FK 506/fluconazole interaction enhances FK 506 nephrotoxicity

In a diabetic liver transplant recipient, immunosuppressed with FK 506, a severe digestive moniliasis required treatment with the antifungal imidazole derivative fluconazole. This was followed by a brisk rise in serum creatinine levels, which returned promptly to baseline when this combination was stopped. Serial measurements of FK 506 concentrations in plasma showed excessive areas under the 24 h time-concentration curve and trough levels during the concomitant intake of imidazole antifungals and FK 506. Eighteen months later, this patient presents with normal renal function. Antifungal imidazole derivatives inhibit the P 450 cytochrome enzyme system and may thus decrease the catabolism of FK 506. Meticulous monitoring of FK 506 trough levels and dosage adaptation are compulsory when concomitant treatment with such a drug is unavoidable. The same is true for cyclosporine in auto-immune diabetic patients receiving cyclosporine A.