Cyclosporine Interactions

St. John's wort is a potent inducer of CYP3A4 and P-glycoprotein, which dramatically accelerates cyclosporine metabolism and efflux. Co-administration reduces cyclosporine blood AUC by roughly 40-50%, producing subtherapeutic levels that have caused documented acute organ rejection in heart, kidney, and liver transplant recipients.

Grapefruit juice contains furanocoumarins that irreversibly inhibit intestinal CYP3A4, raising cyclosporine bioavailability by 35-60% and increasing the risk of nephrotoxicity, hypertension, and neurotoxicity. The effect can persist for 24 hours or longer after a single glass.

Seville orange juice contains furanocoumarins that reduce enterocyte CYP3A4 expression by approximately 40%, although a controlled human study found no significant change in cyclosporine AUC, likely because cyclosporine disposition also depends on intestinal P-glycoprotein, which Seville orange does not inhibit as strongly as grapefruit.

Echinacea is marketed as an immune stimulant and has been shown in vitro and in some animal models to activate macrophages, NK cells, and pro-inflammatory cytokines. While direct pharmacokinetic effects on cyclosporine levels are not well documented in humans, the immunostimulant pharmacology directly opposes the goal of immunosuppression in transplant and autoimmune patients.