Interaction of Chronic Daily Warfarin Therapy and Rifampin

Abstract

To evaluate the interaction between the antibiotic rifampin and the anticoagulant warfarin during chronic therapy, eight normal subjects were given daily doses of warfarin for 21 days to achieve therapeutic hypoprothrombinemia. Daily blood samples were analyzed for one-stage prothrombin activity and for warfarin content spectrophotometrically and chromatographically. One month later, the same warfarin dose was repeated plus rifampin, 600 mg a day orally. For the last 10 days of every experiment, there was a highly significant lessening of both the hypoprothrombinemic effect (P less than 0.001) and the blood levels of warfarin (P less than 0.001). No significant difference in the warfarin levels was found between the spectrophotometric and chromatographic methods. It is concluded that rifampin markedly decreases the hypoprothrombinemic effect of warfarin during long-term therapy by enhancing its elimination from plasma. This conclusion was reinforced by finding increased amounts of warfarin metabolites in urine and stool.

CYP Induction-Mediated Drug Interactions: in Vitro Assessment and Clinical Implications

“…The unfavorable narrow range of therapeutic concentration makes warfarin prone to potentially life-threatening drugYdrug interactions (181). In a clinical study with eight healthy volunteers, the AUC po of warfarin was decreased by about 3-fold after a 21-day treatment with rifampicin 600 mg daily (182). The reduction of warfarin plasma concentration is believed to be a result of the rifampicin-mediated CYP2C9 induction.…”

Acute cardiac failure during treatment with digitoxin‐an interaction with rifampicin.

“…In clinical practice rifampicin has been seen to interact with coumarin drugs (Michot, Burgi & Biittner, 1970;O'Reilly, 1975), digitoxin (Peters, Hausamen & GrosseBrockhoff, 1974), oral contraceptives (Nocke-Finck, Breuer & Reimers, 1973) and cortisol (Edwards, Courtenay-Evans, Galley, Hunter & Tait, 1974 with digitoxin 0.1 mg daily the patient became well compensated. Blood pressure was 180/90 mmHg.…”

Alternative treatment of psoriasis - is rifampicin a mild immunosupressor? / Alternativna terapija psorijaze: da li rifampicin ima blago imunosupresivno dejstvo?

“…rifampicin is administered for more than a year. Data on its side effects and drug interactions have been reported for more than 35 years of clinical experience (29)(30)(31)(32). We used rifampicin in psoriasis patients for 6 months.…”