Isavuconazole (Cresemba)
Isavuconazonium (the prodrug of isavuconazole), a new azole antifungal indicated for treatment of rare mold infections was recently added to the Nebraska Medicine formulary with a restriction of use to the Infectious Disease service. Isavuconazonium is approved for the treatment of invasive aspergillosis and mucromycosis when patients are intolerant of alternative antifungal agents (voriconazole for aspergillosis or amphotericin B for mucormycosis).
Based on a review of the current literature, the Antmicrobial Stewardship Program created the table below to guide clinicians when choosing therapy for invasive fungal infections. Therapeutic decisions should consider the specific organism, severity of infection, patient characteristics, potential medication interactions, and antifungal agent characteristics (bioavailability, tolerability, price, etc.).
| Infection | 1st line Agents | 2nd Line Agents |
|---|---|---|
| Invasive Aspergillosis | Voriconazole | Isavuconazonium |
| Mucormycosis | Amphotericin B | Isavuconazonium |
| Histoplasmosis | Amphotericin B, Itraconazole or Voriconazole | Isavuconazonium or Posaconazole |
| High-risk fungal prophylaxis | Voriconazole | Posaconazole |
| Candidiasis | Micafungin or Fluconazole | Voriconazole |
Dosing
Doses for both indications are 372 mg (200mg isavuconazole) every 8 hours for 6 doses, and then 372 mg daily. It is available in both IV and oral formulations which are considered bioequivalent. It has good oral bioavailability and food does not alter its absorption. Therapeutic drug monitoring is not currently recommended for this agent.
Safety
Adverse effects associated with its use were less common than voriconazole, but still include hepatotoxicity, and optic neuritis. It has the potential to shorten the QT interval rather than extend it. Therapeutic drug monitoring is not currently required.