Voriconazole inhibition of tacrolimus metabolism in a kidney transplant recipient with fluconazole-resistant cryptococcal meningitis.
Fluconazole resistance among Cryptococcus neoformans is unusual in post-transplantation patients. Voriconazole is a triazole agent with good antifungal activity but also with drug-drug interactions because of potent inhibition of the P450 enzyme system. The interaction with immunosuppressive agents, especially calcineurin inhibitors, is of concern in post-transplantation patients. We report the first case of fluconazole-resistant cryptococcal meningitis in a kidney transplant recipient successfully treated with voriconazole, but complicated with a raised serum concentration of tacrolimus and hyponatremia after co-administration. A 43-year-old man with a history of renal transplantation and on long-term immunosuppressive agents, including mycophenolate and tacrolimus, suffered from recurrent cryptococcal meningitis. He was treated with amphotericin B-liposome for 24 days because of fluconazole resistance. However, cryptococci were still found in the cerebrospinal fluid; oral voriconazole was substituted. Six days after co-administration of voriconazole and tacrolimus, the trough concentration of tacrolimus markedly increased and hyponatremia developed. A culture of the CSF did not yield growth of Cryptococcus. Conditions improved after the cessation of tacrolimus for three days followed by reducing the dosage of voriconazole and tacrolimus. When voriconazole is initially added, the dosage of tacrolimus should be reduced. Close monitoring of tacrolimus concentration and its adverse effects, including nephrotoxicity, hyperglycemia, hyperkalemia, and hyponatremia, are mandatory.
Chang
Hui-Hua
HH
Institute of Biopharmaceutical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Lee
Nan-Yao
NY
Ko
Wen-Chien
WC
Lee
Hsin-Chun
HC
Yang
Yea-Hui Kao
YH
Wu
Chi-Jung
CJ
Chang
Chia-Ming
CM
D000328:Adult; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003455:Cryptococcus neoformans / Q000254:growth & development*; D004347:Drug Interactions; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016030:Kidney Transplantation; D008297:Male; D016919:Meningitis, Cryptococcal / Q000188:drug therapy* / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D016559:Tacrolimus / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D065819:Voriconazole
D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole; D016559:Tacrolimus