Possible potentiation of anticoagulant effect of acenocoumarol by omeprazole

Abstract

IntroductionOmeprazole is a benzimidazole derivative used as an antisecretory agent for the treatment of peptic acid disorders. It is metabolized by the cytochrome P-450 system in the liver. Like other imidazoles, omeprazole has the potential to inhibit the metabolism of some drugs by a competitive mechanism at the hepatic microsomal enzyme level [1]. It is now recognized that omeprazole interactions are confined to the limited number of drugs metabolized mainly by the cytochrome P-45011c subfamily [2]; it has been shown that this drug decreases phenytoin [3] and diazepam [4] metabolism but does not influence the disposition of drugs metabolized by other subfamilies within the cytochrome P-450 system, such as theophylline [5], propranolol [6] and ciclosporin [7].Studies of the interaction between omeprazole and warfarin have been performed but the results are controversial. Some studies suggest that omeprazole has little or no significant effect on the disposition of warfarin in healthy volunteers [8] or patients treated with anticoagulants [9]. Opposite to these, an increase in warfarin's effect has been reported in one patient after omeprazole addition [I0].Just like warfarin, acenocoumarol is a 3-substituted 4-hydroxycoumarin derivative and is the most commonly used oral anticoagulant in Europe. Acenocoumarol is a racemic mixture containing R(+) and S(-) enantiomers. As opposed to warfarin, the R(+) isomer of acenocoumarol is several times more potent as an anticoagulant than the S(-) enantiomer [I I]. At present, no interaction between omeprazole and acenocoumarol has been reported. We describe one case of potentiation of an acenocoumarol anticoagulant effect by omeprazole.

Genetic Bleeding Risk Score (GBRS) for Patients on Oral Anticoagulant Therapy

“…Co-administration of proton pump inhibitors (PPIs, Pantoprazole and Rabeprazole) has occasionally been associated with potentiation of acenocoumarol [67,68] and less commonly with warfarin [69][70][71]. However, until now bleeding was not analyzed as an outcome with co-administration of PPI in OAC users.…”

Influence of proton pump inhibitors and VKORC1 mutations on CYP2C9‐mediated dose requirements of vitamin K antagonist therapy: a pilot study

“…In case reports on patients under long-term VKA-treatment, PPI-related elevation of international normalized ratio (INR) levels with the need for dose adjustment (reduction) of the VKA has been described. It is possible that reduced clearance of the drug due to competitive inhibition with PPIs is the underlying cause (Ahmad, 1991;Garcia et al, 1994;Enderle et al, 2001).…”

No effect of short‐term omeprazole intake on acenocoumarol pharmacokinetics and pharmacodynamics

“…In addition, a case was reported recently of a serious bleeding complication The majority of studies on drug interactions with oral anticoagulants, which are administered as racemates, use during acenocoumarol intake, following omeprazole co-administration [9]. warfarin as gold standard.…”