animal bites
iii. contact with soil or manure likely to harbour tetanus organisms
iv. clinical evidence of sepsis

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Specific Anti - Tetanus Prophylaxis
Thorough surgical toilet of the wound is essential whatever the tetanus immunisation
history of the patient.

Immunisation status Type of wound

Clean Tetanus prone
Last of 3 dose course, or
reinforcing dose within last
10 years.
Nil Nil (but give dose of tetanus
immunoglobulin 0.5mL by
deep s.c/i.m. injection if
infection risk is high e.g.
contamination with manure).
Last of 3 dose course or
reinforcing dose more than
10 years previously
Reinforcing dose Adsorbed
diphtheria (low dose) Tetanus
and inactivated poliomyelitis
vaccine (0.5mL by deep
s.c./i.m. Injection).
Reinforcing dose of Adsorbed
Diphtheria (low dose) Tetanus
and inactivated poliomyelitis
vaccine 0.5mL PLUS human
anti - tetanus immunoglobulin
(250units)* by deep s.c./i.m.
injection at different site to the
vaccine e.g. other arm.
Not immunised or
immunisation status
unknown
A full 3 dose course of tetanus
vaccine at one month intervals
A full 3 dose course of tetanus
vaccine PLUS dose of human
anti - tetanus immunoglobulin
(250units)* by deep s.c./i.m.
injection at different site to
vaccine.

*Give 500units:
a) if more than 24 hours since injury,
b) if there is risk of heavy contamination or
c) following burns.
Note: Tetanus vaccine should not be given to anyone suffering an acute febrile illness
except in the presence of a tetanus - prone wound.



Immunoglobulins
- Human anti tetanus immunoglobulin Prophylaxis: 250 - 500units by deep s.c. or
i.m.injection. See table on page 327 for
appropriate use.
Treatment: 150units/kg in multiple injection
sites.

All other immunoglobulins are restricted by NHS directive to approved indications
and patients only. Consultants will be asked to complete a form for the Trust
Immunoglobulins Committee before stock can be issued. Contact Pharmacy for
advice.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

MEDICINES USED IN ANAESTHESIA

Contents (Click on heading to go to that section)


Anaesthesia and Driving

Surgery and Long Term Medication

General Anaesthesia
Intravenous Anaesthetics
Inhalational Anaesthetics
Antimuscarinic Medicines
Sedative and Analgesic Peri-Operative Medicines
Muscle Relaxants
Drugs for reversal of neuromuscular blockade
Antagonists for Central and Respiratory Depression
Antagonists for Malignant Hyperthermia

Local Anaesthesia
Protocol for administration of Lipid emulsion (Intralipid) to treat
overdose of local anesthetic

Guidelines for the perioperative betablockade of patients undergoing major
surgery

Trust Clinical Policy for Continuation of Medicine Therapy in the Peri-Operative
Period: a Guide for Ward Staff
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011



Items marked with (s) in this section are restricted to Anaesthetists and Consultants in
Intensive Therapy Medicine unless stated otherwise. Prescribers who have adequate
and recognised training in their use may prescribe them.

Anaesthesia and Driving

Patients administered a general anaesthetic, sedatives (e.g. intravenous
benzodiazepines) or analgesics during minor surgery (including day case surgery)
should be warned about the risk of driving afterwards. The DVLA advise that it is the
responsibility of the driver to ensure that he/she is in control of the vehicle at all times
and to be able to demonstrate that is so, if stopped by the police. The DVLA also
mention that it might also be reasonable for the driver to check his/her insurance policy
before returning to drive after surgery. It should be noted that suitability to drive does
not only include recovery from general anaesthetic it includes issues such as
unsuitability to drive due to pain etc. The dangers of taking alcohol should also be
emphasised.


Surgery and Long Term Medication

The risk of stopping long - term medication before surgery is often greater than the
risk of continuing it during surgery. For more information on which medicines can be
stopped, refer to the Trust Clinical Policy regarding continuation of medication in the
peri-operative period which is included towards the end of this chapter. If you require
further clarification contact an anaesthetist. For alternative routes of medicine
administration, contact Medicines Information (ext 2096) or your ward pharmacist.


