Coadministration of tacrolimus and ketoconazole in renal transplant recipients: cost analysis and review of metabolic effects.

BACKGROUND: The high cost of tacrolimus is a major problem in Mexico. Ketoconazole increases tacrolimus bioavailability by inhibiting cytochrome P450 3A4 and glycoprotein-p. OBJECTIVE: To demonstrate that the coadministration of tacrolimus and ketoconazole allows a significant dose and cost reduction. PATIENTS AND METHODS: This prospective study administered tacrolimus and ketoconazole to renal transplant recipients with dose adjustment according to tacrolimus blood levels. At 0-1, 1-6, 6-12, and 12-24 months posttransplant demographic, transplant type, immunosuppression, and clinical data were reviewed. The cost of tacrolimus treatment was calculated based on the dose used as compared to the recommended dose (0.15-0.20 mg/kg/d). RESULTS: Eleven patients with an age of 40 years (range, 13-71) were studied from May 2000 to August 2002. Follow-up was 15 +/- 10 months. Graft source was living donor in six patients and cadaveric in five. All patients received tacrolimus + mycophenolate mofetil + prednisone. The mean ketoconazole dose was 87 mg/d. Since the dose of tacrolimus was 0.04 mg/kg/d versus the recommended dose of 0.15-0.20 mg/kg/d, there was a 78% cost reduction (P =.000). Tacrolimus blood levels remained in the therapeutic range. There were no drug-related side effects. CONCLUSIONS: The co-administration of tacrolimus and ketoconazole results in a substantial dose and cost reduction while maintaining therapeutic levels. No adverse metabolic consequences were seen with this combination.