Effect of isavuconazole on the concentration of tacrolimus in a patient with genotype CYP3A5*1/*3: a case report.

Abstract

Background: Azole antifungals are the standard treatment for pulmonary mycosis, which may develop during long-term immunotherapy for kidney transplant. Isavuconazole (ISCZ) is a cytochrome P450 (CYP) 3 A inhibitor that has a risk of interacting with the immunosuppressive drug tacrolimus (TAC). We report a case of simple pulmonary aspergilloma with renal dysfunction due to increased trough levels of TAC after ISCZ coadministration.

Case presentation: A male in his 60s was treated with TAC 3.0 mg/day orally to prevent graft rejection after kidney transplantation. He received a loading dose of ISCZ 600 mg/day orally for two days, followed by a maintenance dose of 200 mg/day for simple pulmonary aspergilloma. The TAC trough concentration increased markedly from 2.4 to 9.9 ng/mL on day 6 after coadministration. The creatinine level increased from 0.70 to 1.08 mg/dL, suggesting renal dysfunction due to TAC. Subsequently, the TAC dosage was reduced, leading to a decreased blood TAC concentration and improved renal function. The patient's genotype was CYP3A5*1/*3.

Conclusions: In the early stages of ISCZ treatment, the blood TAC concentration is higher, and CYP3A5 polymorphisms may partially explain the extent of this interaction. We recommend more careful monitoring of TAC and serum creatinine levels for approximately one week after ISCZ administration.