Isavuconazole

Isavuconazole is an antifungal medication in the azole class used for the treatment of invasive aspergillosis and invasive mucormycosis. It is administered as the water-soluble prodrug isavuconazonium sulfate, which is rapidly converted to the active triazole isavuconazole after administration. The drug is available for both intravenous and oral use, and the two routes are interchangeable.

Isavuconazole works by inhibiting fungal lanosterol 14-α-demethylase, a cytochrome P450 enzyme involved in ergosterol synthesis. This disruption impairs fungal cell membrane formation and function. The agent has activity against Aspergillus species and Mucorales, with variable activity against Candida species; resistance can occur as with other azoles.

Pharmacokinetics and administration: isavuconazole is well absorbed orally, with high bioavailability, and has a long terminal half-life. It is extensively metabolized in the liver, primarily by CYP3A4 and to a lesser extent by UGT enzymes, with elimination mainly via hepatic pathways. Dosing typically begins with a loading phase followed by a maintenance phase, and the IV and oral routes provide similar exposure, allowing a seamless switch from IV to oral without dose adjustment.

Safety and interactions: Common adverse effects include nausea, vomiting, diarrhea, headache, and elevated liver enzymes. QT interval shortening has been observed; infusion-related reactions and rare cases of liver injury can occur. Caution is advised in hepatic impairment. Isavuconazole is a substrate and modest inhibitor of CYP3A4, so coadministration with strong CYP3A4 inhibitors or inducers can alter drug levels and may affect other medications, including calcineurin inhibitors, requiring monitoring and possible dose adjustment.

History and availability: isavuconazole received regulatory approval in the United States in 2015 for invasive aspergillosis and mucormycosis and is marketed under the brand Cresemba. It is used in adults and in some regions for pediatric patients under specific indications.