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 i n serum creatinine levels, which returned promptly to baseline when th is combination was stopped. Serial measurements of FK 506 concentratio ns in plasma showed excessive areas under the 24 h time-concentration curve and trough levels during the concomitant intake of imidazole ant i-fungals and FK 506. Eighteen months later, this patient presents wit h 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 adap tation are compulsory when concomitant treatment with such a drug is u navoidable. The same is true for cyclosporine in auto-immune diabetic patients receiving cyclosporine A.