NAPROSYN (Naproxen)

INTRODUCTION
Naprosyn is a propionic acid derivative with,
• Rapid, reversible, competitive inhibition of cyclo-oxygenase
enzyme,
• analgesic action,
• anti-inflammatory action,
• potent inhibitor of leukocyte migration
• has a long half life,

PHARMACODYNAMICS
Naprosyn is a non selective NSAIDs with anti-inflammatory, analgesic,
and antipyretic effects. Naprosyn inhibits both COX-1 and COX-2
enzymes which are required for PGs synthesis.

PHARMACOKINETICS
Absorption
• Completely absorbed from gut
• Peak levels are achieved with 2 hours
• Less presystemic metabolism (< 5%) therefore high bioavailability
• Food slightly delays absorption with no effect on total absorption.

Distribution
• Highly protein bound > 99%. Therefore less volume of distribution
(0.91 lit/kg)
• Plasma half life - 12-15hrs
• Steady state concentration achieved within 3 days
• Binding to albumin is reduced in cirrhosis and in the elderly.
Synovial fluid concentrations of naproxen increase from 50% of
serum levels at 3 to 4h to 74% at 15h. A steady state therefore
synovial fluid concentrations are equivalent to those in plasma. It
crosses the placenta within 20 to 30 min of oral administration and
appears in the milk of lactating women at approximately 1% of
maternal plasma concentrations. Concentrations achieved in
synovial fluid is half (52%) that of steady state plasma
concentration

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 METABOLISM AND EXCRETION

• Extensively metabolised in the liver. Metabolites are inactive (no

anti-inflammatory effect, 10% excreted unchanged).

• 97-99% of naproxen and its metabolites excreted in urine and very

small percentage excreted in feces.

ADVERSE DRUG REACTIONS

Gastrointestinal
• Heartburn, abdominal pain, nausea, dyspepsia, diarrhoea and
constipation.
• More common in elderly & sick (more in female)
• Depends on dose & duration (increases with both)

Skin Reactions
• Rash, Urticaria, Photosensitivity

Central Nervous System

• Headache, Dizziness, Drowsiness, Tinnitus

Renal systemLong term use leads to interstitial nephritis

INDICATIONS

Acute Conditions
• Relief from mild to moderate pain
• Acute musculo-skeletal disorders (eg. strains & sprains)
• Dysmenorrhoea
• Gout (Acute)
• Menorrhagia
• Migraine
Chronic Conditions
• Osteoarthritis (OA)
• Rheumatoid Arthritis (RA)
• Ankylosing Spondylitis
• Juvenile RA
• Chronic Pain States with inflammatory component

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 RECOMONDED DOSAGE

• Acute conditions : 500 mg stat followed by

250 mg, 6h / 8h
Max. daily dose > 1250 mg/ day.
• Chronic conditions : 250 - 500 mg b.d. /
500 - 1000 mg single dose
• Acute gout : 750 mg stat followed by
250 mg , 8h until attack subsides

• Migraine (Acute attack) :750 mg at first symptom

250 - 500 mg additional half an hour later

• Menorrhagia : First day 375 - 750 mg b.d.

Later > 1000 mg/day

• Children
– Not recommended < 2 years; Maximum > 15 mg/kg/d
– Juvenile Rheumatoid Arthritis, 10 mg/kg/day in 2 divided
doses
– Analgesic / Antipyretic, initial - 10 mg/kg, later - 2.5-5
mg/kg/q8h

CONTRAINDICATIONS
• Hypersensitivity
• History of asthma, rhinitis, nasal polyps and with aspirin
• Active peptic ulcer/active GI bleeding
• Children < 2 yr.

PRESENTATION

Naprosyn 250mg - Each uncoated tablet contains Naproxen

250mg
Naprosyn 500mg - Each uncoated tablet contains Naproxen
500mg
Strip of 10 tablets

USPs OF NAPROSYN

• Known agent
• Good analgesic / anti-inflammatory
• Long duration of action
• Once daily dosing possible
• One amongst most widely prescribed Non-aspirin NSAIDs

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 NAPROSYN SR

COMPOSITION
Naproxen Sustained Release Tablets 750mg

INTRODUCTION
 Naproxen is a propionic acid derivative with,
 Rapid, reversible, competitive inhibition of Cyclo-oxygenase ,
 Analgesic action,
 Anti-inflammatory action,
 Has a long half life,
 Potent inhibitor of leukocyte migration.

Naprosyn SR is a sustained release form of Naproxen. In Naprosyn SR

Naproxen is released as 10 % immediate release and 90% over a period of
22hrs.

MATRIX TECHNOLOGY
Naprosyn SR involves hydrophilic Hydroxypropyl Methylcellulose [HPMC]
The classification of matrix systems is based on matrix structure, release
kinetics, controlled release properties (diffusion, erosion, swelling), and the

4
chemical nature and properties of employed materials Matrix systems are usually
classified in 3 main groups: hydrophilic, inert, and lipidic.

The matrix system has several advantages as follows,

1. It is very simple and easy to establish a stable formulation.

2. The tablet is completely dissolved and thus achieves good bioavailability.
3. Offers sustained release of drug with OD advantage

Figure 1 illustrates the schematic dissolution profile of the matrix tablet.

After administration, hydrophilic matrix tablets made with HPMC hydrate to form
a gel layer, which regulates the drug release pattern. The most important aspect
of this matrix system is the homogeneity of HPMC particle distribution in the
tablet. The selection of HPMC grades affects the initial wetting, swelling,
hydration and gel strength.

PHARMACOKINETICS
Absorption
 Naproxen is completely absorbed from GI tract & In-vitro bioavailability is
95%.
 Peak plasma level is attained after 1-2 hours of oral administration of IR
Tablets.
 Cmax of IR Tablets 97.4 meg/ml
 tmax of IR Tablets 1.9 hrs.
 Food slightly delays absorption with no effect on total absorption.

Distribution
 Highly protein bound > 99%. Vd is 0.16 It./kg
 Half life - 12-17hrs
 Steady state concentration achieved within 4-5 days
 Binding to albumin is reduced in cirrhosis and in the elderly. Synovial fluid
concentrations of naproxen increase from 50% of serum levels at 3 to 4h to
74% at 15h. A steady state therefore synovial fluid concentrations are
equivalent to those in plasma. It crosses the placenta within 20 to 30 min of
oral administration and appears in the milk of lactating women at
approximately 1% of maternal plasma concentrations. Concentrations

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 achieved in synovial fluid is half (52%) that of steady state plasma
concentration

Metabolism and Excretion

 Extensively metabolized in the liver. Metabolites are inactive (no anti-
inflammatory effect
 It is metabolized to 6-0-desmethyl Naproxen.
 >95% of Naproxen is excreted in urine.

Adverse Effects
GI Effects - Average risk ++
- Elderly & sick (more in female)
- Post-marketing studies (PMS) Napexar well tolerated when other
NSAIDs are not.
- Dose- & duration-dependent (increases with both)

Skin Reactions - Urticaria, Rash, Photosensitivity

Preparations
Tablet Naprosyn SR 750mg

INDICATIONS - CHRONIC CONDITIONS

 Rheumatoid Arthritis (RA)
 Osteoarthritis
 Ankylosing Spondylitis
 Pain due to fracture
 Back Pain
 Chronic Pain States with inflammatory component

DOSAGE
 Once daily administration of the total daily dose of Naproxen required can be
achieved by administering the appropriate Naprosyn SR tablet i.e. Naprosyn
SR 750 mg.
 Naprosyn SR tablets should be taken whole and not chewed. The total daily
dose of Naproxen should not exceed 1000 mg.

Naprosyn SR TABLETS ARE NOT INTENDED FOR PATIENTS REQUIRING

SHORT TERM TREATMENT FOR ACUTE INDICATIONS

CONTRAINDICATIONS
Hypersensitivity
History of asthma, rhinitis, nasal polyps within aspirin or other NSAIDs

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Active peptic ulcer/active GI bleeding
Children < 2 yr.

Satisfies all criteria of a good NSAID

 Indication Pain Relief - Yes

 OA / RA - Yes
 Restricted Use - No
 Long Half-life - Yes
 Once Daily - Yes
 ADRs GI Irritation
Peptic Ulcer
CNS Effects Average Risk
Tinnitus (++)
Hepatitis
Renal Effects

USPs OF Naprosyn SR
 Good analgesic / anti-inflammatory as Naproxen inhbits Cyclo-oxygenase
 Long duration of action as Naproxen has longer Half Life
 Once daily dosing possible due to Matrix technology
 Widely prescribed Non-aspirin NSAIDs-Time tested and trusted molecule
internationally.

Naprosyn SR FAQ

1.What is Naprosyn SR?

Naprosyn SR is a sustained release form of Naproxen. In Naprosyn SR
Naproxen is released as 10 % immediate release and 90% over a period of
22hrs.

2.What is the sustained release technology & what are their benefits?
In Sustained release technology, the release of drug is modified in such a way
that it maintains the levels of drug for a longer duration than the regular drug.
The obvious benefit of sustained release drug is improved compliance of the
patient.
The drug level in the blood of the patient is adequate to provide the required pain
relief or analgesia.

3.What is the matrix technology?

Matrix is a mould in which a drug is embedded.
The classification of matrix systems is based on matrix structure, release
kinetics, controlled release properties (diffusion, erosion, swelling), and the

7
chemical nature and properties of employed materials Matrix systems are usually
classified in 3 main groups: hydrophilic, inert, and lipidic
The matrix system has several advantages as follows,

1. It is very simple and easy to establish a formulation.

2. The tablet is completely dissolved and thus achieves good bioavailability.
3. Offers sustained release of drug with OD advantage

4.What is the polymer used in Naprosyn SR?

Naprosyn SR involves hydrophilic Hydroxypropyl Methylcellulose [HPMC] as a
polymer.

5.What are the indications & dosages of Naprosyn SR?

In contrast to plain Naprosyn, the indications of Naprosyn SR are not acute but
the maintenance of chronic conditions like Osteoarthritis, Rheumatoid arthritis
etc. The usual dose is 750 mg once a day after meals.

6.What is duration of Naprosyn SR treatment?

