Tacrolimus Interaction with Clotrimazole

The patient was a 23-year-old African-American woman with a history of end-stage renal disease secondary to membranous glomerulonephropathy who underwent live donor kidney transplantation. Immunosuppressive therapy consisted of tacrolimus 5 mg twice daily; mycophenolate mofetil (CellCept, Roche) 1,000 mg twice daily; and prednisone 30 mg daily, tapered over time to 5 mg daily. Routine prophylaxis with clotrimazole troche (10-mg troches four times daily) was undertaken for the first postoperative month. Discontinuation of clotrimazole was associated with a decrease in tacrolimus trough levels from 13.7 to 5.4 ng/mL over a period of six days (Table 1). After other potential causes of reduced tacrolimus levels were addressed, such as other pharmacological interactions and noncompliance, clotrimazole was restarted. An increased tacrolimus dose of 6 mg twice daily and the restarting of clotrimazole led to an increased level of tacrolimus 19.2 ng/mL on postoperative day 40. The dose of tacrolimus was then decreased to 4.5 mg twice daily, yielding a level of 13.4 ng/mL on postoperative day 44. To achieve the target tacrolimus level of 11 to 12 ng/mL for the second month, the tacrolimus dose was further lowered to 4 mg twice daily. Clotrimazole was subsequently discontinued after the third post-transplant month, when the target tacrolimus level was between 4 and 7 ng/mL. The patient did not experience any adverse events from this drug interaction.