Induction of Warfarin Metabolism by Rifabutin: A Case Report

A 40-year-old woman who had received warfarin potassium (3 mg/day) for deep-vein thrombosis was diagnosed with atypical mycobacteriosism, and concomitant administration of rifampicin, clarithromycin and ethambutol was commenced. The PT-INR of this patient, which had been maintained at around 2.0, was found to have markedly decreased 9 days after beginning co-administration of warfarin and the anti-mycobacterium drugs, suggesting rifampicin induced warfarin metabolism, which is well documented. In view of the decrease in PT-INR, the warfarin dosage was increased up to 5.5 mg/day to attain a PT-INR level in the therapeutic range, but this did not alter the level.Rifampicin was changed to rifabutin since drug-drug interaction is considered to be generally less severe than with rifampicin. However, as there had been no increase in PT-INR, the administration of rifabutin was ceased. A rise in PT-INR was observed 17 and 31 days after the withdrawal of the rifabutin and rifampicin, respectively.Warfarin is known to be metabolized by cytochrome P450 (CYP) isoforms 2C9 and 3A4 and rifampicin has been reported to be a potent inducer of CYP3A4 and 2C9. Although rifabutin has the ability to induce CYP3A4, there have been few reports of drug-drug interaction with warfarin. However, the current case provides the first evidence for rifabutin exerting an influence on warfarin metabolism.In conclusion, our findings suggest that not only rifampicin but also rifabutin induce warfarin metabolism and that its pharmacological effects could be attenuated when combined with these drugs.