Brands, Medical Use, Clinical Data
- Anti-Ulcer Agents
- Enzyme Inhibitors
Brands / Synonyms
Aciphex; Irsogladine Maleate; Rebeprazole sodium
For short-term treatment in the healing and symptomatic relief of erosive or ulcerative gastroesophageal reflux disease (GERD).
Rabeprazole prevents the production of acid in the stomach. It reduces symptoms and prevents injury to the esophagus or stomach in patients with gastroesophageal reflux disease (GERD) or ulcers. Rabeprazole is also useful in conditions that produce too much stomach acid such as Zollinger-Ellison syndrome. Rabeprazole may also be used with antibiotics to get rid of bacteria that are associated with some ulcers. Rabeprazole is a selective and irreversible proton pump inhibitor, suppresses gastric acid secretion by specific inhibition of the H+, K+ -ATPase enzyme system which is found at the secretory surface of parietal cells. It inhibits the final transport of hydrogen ions (via exchange with potassium ions) into the gastric lumen.
Mechanism of Action
Rabeprazole belongs to a class of antisecretory compounds (substituted benzimidazole proton-pump inhibitors) that do not exhibit anticholinergic or histamine H2-receptor antagonist properties, but suppress gastric acid secretion by inhibiting the gastric H+/K+ATPase (hydrogen-potassium adenosine triphosphatase) at the secretory surface of the gastric parietal cell. Because this enzyme is regarded as the acid (proton) pump within the parietal cell, rabeprazole has been characterized as a gastric proton-pump inhibitor. Rabeprazole blocks the final step of gastric acid secretion. In gastric parietal cells, rabeprazole is protonated, accumulates, and is transformed to an active sulfenamide. When studied in vitro, rabeprazole is chemically activated at pH 1.2 with a half-life of 78 seconds.
Absolute bioavailability is approximately 52%.
Biotrnasformation / Drug Metabolism
Rabeprazole is contraindicated in patients with known hypersensitivity to rabeprazole, substituted
benzimidazoles or to any component of the formulation.
Clarithromycin is contraindicated in patients with known hypersensitivity to any macrolide
Concomitant administration of clarithromycin with pimozide and cisapride is contraindicated. There
have been post-marketing reports of drug interactions when clarithromycin and/or erythromycin are co-administered
with pimozide resulting in cardiac arrhythmias (QT prolongation, ventricular tachycardia, ventricular fibrillation,
and torsade de pointes) most likely due to inhibition of hepatic metabolism of pimozide by erythromycin and
clarithromycin. Fatalities have been reported. (Please refer to full prescribing information for clarithromycin.)
Amoxicillin is contraindicated in patients with a known hypersensitivity to any penicillin. (Please refer to full
prescribing information for amoxicillin.)
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 (with supplemental oral dosing). Steady state
interactions of rabeprazole and other drugs metabolized by this enzyme system have not been studied in patients.
There have been reports of increased INR and prothrombin time in patients receiving proton pump inhibitors, including
rabeprazole, and warfarin concomitantly. Increases in INR and prothrombin time may lead to abnormal bleeding and even
In vitro incubations employing human liver microsomes indicated that rabeprazole inhibited
cyclosporine metabolism with an IC50 of 62 micromolar, a concentration that is over 50 times higher than the Cmax in
healthy volunteers following 14 days of dosing with 20 mg of rabeprazole. This degree of inhibition is similar to
that by omeprazole at equivalent concentrations.
Rabeprazole produces sustained inhibition of gastric acid secretion. An interaction with compounds
which are dependent on gastric pH for absorption may occur due to the magnitude of acid suppression observed with
rabeprazole. For example, in normal subjects, co-administration of rabeprazole 20 mg QD resulted in an approximately
30% decrease in the bioavailability of ketoconazole and increases in the AUC and Cmax for digoxin of 19% and 29%,
respectively. Therefore, patients 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
In a clinical study in Japan evaluating rabeprazole in patients categorized by CYP2C19 genotype (n=6
per genotype category), gastric acid suppression was higher in poor metabolizers as compared to extensive
metabolizers. This could be due to higher rabeprazole plasma levels in poor metabolizers. Whether or not interactions
of rabeprazole sodium with other drugs metabolized by CYP2C19 would be different between extensive metabolizers and
poor metabolizers has not been studied.
Combined Administration with Clarithromycin
Combined administration consisting of rabeprazole, amoxicillin, and clarithromycin resulted in
increases in plasma concentrations of rabeprazole and 14-hydroxyclarithromycin.
Concomitant administration of clarithromycin with pimozide and cisapride is contraindicated.