Sealants and haemostatic agents used during surgery

A variety of agents are available to augment traditional haemostatic techniques
during surgery with varying components and licensed indications. Some of these
products are classed as devices, others as drugs. Agents that are approved for use
within the Trust and available from pharmacy are:


Evicel Contraindicated in neurosurgery due to lack of data

Tisseel Ready to use Haemostasis, CSF leaks and small dural defects in
spinal surgery
Not for use in active bleeding
(Replaces Tisseel LYO)

Floseal For active bleeding sites in vascular spine tumour surgery

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

General Anaesthesia

Intravenous Anaesthetics

Etomidate injection (s)
Ketamine injection (CD) (s)

Ketamine is also available as an oral solution (unlicensed).
This is occasionally used as a pre-med / sedation e.g. in
dental hospital it is used as a sedative with midazolam for
patients with special needs.

Propofol 1% injection (s)

Note This preparation is based on a lipid emulsion.
Monitor triglycerides closely, especially if the patient is
receiving an additional source of intravenous lipids e.g. as
part of a parenteral nutrition regime.
Thiopental [thiopentone]
injection
(s) Available as a 500mg vial


Inhalational Anaesthetics


Desflurane (s)
Halothane (s) See CSM advise in BNF re: hepatoxicity
Isoflurane (s)
Sevoflurane (s)
Nitrous oxide 50% / oxygen
50% (Entonox)
Entonox is used to produce analgesia without loss of
consciousness. It is also used for painful procedures
including dressing changes (See separate Trust protocol ).
Note - Exposure of patients to nitrous oxide for prolonged
periods, either by continuous or intermittent administration
may result in megaloblastic anaemia. Depression of white
cell count may also occur.

Antimuscarinic Medicines

Atropine injection (s)
Hyoscine hydrobromide
injection
Effective in reducing respiratory secretions. It also has sedative action,
but may occasionally cause paradoxical excitement
Glycopyrronium bromide
injection
(s)

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Sedative and Analgesic Peri-Operative Medicines

Anxiolytics and Neuroleptics

Diazepam tablets / injection
(Diazemuls).
Long acting benzodiazepine. Drowsiness may occur for
several hours after administration due to active
metabolites. Repeated doses may lead to accumulation,
especially in patients with hepatic and renal impairment.
Lorazepam tablets / injection Sedation more prolonged than for temazepam.
Midazolam injection (CD) The use of midazolam should be restricted to those
prescribers who have adequate and recognised training in
its use. If midazolam is to be used, flumazenil should be
available (benzodiazepine antagonist) in case it is required
to reverse the sedative effects of midazolam. Flumazemil
has a shorter half-life than that of diazepam and midazolam,
and there is a risk that patients may become re-sedated.
Temazepam tablets (CD) Short acting benzodiazepine. Given orally, it has a shorter
duration of action than oral diazepam. Anxiolytic and
sedative effects last for about 90 minutes although there
may be residual drowsiness after this. May need to consider
lowering dose in hepatic impairment.

Non-Opioid Analgesics
Diclofenac
tablets/suppositories/
injection
Max. total dose by any route is 150mg/24 hours. The
maximum licensed duration of parenteral therapy is 48
hours and IV diclofenac should not be infused together
with other medicines.
Ketorolac injection (s). By mouth 10mg every 4 6 hours (elderly 6 8
hours); max 40mg daily; max duration 7 days
By i.m. or i.v injection (over at least 15 seconds), Initially
10mg maximum. Then may increase to 10 30 mg every 4
6 hours as required; max 90mg daily (elderly and patients
weighing <50kg max 60mg daily); max duration 2 days

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Opioid Analgesics
Note: Details of oral / transdermal opioid preparations are listed in Chapter 4

Alfentanil injection (CD) (s) It is available as a 500microgram/ml and a 5mg/ml
injection.
Note Two strengths one is TEN times more
concentrated than the other. The higher strength is
restricted for use in ITU only.
Fentanyl injection (CD) (s)
Morphine injection (CD) Available as 50mg/50ml syringe for patient controlled
analgesia regimens
Pethidine injection (CD)
Tramadol capsules /
injection
Tramadol has an opioid effect in addition to an enhancement
of serotonergic and adrenergic pathways. Its use is
restricted within the Trust.
Remifentanil injection (s)