The duration of Naprosyn SR will be same as Naprosyn which has been used
from 1 year to 4 years as per the clinical trials depending upon the need &
tolerability of the individual patient. But the common principle of NSAID
prescription applies here in which the drug has to be used for minimum possible
time & if at all required to be used for longer duration, a gap of 15 days is given
after 1 to 3 months along with monitoring his GI, Renal & Cardiac status.

7.What are the adverse events of Naprosyn SR?

The adverse events of Naprosyn SR are same as that of plain Naprosyn.

8.What are the advantages of Naprosyn SR over Naprosyn?

Both dosage formulations are important but the choice will depend upon the
doctor to use it. Usually doctors prefer to write plain NSAID for acute conditions &
sustained release for maintenance of chronic conditions.

9. What precautions are to be taken during Naprosyn SR treatment?

Apart from the usual precautions which are taken for any NSAID prescription like
history of the patient, allergy to NSAIDs in the patient etc, the most important
thing during Naprosyn SR therapy is that the tablet should not be chewed but
swallowed as a whole because if the tablet is chewed all the advantage of
sustained release will be lost.

10. How Naprosyn SR acts for 24 hrs when the GI transit time in not more
than 6 to 8 hrs?
This is the most commonly asked question for all the sustained release
formulations. There are two ways to answer this. First is the Bioequivalence
study in which our drug is compared with the already available brand in the
market and both of them show similar dissolution profile. Second logical answer

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which is commonly given is that because of the cellulose present in the polymer
the drug sticks to the microvillus of the small intestine from where it is slowly
absorbed into the circulation so that even if the food moves ahead the drug still
remains in the small intestine.Thirdly , as the water , gastric & intestinal
secretions enter inside the Hydrophilic Matrix, the polymer in the matrix swells
up. This displaces the drug (Naproxen) from the matrix. Intially there will be rapid
release of the drug in the 1st hour (10%) and then there will be gradual release of
the drug (90%) over a period of 24 hours. In the latter part, when all the drug is
released, this matrix undergoes normal wear and tear as seen in any tablet
(disintegration), and is excreted out in the faeces. There is no “Ghost Tablet”
seen in faeces as is common with few SR preparations.

16.What are the other brands of Naprosyn SR available in the market?

Following brands are available in the market
Xenar CR (750 mg) by Elder pharmaceuticals

USPs of the Product

• Naproxen in Naprosyn SR is the S isomer which active form of Naproxen
molecule responsible for the analgesic effects.
• Naprosyn SR 10% immediate release and 90% sustained released over a
period of 24 hrs.Thus a sustained pain relief for 24 hrs.
• Once day dosage.
• Since Naproxen is released in the Intestine in small packets (small
Quantity) ,the GI side effects are much less .
• Naprosyn SR taken at night time assures pain relief at early morning hour
for the patients suffering from Rheumatoid arthritis and Osteoarthritis.Thus
provides a Good pain free morning for patients suffering from Morning
Sickness.
• Lesser GI side effects and Convenient dosage schedule make it a drug of
choice for chronic painful conditions.

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 Naprosyn Suspension

Juvenile arthritis (JA) refers to any form of arthritis or an arthritis-related condition

that develops in children or teenagers who are less than 17 years of age.
Impact of Juvenile Arthritis:
• Nearly 300,000 children under the age of 17 are affected by juvenile arthritis
• Juvenile rheumatoid arthritis (JRA), affecting 50,000 children, is the most
common form of juvenile arthritis and one of the most common childhood
diseases in the US.
• Arthritis and related diseases, such as JA, cost the U.S. economy nearly $128
billion annually in medical care and indirect expenses, including lost wages and
production

Common Symptoms of Juvenile Rheumatoid Arthritis:

• Pain, swelling, tenderness and stiffness of joints, causing limited range of
motion
• Joint contracture, which results from holding a painful joint in a flexed position
for an extended period
• Damage to joint cartilage and bone leading to joint deformity and impaired use
of the joint
• Altered growth of bone and joints leading to short stature
Types of Juvenile Rheumatoid Arthritis:
• Polyarticular JRA affects five or more joints and:
o affects girls more frequently than boys
o most commonly affects knees, wrists and ankles
o can affect weight-bearing and other joints, including hips, neck, shoulders and
jaw
o often affects the same joint on both sides of the body
• Pauciarticular JRA affects four or fewer joints and:
o usually affects the large joints: knees, ankles or wrists
o often affects a joint on one side of the body only, particularly the knee
o may cause eye inflammation (uveitis) which is seen most frequently in young
girls with positive anti-nuclear antibodies (ANA)
• Systemic Onset JRA can:
• affect boys and girls equally
• cause high, spiking fevers of 103 degrees or higher, lasting for weeks
or even months
• cause a rash consisting of pale, red spots on the child’s chest, thighs
and sometimes other parts of the body
• cause arthritis in the small joints of the hands, wrists, knees and ankles
Other Types of Juvenile Arthritis:
• Juvenile Spondyloarthropies (ankylosing spondylitis, seronegative
enthesopathy and arthropathey syndrome) are a group of diseases that involve
the spine and joints of the lower extremities, most commonly the hips and knees
• Juvenile Psoriatic Arthritis is a type of arthritis affecting both girls and boys that
occurs in association with the skin condition psoriasis

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• Juvenile Dermatomyositis is an inflammatory disease that causes muscle
weakness and a characteristic skin rash on the eyelids
• Juvenile Systemic Lupus Erythematosus is an autoimmune disease associated
with skin rashes, arthritis, pleurisy, kidney disease and neurologic movement
• Juvenile Vasculitis is an inflammation of the blood vessels and can be both a
primary childhood disease and a feature of other syndromes, including
dermatomyositis and systemic lupus erythematosus
Causes of Juvenile Arthritis:
• The cause of most forms of juvenile arthritis is unknown, but it is not contagious
and there is no evidence that foods, toxins, allergies or vitamin deficiencies play
a role.
Diagnosis of Juvenile Arthritis:
• A diagnosis of juvenile arthritis is based on a complete medical history and
careful medical examination. Evaluation by a specialist – either a pediatric
rheumatologist or a rheumatologist – is often required
• Laboratory studies including blood and urine tests are often needed to assist in
a diagnosis of JA
• Imaging studies including X-rays or magnetic resonance images may be
needed to check for signs of joint or organ involvement in JA
Management of Juvenile Arthritis:
• Management varies depending on the specific form of juvenile arthritis
• Care by a pediatric rheumatologist is important for most forms of JA
• The primary goals of treatment for juvenile arthritis are to control inflammation,
relieve pain, prevent joint damage and maximize functional abilities
• Treatment plans for children usually include medication, exercise, eye care,
dental care and proper nutrition
• Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first line of medication
used in juvenile arthritis to help control pain and inflammation
• Disease-modifying anti-rheumatic drugs such as methotrexate are often used in
conjunction with NSAIDs to treat joint inflammation and reduce the risk of bone
and cartilage damage
• Corticorticoids such as prednisone can be taken orally to relieve inflammation
or injected into joints that are inflamed
• Biologic Response Modifiers (BRMs) are a class of drugs that inhibit proteins
called cytokines. They must be injected under the skin or given as an infusion in
the vein

The Product:
NAPROSYN suspension contains the active ingredient naproxen and belongs
to a group of medicines called Non-Steroidal Anti-inflammatory Drugs (or
NSAIDs)
Composition:Naproxen 125 mg/5ml..

NAPROSYN suspension relieves pain and reduces inflammation (swelling,

redness and soreness) that may occur in the following different types of arthritis
including rheumatoid arthritis,osteoarthritis and ankylosing spondylitis, muscle

11
and bone injuries such as sprains, strains, low back pain(lumbago), rheumatism
and tendonitis, such as tennis elbow
• swelling and pain after setting broken or dislocated bones
• menstrual cramps (period pain)
• headache, including migraines
• following surgery
• dental pain

Although NAPROSYN suspension can relieve the symptoms of pain and

inflammation.
NAPROSYN suspension is recommended for use in children (over the age of 5)
for the treatment of juvenile rheumatoid arthritis.NAPROSYN suspension is not
addictive. This medicine is available only with a doctor’s prescription.

Juvenile Rheumatoid Arthritis

The recommended dose for children 5years and above is 10 mg/kg given in 2
equal divided doses (i.e. 5 mg/kg twice a day).

USP of Naprosyn Suspension

• Naprosyn suspension is the only FDA approved NSAID for JRA
apart from Ibuprofen.
• Naproxen is available in suspension form for the first time in India.
• Better Safety profile than Ibuprufen.
• Available in tasty tuti-fruity flavor.
• Affordable price

RELIGEL (TOPICAL GEL)

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PHARMACOLOGICAL ROLE OF EACH INGREDIENTS

ROLE OF OLEUM LINI

Also called as linseed oil is extracted from the seed of the plant Linum
usitatissium

PHARMACOLOGY

Linseed oil predominantly contains alpha linolenic acid, which has anti
inflammatory activity. On topical application alpha linolenic acid is absorbed into
the systemic circulation, on metabolism it produces Eicosapentaenoic acid (EPA),
EPA in the presence of the enzyme cyclo-oxygenase and lipooxygenase gets
converted into PGE3 and PGF3 and leukotriene LTA5, LTB6 & LTC5 respectively.

PGE3 is a relatively non-inflammatory prostaglandin while LTA5, LTB6 and LTC5

possesses1-10% of the inflammatory activity compared to that of leukotrines
produced by arachidonic acid.
Further the presence of EPA prevents the action of cyclo-oxygenase on
arachidonic acid which reduces its conversion to PGE 2. Although PGE3 is
relatively non-inflammatory but it still acts as a useful negative feedback regulator
to modulate the inflammatory responses and reduce the production of PGE2

α - linolenic acid
Eicosapentaenoic acid (EPA)
COX Lipooxygen
PGE3
ase
Leuktrines (LTA5, LTB5,
- ve
LTC5)
COX
Arachidonic acid ↓ ↓ PGE2

Thus alpha linolenic acid possesses anti-inflammatory activity by decreasing the

formation of PGE2 by producing relatively non inflammatory PGE3
By producing PGE3 which acts as a negative feedback regulator to reduce the conversion of arachidonic acid
to PGE2.

