Pariet 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.
Pariet 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.