isavuconazonium sulfate: clinical use

Prescribing considerations

• Confirm the invasive fungal diagnosis and susceptibility information when available.
• Complete an interaction review before initiation and whenever medicines change.
• Use in severe hepatic impairment only when anticipated benefit outweighs risk, with close toxicity surveillance.
• Consider the benefit–risk balance carefully for prolonged treatment.
• Be alert to azole hypersensitivity and severe cutaneous reactions.
• Stop intravenous administration if an infusion-related reaction occurs.

Contraindications and cautions

• Hypersensitivity to isavuconazonium sulfate, isavuconazole or formulation excipients
• Familial short QT syndrome
• Concurrent ketoconazole
• Concurrent high-dose ritonavir
• Concurrent strong or moderate CYP3A4/5 inducers listed in the product information

Monitoring

• Hepatic enzymes and suspected hepatic injury
• Clinical and microbiological response where measurable
• Toxicity and efficacy when interacting medicines are started or stopped
• Plasma concentrations of tacrolimus, ciclosporin, sirolimus and digoxin when co-administered
• Isavuconazole concentrations when exposure or toxicity is uncertain, according to specialist practice
• Infusion-related symptoms

Clinical pharmacology

Isavuconazonium sulfate is a water-soluble prodrug rapidly hydrolysed to isavuconazole. The active moiety inhibits fungal lanosterol 14-alpha-demethylase and ergosterol synthesis. Isavuconazole is a CYP3A4/5 substrate and moderate inhibitor, is highly protein-bound and shortens the QT interval.

Formulation and product differences

• Capsules may be taken with or without food but must be swallowed intact.
• The intravenous powder requires reconstitution, further dilution and an in-line filter; it must not be given as a bolus.
• High oral bioavailability supports switching between intravenous and oral administration when clinically appropriate.
• The selected intravenous formulation covers younger children than the selected capsule formulation.

Solution for infusion

Route: Intravenous

Strengths: 200 mg

Capsule

Route: Oral

Strengths: 40 mg, 100 mg