Effects of voriconazole on tacrolimus metabolism in a kidney transplant recipient.
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.
Capone
D
D
Department of Neurosciences, Unit of Clinical Pharmacology, School of Medicine, Federico II University of Naples, Naples, Italy. docapone@unina.it
Tarantino
G
G
Gentile
A
A
Sabbatini
M
M
Polichetti
G
G
Santangelo
M
M
Nappi
R
R
Ciotola
A
A
D'Alessandro
V
V
Renda
A
A
Basile
V
V
Federico
S
S
D000328:Adult; D000935:Antifungal Agents / Q000627:therapeutic use*; D051544:Cytochrome P-450 CYP3A; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000628:therapy; D016030:Kidney Transplantation; D011743:Pyrimidines / Q000627:therapeutic use*; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016896:Treatment Outcome; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
D000935:Antifungal Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D011743:Pyrimidines; D014230:Triazoles; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D065819:Voriconazole; D016559:Tacrolimus