Drug Guide
Isavuconazonium Sulfate
Classification
Therapeutic: Antifungal
Pharmacological: Azole antifungal
FDA Approved Indications
- Invasive aspergillosis in immunocompromised patients
- Mucormycosis (zygomycosis)
Mechanism of Action
Inhibits the synthesis of ergosterol, a vital component of fungal cell membranes, by selectively inhibiting the enzyme lanosterol 14α-demethylase, leading to increased cell membrane permeability and cell death.
Dosage and Administration
Adult: Initial loading dose of 372 mg (equivalent to 200 mg of isavuconazole) every 8 hours for 6 doses, followed by maintenance dose of 372 mg once daily.
Pediatric: Safety and efficacy not established in pediatric patients.
Geriatric: No specific dosage adjustments; use with caution and monitor closely.
Renal Impairment: No dose adjustment recommended for mild to moderate impairment; use caution in severe impairment.
Hepatic Impairment: Dose adjustment may be necessary; consult specific guidelines.
Pharmacokinetics
Absorption: Oral bioavailability approximately 98%.
Distribution: Widely distributed; volume of distribution roughly 450 liters.
Metabolism: Metabolized by hydrolysis and cytochrome P450 enzymes.
Excretion: Excreted mainly in feces; minimal urinary excretion.
Half Life: Approximately 130 hours (about 5.5 days).
Contraindications
- Hypersensitivity to isavuconazole or other azoles.
Precautions
- Monitor liver function due to potential hepatotoxicity.
- Use with caution in patients with hepatic impairment.
- Potential drug interactions; review concomitant medications.
Adverse Reactions - Common
- Junndice, elevated liver enzymes (Less common)
- Headache (Common)
- Nausea (Common)
Adverse Reactions - Serious
- Hepatotoxicity leading to liver failure (Rare)
- Infusion reactions including edema, hypokalemia, hypomagnesemia (Rare)
- QT interval prolongation or shortening (Possible, monitor ECG)
Drug-Drug Interactions
- CYP3A4 inducers or inhibitors (e.g., rifampin, ketoconazole, clarithromycin)
Drug-Food Interactions
- None specific.
Drug-Herb Interactions
- St. John’s Wort and other herbal products affecting CYP pathways.
Nursing Implications
Assessment: Monitor liver function tests (ALT, AST, bilirubin), renal function, electrolytes, and ECG for QT interval changes.
Diagnoses:
- Risk for impaired liver function
- Electrolyte imbalance
- Potential drug interactions
Implementation: Administer as directed, monitor labs and vital signs, and educate patients about potential side effects.
Evaluation: Assess for resolution of infection, monitor for adverse effects, and adjust therapy based on response and labs.
Patient/Family Teaching
- Take medication exactly as prescribed.
- Report signs of liver problems such as jaundice or unusual fatigue.
- Avoid alcohol and hepatotoxic substances.
- Inform healthcare providers of all medications and OTC products.
Special Considerations
Black Box Warnings:
- Hepatotoxicity: serious liver injury has been reported.
- QT interval prolongation or shortening: monitor ECG, especially in patients with cardiac history.
Genetic Factors: None specifically associated.
Lab Test Interference: None known.
Overdose Management
Signs/Symptoms: Nausea, vomiting, liver enzyme elevations, QT changes.
Treatment: Supportive care, monitor cardiac status, and liver function; no specific antidote.
Storage and Handling
Storage: Store at room temperature away from moisture and light.
Stability: Stable until expiration date printed on the packaging.