Drug-Drug Interaction Between Isavuconazole and Tacrolimus: Is Empiric Dose Adjustment Necessary?

A paucity of data currently exists regarding drug-drug interaction (DDI) with tacrolimus and isavuconazole coadministration. Current literature provides conflicting recommendations on whether an empiric tacrolimus dose reduction is necessary when coadministered with isavuconazole. A 47-year-old African American female with acute lymphoblastic leukemia underwent an allogenic stem cell transplant (alloSCT) and was subsequently placed on routine posttransplant therapy including tacrolimus for immunosuppression and posaconazole for antifungal prophylaxis. Tacrolimus was empirically dose reduced due to the expected DDI with posaconazole based on current recommendations. Due to a persistently prolonged QTc interval and need for mold coverage, antifungal prophylaxis was ultimately changed to isavuconazole at standard recommended dosing. Tacrolimus was empirically dose reduced by 40% based on limited available literature at the time; however, tacrolimus trough concentrations subsequently declined, requiring an increase in tacrolimus dose to maintain therapeutic trough concentrations. Adequate isavuconazole absorption was documented through pharmacokinetic and pharmacodynamic data by measuring an isavuconazole trough concentration and directly observing isavuconazole's shortening effect on the QTc interval, respectively. Our experience in an alloSCT patient suggests that an empiric tacrolimus dose reduction is not required when isavuconazole is initiated, but close tacrolimus therapeutic drug monitoring should rather be performed to guide tacrolimus dosing.