Neuromuscular blocking drugs Muscle Relaxants

Non-Depolarising Muscle Relaxants
Atracurium injection (s)
Cisatracurium injection (s)
Mivacurium injection (s)
Rocuronium injection (s)
Pancuronium injection (s)
Vecuronium injection (s)

Depolarising Muscle Relaxants
Suxamethonium injection (s)


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Drugs for reversal of neuromuscular blockade

These drugs are used to reverse the effect of the non-depolarising muscle
relaxants.
Caution May prolong action of depolarising drugs such as suxamethonium.

Neostigmine injection (s)
Neostigmine with
Glycopyrronium injection
(Robinul - Neostigmine)

Sugammadex
(s) Glycopyyronium prevents bradycardia, excessive
salivation, and other muscarinic effects of neostigmine.


(s) For reversal of neuromuscular blockade induced by
rocuronium or vecuronium only. Restricted use.


Antagonists for Central and Respiratory Depression
Doxapram injection See Section 2 for administration details.

Flumazenil injection (s) Flumazenil may be used to reverse the central sedative
effects of benzodiazepines. Flumazenil has a shorter half-life
than that of diazepam and midazolam, and there is a risk
that patients may become re-sedated. Repeated doses may
be required.

Naloxone injection Naloxone may be used to reverse opioid-induced
respiratory depression. It will also antagonise the
analgesic effect. The dose may have to be repeated
because of its short duration of action.


Antagonists for Malignant Hyperthermia
Dantrolene injection (s) Available in all trust operating theatres


The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Local Anaesthesia

Topical Preparations
Ethyl chloride spray
Lidocaine [lignocaine] 2% gel
Lidocaine [lignocaine] 5% ointment
Lidocaine [lignocaine] 10% spray
Lidocaine [lignocaine] 4% spray (Laryngojet)
Lidocaine [lignocaine] topical soln. 4%, 10%
Lidocaine [lignocaine] with chlorhexidine antiseptic gel 2%
Emla cream (Lidocaine [lignocaine] and Prilocaine)
Adrenaline (epinephrine) 1 in 1000 topical solution
Cocaine topical solution (CD) 2.5%, 4%, 10%
Tetracaine (amethocaine) gel 4% (Ametop) (s)


Parenteral Preparations

Bupivacaine 0.25%, 0.5%
with adrenaline
(epinephrine) injection

Bupivacaine Heavy 0.5%
(s)



(s) For intrathecal anaesthesia
Levobupivacaine 0.125%
and Fentanyl
4micrograms/ml in 500ml
Sodium Chloride 0.9%
(CD)
(s) This solution is for epidural use only

Levobupivacaine injection
injection 0.25%, 0.5%,
0.75%
(s) Note Levobupivacaine 0.75% injection restricted for use
in Ophthalmology Theatres.

Lidocaine [lignocaine] 0.5 -
2% with adrenaline
(epinephrine) 1 in 80,000
to 1 in 200,000 injection.

Prilocaine 1%, 2%, 4%
injection


Prilocaine 3% with
octapressin injection


Ropivacaine injection 0.2%
200ml
(s) Epidural infusion

Dehydrated alcohol Injection. Used very occasionally for chronic pain blocks.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Protocol for administration of Lipid emulsion (Intralipid) for the
management of severe local anaesthetic toxicity

This policy is based on the Association of Anaesthetists of Great Britain & Ireland
(AAGBI) safety guideline 2010.

