Cresemba®Isavuconazonium Sulfate Capsules

1. Indications and Usage
Invasive Aspergillosis: Treatment of adult patients with invasive aspergillosis .
Invasive Mucormycosis: Treatment of adult patients with invasive mucormycosis .
2. Dosage and Administration
Administration: Oral capsules should be swallowed whole. Do not chew, crush, dissolve, or open the capsules. Can be taken with or without food .
Loading Dose: 372 mg (equivalent to 200 mg isavuconazole base) every 8 hours for 6 doses (first 48 hours) .
Maintenance Dose: 372 mg (equivalent to 200 mg isavuconazole base) once daily starting 12-24 hours after the last loading dose .
Renal Impairment: No dosage adjustment is required for patients with renal impairment or those on dialysis .
Hepatic Impairment: No dosage adjustment for mild or moderate impairment (Child-Pugh Class A and B). Not recommended for severe impairment (Child-Pugh Class C) .
3. Mechanism of Action
Isavuconazonium sulfate is a prodrug of isavuconazole.
Isavuconazole is a broad-spectrum triazole antifungal agent that inhibits the fungal enzyme lanosterol 14α-demethylase (CYP51).
This inhibition prevents the conversion of lanosterol to ergosterol, an essential component of the fungal cell membrane, leading to increased membrane permeability and fungal cell death .
4. Safety and Warnings
Contraindications: Hypersensitivity to isavuconazonium sulfate or any excipients; Familial Short QT Syndrome .
Hepatic Impairment: Liver function tests should be performed prior to and during therapy. Discontinue if severe hepatic toxicity occurs .
QT Interval: Unlike some other azoles, isavuconazole shortens the QT interval. It is contraindicated in patients with familial short QT syndrome. Monitoring is advised in patients with cardiac conditions .
Adrenal Insufficiency: Rare cases of adrenal insufficiency have been reported; monitor if signs/symptoms occur .
5. Adverse Reactions
The most common adverse reactions (incidence ≥10%) include:
Nausea
Vomiting
Diarrhea
Headache
Elevated liver enzymes (ALT/AST)
Hypokalemia
6. Drug Interactions
Strong CYP3A4 Inhibitors/Inducers: Contraindicated with strong inhibitors (e.g., ketoconazole, high-dose ritonavir) and strong inducers (e.g., rifampin, carbamazepine, phenobarbital, St. John’s wort) .
Moderate CYP3A4 Inducers: Contraindicated (e.g., modafinil) .
P-gp Inhibitors: May increase isavuconazole plasma concentration .
Substrates of CYP2C8/2C9/3A4: Isavuconazole may increase plasma concentrations of substrates (e.g., cyclosporine, sirolimus, tacrolimus); monitor levels closely .
7. Pharmaceutical Information
Chemical Name: (R)-3-[(2-hydroxyethyl)-2-methyl-4-(4-methyl-1,3-thiazol-5-yl)phenoxy]methyl]oxetan-2-yl]methyl]pyridinium dihydrogen phosphate ester sulfate (1:1) [Standard Isavuconazonium structure].
Molecular Formula: C22H23N4O4S+ (Isavuconazole cation) .
Storage: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) .