Isavuconazole

Coadministration is contraindicated. Itraconazole increases plasma concentrations, potentially increasing pharmacologic effects and adverse reactions.

Mild or Moderate CYP3A Inhibitors, such as: antibiotics (e.g., erythromycin), calcium channel blockers (e.g., verapamil, diltiazem, nifedipine, nicardipine), amiodarone, danazol, ethinyl estradiol, cimetidine, lansoprazole and omeprazole, azole antifungals (e.g., clotrimazole, fluconazole, isavuconazole), imatinib, nilotinib, letermovir May increase tacrolimus whole blood trough concentrations and increase the risk of serious adverse reactions (e.g., neurotoxicity, QT prolongation) [see Warnings and Precautions (5.6 , 5.9 , 5.10) ].

Other: trazodone ↑ trazodone Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole ↑ darunavir ↑ itraconazole ↑ isavuconazole ↑ ketoconazole ↔ posaconazole Monitor for increased darunavir/ritonavir and/or antifungal adverse events with concomitant use of these antifungals.

Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole voriconazole ↑ darunavir ↑ itraconazole ↑ isavuconazole ↑ ketoconazole ↔ posaconazole ↓ voriconazole Monitor for increased darunavir/ritonavir and/or antifungal adverse events with concomitant use of these antifungals.

amitriptyline, desipramine, imipramine, nortriptyline ↑ TCAs Other antidepressants: trazodone ↑ trazodone Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole ↑ darunavir ↑ cobicistat Monitor for increased darunavir or cobicistat and/or antifungal adverse reactions. ↑ itraconazole ↑ ketoconazole ↑ isavuconazole ↔ posaconazole Specific dosing recommendations are not available for co-administration with these antifungals.

Tricyclic Antidepressants (TCAs): e.g., amitriptyline, desipramine, imipramine, nortriptyline ↑ TCAs Other antidepressants: trazodone ↑ trazodone Antifungals: itraconazole, isavuconazole, ketoconazole, posaconazole ↑ darunavir ↑ cobicistat Monitor for increased darunavir or cobicistat and/or antifungal adverse reactions. ↑ itraconazole ↑ isavuconazole ↑ ketoconazole ↔ posaconazole (not studied) Specific dosing recommendations are not available for co-administration with these antifungals.

7 DRUG INTERACTIONS Isavuconazole is a sensitive substrate of CYP3A4. CYP3A4 inhibitors or inducers may alter the plasma concentrations of isavuconazole. Isavuconazole is a moderate inhibitor of CYP3A4, and a mild inhibitor of P-glycoprotein (P-gp), and organic cation transporter 2 (OCT2).

Prevention or Management Monitor patients for alterations in efficacy or mycophenolate mofetil related adverse reactions when these drugs are co-administered with mycophenolate mofetil Examples Telmisartan (induces glucuronidation); isavuconazole (inhibits glucuronidation).

Inhibits glucuronidation, increasing mycophenolic acid systemic exposure and potentially increasing risk of Mycophenolate Mofetil adverse reactions. Monitor for alterations.