Ketoconazole to reduce the need for cyclosporine after cardiac transplantation

Because ketoconazole can markedly reduce the need for cyclosporine and because it also has antimicrobial properties, it may offer benefits in the treatment of patients after cardiac transplantation.

We randomly assigned 43 patients at the time of cardiac transplantation to receive ketoconazole (200 mg per day) (23 patients) or no ketoconazole (20 patients). The main end points were the dose of cyclosporine required and the incidence of cardiac rejection and infection.

Ketoconazole reduced the dose of cyclosporine needed to maintain target levels by 62 percent at one week and by 80 percent at one year. The cost savings per patient (in U.S. dollars, inclusive of the cost of ketoconazole) was about $5,200 in the first year and about $3,920 in each subsequent year. The mean (+/- SD) rate of rejection in the first month was lower in the ketoconazole group than in the controls (4.2 +/- 0.8 vs 5.7 +/- 1.0 episodes per 100 patient-days, P < 0.001), and the average number of days to the first rejection was higher (30 +/- 29 vs. 15 +/- 8, P = 0.03). In the first year, 22 percent of the ketoconazole group required cytolytic therapy, as compared with 35 percent of the controls, and 9 percent of the ketoconazole group required total lymphoid irradiation, as compared with 15 percent of the controls (P = 0.07). The incidence of infection was lower in ketoconazole-treated patients than in controls in the second month (1.4 +/- 0.5 vs. 2.8 +/- 0.7 episodes per 100 patient-days, P < 0.001) and in the third month (0.8 +/- 0.3 vs. 2.3 +/- 0.6 episodes per 100 patient days, P < 0.001). Transient, asymptomatic cholestasis was observed in the ketoconazole group.

After cardiac transplantation, ketoconazole greatly reduced the need for cyclosporine, resulting in substantial cost savings. Ketoconazole also reduced the rates of rejection and infection, without persistent toxic effects. We now use ketoconazole routinely in cardiac-transplant recipients.