Interaction of Rifampin and Warfarin

Oh, Yeon Mok

Abstract

BACKGROUND: It is well known that rifampin decreases the hypoprothrombinemic effect of warfarin by induction of cytochrome p-450 enzyme in healthy volunteer. However, in patients the dosage schedule o f warfarin during rifampin therapy is not established. Therefore, patients taking both rifampin and warfarin were reviewed to find out the adequate dosage schedule of warfafin in addition to side effects by interaction of two drugs. METHOD: Patients taking both rifampin and warfarin were retrieved from patients who were admitted due to heart disease and tuberculosis at Boochun Sejong Hospital from January of 1995 to August of 1999. To decide the adequate dosage of warfarin, the dosage of warfarin before, during, and after rifampin was evaluated in patients who kept adequate hypoprothrombinemic effect of warfarin during rifampin. To decide the adequate dosage schedule of warfarin, the time interval from the beginning of rifampin to normalization of prothrombin time(INR RESULTS
All 12 patients taking both rifampin and warfarin were retrieved. Among them only 6 kept adequate hypoprothrombinemic effect of warfarin during rifampin. The dosage of warfarin during rifampin was 2.4 +/- 0.6(mean +/- standard deviation) times as much as that before rifampin but the dosage after rifampin was the same as that before rifampin. The time interval from the beginning of rifampin to normalization of prothrombin time was 5.8 +/- 2.9(mean +/- standard deviation) days. 2 out of 12 had complication related to the interaction of rifampin and warfarin, one cerebral embolism just after the beginning of rifampin and the other cerebral hemorrhage just after the discontinuation of rifampin.
CONCLUSION
When both rifampin and warfarin are prescribed, it would be a possible method to be confirmed by prospective study that warfarin be gradually increased about 2 times more than that without rifamin over 1 week or so after the beginning of rifampin and be tapered to the same dosage as that before rifampin when rifampin is discontinued. And, it would be prudent that prothrombin time be monitored frequently during rifampin and warfarin therapy, especially the beginning or discontinuation of rifampin.