Interactions between cyclosporine(cycloSPORINE) and Hypericum perforatum (St. John's wort)
cycloSPORINE and St. John's wort (Major Drug-Drug)
GENERALLY AVOID: Coadministration with St. John's wort may decrease the blood concentrations and pharmacologic effects of cyclosporine and probably sirolimus and tacrolimus. The mechanism involves reduced absorption as well as accelerated clearance of these agents due to induction of intestinal P-glycoprotein drug efflux pumps and hepatic/intestinal CYP450 3A4 isoenzymes by constituents of St. John's wort. There have been case reports of transplant patients whose cyclosporine blood levels dropped significantly or became subtherapeutic following the initiation of St. John's wort. A few experienced acute rejection episodes. In a study of 11 renal transplant patients stabilized on cyclosporine, St. John's wort extract (600 mg daily for 14 days) decreased the dose-corrected peak blood concentration (Cmax), trough concentration (Cmin) and area under the concentration-time curve (AUC) of cyclosporine by 42%, 41% and 46%, respectively, compared to baseline. Cyclosporine doses increased from a median of 2.7 mg/kg/day at baseline to 4.2 mg/kg/day on day 12, and all patients required the first dose adjustment 3 days after initiation of St. John's wort. The reversal of these effects after discontinuation of St. John's wort took longer than 2 weeks in 8 of 11 patients.
MANAGEMENT: Given the risk of organ rejection associated with inadequate immunosuppressant blood levels, St. John's wort should preferably not be used in transplant patients treated with cyclosporine, tacrolimus or sirolimus. Caution is advised if these agents are used together. Immunosuppressant blood levels should be closely monitored and the dosage(s) adjusted accordingly, particularly following initiation, discontinuation or change of dosage of St. John's wort in patients who are stabilized on their anti-rejection regimen. Transplant patients should be advised to consult their caregiver before using any alternative medicines.