Procedure
1. Gently shake bag of Intralipid 20% two or three times before use.
2. Immediately give an initial intravenous bolus injection of 20% lipid emulsion
1.5 ml/kg over 1 min AND start an intravenous infusion of 20% lipid emulsion
at 15 ml/kg/hr
3. After 5 minutes give a maximum of two repeat boluses (same dose) if:
cardiovascular stability has not been restored or
an adequate circulation deteriorates
Leave 5 min between boluses
A maximum of three boluses can be given (including the initial bolus)
4. Continue infusion at same rate, but:
Double the rate to 30 ml/kg/hr at any time after 5 min, if:
cardiovascular stability has not been restored or
an adequate circulation deteriorates
Continue infusion until stable and adequate circulation restored or maximum
dose of lipid emulsion given

Do not exceed a maximum cumulative dose of 12 ml/kg


Model example for resuscitating an adult weighing 70kg who has accidentally
received a toxic dose of local anaesthetic and who has consequent cardiovascular
collapse.

1. Take a 500 ml bag of Intralipid 20% from CD cupboard in Theatre
(labelled For use during resuscitation only) and a 50 ml syringe.
2. Give an initial intravenous bolus injection of 20% lipid emulsion 100 ml over 1
min (Draw up 50 ml and give over 30 seconds, repeat for another 50ml)
3. Attach remaining Intralipid 20% bag (400ml) to a giving set and run it
intravenously at 1000ml/hr
4. After 5 minutes give a maximum of 2 repeat boluses of 100ml (if indicated)
5. Continue infusion at same rate but double rate to 2000 ml/hr at any time (if
indicated)

Do not exceed a maximum cumulative dose of 840 ml


Exclusions: Allergy to intralipid.
Pre-existing severe disorders of fat metabolism

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Guidelines for the perioperative betablockade of patients
undergoing major surgery

Beta-blockade should be started pre-operatively and continued post-operatively
according to the following guidance.

The ultimate decision on whether or not to implement this guideline rests with the
responsible anaesthetist. Additionally, modification may be necessary when it is
planned to carry out regional anaesthesia.

For further information contact: Drs C.J.R. Parker, R. Wenstone and O. Zuzan

Indications Patients who are scheduled to undergo a major surgical procedure
e.g.intraperitoneal, intrathoracic, peripheral vascular surgery or
replacement of a large joint and who have any of the following risk factors
Risk factors Age > 70 years
Current angina
Previous myocardial infarction
Congestive cardiac failure
Previous cerebrovascular accident
Diabetes, requiring treatment other than dietary restriction alone
Renal dysfunction (defined as creatinine > 177 micromol/L)
Contra-
indications
(i.e. exclude
the following):
Patients who have asthma.
Patients who fulfill the criteria for NYHA class IV cardiac failure (i.e.
symptoms with any activity or dyspnoea at rest)
Patients who have 2 or 3 heart-block
Protocol: 1. If already receiving regular beta-blocker medication this must be
continued.

2. If not already receiving regular beta-blocker medication, start atenolol
as follows:
Start 50 100 mg daily orally from admission. Titrate to a heart rate
of < 65/min.
50 mg orally with premed (or 5 10 mg IV in the anaesthetic room
pre-op at the discretion of the anaesthetist) and
50 100 mg/day orally (or 5 mg IV BD if GI route not available) for 7
days or until discharge if sooner.

Hold doses if HR < 55/min or systolic BP < 100mmHg.

Reduced dosage may be needed in patients with renal impairment.

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

Guidelines regarding continuation of medicines in the Peri-
Operative Period

This section aims to provide a brief overview of the administration of medication in
the peri-operative period, and should be a useful guide to clinical staff who routinely
prescribe and administer medicines during the peri-operative period. The guide
includes brief information relating to those medicines which MUST be continued peri-
operatively, and those which may require withholding peri-operatively.

It is beyond the scope of this section to include examples of all drug form, route and
formulation changes. Please contact Medicines Information (ext 2096) for further
information


BNF Chapter Medicine type /
name
Recommendation / Comment
1: Gastro -
Intestinal
System
Antacids Usually continued, to reduce risk of acid aspiration
Antispasmodics /
Antimuscarinics
Usually continued, but may omit on day of surgery
to reduce risk of ileus
H
2
antagonists /
Proton-pump inhibitors
Usually continued, to reduce risk of rebound acid
secretion
Some patients may benefit from short-term initiation
of H2 antagonist / PPI therapy in the NBM
period