ROLE OF DICLOFENAC DIETHYLAMMONIUM

Diclofenac diethylammonium is a clinically proven topical NSAID in the treatment

of pain and inflammation associated with musculoskeletal disorders.

PHARMACOLOGY

13
Diclofenac exhibits its anti-inflammatory activity by dual mode of action. It prevents
the conversion of arachidonic acid to PGE2 by inhibiting the enzyme cyclo-
oxygenase. More over it also enhances the uptake of arachidonic acid into the
phospholipid pool.The uptake of AA into the phospholipid pool limits the
availability of AA into the lipo-oxygenase pathway the resultant effect is a
decrease in PGE2 and LTB4 which together effectively counteracts the clinical
signs and symptoms of inflammation. Thus Diclofenac and alpha linolenic acid
work synergistically.

ROLE OF METHYL SALICYLATE

Methyl Salicylate is used topically as a counter irritant. on topical application it is

absorbed through the skin and is applied for the relief of pain in rheumatic
conditions and painful muscles and joints.

ROLE OF MENTHOL

On topical application menthol dilates the blood vessels causing a sensation of

coldness followed by an analgesic effect. Menthol also acts as a penetration
enhancer. It increases the penetration of the drugs when applied on the skin to
give a faster onset of action. Menthol acts as a penetration enhancer either due to
its vasodilation property or as it readily penetrates the skin.

PHARMACOKINETICS
Rapidly and completely absorbed from skin
90% reversibly bound to plasma protein
Plasma half life (t ½) - 2 hrs
Metabolized in liver
65% drug is excreted in urine
35% in bile
Good tissue concentration in synovial fluid
(93 times longer than in plasma)

ADVERSE DRUG REACTIONS

G.I. Tract
Occasional : Epigastric pain, nausea, vomiting, diarrhoea, abdominal
cramps,
Dyspepsia, flatulence and anorexia
Rare : GI bleeding, peptic ulcer, bloody diarrhoea

Central Nervous System

Occasional : Headache, light headedness/vertigo
Rare : Drowsiness

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Skin
Occasional : Rashes
Hypersensitivity: Rare

Liver
Occasional : Elevation of serum aminotransferases
Rare : Hepatitis with/without jaundice

CONTRAINDICATIONS

• Peptic ulcer
• Hypersensitivity to Diclofenac/Aspirin
• Attack of asthma, urticaria precipitated by aspirin or other NSAIDs.

PRESENTATION

Religel - 30gm tube in printed carton

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 Nufex-beta
(Cefixime+Clavulanate)

Description :

Cefixime is a white to light yellow powder.

Slightly soluble in water,
soluble in methanol.
Cefixime is an oral betalactam antibiotic in a
class of drugs called cephalosporin’s. Cefixime
Cefixime is the third generation
cephalosporin. Cefixime fights bacteria in the body. Cefixime is used to treat
many different types of bacterial infections.

Molecular Formula: C16H15N5O7S2

Molecular Weight: 453.452 g/mol

Clavulanic acid is a beta-lactamase inhibitor sometimes combined with penicillin

group antibiotics to overcome certain types of antibiotic resistance. It is used to
overcome resistance in bacteria that secrete beta-lactamase, which otherwise
inactivates most penicillin’s.

The name is derived from the Streptomyces clavuligerus, which produces

clavulanic acid. Clavulanic acid is biosynthetically generated from the amino acid
arginine and the sugar glyceraldehyde 3-phosphate.

Molecular Formula: C8H9NO5

Molecular Weight: 199.16g/mol

MOA of Cefixime

Cefixime inhibits cell wall synthesis in actively dividing microbial cells.

As the shape & structure of Β-lactams resembles with the peptide chains &
hence does not allow the cross linkage of cell wall & makes the cell wall fragile.

MOA of Clavulanic acid

Clavulanic acid has negligible antimicrobial activity. Clavulanic acid act as a
competitive inhibitor of beta-lactameses, an enzyme which destroys the beta-
lactam ring of the cefxime. If this beta-lactam ring is destroyed , then cefixime will
not be able to inhibit the cell wall synthesis of the organism.

16
Pharmacology

Cefixime
Bioavailability 40% to 50%
Protein binding approximately 60%
Metabolism ?
Half life Variable Average 3 to 4 hours
Excretion Renal and biliary (add %)

Clavulanic acid
Bioavailability well absorbed
Protein binding ?
Metabolism Hepatic (extensive)
Half life 1 hour
Excretion Renal (30–40%)

Spectrum

Cefixime in Nufex-Beta offers wide coverage against majority of gram (+) ve,
gram (-) ve, & anaerobic bacteria.

Gram (+) ve Gram (-) ve Anaerobes

S.Pneumoniae E.coli Mycoplasma pneumoniae

S,Pyogenes H.Influenzae Mycoplasma hominis

S.Epidermidis M.Catarhallis Bacteroides fragilis

Clostridium Tetani Salmonella Fusobacterium

Corynebacterium Dip. Shigella Peptococcus sp

Neiserria gonorrhoeae

P.Mirabillis

Moreover addition of clavulanic acid to cefixime increases the

– Anti-staphylococcal activity of cefixime
– Gram negative activity comparable to most cephalosporins.
– Anaerobic activity comparable with metronidazole and better than
clindamycin.
– Coverage against (ß-lactamase-producing strains of various gram
negative and positive organisms.

17
Indication:
Pharyngitis
Tonsillitis
Otitis media
Sinusitis
Acute bronchitis
Pneumonia
Typhoid
Acute uncomplicated Pylonephritis
Cystitis
Urethritis
Uncomplicated Gonorrhea

Contraindication
Nufex Beta is contraindicated in patients with known allergies to the
cephalosporin or penicillin antibiotics.
Precaution
If an allergic reaction to Nufex Beta occurs, the drug should be discontinued,
and, if necessary, the patient should be treated with appropriate agents, e.g.,
pressor amines, antihistamines, or corticosteroids.
Nufex Beta should be prescribed with caution in patient with history of
gastrointestinal disease.
Renal Impairment:
Nufex beta may be administered in the presence of impaired renal function, but
dose modification is recommended for patients with moderate or severe renal
impairment (i.e., creatinine clearance of < 40 mL/min).

Adverse Drug Reaction

Headaches, Dizziness, Diarrhea , Stool changes ,Nausea , Abdominal pain ,
Dyspepsia Flatulence and Vomiting.
Transient elevations of SGPT, SGOT and alkaline phosphatase.
Transient elevations in Blood Urea Nitrogen (BUN) or creatinine.
Skin rashes, Drug fever and pruritus. Anaphylactic reactions (urticaria and
angioedema) have been reported rarely.

Dosage & administration

Adults:
The recommended dose of cefixime Nufex beta is 400 mg once daily. When
necessary, a dose of 200 mg (one-half of a 400 mg tablet) given twice daily may
be considered except for urinary tract infections where once daily dosing must be
used.
For treatment of uncomplicated gonococcal infections, a single oral dose of 400
mg is recommended.

18
Children:
The recommended dose of cefixime in Nufex beta is 8 mg/kg/day once daily.
When necessary, a dose of 4 mg/kg given twice daily may be considered except
for urinary tract infections where once daily dosing must be used.

Rationale for a beta lactam-beta lactam inhibitor combination antibiotic

As the usage of cephalosporin’s has increased globally the resistance to this
group of antibiotic has also increased.
Hence to overcome this resistance a Combination of cephalosporin’s with beta
lactamase inhibitors is an attractive preposition for following reasons.
• Production of beta lactamase is the most common mechanism of
resistance to beta lactam antibiotics, especially in gram negative bacteria.
• Convenience of use and more essentially an understanding that using
such combination empirically may help in not only overcome therapeutic
failures due to resistant bacteria but will also delay resistance
development in susceptible bacteria.
• Minimize use of newer antibacterial so that they remain effective
antibacterial for specific use.
• Has a broad spectrum antibiotic activity.
• Highly effective combination in switch therapy
• Well established safety and efficacy profile

Nufex-Beta in Pneumonia

Pneumonia is an inflammatory illness of the lung. Frequently, it is described as

lung parenchyma/alveolar inflammation and abnormal alveolar filling with fluid.
Cause- Pneumonia can result from a variety of causes, including infection with
• bacteria,
• viruses,
• fungi, or
• parasites,
• and chemical or physical injury to the lungs.

Symptoms-
• Cough producing greenish or yellow sputum, or phlegm.
• High fever that may be accompanied by shaking chills.
• Shortness of breath
• Chest pain,
• Cough up blood,
• Loss of appetite
• Blueness of the skin, nausea, vomiting

19
Pathophysiology:
The most common causes of pneumonia are viruses and bacteria. Less common
causes of infectious pneumonia are fungi and parasites.

Virus:
 Influenza virus,

Bacteria:
• Streptococcus pneumoniae,
• Staphylococcus aureus,
• Haemophilus influenzae,
• Klebsiella pneumoniae,
• Escherichia coli,
• Pseudomonas aeruginosa and
• Moraxella catarrhalis.
• Chlamydophila pneumoniae,
• Mycoplasma pneumoniae, and
• Legionella pneumophila

Clinical classification

Community-acquired pneumonia
Community-acquired pneumonia (CAP) is infectious pneumonia in a person who
has not recently been hospitalized. CAP is the most common type of pneumonia.
The most common causes of CAP include Streptococcus pneumoniae, viruses,
the atypical bacteria, and Haemophilus influenzae. Overall, Streptococcus
pneumoniae is the most common cause of community-acquired pneumonia
worldwide.

Hospital-acquired pneumonia
Hospital-acquired pneumonia, also called nosocomial pneumonia, is pneumonia
acquired during or after hospitalization for another illness or procedure with onset
at least 72 hrs after admission. The causes, microbiology, treatment and
prognosis are different from those of community-acquired pneumonia. Up to 5%
of patients admitted to a hospital for other causes subsequently develop
pneumonia. Hospital-acquired microorganisms may include resistant bacteria
such as MRSA, Pseudomonas, Enterobacter, and Serratia.

Why Nufex-Beta in pneumonia?

