Interaction between Warfarin and Proton Pump Inhibitors

Abstract

Background: Interaction between proton pump inhibitors (PPI) and warfarin is controversial. Previous clinical studies have only a short follow-up period. Methods and Results: All patients (n = 716) for whom warfarin was prescribed from November 1, 2010 to October 30, 2011 were extracted from electronic health records. In retrospective analysis for 1 year, PPI were prescribed to 404 patients. Among them, 108 patients were taking warfarin for more than 6 weeks before and after PPI. The profile of these patients was analyzed: 63 patients took lansoprazole; 15 patients took omeprazole; 30 patients took rabeprazole. No statistical difference was observed among 3 groups in age, body weight, concomitant use of other drugs, and comorbidity. Warfarin dose and INR did not change after PPI. Multivariate stepwise logistic regression analysis revealed that upper quartile of increment of INR was associated with the presence of atrial fibrillation (OR 3.77, 95% CI 1.16 -12.27). The patients who had warfarin for shorter periods before PPI, or those who had PPI first (n = 141) had similar dose of warfarin and INR. In all patients analyzed (n = 404), including patients whose follow-up periods were shorter than 6 weeks (n = 155), a patient had cerebral bleeding, and 2 patients had cerebral infarction. Conclusions: Unfavorable interaction between warfarin and PPI was negligible in clinical use. Relatively higher INR was achieved after PPI in the presence of atrial fibrillation.

SAFETY OF LONG-TERM THERAPY WITH WARFARIN: HEMORRHAGE FREQUENCY AND CLINICAL PREDICTORS (results of a prospective 15-year follow-up)

“…Связь развития геморрагических осложне-ний с приемом омепразола описана в ряде ра-бот [40][41][42]. Американской организацией по контролю за лекарственными препаратами и пищевыми продуктами (FDA) было подтвер-ждено, что прием омепразола может замедлять выведение варфарина, что приводит к повы-шению МНО и тем самым провоцирует разви-тие кровотечения.…”

“…Пациенты, получающие ле-чение омепразолом и варфарином, нуждаются в тщательном мониторировании значений МНО. При этом в отличие от омепразола на-значение рабепразола не связано с развитием чрезмерной гипокоагуляции и кровотечения-ми [40,42]. В нашем исследовании подавляю-щее большинство больных, кроме двух паци-ентов, принимали омепразол, а результаты проведенного дискриминантного анализа ука-зывают на наличие достоверной связи разви-тия кровотечений с приемом омепразола.…”

Proton pump inhibitors co‐prescribed with warfarin reduce warfarin control as measured by time in therapeutic range

“…However, while warfarin metabolism is reported to be altered by some PPIs particularly omeprazole and esomeprazole, Unge et al describe no change in coagulation time despite an increase in warfarin concentration when administered with omeprazole. Similarly, Henriksen et al reported no evidence that PPIs affected INR values in the few weeks after PPI initiation, whilst Shirayama et al reported no change in warfarin dose or INR for more than 6 weeks after addition of PPIs. In terms of bleeds, Nagata et al reported no increased risk of bleeding with PPIs, whilst two studies by Ray et al reported a reduced risk of gastrointestinal bleeds in patients taking PPIs with warfarin.…”