Interactions between rifampin and Neoral (cycloSPORINE)
rifampin and cycloSPORINE (Major Drug-Drug)
MONITOR CLOSELY: The coadministration with rifamycins, particularly rifampin, may decrease the blood concentrations and pharmacologic effects of cyclosporine. The mechanism probably involves reduced absorption as well as accelerated clearance of cyclosporine 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 orally at bedtime for 11 days) increased the average blood clearance of cyclosporine (10 mg/kg orally and 3 mg/kg intravenously) by 40% and decreased its oral bioavailability from 27% to 10%. There have also been case reports of transplant patients whose cyclosporine blood levels dropped significantly, often below assay detection limits, as early as two days following the initiation of rifampin. The decreases were associated with acute rejection episodes in many cases, subsequently requiring discontinuation of rifampin or substantial increases in cyclosporine 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 cyclosporine must be coadministered with rifamycins, particularly rifampin. Cyclosporine 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.