1.Cefixime in Nufex-beta is having very low mic against most common pathogen
responsible for causing pneumonia hence achieve high kill rate & better cure
rate.

20
 H. influenzaea M.catarrhalis S.pneumonia
e
Cefuroxime 2 2 0.12
Cefixime 0.13 .40 0.29
Cefpodoxime 0.12 0.50 .03

Co – amoxy 0.5 0.5 0.02

clav

2. As per American Family Physician when clinician cause of concern is Beta

lactamase positive H.Influenzae the first drug of choice is cefixime.

3. As per Clinical Drug Investigation The concentrations of cefixime found in

bronchial mucosa exceeded these MIC90 values 4.3 ± 0.6 hours after the last
dose. However, 8 hours after a 400mg oral dose, lung parenchyma
concentrations were higher than MIC90 values for sensitive strains. This ensures
better cure with cefixime as compared with other cephalosporins.

4. The majority of pathogens causing acute bacterial LRTIs are primarily located
extracellularly, and for this reason there is a consensus that antibiotics should be
present in the extra cellular fluid. The concentration of cefixime in ECF exceeds
the mic of common respiratory pathogen & ensures better cure & concentrations
of cefixime in ECF is sufficient to inhibit H. influenzae and S. pneumoniae.

5. As per Chemotherapy 1998 Cefixime is one such agent, which possesses

excellent efficacy against a broad spectrum of pathogens, including Haemophilus
influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Clinical
success rates are similar to cefaclor, clarithromycin, and other cephalosporins.
Importantly, cefixime also possesses excellent activity against beta-lactamase-
producing strains.

6. Cefixime is the most preferred drug as a switch therapy as it offers coverage &
efficacy at par with most intravenous agent.

Bacterial Cefotax Ceftizox Ceftaz Ceftriax Cefixime

Species
S. aureus 2 16 16 4 17
S. pneumoniae < 0.1 0.1 0.5 0.08 .29
S. pyogenes 0.1 0.25 0.12 0.1 .16
E. Coli 0.1 0.25 0.5 0.1 .71
Klebsiella spp. < 0.5 0.25 0.5 0.1 .34

21
7. More over addition of clavulanic acid in Nufex-beta make cefixime more
effective against:
1. Staph. Aureus
2. Gram (-) ve & anaerobic bacteria.

Nufex-Beta in Otitis media

Why Nufex-Beta in Otitis media?

1. Cefixime in Nufex-beta is having very low mic against most

common pathogen responsible for causing otitis media hence
achieve high kill ratio & better cure rate.

H. M.catarrhalis S.pneumonia
influenzaea e
Cefuroxime 2 2 0.12
Cefixime 0.13 .40 0.29
Cefpodoxime 0.12 0.50 .03

Co – amoxy 0.5 0.5 0.02

clav

2. Cefixime is an extended spectrum cephalosporin that has been shown to

be more effective than amoxicillin in treating OM caused by Haemophilus
influenzae. (Pediatr. Infect. Dis. J., 13, S30 (1994). )

3. Amoxicillin-clavulanic acid is having excellent coverage against S.

pneumoniae but major concern is diarrhea which affects the compliance.

4. Amoxicillin-clavulanic exhibit inoculum effect whereas cefixime do not

exhibit inoculum effect.

5. AOM is likely to be caused by betalactamase-producing Haemophilus

influenzae or Moraxella catarrhalis & Two beta-lactamase-stable agents
commonly used for empirical treatment of AOM are amoxicillin/clavulanate
and cefixime. Studies has demonstrated that CFX has comparable clinical
efficacy and a better adverse events profile than A/C when used to treat AOM
of childhood. (Pediatric Drugs)

22
 Nufex-beta in Typhoid

Why Nufex-Beta in Typhoid?

• The mic required for cefixime is very low as compared to co-amoxyclav &
other cephalosporin.

Molecule mic
Cefixime 0.21mcg/ml
Amoxy-clav 1mcg/ml
Cefuroxime axetil 4mcg/ml
Ofloxacin 0.12 mg/l

• The conc. Of cefixime in gall bladder & spleen is higher as compared to

other antibacterial. This will prevent the chance of further relapse.

Organ Concentration of CFX mic for salmonella

Serum 2.98 micrograms/ml 0.21mcg/ml
Gallbladder 25.02 micrograms/g 0.21mcg/ml
Biliary level 8.8 micrograms/ml 0.21mcg/ml

• Temp. defervescence will take by 4-5 day as compared to 6-7 day with co-
amoxyclav & other cephalosporin. This will reduce the duration as well
cost of therapy.
• Cefixime showed excellent activity against all 73 strains with an MIC90
value of 0.25 mcg/ml. Reflecting its high beta-lactamase stability, cefixime
also had excellent activity against beta-lactamase-producing amoxicillin-
resistant strains. Antibacterial activity of cefixime was comparable to
ceftriaxone, ofloxacin, and ciprofloxacin, which are often used for the
treatment of typhoid fever. clinical data, which showed that oral cefixime
provides a safe and effective alternative for the treatment of typhoid fever,
even in cases of multidrug-resistant S. typhi.
(J Infect Chemother. 1999 )

23
 Nufex-Beta in UTI

Nufex-beta in UTI:

Cefixime Ofloxacin Amoxy-clav

Escherichia coli 0.71 0.12 8

(90%)
Ureaplasma 0.71 2 2
urealyticum

Neisseria 0.06 0.06 0.71

gonorrhoeae
Chlamydia 0.50 0.5 1
trachomatis

Mycoplasma hominis 0.80 1 4

Klebsiella 0.10 0.2 4

pneumoniae

Proteus mirabilis 0.06 0.2 4

24
 NUFEX

INTRODUCTION

Nufex contains Cephalexin which belongs to first generation Cephalosporin, oral

administration. It is a semi-synthetic analog of Cephalosporin.

PHARMACODYNAMICS

Inhibition cell wall synthesis of bacteria.

PHARMACOKINETICS

• Nufex is acid stable and may be given without regard to meals. It is rapidly
absorbed after oral administration.
• Nufex following doses of 250 mg, 500 mg, and 1 g, average peak serum
levels of approximately 9, 18, and 32 μg/ml respectively were obtained at
1 hour.
• Measurable levels were present 6 hours after administration.
• Nufex is excreted in the urine by glomerular filtration and tubular secretion.
Studies showed that over 90% of the drug was excreted unchanged in the
urine within 8 hours.
• During this period, peak urine concentrations following the 250 mg, 500
mg, and 1 g doses were approximately 1000, 2200, and 5000 μg/ml
respectively

ANTIBACTERIAL ACTIVITY

Aerobes, Gram-positive Aerobes, Gram-

negative:

Staphylococcus aureus Escherichia coli.

(including penicillinase-
producing strains).
Staphylococcus epidermidis
(penicillin-susceptible strains).
Streptococcus pneumoniae.
Streptococcus pyogenes
Haemophilus influenzae.
Klebsiella pneumoniae.
Moraxella (Branhamella)
catarrhalis.
Proteus mirabilis.

INDICATIONS

Nufex is used as a bactericidal agent against a wide range of Gram +ve and
Gram-ve organisms. It does not possess activity against Pseudomonas

25
aeruginosa or Mycobacterium tuberculosis. It is indicated for the treatment of the
following conditions, when caused by susceptible bacteria.

a. Respiratory tract infections - Acute and chronic bronchitis,

bronchopneumonia and infected bronchiectasis.
b. Ear, nose and throat infections - Otitis media, mastoiditis, sinusitis,
follicular tonsillitis and pharyngitis.
c. Urinary tract infections - Acute and chronic pyelonephritis, cystitis and
prostatitis, prophylaxis of recurrent urinary tract infections.
d. Gynaecological and obstetrical infections
e. Skin, soft tissue, bone and joint infections
f. Gonorrhoea, syphilis and prophylaxis in dental procedures (when penicillin
is unsuitable)
g. Other infections including septicaemia and endocarditis.

CONTRAINDICATIONS

It is contraindicated in patients with known hypersensitivity to cephalosporins.

RECOMMENDED DOSAGE

ADULTS

The dosage ranges from1-4g daily in divided doses. For skin and soft tissue
infections, streptococcal pharyngitis and mild, uncomplicated urinary tract
infections, the usual dosage is 250mg every 6 hours, or 500mg every 12 hours.
Cystitis therapy should be continued for 7-10 days. For most acute infections,
treatment should continue for at least 2 days after symptoms have subsided. In
severe systemic infections doses upto 4g/day can be used. In chronic recurrent
or complicated urinary tract infections and syphilis, 500mg cephalexin should be
given every 6 hours for two weeks.

Gonorrhoea - a single dose of 3g with 1g probenecid for males or 2g with 0.5g

probenecid for females is usually effective.

CHILDREN

Usual recommended dose in divided doses is 25-50mg/kg/day for most-

infections and upto 100mg/kg/day for chronic, severe or deep-seated infections.
For skin and soft tissue infections, streptococcal pharyngitis and mild,
uncomplicated urinary tract infections, total daily dose may be administered
every 12 hours.

26
For most infections dosage schedule suggested is:

Neonates : 62.5 - 125mg bid

1-5 yrs : 125mg tid
6-12 yrs : 250mg tid

In severe infections dosage may be doubled. In otitis media, dose of 75-

100mg/kg/day in 4 divided doses may be required.

In treatment of beta hemolytic streptococcal infections, therapeutic dose is to be

administered for atleast 10 days.

IN RENAL FUNCTION IMPAIRMENT

When renal function is impaired the dosage of cephalexin should be reduced to

prevent accumulation as follows:

The dosing intervals should be longer. The following guidelines for approximate
dosing intervals are recommended:

Creatinine 50 50-20 20
Clearance
(ml/min)
Approximate 8h 12h 24h
dosing intervals
for 500mg

The maximum dosage given in the table should not be exceeded:

Creatinine MAXIMUM DOSAGE

Clearance (ml/min)

Adults (g/day) Children (mg/kg/day)

20-50 3.0 50
5-20 1.5 25
<5 0.5 8

27
In patients on intermittent haemodialysis, an additional dose of 500mg at the end
of each dialysis is recommended in addition to the daily dose.

