CYCLOSPORINE-KETOCONAZOLE INTERACTION - LONG-TERM FOLLOW-UP AND PRELIMINARY-RESULTS OF A RANDOMIZED TRIAL

Forty-three renal transplant recipients receiving cyclosporine were st arted on 200 mg/day of oral ketoconazole 10 days to 75 months posttran splant. The cyclosporine dose was reduced by 70% when ketoconazole was started. The mean cyclosporine dose was 5.6 mg/kg/day preketoconazole , and 0.9, 0.8, and 0.7 mg/kg/day at one, two, and three years after a ddition of ketoconazole (cyclosporine dose reduction 84%, 86%, and 88% at one, two, and three years, respectively). Two patients died after two years of combination therapy, six patients returned to dialysis, a nd ketoconazole was discontinued in four. Renal function in patients o n ketoconazole remained stable (serum creatinine 1.8, 1.7, 1.7, and 1. 8 mg/dl preketoconazole and at one, two, and three years, respectively ). In a second study, 52 patients were randomized to standard doses of cyclosporine (n=28), or reduced doses of cyclosporine with ketoconazo le (n=24); seven of the patients were not started on ketoconazole. In 28 patients on standard-dose cyclosporine, there were two deaths and o ne graft loss. In 17 patients receiving ketoconazole there were two de aths and no graft losses. Renal function and the frequency of rejectio n episodes was similar in the two groups. In the ketoconazole group, t he cyclosporine dose was <20% of that in the patients on standard dose s. In both studies addition of ketoconazole to cyclosporine-treated pa tients resulted in significant inhibition of cyclosporine metabolism a nd decrease in dosage in patients followed for up to four years. This drug interaction provides a significant reduction in cost of immunosup pressive therapy in organ transplant recipient.