Anti-diarrhoeals Usually continued but review need in the light of
presenting complaint

Aminosalicylates Usually continued

Laxatives Usually continued, but note contra-indications for
each and review in the context of presenting
complaint
Isphagula is contra-indicated in intestinal
obstruction and colonic atony
Docusate is contra-indicated in abdominal pain,
nausea, vomiting or intestinal obstruction
Senna is contra-indicated in undiagnosed acute or
persistent abdominal symptoms
2:
Cardiovascular
system
General comment: continuing antihypertensive medicines improves
cardiovascular stability and reduces morbidity. Always check BP before
prescribing / administering an anti-hypertensive, and if unsure check with
anaesthetist.
Oral inotropes e.g.
digoxin
Usually continued
Refer to anaesthetist if hypokalaemic,
hypomagnesaemic or hypercalcaemic, as these
can increase myocardial sensitivity to digoxin,
which may result in toxic digoxin levels.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

BNF Chapter Medicine type / Recommendation / Comment
name
Check level as part of routine pre-op assessment
(at least 6-8 hrs after previous days dose). This
may not be necessary in patients who are
stable on a maintenance dose.
100 micrograms IV digoxin approximately
equivalent to 125 micrograms oral digoxin
Thiazide / Loop
diuretics
e.g.
bendroflumethiazide
and furosemide
Usually continued, especially if used for heart
failure or advanced renal failure. May omit if
patient admitted for minor procedure under local
anaesthetic.
Antihypertensive and diuretic effect (especially loop
diuretics) may be reduced by concomitant
NSAIDs such as indometacin, piroxicam,
diclofenac and naproxen.
Max i.v. rate for furosemide = 4mg/minute
Potassium-sparing
diuretics
e.g. amiloride, co-
amilofruse, co-
amilozide,
spironolactone etc
Usually continued, but anaesthetist or surgeon may
omit on the morning of surgery because
hyperkalaemia may arise as a result of reduced
renal perfusion post-surgery. An alternative
diuretic may be prescribed.
Anti-arrhythmics e.g.
amiodarone
Usually continued, to reduce risk of peri-operative
arrhythmias
All parenteral administration MUST be
accompanied by ECG monitoring
Beta-blockers Usually continued to avoid withdrawal symptoms
and decrease peri-operative morbidity.
In some cases e.g. post-thyroidectomy, dose may
gradually be tapered to zero
If stopped may worsen cardiovascular morbidity.
Centrally acting anti-
hypertensives
Usually continued, to avoid rebound symptoms and
hypertensive crisis
Continuation decreases peri-operative morbidity. If
stopped may worsen cardiovascular morbidity.

Alpha-adrenoceptor
blockers
Usually continued. Continuation reduces peri-
operative cardiovascular morbidity e.g.
myocardial ischaemia and improves
haemodynamic stability
ACE inhibitors Usually continued, unless otherwise specified by
the anaesthetist.
If discontinuation requested by anaesthetist, the
half-life of the drug needs to be taken into
consideration to decide when to stop the ACEI -
stop captopril and quinapril 12 hours pre-
surgery, and enalapril, lisinopril and ramipril at
least 24 hours pre-surgery. Monitor BP closely

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

BNF Chapter Medicine type / Recommendation / Comment
name
Angiotensin II
antagonists
Usually continued, unless otherwise specified by
the anaesthetist.

Nitrates Usually continued to avoid recurrence of
symptoms.
Do NOT crush modified release preparations. Will
need to convert to a lower dose shorter acting
preparation with more frequent dosing. Other
options for administering nitrates include
trandermal delivery (e.g GTN patch) and
parenteral route (isosorbide dinitrate infusion)
the latter requires specialist monitoring.
Potassium channel
activators
Usually continued, unless otherwise specified by
the anaesthetist.