ADVERSE DRUG REACTIONS (ADRs)

The common side effects with Nufex are diarrhoea, nausea and vomiting.
Headache, dizziness, allergic reactions and raised serum transaminase levels
have also been reported. Eosinophilia and very rarely neutropenia, which is
reversible, have occured in a few patients.

As with other broad spectrum antibiotics overgrowth of Candida and rare

instances of pseudomembranous colitis can occur.

PRESENTATION
Nufex 250mg/500mg - Each tablet contains Cephalexin 250mg/500mg
Strip of 10 tablets

28
 NUFEX SR (CEPHALEXIN)

COMPOSITION

NUFEX SR 375

Each sustained release film coated tablet contains :

Cephalexin I.P. 375 mg

(on anhydrous basis)

NUFEX SR 750

Each sustained release film coated tablet contains :

Cephalexin I.P. 750 mg

(on anhydrous basis)

INDICATIONS

Cephalexin is used as a bactericidal agent against a wide range of Gram +ve and
Gram-ve organisms. It does not possess activity against Pseudomonas
aeruginosa or Mycobacterium tuberculosis. It is indicated for the treatment of the
following conditions, when caused by susceptible bacteria.

a. Respiratory tract infections - Acute and chronic bronchitis,

bronchopneumonia and infected bronchiectasis.
b. Ear, nose and throat infections - Otitis media, mastoiditis, sinusitis,
follicular tonsillitis and pharyngitis.
c. Urinary tract infections - Acute and chronic pyelonephritis, cystitis and
prostatitis, prophylaxis of recurrent urinary tract infections.
d. Gynaecological and obstetrical infections
e. Skin, soft tissue, bone and joint infections
g. Gonorrhoea, syphilis
h. Prophylaxis in dental procedures (when penicillin is unsuitable)
h. Other infections including septicaemia and endocarditis.

CONTRAINDICATIONS

It is contraindicated in patients with known hypersensitivity to cephalosporins.

29
DOSAGE AND ADMINISTRATION

The sustained release tablets should not be cut, crushed or chewed but should
be swallowed whole with a glass of water.

Usual Adult Dosage :

750 mg twice daily.

In milder infections, 375 mg twice daily may be given.
In severe infections, 2 tablets of 750 mg two times daily may be given.
A maximum dose of 4 g/day should not be exceeded.

NOTE :

375 mg Cephalexin sustained release tablet administered twice a day is clinically

equivalent to 250 mg Cephalexin conventional release tablet administered thrice
a day.

750 mg Cephalexin sustained release tablet administered twice a day is clinically

equivalent to 500 mg Cephalexin conventional release tablet administered thrice
a day.

IN RENAL FUNCTION IMPAIRMENT

No dosage adjustments are essential for patients with a creatinine clearance

greater than 50 ml/min. For patients with renal dysfunction, or renal failure
dosage should be reduced.

SIDE EFFECTS

The common side effects with cephalexin are diarrhoea, nausea and vomiting.
Headache, dizziness, allergic reactions and raised serum transaminase levels
have also been reported. Eosinophilia and very rarely neutropenia, which is
reversible, have occurred in a few patients.

As with other broad spectrum antibiotics overgrowth of Candida and rare

instances of pseudomembranous colitis can occur.

PRECAUTIONS

Cephalexin should be administered with caution in the presence of markedly

impaired renal function. Dosage of cephalexin in such cases should be suitably
reduced.

30
In patients receiving cephalexin, false positive reaction for glucose in the urine
may occur with copper reduction reagents (Benedict’s or Fehling’s solution or
with ‘Clinitest’ but not with enzyme based tests, e.g. ‘Clinistix’).

Positive direct Coomb’s tests have been reported during treatment with
cephalosporin antibiotics.

Generally cephalexin is well tolerated by patients sensitive to penicillin but as

cross reactions have been encountered rarely, cephalexin should be given
cautiously to penicillin sensitive patients.

Use of any drug in women of child bearing potential requires that the benefits of
the therapy be weighed against possible hazards to the mother and foetus.
However, laboratory and clinical experience to date has shown no evidence of
teratogenicity.

OVERDOSAGE

Serum levels of cephalexin can be greatly reduced by peritoneal dialysis or

haemodialysis.

STORAGE

In a cool, dry place.

31
 Qugyl-O
Composition :
Each tablet of Qugyl-O offers:
Ofloxacin- 200mg
Ornidazole-400mg
Description
Ofloxacin is a synthetic broad-spectrum antimicrobial agent for oral
administration.
The chemical structure is:

Its empirical formula is C18H20FN3O4,

Ofloxacin is considered to be soluble in aqueous solutions with pH between 2
and 5. It is sparingly to slightly soluble in aqueous solutions with pH 7 and freely
soluble in aqueous solutions with pH above 9.
Ofloxacin has the potential to form stable coordination compounds with many
metal ions.

Ornidazole is a 5-nitroimidazole derivative drug which has antimicrobial action. It

is used in the treatment of protozoal infections,and also in the treatment and
prophylaxis of anaerobic bacterial infections.
The chemical structure is

Formula: C7H10ClN3O3

MOA Of ofloxacin:
Ofloxacin is a DNA gyrase inhibitor. DNA gyrase is an essential bacterial enzyme
that maintains the superhelical structure of DNA. DNA gyrase is required for DNA
replication and transcription, DNA repair,

32
MOA of Ornidazole:
The antimicrobial activity of ornidazole is due to the reduction of the nitro group
to a more reactive amine that attacks microbial DNA, brings about loss of helical
structure of DNA and subsequent DNA breakage thus inhibiting further synthesis
and causing degradation of existing DNA.

Pharmacology:
Ofloxacin:

Protein binding 32%

Half life 9hr
Metabolism ?
Excretion Primarily urine (as unchanged drug)
Bioavailability 98%
Ornidazole:

Protein binding 11 to 13%.

Half life 13hr
Metabolism Metabolised via the liver, excreted in the
Urine and Feces
Excretion 85% of single oral dose is eliminated
with 5 days - Urine (63%) and Feces
(22%)
Bioavailability More than 90%

Spectrum of Ofoxacin
• Ofloxacin being a second generation quinolone offers strong coverage
against Gram (-)ve pathogen including Pseudomonas species, Gram (+)ve
and some atypical pathogen.

• Acinobacter, Citrobacter,Enterobacter,E. coli,H. influenza, K.

pneumonia,Proteus species,

• Pseudomonas species,Serratia marcescsns,Enterococcus faecalis,Staph

aureus,Strep. pneumonia.

• It is also active against Propionobacterium acne and Chlamydia.

Spectrum of Ornidazole:

Ornidazole is active against a large number of anaerobic organisms including:

Bacteroides fragilis, prevotellia, Fusobacterium,Gardenellla,Peptococcus,
Clostridium species, and Eubacterium.
Ornidazole is also effective against human parasitic protozoa like Entamoeba
histolytica and Giardia lamblia.

33
Indication:
Polymicrobial infections (Mixed infections) such as –

• Diarrhea and dysentery of bacterial, protozoal and mixed origin

• Intra-abdominal infections
• Post operative infections
• Pelvic infections
• Pelvic inflammatory disease
• Diabetic foot ulcers
• Skin and skin structure infections
Contraindication:

Hypersentivity to quinolone or nitroimidazoles

Precaution & Side effect:

Generally ofloxacin plus ornidazole combination is well tolerated but very few
patients can feel the side effects like dizziness, nausea, diarrhea, vomiting,
abdominal pain and discomfort, headache, restlessness, and urticaria etc.
Impaired renal or hepatic infection, alcohol intake, convulsions, avoids drinking or
operative heavy machinery.Contraindicated

Dose:
One tablet twice daily.

Talking points:

•Broad spectrum: Ofloxacin & Ornidazole in Qugyl-O offers coverage

against broad range of pathogen which includes gram(+)ve, gram(-)ve &
anaerobes.
• High bioavailability
• Serum concentration above MICs
• Negligible bacterial resistance reported
• High renal excretion as unchanged drug
• Longer half life
• BD dosing
• No taste alterations (unlike Tinidazole & Metronidazole)
• Negligible adverse events.
Competitor:

Brand Company
Brakke Franco India
O2 Medley
Oflatoon-OZ Zy.Cadila
Zenflox-OZ Mankind

34
 Rabee

Composition
Each enteric coated Rabee 20mg tab.Contains: Rabeparazole sodium 20mg

Description
Rabeprazole is an oral drug that is used for the treatment of conditions caused
by acid. It is in a class of drugs called proton pump inhibitors or PPIs. Other
drugs in the same class include lansoprazole, omeprazole, pantoprazole ,and
esomeprazole .

MOA
Rabee act by irreversibly blocking the hydrogen/potassium adenosine
triphosphatase enzyme system (the H+/K+ ATPase, or more commonly just
gastric proton pump) of the gastric parietal cell. The proton pump is the terminal
stage in gastric acid secretion, being directly responsible for secreting H+ ions
into the gastric lumen, making it an ideal target for inhibiting acid secretion.
Targeting the terminal-step in acid production, as well as the irreversible nature
of the inhibition, results in up to 99% reduction of gastric acid secretion.
Pharmacology

Bioavailability: 52%
Absorption: Rabeprazole may be taken without regard to timing of meals.
Protein Binding: 96.3%
Excretion: Approximately 90% in urine, 10% in the feces.
Metabolism Hepatic
Half life 1 - 1.5 hours
Excretion Renal

Indication

• gastric ulcer
• peptic ulcer (PUD)
• Maintenance of Healing of Erosive or Ulcerative GERD
• Healing of Erosive and Ulcerative GERD
• Healing of Duodenal Ulcers.
• Treatment of Symptomatic GERD
• Treatment of Pathological Hypersecretory conditions (Zollinger-Ellison)
• Helicobactor Pylori Eradication to Reduce Risk of Duodenal Ulcer
Recurrence

Contraindication

• Hypersensitivity to Rabeprazole, substituted benzimidazoles or any of

components of its pharmaceutical forms.
• Pregnancy & lactation

35
Drug to drug interaction
Potentiates action of warfarin, Causes accumulation of cyclosporine,
reduces the absorption of ketoconazole and increases the absorption of digoxin.

