Products
Isavuconazonium sulfate is commercially available as a powder for a concentrate for the preparation of an infusion solution and in capsule form (Cresemba). It was approved in the US and EU in 2015 and in many countries in 2017.
Structure and properties
Isavuconazonium sulfate (C35H35F2N8O5S+ – HSO4– Mr = 814.8 g/mol) is a prodrug of isavuconazole, an azole antifungal. It exists as an amorphous, white to yellow-white powder. Isavuconazonium sulfate is rapidly hydrolyzed in the body by esterases to the active ingredient. Isavuconazole is a triazole derivative.
Effects
Isavuconazole (ATC J02AC05) has antifungal (fungicidal) properties. The effects are due to inhibition of the synthesis of ergosterol, an important component of the fungal cell membrane. Isavuconazonium sulfate inhibits the enzyme lanosterol 14α-demethylase, which converts lanosterol to ergosterol. This leads to accumulation of methylated sterol precursors and depletion of ergosterol, which disrupts membrane structure and function.
Indications
- Invasive aspergillosis
- Invasive mucormycosis (mucormycosis in patients in whom treatment with amphotericin B is not indicated).
Dosage
According to the professional information. The drug is administered as an intravenous infusion. The capsules are taken perorally.
Contraindications
- Hypersensitivity
- Combination with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) or strong CYP3A4 inducers (e.g., rifamycins, barbiturates)
- Familial short-QT syndrome.
For complete precautions, see the drug label.
Interactions
The active ingredient, isavuconazole, is a substrate of CYP3A4/5, and CYP inhibitors and inducers may cause interactions. Isavuconazole is additionally also a moderate inhibitor of CYP3A, a weak inhibitor of P-glycoprotein, and of OCT2.
Adverse effects
The most common potential adverse effects include altered liver enzymes, nausea, vomiting, dyspnea, abdominal pain, diarrhea, injection site reactions, headache, hypokalemia, and a skin rash. These data are for intravenous therapy.