Calcium channel
blockers
Usually continued. Risk of rebound hypertension or
coronary artery spasm if stopped abruptly
Avoid using sublingual nifedipine capsules for
treating hypertension, as these have been
associated with an increased risk of strokes
Warfarin Usually converted to heparin or a low molecular
weight heparin.
For specific advice refer to Trust policy
Management of the warfarinised patient
requiring urgent surgery or contact
Haematology
Aspirin / Clopidogrel Where aspirin is to be withdrawn, this should
normally be done at least 7-10 days before
surgery in patients at high risk of postoperative
bleeding. When deciding whether or not
continue aspirin, a balance between risk of a
VTE event and bleeding needs to be taken into
account. Usually continued in vascular surgery.

Dipyridamole Stop 24 hours before surgery, unless otherwise
directed by anaesthetist (manufacturers
advice). Usually continued in vascular surgery.
3: Respiratory
system
Theophylline Usually continued, unless otherwise specified by
the anaesthetist.
Due to its narrow therapeutic index, theophylline
levels need to be guided by therapeutic drug
level monitoring. Consult the Medicines
Information (ext: 2096) for information relating
to formulation/dose/preparation substitution.
Corticosteroids MUST continue corticosteroid replacement
May need to convert oral prednisolone to i.v.
hydrocortisone
5mg oral prednisolone approximately equivalent to
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

BNF Chapter Medicine type / Recommendation / Comment
name
20mg i.v. hydrocortisone
Requirements increased due to stress of surgery so
may need extra i.v. hydrocortisone above
equivalence of usual oral dose.
Inhalers e.g.
salbutamol and
ipratropium bromide
Usually continued. Inhaled therapy can be
substituted with nebulised therapy where
appropriate.
4: Central
nervous
system
Hypnotics Usually continued, unless otherwise specified by
the anaesthetist.
Risk of withdrawal symptoms if omitted
Anxiolytics Usually continued, unless otherwise specified by
the anaesthetist.
Risk of withdrawal symptoms if omitted
Barbiturates Usually continued, unless otherwise specified by
the anaesthetist.
Risk of withdrawal symptoms if omitted
Lithium Usually continued but MAY stop at least 24 hours
pre-operatively due to potential electrolyte and
fluid balance disturbance. Any decision to stop
lithium must be first discussed with the patients
psychiatrist.

Watch for renal impairment or hyponatraemia, as
these can contribute to lithium toxicity.
Avoid NSAIDs if possible, these reduce the
elimination of lithium.
Avoid dehydration (caution with diuretics)
Lithium carbonate 200mg approximately equivalent
to Lithium citrate 509mg (liquid)
TCADs / SSRIs Usually continued, unless otherwise specified by
the anaesthetist.
Note SSRIs can interact with medicines such as
pethidine and tramadol (which block
presynaptic reuptake of serotonin), to
precipitate serotonin syndrome, which can be
fatal.
Due to long half-life, omission of a single dose
unlikely to cause withdrawal symptoms,
although it has been reported with prolonged
dose omission
In the case of tricyclic anti-depressants (TCADs),
there is a risk of intra-operative arrythmias if
continued, hence continued administration must
be highlighted
MAOIs MUST always check with anaesthetist before giving
dose.
MAOIs and pethidine may result in excitatory
reactions due to excessive serotonergic activity.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

BNF Chapter Medicine type / Recommendation / Comment
name
CNS depression has also been reported.
If continued, will require safe anaesthetic
technique, due to potential for interaction with
anaesthetic agents
Analgesia Usually continued unless otherwise specified by the
anaesthetist. Post-operative analgesic
requirements are additional to chronic therapy
Anti-epileptics MUST continue.
Very important to maintain therapeutic
concentrations to avoid seizures.
Carbamazepine 100mg tablets approximately
equivalent to Carbamazepine 125mg
suppositories
Sodium valproate i.v. dose approximately
equivalent to oral dose
Phenytoin sodium 100mg capsule approximately
equivalent to 90mg phenytoin liquid. Note For
tube-fed patients, the feed should be stopped
for 2 hours before phenytoin dose and 2 hours
after dose.
Phenobarbitone Injection only licensed for status
epilepticus
Anti-parkinsonian
medicines
Usually continued, unless otherwise specified by
the anaesthetist.
Continue co-careldopa or co-beneldopa if able to.
MUST inform anaesthetist, if on selegiline.
Selegiline interacts with pethidine to cause
hyperpyrexia and CNS toxicity. If to continue
selegiline, use safe anaesthetic technique. If
stopped may need to increase l-dopa dose
Avoid prochlorperazine and metoclopramide in
patients with Parkinsons disease
6: Endocrine
system

