Two-year experience with tacrolimus in renal transplantation after late conversion from cyclosporine therapy.

Introduction: Calcineurin inhibitors are associated with chronic allograft nephropathy. Protocols to reverse nephrotoxicity incorporate dosage reduction or withdrawal of these agents. Using ketoconazole as a sparing agent with mean cyclosporine doses of less than 50 mg/d, we have usually observed adverse cosmetic effects. One cohort of patients exhibited severe gingival hyperplasia that required gum resection; some also had hypertricosis.
Objective: To evaluate the effects of conversion from cyclosporine (CsA) to a tacrolimus generic formulation (TAC) in patients with adverse cosmetic effects from CsA.
Patients and Methods: Twenty-three patients were studied at a mean (SD) of 56 (48) months posttransplantation; serum creatinine concentration was 1.91 (0.68) mg/dL. All had eyebrow and facial hypertricosis, and 10 also had gum hyperplasia. Cyclosporine C0 or C2 levels and CsA dosage had previously been changed simultaneously with ketoconazole. The day after withdrawal of CsA, TAC therapy was started at a dose of 0.065 to 0.030 mg/kg/d. Patients were followed up for 18 months (12.76 [7.57]) with routine laboratory tests.
Results: Twenty patients without proteinuria demonstrated improved renal function at 1-month follow-up; serum creatinine concentration was 1.76 (0.42) mg/dL vs 1.47 (0.37) mg/dL (P < .02). Levels of tacrolimus were 13.82 (7.95) ng/mL at 15 days and 7.3 (3.5) ng/mL at 2 months after the dosage was decreased to 0.042 mg/kg/d. Gum hypertrophy and hypertrichosis resolved in all patients. One patient died 18 months after conversion of cardiovascular disease and chronic allograft nephropathy. Neither diabetes nor dislipidemia were noted.
Conclusion: Generic TAC is a good therapeutic alternative in renal transplant recipients with adverse reactions to CsA.