Product transition

Nairobi sensitization
 Presentation Outline
•Why new ARVs?
•Nairobi county 1st line ART patients numbers
•Factors to be considered in transition
•Transition process
•Product Transition timelines
 Why new products?
• Reduced toxicity

• Reduce pill burden/improve adherence

• Improve sequencing of ART treatment

• Harmonization of regimens across different age groups and

populations

• Better treatment outcomes

National ART Patients Numbers
 Current Adult 1st ART patient numbers &
Regimen splits
Distribution of Nairobi county patients by regimen
Women Male +Women
Regimen Totals <49years >49years
AF1A | AZT + 3TC +
NVP 20109 10658 9451
AF1B | AZT + 3TC +
EFV 6824 3617 3207
AF2A | TDF + 3TC +
NVP 12623 6690 5933
AF2B | TDF + 3TC +
EFV 92146 48837 43309
AF2E | TDF + 3TC +
DTG 2872 1522 1350
Total 134,574 71324 63250
Proportion of patients by regimen (N42,627)
Age, gender distribution of adult 1st line (N
42,627)
Factors to be considered in
transition
Factor 1: Commodity Stock status
• Stock levels at central & facility level
considered e.g. TLE400 currently at
zero stocks centrally
• Avert expiries e.g. ZLN stocks still high
at central level
• These factors determine timing of
transition
• For NBI county, regimens targeted
from July 2018 are ZLE, TLN & TLE in
eligible patients as illustrated
• Others are NVP & EFV based 1st line
e.g. ABC+3TC+NVP, ABC+3TC+EFV
 Factor 2-Patient visits to facilities

Current Patient appointment • Based on this, it is estimated

distribution that 25% of patients visit a
given facility every month
8% • For Nairobi County, it is
42% 19% recommended that patients
without current VL to be given 1
month prescription next time
31%
they visit then,
• Draw sample for VL & make
decision on next appointment
>90 days 1-30 days
31-60 days 61-90 days
Factor 3 - Viral Load suppression
• VL results will determine who is
to be switched & when
• Overall 2017 viral Load
Suppression for Nairobi 84.6%
• It is estimated that 50 % of all
patient likely to have recent VL
result (within last 6 months)
• Suppressed eligible patients to
be switched to TLD
Transition of Adult Patients on
Selected 1st line Regimens in
Nairobi County
 Recommendations for Transition: Nairobi
County
Women ( 15 – 49 years ) Women > 49 years and Men
Current 1st line Transition to; Current 1st line Transition to;
ARV regimen ARV regimen
TDF/3TC/NVP TDF/3TC/EFV600 TDF/3TC/NVP TDF/3TC/DTG
mg
TDF/3TC/EFV400 TDF/3TC/EFV600 TDF/3TC/EFV400 TDF/3TC/DTG
mg mg mg
AZT/3TC/EFV TDF/3TC/EFV600 AZT/3TC/EFV TDF/3TC/DTG
mg
 Considerations for Transition
• Three main regimens targeted are TLE, TLN and ZLE

• ‘Smart PUSH’ for TLD and TLE600 to be done in early July 2018
• Stocks to cater for 43% and 57 % of adult patients per facility for 3 months
• Facilities to ‘PULL’ stocks from August onwards
• To be considered, reports to be submitted via DHIS2 only

• Patients who are not suppressed to continue on current regimen till

suppression is achieved (Note: TLE600 to be used once stocks of
TLE400 are exhausted)

• Prioritize transition in those eligible so as to spare existing stocks for

non-suppressed patients
 Other recommendations

• Transition of adult patients who are suppressed from LPV/r to

ATV/R;
• to start once LPV/r stocks are exhausted at central (KEMSA) level

• Start date to be communicated by NASCOP-estimated to be from Sep 2018

• ABC/3TC 600mg to replace single ABC and 3TC

• Supply of FDC to be done once central stocks of single products are
exhausted
• Exhaust facility stocks before switch to FDC

• Transition of adult clients on ZLN to start in Feb 2019

 Medication Use Counseling
• Educate the patient on new medication
• What is the new product?
• why is it being introduced?
• Possible adverse effects
• Dosing & dosing frequency
• Change in number of pills, where applicable
• Storage of medicines
•Reinforce adherence messages
• Ensure that the patient understands everything about the
product-adequately handle any query that may arise

16
 Other special considerations
• On-transit Patients; TLD will only be available in Nairobi county
initially

• Some eligible clients may decline to be transitioned to TLD

• Others will request to continue on TLE400

• Such clients to be handled on a case by case basis

 Monitoring of Transition Process
• Facilities to submit monthly reports to NASCOP on the prescribed
template (to be sent to facilities by Mid July 2018)

• This will be in addition to the usual commodity reports

• It is recommended that redistribution of commodities be done to

ensure a balance between current & transition regimen stocks.

