What is the dosage and treatment duration of Isavuconazole (Isavuconazonium sulfate) for invasive aspergillosis and mucormycosis?

Isavuconazole Dosage for Invasive Aspergillosis and Mucormycosis

For invasive aspergillosis and mucormycosis, isavuconazole (isavuconazonium sulfate) should be administered at 200 mg every 8 hours for 6 doses (loading), followed by 200 mg daily for maintenance therapy. 1

Dosing Regimen

• Isavuconazole is administered as its prodrug, isavuconazonium sulfate, which is available in both intravenous and oral formulations 2
• Loading dose: 200 mg every 8 hours for 6 doses (first 48 hours) 1
• Maintenance dose: 200 mg once daily, starting after completion of the loading regimen 1
• No dose adjustments are required when switching between intravenous and oral formulations due to high bioavailability 2

Duration of Therapy

• For invasive aspergillosis: Treatment should continue for a minimum of 6-12 weeks 1
• For mucormycosis: In the VITAL study, the median duration of treatment was 84 days (range 2-882 days) 3
• Treatment duration should be individualized based on:
  • Clinical response to therapy 1
  • Resolution or stabilization of radiographic findings 1
  • Degree and duration of immunosuppression 1
  • Site of infection (e.g., CNS involvement may require longer treatment) 1

Efficacy and Indications

• Isavuconazole is FDA-approved for the treatment of:
  • Invasive aspergillosis 1, 4
  • Mucormycosis 3, 4
• For invasive aspergillosis, isavuconazole is considered a first-line therapy option alongside voriconazole 1, 4
• For mucormycosis, isavuconazole is an alternative first-line therapy to liposomal amphotericin B, especially in patients with underlying renal impairment 4

Special Considerations

• No dose adjustments are required for patients with renal impairment or mild to moderate hepatic impairment 2
• Therapeutic drug monitoring may be beneficial, with a target average AUC24 of at least 60 mg·h/L 5
• Isavuconazole has fewer drug-drug interactions compared to other triazoles like voriconazole 4, 2
• Unlike voriconazole, isavuconazole does not cause QTc prolongation, making it a safer option for patients with cardiac issues 2

Safety Profile

• In clinical trials, isavuconazole demonstrated a favorable safety profile compared to other antifungal agents 2
• Common adverse events include:
  • Gastrointestinal disorders 2
  • Elevated liver enzymes 2
  • Headache 2
• In a real-world study, only 12.6% of patients reported adverse drug reactions, with 2.7% experiencing serious adverse events 6

Clinical Pearls

• For patients with mucormycosis who cannot tolerate amphotericin B, isavuconazole is a viable alternative 3, 4
• In cases of suspected mucormycosis, initial therapy with a polyene (amphotericin B) should be considered until mucormycosis is excluded 1
• Surgical debridement should be considered as adjunctive treatment to antifungal therapy for mucormycosis when possible 1
• For CNS aspergillosis, be aware of potential drug interactions between anticonvulsants and triazoles 1

Combination Therapy

• Primary combination therapy is not routinely recommended for invasive aspergillosis 1
• For refractory cases or salvage therapy, combination with another antifungal class may be considered 1, 6
• In a real-world study, combination therapy tended to show lower mortality rates than monotherapy, except for patients with mucormycosis receiving primary isavuconazole 6