黴菌感染
Aspergillosis: Treatment of invasive aspergillosis in adults
Mucormycosis: Treatment of invasive mucormycosis in adults
#仿單變更2021

Antifungal Agent, Azole Derivative
Isavuconazonium sulfate is a prodrug that is rapidly hydrolyzed in the blood to active isavuconazole. Isavuconazole inhibits the synthesis of ergosterol, a key component of the fungal cell membrane, through the inhibition of cytochrome P-450 dependent enzyme lanosterol 14-alpha-demethylase. This enzyme is responsible for the conversion of lanosterol to ergosterol. An accumulation of methylated sterol precursors and a depletion of ergosterol within the fungal cell membrane weakens the membrane structure and function.

Distribution:
Protein binding: >99% (primarily to albumin)
Metabolism:
1. Isavuconazonium sulfate (prodrug) is rapidly hydrolyzed in the blood by esterases to active isavuconazole and an inactive cleavage product.
2. Isavuconazole is metabolized by CYP3A4, CYP 3A5, and UGT.
Excretion:
Urine (<1% as unchanged isavuconazole); feces (33% as unchanged isavuconazole)
Pharmacodynamics:
1. Bioavailability: 98%
2. Time to peak: 2-3 hours

Hypersensitivity to isavuconazonium sulfate (eg, isavuconazole) or any component of the formulation; concurrent use of strong CYP3A4 inhibitors (eg, ketoconazole, high-dose ritonavir [400 mg every 12 hours]); concurrent use of strong CYP3A4 inducers (eg, rifampin, carbamazepine, St. John’s wort, long acting barbiturates); familial short QT syndrome

Use of alternative antifungals is recommended in pregnant women.

The manufacturer recommends breastfeeding be discontinued during maternal isavuconazonium sulfate therapy.

1. Cardiovascular: Peripheral edema
2. Central nervous system: Headache, fatigue, insomnia
3. Endocrine & metabolic: Hypokalemia
4. Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain, constipation
5. Hepatic: Increased liver enzymes
6. Respiratory: Dyspnea, cough

1. Initial: 372 mg (isavuconazole 200 mg) every 8 hours for 6 doses
2. Maintenance: 372 mg (isavuconazole 200 mg) once daily; start maintenance dose 12 to 24 hours after the last loading dose

No dosage adjustment necessary.

1. Mild or moderate impairment (Child-Pugh class A or B): No dosage adjustment necessary.
2. Severe impairment (Child-Pugh class C): There are no dosage adjustments provided in the manufacturer's labeling (has not been studied); use with caution.