Adverse Drug Reaction

• In clinical trials the most common side effect assessed as possibly or

probably related to Rabeprazole was Headache in 2.4% of patients vs
1.6% taking placebo.
• diarrhea vomiting
• nausea abdominal pains
• constipation dry mouth
• increased or decreased appetite headache
• anxiety achlorhydria

Dosage & Administration

Indication Dose

GERD in adults 20 mg daily for 4-8 weeks & If healing

does not occur after 8 weeks, another 8
week course may be considered. The
recommended maintenance dose is 20
mg daily.

Heartburn 20 mg daily for 4 weeks and an

additional 4 weeks if symptoms do not
resolve.

Ulcers 20 mg daily for 4 weeks

Zollinger-Ellison Syndrome 60-80 mg daily

For eradication of Helicobacter pylori rabeprazole 20 mg, clarithromycin 500

mg, amoxicillin 1000 mg all given twice
daily (morning and evening) for 7 days

Tablets should be swallowed whole and should not be crushed, split or chewed.
Rabeprazole can be taken with or without meals since food has little effect on its
absorption.

USP’S OF RABEE

36
Based on the experimental and clinical evidence, following are the USP’s of
RABEE.
 Quick onset of action
 Apart from acid inhibition, It also offers additional cytoprotective benefits
by
 significantly augmenting production of gastric mucus and mucin
 Greater antisecretory effect over 24 hr period than omeprazole,
esomeprazole and lansoprazole
 Significantly better control of day as well as night time heartburn
symptoms compared to placebo and omeprazole
 Significantly more effective than placebo in relieving heartburn and various
other gastrointestinal symptoms in non erosive GERD
 Effective long term ( upto 2 years) maintenance of healing and prevention
of symptoms in patients with healed GERD
 Achieved eradication rates of >85% as a part of triple therapy in
management of H. pylori eradication
 Low propensity for drug interactions
 Well tolerated during long term (upto 2 years) studies Bioavailability not
affected by food. Can be taken irrespective of meal timings

Competitor
Direct competitor Indirect competitor
Brand Company Brand company
Razo DRL Lanzap DRL
Rablet Lupin Lanzofast Zydus
Happi G. Remedies Splanz Sun
Rabeloc Cadila Olit Cadila
Rabicip Cipla Pantocid Sun

What is the evidence in favour of Rabee providing additional

cytoprotection?
Rabeprazole is a unique PPI in providing added cytoprotective action by
enhancing mucus production and by increasing viscosity translating to
cytoprotection provided to mucosa cells. This action may be responsible for
superior healing rates and maintenance of healing with Rabeprazole.
Rabeprazole has unique pharmacological property of augmenting the production
of gastric mucus and mucin, which may provide additional protection to mucosa
during acid related challenge.

37
 Rabee-D
Composition
Rabee –D is a capsule containing Rabeprazole sodium 20 mg (as enteric coated
pellets) and Domperidone BP 30 mg (as sustained release pellets).

Description
Rabeprazole is an oral drug that is used for the treatment of conditions caused
by acid. It is in a class of drugs called proton pump inhibitors or PPIs.
Domperidone is a dopamine antagonist with anti emetic and gastroprokinetic
properties.

MOA
Rabeprazole act by irreversibly blocking the hydrogen/potassium adenosine
triphosphatase enzyme system (the H+/K+ ATPase, or more commonly just
gastric proton pump) of the gastric parietal cell. The proton pump is the terminal
stage in gastric acid secretion, being directly responsible for secreting H+ ions
into the gastric lumen, making it an ideal target for inhibiting acid secretion.
Targeting the terminal-step in acid production, as well as the irreversible nature
of the inhibition, results in up to 99% reduction of gastric acid secretion.
The mechanism of action of domperidone is related to its peripheral dopamine
receptor blocking properties.
Domperidone does not readily cross the blood-brain barrier and therefore is not
expected to have central effects.
Pharmacology
Rabeprazole : Refer Rabee

Domperidone
Absorption: Domperidone is rapidly absorbed
Protein Binding: 91-93%
Metabolism: Hepatic
Excretion: Approximately 31%in urine, 66% in the feces.
Half life 7-9 hours

Contraindication

The fixed dose combination of Rabeprazole and Domperidone is contraindicated

in patients with known hypersensitivity to either drug or their substitutes. Also
fixed dose combination is contraindicated in the presence of gastro-intestinal
hemorrhage, obstruction or perforation.

Drug to drug interaction

Drugs like warfarin, theophylline, diazepam, phenytoin, anticholinergic drugs,
Antimuscarinic agents and opiod analgesics must be used with caution while
administering this combination.

38
Adverse Drug Reaction
In general, both the drugs separately are well tolerated. Following adverse drug
reactions may occur with this fixed drug combination headache, asthenia, skin
rash, diarrhea, flatulence, constipation and dry mouth.

Indication
1. Dyspepsia
2. GERD
3. Nausea associated with acid peptic disorders
4. Post-operative nausea and vomiting
5. Chronic gastritis

Dosage & Administration

Indication Dose

GERD in adults One cap. daily for 4-8 weeks & If

healing does not occur after 8 weeks,
another 8 week course may be
considered.

Heartburn One cap. daily for 4 weeks and an

additional 4 weeks if symptoms do not
resolve.

Capsule should be swallowed whole and should not be crushed, split or chewed.
Rabeprazole can be taken with or without meals since food has little effect on its
absorption.

RATIONALE OF COMBINATION THERAPY

1. Hyperacidity and Hypomotility are common GIT problems and frequently
coexist together.
2. Excess hydrochloric acid and defective clearance of the acid and other
gastric content from the stomach together or individually give rise to
nausea, vomiting and upper abdomen discomfort due to irritation of gastric
mucosa.
3. Only acid suppression or only prokinetic therapy by itself would not serve
the purpose.
4. Rabeprazole a PPI is a drug of choice for acid suppression and
Domperidone is drug of choice for stimulation of gastric motility.
5. Both the drugs are devoid of any major side effects. Domperidone does
not cross Blood Brain Barrier (BBB), so no extra pyramidal syndrome.
6. Both the drugs are in pellet form. Different colour pellets are packed in
same

39
 capsule, so the compliance of the patient will be excellent.
7. Domperidone has short half-life, which makes it necessary to take it three
times a day. Therefore it has been formulated as sustained release
pellets. The advantages of domperidone sustained release pellets include
round the clock symptom control, better patient compliance with fewer
side effects.
8. Rabeprazole 20mg is formulated as enteric-coated pellets. It reduces
fluctuations in drug plasma concentrations improves effectiveness and
controls the site of drug delivery in the GI tract.
9. Combination of Rabeprazole and Domperidone gives a complete
symptomatic relief from Dyspepsia, heartburn, and Acid-Pepsin disorder
associated with nausea, vomiting and epigastric pain.

USP’S OF RABEE -D
A. • Precise Microtechnology
Uniform size pellets and less than 1mm that offers low dose
dumping and uniform absorption
B. • Precise Chemistry
i. 24 hours controlled release Domperidone.
ii. 10mg out of 30mg Domperidone in Rabee-D is released in
the 1st hour for faster action.
C. Once a day dosage.
D. Pellet diameter is less than 1.0mm to 1.5 mm hence the pellets can pass
the pyloric sphincter even when it is closed.

Precise 4 dimensional action

1. Increases LES pressure that prevents reflux.
2. Increases mucin and mucus secretion that improves
GI protection.
3. Accelerates Gastric emptying that reduces bloating.
4. Faster Inhibition of proton pump that controls hyperacidity and
epigastric
pain.

Competitor
Brands Marketed by Composition
Algibra – D CFL Each hard gelatin capsule contains
Rabeprazole sodium (as enteric coated
tablet) 20 mg, Domperidone B.P (tablet)
20 mg SR, Domperidone BP (tablet)
10mg IR

Rabemac Macleods Each hard gelatin capsule contains

DSR Rabeprazole sodium (as enteric coated
tablet) 20 mg, Domperidone B.P (tablet)

40
 20 mg SR, Domperidone BP (tablet)
10mg IR
Rabicip-D Cipla Each capsule contains Rabeprazole
Sodium 20 mg (as enteric coated pellets)
+ Domperidone BP 30 mg (as sustained
release pellets)
Veloz D Torrent Each capsule contains Rabeprazole
Sodium 20 mg + Domperidone 30 mg SR

41
 Rabee ISR

Product Manual: Rabeprazole 20 mg + Itopride ER 150 mg

PROKINETICS
In general, GI motility is mainly described as peristalsis. Peristalsis is controlled by 3
mechanisms.
1. Mechanical - Presence of bolus of food or distension of gut stimulates peristalsis.
2. Nervous - It is central in origin. The vagus nerves innervate the smooth muscle through the
myentric plexus. The myentric plexus is the programmer for all motility programs in the GIT
e.g. it regulates the following functions.
i. Reservoir function - e.g. in fundus of stomach.
ii. Mixing function - e.g.in small intestine.
iii. Barrier function e.g. in LES
iv. Propulsive function at all levels.
The inputs come from mechanical and chemical receptors in gut wall & CNS. Hence it is
called "little brain" or "gut brain".
3. Chemical - Through neurotransmitters mainly acetylcholine.

Any impairment in GI motility leads to reflux of the contents, vomiting, nausea, and constipation.
Also symptoms like heartburn, nausea, vomiting, regurgitation, dyspepsia, pain.

Other condition in which there can be GI motility impairment is gastroparesis i.e. paralysis of gut
wall. It presents itself as a motility disorder of poor gastric emptying.

The drugs used in the treatment of these hypomotility conditions are prokinetics.
Antidopaminergic drugs can also be used but they may precipitate side effects.

What is Itopride?

Itopride is a prokinetic benzamide derivative. This drug inhibits dopamine and has a gastrokinetic
effect (result in increased gastrointestinal motility)

What are the pharmacological actions of Itopride?

Itopride increases acetylcholine concentrations by inhibiting dopamine D2
receptors and acetylcholinesterase. Higher acetylcholine increases GI peristalsis,
increases the lower esophageal sphincter pressure, stimulates gastric motility,
accelerates gastric emptying, and improves gastro-duodenal coordination.