• Pharmacists/Pharmtechs to improve inventory management at

facility level
• To prevent overstocks/understocks

• Accountability for expired commodities, if any, by facilities

Pharmacovigilance
 Outline
• Definitions

• Rationale for PV

• Clinical assessment of AEs

• Management of AEs

• Monitoring of AEs
 Summary of Definitions
Pharmacovigilance (PV): the science and activities relating to the detection,
assessment, understanding and prevention of adverse effects or any other
drug-related problem.
Side effect Adverse Event or Adverse drug Reaction Serious Adverse Event /
Adverse Experience (ADR) Reaction
(AE)
Any unintended Any untoward medical A response to a Any untoward medical
effect of a occurrence that may medicine which is occurrence that at any
pharmaceutical present during treatment noxious and dose;
product occurring at with a pharmaceutical unintended, and which – Results in death
normal doses used product but which does occurs at doses – Life threatening
in humans, related not necessarily have a normally used in – Requires inpatient
to the causal relationship with humans for the hospitalization or
pharmacological this treatment. prophylaxis, diagnosis or prolongation of existing
properties of the therapy of disease, or for hospitalization
medicine the modification of – Persistent of significant
physiological function disability or incapacity
Side Effects vs. Adverse Drug Reaction vs.
Adverse Event

Side effects

Harmful/ Adverse Harmless/

Effects Beneficial Effects

Adverse drug Reactions

Adverse Events (no
causal relationship) (causal relationship has
been established)
Rationale for PV
Why the need to strengthen pharmacovigilance?
Consequences of poor PV
• AEs poorly assessed &
managed, as well as poor
reporting (no data)
• AEs can affect quality of life
• Unnecessary drug
substitutions, thereby
limiting options
• May lead to
disability/morbidity or even
death
Benefits of PV
• Generates local evidence
on prevalence of AE due to
various medicines e.g.
DTG
• Opportunity to offer better
available options to
patients
• Can impact future ART
guidelines
recommendations
• Contribution to global body
of knowledge
 Rationale for Pharmacovigilance
• Improves patient level management of AE / ADR
• However, documentation and reporting remains sub optimal
• Evidence on AEs / ADRs will inform future recommendations on new molecules e.g.
DTG (currently, limited use globally)
• Reporting can help identify hazards and risks, to assure patient safety
• ARVs studies take long to exhibit some AEs in certain populations e.g. pregnant and
breastfeeding women.
• Observing these populations in clinical practice provide additional evidence on
safety
• Countries need to strengthen / establish pregnancy registries for ARV toxicity
monitoring
Clinical Assessment of Adverse
Events
 Steps to identifying AE / ADR

• Good clinical practice is important for prompt identification and

management of ADRs
• Actively review PLHIV for adverse events (AE) / adverse drug
reactions (ADR) during at every visit
• Manage any identified AE / ADR appropriately
• Conduct monthly reviews at facility level, of all reported AEs /
ADRs.
• Discuss PV in Multidisciplinary Teams (MDTs) and Medicines and
Therapeutics Committees (MTCs)
• Document and report all cases of suspected AE / ADR to national
level
 General Principles for Identification and Management
of ADRs
1. At every clinic visit, client on ART should be monitored clinically for
possible toxicities;
• Use appropriate history (probe for symptoms that suggest toxicity)

• physical examination (relevant signs)

• Targeted laboratory assessment may be used to confirm specific toxicities

2. Evaluate concurrent medications and establish causality to ARV drug (s)

• or to a non-ARV medication being taken at the same time. Consider herbal
medicines and/or other disease processes (e.g. concurrent infectious processes or
IRIS)

3.All toxicities should be graded. Manage the adverse event

according to severity
 Grading of AEs Based on Severity & action
GORY
CATE
to be taken
Grade 1: Mild Grade 2: Moderate Grade 3: Severe Grade 4: Severe Life-
Reaction Reaction Reaction Threatening Reaction
Generally Transient or Mild to moderate limitation Marked limitation in Extreme limitation in activity,
mild discomfort, in activity; activity, significant assistance
no limitation in activity; some assistance may be some assistance required;
DEFINITION

no medical needed; usually required; significant medical

intervention/ therapy no or minimal medical medical/intervention/ intervention/therapy
required intervention/therapy therapy required, required,
Usually observed
required hospitalisation possible hospitalisation or hospice
during initiation of
care probable
treatment ;

