Interactions between rifampin and Prograf (tacrolimus)
rifampin and tacrolimus (Major Drug-Drug)
MONITOR CLOSELY: Coadministration with rifamycins, particularly rifampin, may significantly decrease the plasma concentrations and pharmacologic effects of tacrolimus. The mechanism probably involves reduced absorption as well as accelerated clearance of tacrolimus due to induction of both intestinal P-glycoprotein drug efflux pumps and hepatic/intestinal CYP450 3A4 isoenzymes by rifamycins. In a study of six healthy volunteers, rifampin (600 mg daily for 18 days) increased the average clearance of tacrolimus (0.1 mg/kg orally and 0.025 mg/kg/4 hours intravenously) by 47% and decreased its oral bioavailability from 14% to 7%. There have been case reports of transplant patients whose tacrolimus blood levels dropped significantly or became subtherapeutic as early as two days following the initiation of rifampin, subsequently requiring discontinuation of rifampin or substantial increases (up to ten-fold over several months) in tacrolimus dosage. This interaction is likely to occur with other rifamycins but to a lesser extent. In vitro and in vivo enzyme studies have suggested rifapentine induction potential to be less than that of rifampin but greater than that of rifabutin.
MANAGEMENT: Given the risk of organ rejection associated with inadequate immunosuppressant levels, caution is advised if tacrolimus must be coadministered with rifamycins, particularly rifampin. Tacrolimus blood levels should be closely monitored and the dosage adjusted accordingly, particularly following initiation or discontinuation of rifamycin therapy in patients who are stabilized on their anti-rejection regimen.
