Review article: drug interactions with agents used to treat acid‐related diseases

Abstract

Patients with acid-related diseases often need to take multiple medications. Treatment of Helicobacter pylori infection often includes either a histamine type 2 (H2)-receptor antagonist or a proton pump (H+,K(+)-ATPase) inhibitor (proton pump inhibitor), administered in conjunction with one or more antimicrobials. Also, treatment for acid-related diseases often requires extended therapy during which many concomitant medications may be administered for concurrent disease states. Polypharmacy may be the result, particularly in elderly patients, who are at increased risk for both acid-related and many other diseases. Thus, it is important to understand the potential for clinically significant drug-drug interactions in this setting. H2-receptor antagonists and proton pump inhibitors can influence the pharmacokinetic profiles of other commonly administered medications by elevating intragastric pH, which can alter drug absorption, and by interacting with the cytochrome P (CYP) 450 enzyme system, which can affect drug metabolism and clearance. Such interactions are particularly important when they affect the pharmacokinetics of drugs with narrow therapeutic ranges (e.g. warfarin, digoxin). In these cases, drug-drug interactions can result in significant toxicity and even death. There are marked differences among H2-receptor antagonists and proton pump inhibitors in their potential for such interactions. The oldest drugs in each class, cimetidine and omeprazole, respectively, have the greatest potential to alter CYP activity and change the pharmacokinetics of other drugs. The most recently developed H2-receptor antagonist, famotidine, and the newer proton pump inhibitors, rabeprazole and pantoprazole, are much less likely to induce or inhibit CYP and thereby change the metabolism of other medications. These differences are important when choosing medications for the safe treatment of patients with acid-related diseases.

DUEXIS® (ibuprofen 800 mg, famotidine 26.6 mg): a new approach to gastroprotection for patients with chronic pain and inflammation who require treatment with a nonsteroidal anti-inflammatory drug

“…Available results suggest no significant interaction between famotidine (administered at a total dosage of 40 mg/day) and clopidogrel [Taha et al 2009]. This is consistent with the lack of effect of famotidine on cytochrome P450 isozymes [Humphries and Merritt, 1999;Humphries, 1987].…”

A Prospective Randomized Trial of Either Famotidine Or Pantoprazole for the Prevention of Bleeding After Endoscopic Submucosal Dissection

“…These results are consistent with famotidine's very limited ability to alter the activity of cytochrome P450 isoenzymes (25). Pantoprazole did not interact with digoxin, nifedipine, theophylline, diazepam, warfarin, phenytoin, or oral contraceptives (26). Pantoprazole has been reported to have few clinical significant drug-drug interactions (26).…”

“…Pantoprazole did not interact with digoxin, nifedipine, theophylline, diazepam, warfarin, phenytoin, or oral contraceptives (26). Pantoprazole has been reported to have few clinical significant drug-drug interactions (26).…”

A summary of Food and Drug Administration‐reported adverse events and drug interactions occurring during therapy with omeprazole, lansoprazole and pantoprazole

“…In spite of their excellent safety record, the relative safety of different proton pump inhibitors has been widely publicized over the last few years, with particular emphasis on drug-drug interactions. [1][2][3][4][5][6][7][8][9] It has been suggested that pantoprazole is less likely than omeprazole or lansoprazole to interact with other drugs as a result of minor differences in its metabolic profile. 10,11 In a recent retrospective survey of patient treatment records from US veterans, it was concluded that the co-prescription of omeprazole or lansoprazole with warfarin, clarithromycin or diclofenac led to an increase in adverse events, requirements for care and total costs of care.…”