Impact of Cotherapy With Some Proton Pump Inhibitors on Medical Claims Among HMO Patients Already Using Other Common Drugs Also Cleared by Cytochrome P450

Abstract

Adverse drug event (ADE) rates resulting from coadministration of proton pump inhibitors (PPIs) and other drugs with potential for interaction with PPIs (DPIs) are unknown. This retrospective study assesses the occurrence of such ADEs and their potential impact on medical care costs by reviewing integrated medical and pharmacy claims. Managed care patients receiving one or more DPIs were identified. Within this sample, those who were also prescribed omeprazole or lansoprazole (DPI + PPI) were included. A second cohort (DPI alone) was created, matching for age, gender, and DPI use. Rates of ADEs were followed for 6 months after entry. Among PPI users, 58% used one or more DPIs, whereas 7% of DPI subjects used a PPI. Among claims arising from ADEs occurring in more than 1% of patients, 14 occurred in the DPI + PPI group and 2 occurred in the DPI-alone cohort, respectively, a highly significant difference. Crude odds ratios for the risks of specific ADEs were significantly increased for cotherapy with a PPI and warfarin, clarithromycin, corticosteroids, carbamazepine, nifedipine, or diclofenac. After adjustment, the first three associations remained significant. Coprescription of a PPI with potentially interacting drugs was common in practice and associated with significantly increased claims for medical care.

Risk Factors of Peptic Ulcer in 4943 Inpatients

“…12,13 Though the daily use of PPIs is sometimes not regarded as corresponding to the indications for this class of drugs, [14][15][16] it is certainly due to their cost 17 and not to their possible, rare side effects that their use is debatable. 18,19 H 2 -antagonists are not associated with the incidence of endoscopically diagnosed peptic ulcer disease, as documented in our study. It should be noted, moreover, that only double doses of H 2 -antagonists, that is, doses higher than those assessed here, have proved effective in preventing peptic ulcer disease.…”

Main comedications associated with major bleeding during anticoagulant therapy with coumarins

“…Extending the analyses for reasons of comparison, pantoprazole, like omeprazole, was not associated with a significant increased risk of bleeding (RR 2.8; 95% CI 0.4-19.7). Our finding that the results were similar for all PPIs is in line with a recent evaluation of the Food and Drug Administration's database of reported adverse events and drug interactions [10], and disagrees with previous suggestions that omeprazole [19] or omeprazole and lansoprazole [14] bear a higher risk of interactions than pantoprazole.…”

Influence of Different Proton Pump Inhibitors on Activity of Cytochrome P450 Assessed by [13C]‐Aminopyrine Breath Test

“…Various reports have described drug—drug interactions of PPIs with other drugs. McCarthy et al 8 reported that concomitant use of a PPI significantly increased the incidence of adverse events for other drugs with potential for interaction with PPIs, such as warfarin, clarithromycin, and corticosteroids. Ishizaki et al 16 reported that omeprazole significantly decreased the mean clearance of diazepam and increased its half‐life, AUC for plasma concentration—time, and mean residence time in RMs and IMs of CYP2C19.…”

“…PPIs are mainly metabolized in the liver by cytochrome P450 (CYP) 2C19. Several reports have described drug—drug interactions with PPIs via hepatic CYPs 8 . Because patients often take various drugs for concomitant illnesses, a risk of drug—drug interactions exists, and such interactions may increase the risk of adverse drug events or altered efficacy of therapeutic agents 9 .…”