Clinical Use and Dosage:

Typically, itopride is indicated in the treatment of GI symptoms caused by
reduced GI motility:

• dyspepsia of a non-ulcer type (gastric "fullness", discomfort, and possible pain)

• anorexia
• heartburn
• regurgitation

42
 • bloating
• nausea and vomiting
• other possible gastric, prolactin, or dopamine related conditions

Typical adult dosage is usually 150mg/24hrs in 3 divided doses. However,

Itopride ER 150 mg is administered once a day. The dose is usually taken on an
empty stomach about an hour before meals. However, the dosage and details of
administration may vary depending on the patient’s age, symptoms, and other
factors.
Itopride was shown to significantly improve symptoms in patients with functional
dyspepsia and motility disorders in placebo-controlled trials.
Contraindications and precautions
Itopride is contraindicated in hypersensitivity to itopride or benzamides; lactation,
GI hemorrhage, obstruction or perforation. Itopride may not be indicated for those
suffering from Parkinson's disease or other conditions involving dopamine
regulation issues. Itopride should be used with special caution in the young and
the elderly. Little information is available at this time regarding the safe use of
itopride during pregnancy.

Adverse drug reactions

Some common side-effects of itopride may include: rash, diarrhoea, giddiness,
exhaustion, back or chest pain, increased salivation, constipation, abdominal
pain, headache, sleeping disorders, dizziness, galactorrhea, and gynecomastia.
Other side-effects may also be present.
Leukopenia, a reduction in the normal level of white blood cells, can be a
potentially life-threatening reaction to itopride.

PROTON PUMP INHIBITORS

PPIs act by inhibiting the proton pump H+-K+-ATPase which is the ultimate mediator of gastric
acid secretion. As the name suggests H+-K+-ATPase is an enzyme which utilizes ATP to catalyse
the outward transport of H+ in exchange for the inward transport of K+.

All available Pips viz. Omeprazole, lansoprazole and pantoprazole being weak bases,
accumulate in the acidic compartment of parietal cells and get highly ionized at low pH. They are
prodrugs, which are rapidly converted to the active form,, cationic sulfenamides. These bind
covalently to the cysteine molecules of H+-K+-ATPase, thus blocking the H+-K+-channels of the
enzymes involved in the expulsion of H in exchange for K . Since activation of H +-K+-ATPase is
the terminal step in the gastric acid secretion, PPIs inhibit HCl acid secretion in response to all
stimulii.

What is Rabeprazole?

Rabeprazole is an antiulcer drug in the class of proton pump inhibitors.

43
Clinical Use and Dosage:

• Gastric ulcer
• Peptic ulcer (PUD)
• Maintenance of Healing of Erosive or Ulcerative GERD
• Healing of Erosive and Ulcerative GERD
• Healing of Duodenal Ulcers.
• Treatment of Symptomatic GERD
• Treatment of Pathological Hypersecretory conditions (Zollinger-Ellison)
• Helicobactor Pylori Eradication to Reduce Risk of Duodenal Ulcer Recurrence

It is given 20 Mg Once a day.

Contraindications and precautions

• Hypersensitivity to Rabeprazole, substituted benzimidazoles or any of components of its

pharmaceutical forms.
• Pregnancy
• Lactation

Adverse drug reactions

• Some common side-effects of Rabeprazole may include: headache,

diarrhea , vomiting, nausea, abdominal pains , constipation, meteorism,
dry mouth, increased or decreased appetite, asthenia , headache, anxiety,
sleeplessness, vertigo, thrombocytopenia, granulocytopenia,
leukocytopenia, skin eruption, erythema, myalgia, arthralgia, muscle or
bone pain

Other side-effects may also be present.

Pharmacokinetics:

Bioavailability 52%
Metabolism Hepatic
Half life 1 - 1.5 hours
Excretion Renal

Rabeprazole + Itopride Rationale for combination:

In GERD, treatment aims at decreasing the amount of reflux or reducing damage
to the lining of the esophagus from refluxed materials. Thus, Itopride by
increasing acetylcholine concentrations by inhibiting dopamine D2 receptors and
acetylcholinesterase, increases GI peristalsis, increases the lower esophageal
sphincter pressure, stimulates gastric motility, accelerates gastric emptying, and

44
improves gastro-duodenal coordination and thus decreases the amount of reflex.
On other hand Rabeprazole reduces the damage to the esophagus lining by
suppressing the gastric acid secretion by inhibiting the gastric H+-K+-ATPase at
the secretory surface of the gastric parietal cell. Moreover, Rabeprazole and ER
Itopride are given as once a day dosage and thus ideal for combination.

Indication and Dosage: 1 capsule once daily before food in patiens wih GERD.
Contraindication:

• Hypersensitivity
• Lactation

It should b used with caution in patients with severe hepatic impairment and in
pregnancy.

Drug Inteaction:
Rabeprole increases eliminationT ½ of digoxin, decreases effects with
aminoglutethimide, carbamazepine, phenotoin and rifampin and reduces
aborption of ketoconazole and itracnazole.
Anti cholinergic agents reduces the action of Itopride

Adverse Drug Reaction:

Headache, diarrhoea, dizziness, rash.
Potential Life threatening: Anaphylaxis, agranulocytosis

TRICAINE- MPS

ANTACIDS

These are oral medications that neutralize the amount of acid present
within the stomach or duodenum or esophagus. These medications act
quickly but by different mechanisms than histamine to receptor
antagonists and proton pump inhibitors. Antacids typically act by directly

45
neutralizing the HCL (hydrochloric acid) present within the stomach or
duodenum or esophagus.

COMPOSITION

Aluminum hydroxide 300mg

Magnesium hydroxide 150 mg
Simethicone 125 mg
Oxethazaine 10 mg

PHARMACODYNAMICS

Alumina gel and magnesium hydroxide react chemically to neutralize or

buffer existing quantities of acid, but have no direct effect on its
production.

Oxethazaine exerts a prolonged topical anaesthetic action.Oxethazaine is

a topical anaesthetic, which, when applied to the mucous membranes
produces a more potent anaesthesia of longer duration than either
cocaine hydrochloride or lidocaine hydrochloride.

Simethicone is used to help relieve pain and bloating caused by trapped

wind. It works by bringing together all the small bubbles of gas to form a
large bubble, which is expelled either by belching or flatulence.

PHARMACOKINETICS

Studies have shown that a small amount of aluminium from aluminium

hydroxide is absorbed from the intestine. Approximately 10% of the
magnesium in agnesium hydroxide is absorbed from the intestine.After
oral administration of oxethazaine contained in 10 mL of alumina gel with
magnesium hydroxide, the peak oxethazaine plasma level was
approximately 20 ng/mL and occurred about one hour after
dosing.Oxethazaine undergoes rapid and extensive biotransformation
resulting in a short plasma half-life of approximately one hour. Less than
0.1% unchanged oxethazaine was recovered in the urine within 24 hours.
Major metabolites were beta-hydroxy-mephentermine and beta-hydroxy-
phentermine. Mephentermine and phentermine appeared in the plasma in
pharmacologically insignificant amounts and their cumulative 24-hour
urinary excretion was less than 0.1% of the dose administered.
Simethicone not absorbed.

INDICATIONS

It acts as an antacid in dyspepsia and is used for the symptomatic relief of

hyperacidity associated with peptic ulcer, gastritis, esophageal reflux

46
 with heartburn. It may be of benefit if symptomatic relief could not be
obtained with antacid therapy alone.

CONTRAINDICATIONS

• Tricaine – MPS should not be given to any patient who has

demonstrated sensitivity to it.
• Do not use Tricaine – MPS if patient is presently taking a
prescription antibiotic drug containing any form of tetracycline.
• Tricaine – MPS contra-indicated in patients with symptoms of
appendicitis since these medicines may increase the danger of
perforation or rupture due to their constipating or laxative effects.
• The use of aluminium-containing antacids (except those containing
aluminium phosphate) is contra-indicated in patients with
hypophosphataemia due to the phosphate binding properties of
aluminium salts.
• The use of magnesium-containing antacids is contra-indicated in
patients with severe renal function impairment due to increased danger
of occurrence of hypermagnesaemia.

SAFETY IN PREGNANCY AND LACTATION HAS NOT BEEN

ESTABLISHED.

RECOMMENDED DOSAGE

The recommended Tricaine – MPS adult oral dose is one to two 5 ml

measures, four times daily, 15 minutes before meals and at bedtime. Do
not exceed the recommended dosage. Tricaine - MPS should preferably
be taken undiluted; however, if desired, a sip of water may follow it.

ADVERSE DRUG REACTIONS (ADRs)

Medicines and their possible side effects can affect individual people in
different ways. The following are some of the side effects that are known
to be associated with Tricaine – MPS. Because a side effect is stated
here, it does not mean that all people using this medicine will experience
that or any side effect. Disturbances of the gut such as diarrhoea,
constipation, nausea, vomiting or abdominal pain

DRUG INTERACTIONS
Fluoroquinolones (medicine for infection)-Antacids may decrease the effects of
these medicines

47
Isoniazid taken by mouth (e.g., INH)-Aluminum-containing antacids may
decrease the effects of isoniazid; isoniazid should be taken at least 1 hour before
or after the antacid

Ketoconazole -Antacids may decrease the effects of ketoconazole, should be

taken 3 hours before the antacid
Tetracyclines (medicine for infection) taken by mouth-Use with antacids may
decrease the effects of both medicines; antacids should not be taken within 3 to
4 hours of tetracyclines
PRESENTATION

Tricaine MPS Gel - Each 180ml contains Oxethazaine 10mg + Aluminium

Hydroxide Gel
equivalent to Dried Aluminium Hydroxide Gel 300mg Paste
equivalent to Magnesium Hydroxide 150mg + Simethicone
40mg
Bottle of 180ml

USP’S OF TRICAINE – MPS

Al (OH)3: Sustained Acid neutralization

Mg (OH)2:Rapid Acid neutralization

Balanced 2:1 ratio Laxative (Mg) & constipation (Al) effects balanced

Simethicone: Anti-flatulent effect

Oxethazaine: pain relief by local anesthesia & reduced acid secretion

American mint flavor: Better patient compliance

Daslin NF Cough Syrup

Composition:

Each 5ml contains:

Loratadine HCL USP 5 mg

48
Ambroxol HCl BP 30 mg
Guaiphenesin IP 50 mg
Menthol IP 0.5 mg

Loratidine:
Loratidine, a piperidine derivative related to azatadine is a non-acting, non-
sedating antihistamine with no significant muscaranic activity. It is used for the
symptomatic relief of allergic conditions in Rhinitis.

