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.


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.
Soltero
L
L
Division of Nephrology, Multiorgan Transplant Center, San José-Tec de Monterrey Hospital, Monterrey, Mexico.
Carbajal
H
H
Rodríguez-Montalvo
C
C
Valdés
A
A
D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000191:economics / Q000627:therapeutic use; D002102:Cadaver; D003365:Costs and Cost Analysis; D003710:Demography; D004359:Drug Therapy, Combination; D006801:Humans; D007166:Immunosuppressive Agents / Q000191:economics / Q000627:therapeutic use; D007654:Ketoconazole / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000276:immunology*; D019520:Living Donors; D008800:Mexico; D008875:Middle Aged; D016559:Tacrolimus / Q000191:economics* / Q000627:therapeutic use*; D013997:Time Factors; D014019:Tissue Donors / Q000706:statistics & numerical data
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D007654:Ketoconazole; D016559:Tacrolimus