Drug interaction between St. John's wort and cyclosporine

OBJECTIVE: To report a probable drug interaction between the herbal dietary supplement St. John's wort and cyclosporine. CASE REPORT. A 29-year-old white woman who received a cadaveric kidney and pancreas transplant, with stable organ function and stable cyclosporine con centrations began self-medicating with St. John's wort. After taking St. Jo hn's wort supplements for four to eight weeks, her cyclosporine concentrati ons became subtherapeutic; this was associated with organ rejection. Four w eeks after stopping St. John's worth, her cyclosporine concentrations again became therapeutic. Subsequent to this rejection episode, she has develope d chronic rejection and now has returned to dialysis. DISCUSSION: St. John's wort is suspected to be a significant inducer of CYP 3A4 isoenzyme activity and of P-glycoprotein (P-gp) expression, both of whi ch are important in the metabolism and absorption of cyclosporine. Cyclospo rine exhibits a relatively small therapeutic window and is sensitive to med ications that can modulate the CYP3A4 isoenzyme and P-gp in both the liver and small intestines. CONCLUSIONS: Patients taking St. John's wort concomitant with other prescri ption medications whose absorption and metabolism are mediated by the CYP3A 4 isoenzyme and P-gp require close monitoring. Patient medication histories should include inquiries into the use of herbal dietary supplements.