In Seasonal allergic Rhinitis, the recommended dosage of Loratidine in adults is

10 mg once daily.

In children aged between 2-5 years of age the recommended dosage is 5 mg

once daily.

Ambroxol:
Ambroxol is a metabolite of Bromhexine. It is a mucolytic agent. Studies showed
that it enhances both bronchial glandular cell secretions. These secretions get
mixed with the thick mucus thereby reducing its viscosity and helping easy
expectoration. It also stimulates cilliary motility and accelerates mucocilliary
transport.

Studies have also shown that Ambroxol affects the secretomotor activity of
serous glands, facilitates the repair of bronchial epithelium and accelerates
mucociliary transport and clearance.

It has daily dose of 30 to 120 mg by mouth in to 2 to 3 divided doses.

It is rapidly absorbed from the gastrointestinal tract and has a very high
bioavailability.
Ambroxol is been seen to increase the concentration of antibiotics in the lungs,
when co – prescribed.

Guaiphenesin:
Guaiphenesin is used as an expectorant in symptomatic management of coughs
associated with common cold, bronchitis, laryngitis, pharangytis, pertusis,
influenza, measles, and coughs provoked by chronic paranasal sinusitis.
Guaiphenesin is an expectorant, which increases the respiratory tract fluid and
helps loosen the mucus and bronchial secretions. By reducing the viscosity of
secretion, guaiphenesin increases the efficiency of the mucociliary mechanism in
removing accumulated secretion from the airways. It has been frequently used in
the management of productive cough.

Doses recommended:

49
Adults: Oral Doses of 200 to 400 mg every 4 hours
Children 6 to 12 years: 100 to 200 mg every 4 hours.
Children 2 to 6 years: 50 to 100 mg every 4 hours.

Menthol:
Provides soothing actions.

Indications:

• In Productive cough associated with seasonal allergic rhinitis & perennial

allergic rhinitis.
• In allergic bronchial asthma.
• In drug induced allergy.

Dosage:
Adults & children above 12 years - 1 to 2 teaspoonful 2 times daily

Children between 6 to 12 years – ½ to 1 teaspoonful 2 times daily

Children between 2 to 6 years – ½ to 1 teaspoonful 2 times daily

Unique Selling Point Of Daslin NF.

• Unique combination, one of the best antihistamine, - Loratidine not only takes
care of allergic productive cough but also inhibits histamine induced
bronchoconstriction.
• Sedation free cough formulae which can be easily prescribed to working
class.
• Sugar free base, which can be prescribed to diabetic, & to calorie conscious
patients.

• Improves pulmonary function without tremors, thus offering a tremor free

treatment.

• Only such combination available with menthol.

50
 Daslin Cd Cough Syrup
Composition:
Each 5ml contains:
Chlopheniramine maleate. I.P. 4 mg
Codeine Phosphate. IP 10 mg

Chlorpheniramine maleate:

Chlorpheniramine maleate is an alkyl amine (propylamine) – derivative, first

generation antihistamine. It is an H 1 receptor antagonist. These are to be
administered orally.

Dosage: Chlorpheniramine maleate is been given by mouth in doses of 4 mg

every 4 to 6 hrs. up to maximum dose of 24 mg daily , Doses for children are 1 to
2 yrs. , 1 mg twice daily; 2 to 5 years, 1 mg every 4 to 6 hours (maximum 6 mg
daily) ; 6 to 12 years , 2 mg every 4 to 6 hrs (maximum 12 mg daily).

Codeine Phosphate:
Codeine inhibits the receptor in the cough center of the medulla oblongata and
acting on the brain to reduce the cough reflex, without the suppression of the
respiratory center.
Codeine is used in combination with other antitussives or expectorants, in the
symptomatic relief of non-productive cough. Since the cough reflex may be
useful physiologic mechanism, which clears the respiratory passages of foreign
material and excess of secretion and may aid in preventing or reversing
atlectasis, cough suppressants should not be used indiscriminately.
Dosage: Codeine preparation should be given in the smallest effective dose and
infrequently as possible to minimize the development of tolerance and physical
dependence. Reduced dosage is indicated in poor risk patients, in very young or
very old patients, and in-patients receiving other CNS depressants.

Dosage:
The usual oral antitussive dosage of Codeine Phosphate for adults and children
and of 12 years and older is 10- 20 mg every 4 to 6 hrs not to exceed 120 mg
daily.
The usual antitussive dosage for children 6 to 12 years of age is 5-10 mg every 4
to 6 hrs not to exceed 60 mg daily.
The usual antitussive dosage for children 2 to younger than 6 years of age is 1
mg/Kg. Daily given in 4 equally divided doses every 4 – 6 hrs.

Indications:

 In Allergic & Non specific dry cough.

 Tubercular cough.

51
 Haemoptysis.
 Nighttime cough.
 Post Surgical cough
RINOSTAT XL
0.1% Nasal Drops

Composition;

Xylometazoline Hydrochloride IP 0.1% w/v.

In an aqueous isotonic solution using purified water i.p.

Preservative: Benzalkolium chloride USP 0.011% w/v.

Dosage: Adults and Children over 6 years: 2-3 drops into each nostril per
application.

A total of 3-4 applications per day are usually sufficient.

Rinostat XL 3 drops 3 times for 3 days provides 333 express relief from nasal
congestion.

Rinostat XL provides 333 express relief within 10 minutes without any rebound
congestion.

Xylometazoline: Xylomeatzoline is a directly acting sympathomimetic with

marked alpha adrenegeric activity. It is a vasoconstrictor, which reduces swelling
and congestion when applied to mucous membranes. The effect begins from 5 to
10 minutes.

Indication:

 Acute or chronic Rhinitis

 Acute Sinusitis.

 Common cold.

52
 Rinostat Plus

Rinostat Plus is available in tablets and Syrup form

COMPOSITION:
For tablets:
Each uncoated tablet contains:
Acetaminophen IP - 500 mg
Phenylpropanolamine HCl BP - 25 mg
Chlorpheniramine Maleate IP - 4 mg
Excipients - q.s.

For Syrup:
Each 5 ml contains:
Acetaminophen IP – 125 mg
Phenylpropanolamine HCl BP – 12.5 mg
Chlorpheniramine maleate IP – 1 mg

Indications:
• Symptomatic relief of common cold and other upper respiratory infections
such as fever, aches, pains, nasal and sinus congestion, etc.
• 7 symptoms of COLD –
Runny nose, Nasal congestion, Sneezing, Watery eyes, Body aches,
Headache, Fever

FEATURES:
Rinostat Plus is paracetamol + CPM combination (analgesic and anti-histamine).
Therefore, can be used for symptomatic relief of common cold.
Rinostat Plus Syrup is available in rose flavour.

53
 Pro-Banthine

COMPOSITION:
Each sugar-coated tablet contains:
Propantheline Bromide IP … 15 mg

What is Pro-Banthine?
Pro-Banthine is an anticholinergic drug.

What is anticholinergic drug?

An anticholinergic drug is the one that blocks the neurotransmitter called
Acetylcholine (Ach).

Thereby, reducing the effects mediated by Ach on its receptors in neurons

(eg: reducing the spasms of the smooth muscle).

These drugs act on Ach receptors that are present on smooth muscle in
the gut, bladder, etc. This smooth muscle is not under voluntary control.

INDICATIONS
Irritable bowel syndrome (IBS)
Urinary incontinence and enuresis
To reduce salivation during dental procedures

What is IBS?

IBS – a functional bowel disorder in which abdominal pain or discomfort is

associated with defecation or a change in bowel habit and with features of
disordered defecation.

Symptoms of IBS
The most common symptom is abdominal pain associated with diarrhea,
constipation or both.
• Other symptoms include gas, bloating, cramping and indigestion.

Factors that trigger IBS Symptoms:

• Stress
• Foods like milk products, chocolate, caffeine,carbonated drinks, alcohol,
and food with high fat content.

Some facts about IBS:

• Constitutes a major health problem with gastrointestinal symptoms
• The cause of IBS is unknown.
• The condition is more frequent in women.

54
What is the role of Role of Ach in the gut?
Ach binds to the Ach-receptors in the gut & causes gastric motility.
Excess of Ach in gut increases the gastric motility & gives the feeling of
frequent defecation.

How does Pro-Banthine help in IBS?

• Pro-Banthine works by blocking Ach receptors in gut. This prevents the
action of Ach. Hence, causes smooth muscle to relax .& prevents the
muscle spasms occurring in IBS. By relaxing the gut muscle, Pro-Banthine
relieves the IBS symptoms.

How does Pro-Banthine help in Urinary Incontinence & Enuresis?

Urinary Incontinence (UI):
• Any involuntary leakage of urine.

Enuresis (Bed-wetting):
• A repeated involuntary or unintentional discharge of urine into bed or
clothes beyond the expected age for controlling urination.

In normal condition Ach. Helps in the contraction of smooth muscle of

urinary bladder & helps in urination but when the level of Ach. increases
then it causes UI & Enuresis.
Pro-Banthine works by blocking Ach receptors in urinary bladder. This
prevents the action of Ach hence, causes smooth muscle to relax &
prevents the muscle spasms occurring in bladder & prevents the
involuntary spasms which can allow leakage of urine from the bladder.

DOSAGE AND ADMINISTRATION:

• For IBS: 15 mg tid
• For Urinary Incontinence: 15 mg tid
• For Enuresis: 15 mg tid and 30 mg during bed-time
• To reduce salivation during dental surgery:
30 mg one hour before surgery and 15 mg tid
• Hyperhidrosis: 15 mg tid

_______________

55