General guidance
for type 1 and type 2
diabetic patients
using insulin)


Omission of food
and fluids in type 2
diabetic patients
who are either diet-
controlled or who
take oral
hypoglycaemics
ONLY


Pre-operative assessment
Note the presence / absence of complications e.g.
retinopathy, nephropathy, hypertension,
ischaemic heart disease, neuropathy
(peripheral and autonomic) and foot problems
(vascular or neuropathic). Take special care of
the heels and malleoli (either side of the ankle
joint) in patients with neuropathic feet.

Investigations
Urinary protein, ECG, U and E profile, HbA1c.
Patients with uncontrolled diabetes mellitus
should be referred to a diabetes specialist.
Admission to hospital and timing of operation
Admit at least 24 hours prior to surgery, where
possible. The operation should preferably be in
the morning.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

BNF Chapter Medicine type / Recommendation / Comment
name




















Oral Anti-diabetics

Infusion fluids
Consider avoiding lactate containing infusions e.g.
Hartmanns.

Other
Take the opportunity to assess the patients skills in
injection technique, use of blood glucose
monitoring sticks, use of urine testing sticks etc.
Re-educate if problems are identified
Morning list - Restrict to clear non-fizzy fluids from
midnight of the previous night. Render patient
nil by mouth from 06.00 on day of surgery,
therefore NO breakfast on the morning of
surgery.
Afternoon list Can have light breakfast on day of
surgery before 0700. Then restrict to clear non-
fizzy fluids until 11.00. After 11.00 render
patient nil by mouth.
If taking sulphonylureas or metformin, see below;

Sulphonylureas
Morning list - Omit oral short-acting
sulphonylureas e.g. gliclazide on the morning of
surgery.
Afternoon list Take morning short-acting
sulphonylureas, but omit lunchtime dose.
Longer acting sulphonylureas may need to be
stopped during the NBM period
Patients taking sulphonylureas may sometimes
require converting to insulin. This decision
should only be taken by a senior doctor or
anaesthetist
Restart sulphonylurea at usual pre-operative dose
after first post-operative meal

Metformin
Doses usually omitted on day of surgery.
Metformin may be stopped 24-48 hours before
surgery (or patients due to receive radio-
contrast media), to avoid risk of precipitating
lactic acidosis, especially in patients with renal
impairment. Recheck U and Es before
recommencing metformin.

For patients using
insulin
MORNING OPERATION LIST
On the night before surgery;
Administer all short and intermediate/long-acting
insulins on the night prior to surgery, unless
otherwise specified by the anaesthetist
Restrict to clear non-fizzy fluids from midnight of
the night prior to surgery until 0600 on day of
surgery.
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

BNF Chapter Medicine type / Recommendation / Comment
name
On the morning of surgery;
Render patient nil by mouth from 06.00 on day of
surgery. (NO breakfast on morning of surgery)
Omit all morning s.c. insulin doses and convert to
i.v. insulin regimes e.g. GLIK / Alberti or
sliding scale Refer to separate Trust
guidelines (page 219)
Reconverting to subcutaneous insulin;
Continue i.v. insulin regime until first post-operative
meal
Give first s.c. insulin injection 20 minutes BEFORE
the i.v. insulin regime is discontinued and the
patient starts the meal For minor operations
where the patient is expected to recover and
start eating soon, the patients usual insulin
regimen may be restarted.

