Tacrolimus and isavuconazole therapy: What about the drug interaction?
Gill C, Mercuro N, Kenney R, Jantz A, Summers B, Sulejmani N, and Davis S. Tacrolimus and isavuconazole therapy: What about the drug interaction? Am J Transplant 2018; 18:885.
American Journal of Transplantation
Introduction: Isavuconazole (ISV) is a triazole antifungal that is often utilized in solid organ transplant recipients (SOTR) for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is a moderate inhibitor while voriconazole (VOR) is a strong inhibitor of CYP3A4. The purpose of this study is to categorize the effect of ISV therapy on tacrolimus (FK506) dosing in SOTRs. We also evaluated the change in FK506 dosing requirements in patients who transition from VOR to ISV versus patients who start directly on ISV. Methods: This was a retrospective, cross-sectional analysis of SOTRs treated with ISV from 2015-2017. Patients were included if they received ISV and FK506 concomitantly. The primary endpoint was the percent change in FK506 dose required to maintain target trough levels at day 7 of ISV therapy (vs. day-2 ISV). Results: Twenty-eight patients met inclusion criteria and 10 (35.7%) were female. Lungs were the most commonly transplanted organ in the study population (n=12, 42.9%), followed by intestinal transplant (n=5, 17.9%). ISV therapy was utilized for treatment in 23 patients (82.1%) and prophylaxis in 5 patients (17.9%). Concomitant CYP3A4 interacting medications were utilized in 4 patients (14%). Approximately a 14% dose increase was needed to maintain target FK506 trough levels. Nine Patients (32%) were treated with VOR prior to ISV. Patients who transitioned from VOR to ISV required a median (IQR) of 0.25 mg increase (-4.5, 0.875) in FK506 dosing vs. patients started on ISV, 1 mg increase ([IQR-4.25, 2], p = 0.197). (Table presented) Conclusion: Increases in FK506 dosing in SOTRs after initiation of ISV were inconsistent with the contemporary literature. Larger studies are needed to evaluate the clinical effects of drug interactions with these medications in the setting of fungal infections where the target FK506 trough levels are changing and also when changing between azole antifungals with varying magnitude of CYP3A4 inhibition.