Rabeprazole sodium
Therapeutic category:
Proton pump inhibitor
Composition:
Zen-Prazols- 10 mg
Each enteric coated tablet
contains:
Rabeprazole Sodium: 10 mg
Colours : Yellow Oxide of Iron
& Titanium Dioxide IP
Zen-Prazole~20mg
Each enteric coated tablet
contains:
Rabeprazole Sodium- 20 mg.
Colours : Yellow Oxide of Iron
& Titanium Dioxide IP
DESCRIPTION
Rabeprazole sodium is a substituted benzimidazole that in-
hibits gastric acid secretion. Rabeprazole sodium is known
chemically as 2-[[[4-(3-Methoxypropoxy)-3-methyl-2-
pyridinyl]methyl]sulfinyl]-1 H-benzimidazole sodium salt. It has
an empirical formula of C,,H,,N,NaO,S and a molecular
weight of 381.43.
CLINICAL PHARMACOLOGY
Mechanism of Action
Rabeprazole belongs to a class of antisecretory compounds
(substituted benzimidazole proton-pump inhibitors) that do
not exhibit anticholinergic or histamine H -receptor antago-
nist properties, but suppress gastric acid secretion by inhib-
iting the gastric H*, K'ATPase at the secretory surface of the
gastric parietal cell. Rabeprazole blocks the final step of gas-
tric acid secretion. In gastric parietal cells, rabeprazole is
protonated, accumulates, and is transformed to an active
sulfenamide.
Pharmacokinetics and Metabolism
After oral administration of 20 mg C of rabeprazole oc-
curred over a range of 2.0 to 5.0 hours (T~J. The rabeprazole
C and AUC are linear over an oral dose range of 10 mg to
40 mg. There is no appreciable accumulation when doses
of 10 mg to 40 mg are administered every 24 hours; the
pharmacokinetics of rabeprazole are not altered by multiple
dosing. The plasma half-life ranges from 1 to 2 hours. Abso-
lute bioavailability for a 20 mg oral tablet of rabeprazole (com-
pared to intravenous administration) is approximately 52%.
The effects of food on the absorption of rabeprazole have
not been evaluated. Rabeprazole is 96.3% bound to human
plasma proteins. Rabeprazole is extensively metabolized.
The thioether and sulphone are the primary metabolites
measured in human plasma. Rabeprazole is primarily me-
tabolized in the liver by cytochromes P450 3A (sulphone
metabolite) and 2C19 (desmethyl rabeprazole). The thioether
metabolite is formed by reduction of rabeprazole.
Following a single 20 mg oral dose of 14C-labeled
rabeprazole, approximately 90% of the drug was eliminated
in the urine, primarily as thioether carboxylic acid; its glucu-
ronide, and mercapturic acid metabolites. The remainder of
the dose was recovered in the feces. Total recovery of ra-
dioactivity was 99.8%. No unchanged rabeprazole was re-
covered in the urine or feces.
In patients with stable, end-stage, renal failure requiring
maintenance haemodialysis (creatinine clearance <5 mL/
min/1.73 m2), the disposition of rabeprazole sodium was very
similar to that in healthy volunteers. Elimination of
rabeprazole sodium was somewhat decreased in the eld-
erly. Following 7. days of daily dosing with 20 mg of
rabeprazole sodium, the ALJC approximately doubled, the
Cmax increased by 60% as compared to healthy young volunteers.
However there was no evidence of rabeprazole so-
dium accumulation.
INDICATIONS
The preparation shall be indicated in the treatment of :
Β» Gastroesophageal Reflux Disease (GERD)
β’ Duodenal Ulcers
«» Zollinger-Ellison Syndrome
CONTRAINDICATIONS
Rabeprazole is contraindicated in patients with known
hypersensitivity to rabeprazole, substituted benzimidazoles
or to any component of the formulation.
PRECAUTIONS
Symptomatic response to therapy with rabeprazole sodium
does not preclude the presence of gastric or oesophageal
malignancy, therefore the possibility of malignancy should
be excluded prior to commencing treatment with
Rabeprazole.
Caution should be exercised when treatment with
Rabeprazole is first initiated in patients with severe hepatic
dysfunction.
Pregnancy {Pregnancy Category B):
Animal studies revealed no evidence of impaired fertility or
harm to the fetus due to rabeprazole. There are, however,
no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predic-
tive of human response, this drug should be used during
pregnancy only if clearly needed.
Nursing Mothers
it is not known if unmetabolized rabeprazole is excreted
in human breast milk and hence should be used with caution in
nursing mothers.
Pediatric Use
The safety and effectiveness of rabeprazole in pediatric pa-
tients under 18 years of age have not bean established.
Drug Interactions
Rabeprazole is metabolized by the cytochrome P450
(CYP450) drug metabolizing enzyme system. Studies in
healthy subjects have shown that rabeprazole does not have
clinically significant interactions with other drugs metabolized
by the CYP450 system, such as warfarin and theophylline
given as single oral doses, diazepam as a single intravenous
dose, and phenytoin given as a single intravenous dose.
in vitro incubations employing human liver microsomes indi-
cated that rabeprazole inhibited cyclosporine metabolism with
an iC50 of 62 micromolar, a concentration that is over 50 times
higher than the C in healthy volunteers following 14 days
of dosing with 20 mg of rabeprazole.
In normal subjects, co-administration of rabeprazole 20 mg
QD resulted in an approximately 30% decrease in the
bioavailability o? ketoconazole and increases in the AUC and
C . for digoxin of 19% and 29%, respectively. Therefore, pa-
tients may need to be monitored when such drugs are taken
concomitantly with rabeprazole. Co-administration of
rabeprazole and antacids produced no clinically relevant
changes in plasma rabeprazole concentrations.
ADVERSE REACTIONS
The most common adverse events were headache, diarrhoea
and nausea. Other adverse events were rhinitis, abdominal
pain, asthenia, flatulence, pharyngitis, vomiting, non-specific
pain/back pain, dizziness, flu syndrome, infection,
cough, constipation and insomnia. Further less frequent ad-
verse events were rash. myalgia, chest pain, dry mouth, dys-
pepsia, nervousness, somnolence, bronchitis, sinusitis, chills,
eruction, leg cramps, urinary tract infection,
arthralgia and fever. In isolated cases, anorexia, gastritis,
weight gain, depression, pruritus, vision or taste disturbances,
stomatitis, sweating and leucocytosis have been observed.
Increased hepatic enzymes have been observed in 2% of
patients.There have been reports of
thrombocytopenia.neutropenia and leukopenia.
Bullous eruptions have been reported and other dermato-
logical reactions including erythema have been reported.
Treatment should be stopped immediately at the recurrence
of skin lesions.
OVERDOSAGE
There has been no experience with large overdoses with
rabeprazole. No specific antidote for rabeprazole is known.
Rabeprazole is extensively protein bound and is not readily
dialyzable. In the event of overdosage, treatment should be
symptomatic and supportive. Gastric lavage is recom-
mended. -
DOSAGE AND ADMINISTRATION
Doses upto l00 mg once daily and 60 mg twice daily have
been administered
No dosage adjustment is necessary in elderly patients, in
patients with renal disease or in patients with mild to
moderate hepatic impairment.