AFTERNOON OPERATION LIST
On the night before surgery;
Administer all short and long-acting insulins on the
night prior to surgery, unless otherwise
specified by the anaesthetist
On the morning of surgery;
Can have light breakfast on day of surgery. Then
restrict to clear non-fizzy fluids until 11.00. After
11.00 render patient nil by mouth.
Omit all morning s.c. insulin doses and convert to
i.v. insulin regimes e.g. GLIK / Alberti or
sliding scale Refer to separate Trust
guidelines (See here)

Reconverting to subcutaneous insulin;
Continue i.v. insulin regime until first post-operative
meal
Give first s.c. insulin injection 20 minutes BEFORE
the i.v. insulin regime is discontinued and the
patient starts the meal For minor operations
where the patient is expected to recover and
start eating soon, the patients usual insulin
regimen may be restarted.
Levothyroxine Usually continued, unless otherwise specified by
the anaesthetist.
If NBM period prolonged, convert oral levothyroxine
(thyroxine) to liothyronine injection
Oral levothyroxine (formally known as thyroxine)
100micrograms approximately equivalent to
liothyronine injection 20 micrograms
Anti-thyroid
medicines e.g.
carbimazole
Usually continued, unless otherwise specified by
the anaesthetist, for example following total
thyroidectomy.
Anti-thyroid drugs may be continued as part of a
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

BNF Chapter Medicine type / Recommendation / Comment
name
block-replace regime following partial
thyroidectomy
HRT Usually continued, unless otherwise specified by
the anaesthetist.
Assess risk of venous thromboembolism versus
recurrence of menopausal symptoms.
If to stop, need to discontinue 4 weeks before major
elective surgery.
Combined Oral
Contraceptives
Usually continued, unless otherwise specified by
the anaesthetist.
Assess risk of venous thromboembolism versus
pregnancy.
If to stop, discontinue 4 weeks (some
manufacturers state 6 weeks) pre-surgery, and
re-started at the first menses occurring at least
2 weeks after full mobilisation.
Progesterone Only
Pills
Usually continued, unless otherwise specified by
the anaesthetist.
No evidence to suggest increased risk of PE/DVT,
but there have been reports of desogestrel and
gestodene being associated with increased risk
of venous thromboembolism.
8: Treatment of
malignant
disease and
immuno -
suppression
Immuno -
suppressants
Usually continued, unless otherwise specified by
the anaesthetist.
Do NOT open/crush mycophenolate
capsules/tablets, to avoid risk of exposure to
medicine
Tamoxifen Consider stopping 4 weeks (some manufacturers
suggest 6 weeks) before surgery due to
increased risk of thromboembolism. Discuss
with the breast unit before discontinuation.
If stopped, recommencing should be guided by
degree of mobility and risk of continued
omission of tamoxifen
If continued, consider for thromboprophylaxis as
appropriate (See separate guidelines)
10: Musculo
skeletal and
joint diseases
NSAIDs Usually continued, unless otherwise specified by
the anaesthetist.
Assess risk of bleed versus pain management.

11: Medicines
acting on the
eye
Eye drops for
glaucoma
Usually continued, to avoid risk of increase in
intraocular pressure if stopped
Herbal
medicines
Echinacea Discontinue as far in advance of surgery as
possible because of immuno-stimulatory effect
Note Long term use has potential for
immunosuppression
The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011

The Royal Liverpool University Hospitals Formulary and Prescribing Guidelines October 2011
BNF Chapter Medicine type /
name
Recommendation / Comment
Key reference
for this section
Herbal
Medicines and
Perioperative
Care.
JAMA.2001;
286: 208-216.
Ephedra Stop at least 24 hours before surgery
Causes increase in heart rate and blood pressure
With MAOIs may result in life-threatening
complications
Garlic Stop 7 days before surgery due to its potential for
irreversible inhibition of platelet function, hence
increased risk of bleeding
Gingko biloba Stop 36 hours before surgery due to its potential for
inhibiting platelet-activating factor, hence
increased risk of bleeding
Ginseng Stop 7 days before surgery due to its potential for
irreversible inhibition of platelet function, hence
increased risk of bleeding
Kava Stop at least 24 hours before surgery because it
has the potential to increase sedative effects of
anaesthetics
St Johns Wort Stop 5 days before surgery because it induces
cytochrome p450 enzymes, hence resulting in
increased metabolism of medicines metabolized
via this pathway.
Valerian Continue until the day of surgery because abrupt
withdrawal may be associated with a
benzodiazepine-like withdrawal symptom

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