Drug Interactions

Rabeprazole sodium, as is the case with other members of the proton pump inhibitor (PPI) class of compounds, is metabolized through the cytochrome P450 (CYP450) hepatic drug metabolizing system. Specifically, in vitro studies with human liver microsomes indicated that rabeprazole sodium is metabolized by isoenzymes CYP2C19 and CYP3A4.

Studies in healthy subjects have shown that rabeprazole sodium does not have pharmacokinetic or clinically significant interactions with warfarin, phenytoin, theophylline or diazepam (regardless of whether the subject was an extensive or poor diazepam metabolizer), each of which is metabolized by the CYP450 system.

Combination therapy with antimicrobials – 16 healthy volunteers were given 20 mg rabeprazole sodium, 1000 mg amoxicillin, 500 mg clarithromycin, or the combination of all 3 rabeprazole, amoxicillin, and clarithromycin (RAC) in a four way crossover study. The AUC and Cmax for clarithromycin and amoxicillin were similar during combined treatment compared to monotherapy. The rabeprazole AUC and Cmax increased by 11 % and 34% and the 14-hydroxyclarithromycin (active metabolite of clarithromycin) AUC and Cmax increased by 42% and 46% during the combined treatment compared to values obtained during monotherapy. This increase in exposure to rabeprazole and the 14-hydroxyclarithromycin is not considered to be clinically significant.

Rabeprazole sodium produces a profound and long lasting inhibition of gastric acid secretion. An interaction with compounds whose absorption is pH dependent may occur. Co-administration of rabeprazole sodium with ketoconazole or itraconazole may result in a significant decrease in antifungal plasma levels. Therefore, individual patients may need to be monitored to determine if a dosage adjustment is necessary when ketoconazole or itraconazole are taken concomitantly with Rabeprazole sodium (PARIET®).

Co-administration of atazanavir 300 mg / ritonavir 100 mg with omeprazole or atazanavir 400 mg with lansoprazole to healthy volunteers resulted in a substantial reduction in atazanavir exposure. The absorption of atazanavir is pH dependent. Although co-administration with rabeprazole was not studied, similar results are expected with other proton pump inhibitors. Therefore, rabeprazole should not be co-administered with atazanavir.

In clinical trials, antacids were used concomitantly with the administration of Rabeprazole sodium (PARIET®) and, in a specific study designed to define this interaction, no interaction with liquid antacids was observed.

Administration of rabeprazole sodium with a high fat meal may delay its absorption up to 4 hours or longer; however, the Cmax and the extent of absorption (AUC) are not altered.

Methotrexate

Case reports, published population pharmacokinetic studies, and retrospective analyses suggest that concomitant administration of PPls and methotrexate (primarily at high dose; see methotrexate prescribing information) may elevate and prolong serum levels of methotrexate and/or its metabolite hydroxymethotrexate. However, no formal drug interaction studies of methotrexate with PPls have been conducted.