Comparative interaction of cimetidine and ranitidine with racemic warfarin in man

Abstract

Cimetidine potentiates the anticoagulant effect of warfarin sodium, but in one small study ranitidine hydrochloride did not. Furthermore, these drugs have not been compared in the same subjects. Eleven normal subjects received single oral doses of 1.5 mg/kg racemic warfarin sodium alone, with cimetidine (1,200 mg/day orally), or with ranitidine (300 mg/day orally), beginning three days before the warfarin and daily thereafter for the duration of hypoprothrombinemia. Blood samples were obtained daily for determination of prothrombin times and warfarin concentrations. Cimetidine augmented both the hypoprothrombinemia and the blood concentrations of warfarin, but ranitidine did not. Substituted imidazoles like cimetidine inhibit hepatic microsomal activity, which may cause reduced metabolic clearance of warfarin and augment its anticoagulant effect. Ranitidine, lacking these effects, may be safer for patients undergoing anticoagulation who require H2-receptor antagonists.