Continue ARVs, offer Continue ARVs as long Substitute offending Immediately discontinue
symptomatic relief (if as feasible, offer drug without ALL drugs, including ARVs
appropriate) symptomatic relief if discontinuing ART. and manage the medical
ACTION

appropriate. If no Monitor the patient event. Often requires

improvement consider closely hospitalization. When
single drug substitution stabilized, reintroduce ARVs
using a modified regimen
(substitute the offending
 Example: Grading of ADRs - Rash and
Anaemia
Grade 2: Grade 4: Severe
Grade 1: Mild Grade 3: Severe
CATEGORY Moderate Life-Threatening
Reaction Reaction
Reaction Reaction
Localized Diffuse Diffuse rash with Extensive bullous
itchiness, maculopapular vesicules , limited lesions of SJS or
redness involving rash involving > bullae, superficial ulceration of
NVP associated < 50% of body 50% of the body ulceration of mucous
rash mucous membrane
membranes involving two or
limited to one site more distinct
mucosal sites
8.5- 9.4 7.5 – 8.4 6.5 – 7.4 ≤ 6.4
AZT associated
anaemia – Hb
(g/dL)
 Common ADRs Associated with ARVs
ARV Agent Common Adverse Drug High Risk Situations/Comments
Reactions
NRTIs
ABC ABC hypersensitivity reaction Do not re-challenge
Anaemia, neutropenia CD4 count < 200 cells/mm3; BMI < 18.5 (or body weight < 50 kg);
AZT anemia at baseline
Lactic acidosis Pregnancy; obesity
Lipoatrophy Low CD4 count
Underlying renal disease; Age > 40 years; BMI < 18.5 (or body
TDF Renal Dysfunction
weight < 50 kg); diabetes; hypertension; concomitant PI use or
nephrotoxic drug
NNRTIs

All NNRTIs Rash/hypersensitivity For NVP: women with CD4 count > 250 cells/mm3; men with CD4
(NVP>>EFV>ETR) count > 400 cells/mm3
Ddizziness, trouble sleeping
Pre-existing psychiatric disorder
EFV (insomnia), drowsiness, unusual
dreams, trouble concentrating
Gynecomastia Consult
HBV or HCV co-infection; concomitant use of hepatotoxic drugs;
NVP Hepatotoxicity women with CD4 count > 250 cells/ mm3; men with CD4 count >
 Common ADRs Associated with ARVs
ARV Agent Adverse Drug Reaction High Risk Situations/Comments
Protease Inhibitors
GI intolerance
All PIs
(LPV/r>DRV/r>ATV/r) Consult
boosted
Dyslipidaemia Obesity; sedentary lifestyle; diet high in saturated fats
with RTV
(LPV/r>DRV/r>ATV/r) and cholesterol
Note: this only requires drug substitution if cosmetic
ATV/r Hyperbilirubinemia effect of jaundice is likely to interfere with patient
adherence
DRV/r Rash/hypersensitivity Sulfa allergy

INSTIs
Insomnia, headache, Older age (> 60 years) and co-administration with
DTG nausea, diarrhea ABC
All INSTIs Rash/hypersensitivity Consult
Reporting of suspected ADRs
and PQMPs
The Kenya Pharmacovigilance Electronic
Reporting System (PVERS)
 What is PVERS?

• Suite of software applications implemented by PPB for

collection and processing of information on suspected Adverse
Drug Reactions (sADRs) and Poor Quality Medicinal Products
(sPQMPs)

• Enables electronic submission of PV reports via a web portal

using either a computer or mobile device
 How can one use the PV ERS?
Two options exist:

• Log in directly to the web application online

• www.pv.pharmacyboardkenya.org
• Use the yellow form for sADR and pink form for SPQMPs
• Issue alert cards to eligible clients

• Download the appropriate application for the device being used

e.g. desktop, Nokia phone
• Enables both online and offline access to the reporting forms
• Useful when internet is fluctuating or unreliable 35
 Reported ADRs due to DTG
(Oct 2017 to May 2018)….PPB Data
• 147 DTG related ADR reports received at PPB
• 76 out of 99 females do not have pregnancy data
• Most common ADRs are CNS related
• 84% were mild reactions; 7% moderate; 7% severe
• Challenges: Completing follow-up reports – no fatality cases
• Are there further follow-up patient reviews?
• Considerations to review severe cases such as the hyperglycemic cases to rule
out other
• Systematized way to identify and report ADRs
• Coordination with NASCOP on sending out communication to health care
providers
THANK YOU
“You need not be certain…

Just be suspicious”

Report all SUSPECTED

adverse drug reactions