Effects of voriconazole on tacrolimus metabolism in a kidney transplant recipient

J Clin Pharm Ther. 2010 Feb;35(1):121-4. doi: 10.1111/j.1365-2710.2009.01070.x.

Abstract

Infection occurs frequently in the organ transplant recipients during the post-transplant period because of immunosuppression. Therefore, prophylactic antimicrobial agents are often used. The azole antifungals, widely prescribed prophylactically, are known to have many drug-drug interactions. This report presents a case of drug-drug interaction between voriconazole and tacrolimus in a kidney transplant recipient. Voriconazole treatment led to a dramatic increase in tacrolimus concentration that required its discontinuation in spite of the manufacturer's guidelines that recommend a reduction of tacrolimus dosage by one-third. The present drug-drug interaction can be attributed to a strong inhibitory effect on cytochrome P450-3A4 activity by voriconazole. When voriconazole and tacrolimus are coadministered, close monitoring of tacrolimus blood levels is recommended as the rule-of-thumb reduction of tacrolimus dose by one-third may not be satisfactory.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Antifungal Agents / therapeutic use*
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 CYP3A Inhibitors
  • Drug Interactions
  • Drug Monitoring
  • Drug Therapy, Combination
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Humans
  • Immunosuppressive Agents / blood
  • Immunosuppressive Agents / pharmacokinetics*
  • Immunosuppressive Agents / therapeutic use
  • Kidney Failure, Chronic / therapy
  • Kidney Transplantation*
  • Pyrimidines / therapeutic use*
  • Tacrolimus / blood
  • Tacrolimus / pharmacokinetics*
  • Tacrolimus / therapeutic use
  • Treatment Outcome
  • Triazoles / therapeutic use*
  • Voriconazole

Substances

  • Antifungal Agents
  • Cytochrome P-450 CYP3A Inhibitors
  • Enzyme Inhibitors
  • Immunosuppressive Agents
  • Pyrimidines
  • Triazoles
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • Voriconazole
  • Tacrolimus