Isavuconazole Dosage and Treatment Guidelines for Invasive Aspergillosis and Mucormycosis
For adult patients with invasive aspergillosis or mucormycosis, isavuconazole should be administered at a loading dose of 200 mg every 8 hours for 6 doses (48 hours), followed by a maintenance dose of 200 mg once daily. 1
Adult Dosing Regimen
Loading Dose
- 200 mg isavuconazole (as isavuconazonium sulfate) every 8 hours for 6 doses (48 hours)
- Can be administered intravenously or orally
Maintenance Dose
- 200 mg isavuconazole once daily
- Start after completion of the loading dose
- Can be administered intravenously or orally
- Continue until resolution of infection, failure, or for at least 6-12 weeks
Pediatric Dosing Regimen
For pediatric patients (1 to <18 years):
- 10 mg/kg isavuconazonium sulfate daily (maximum 372 mg; equivalent to 5.4 mg/kg or 200 mg isavuconazole) 2
- Duration:
- Invasive aspergillosis: up to 84 days
- Mucormycosis: up to 180 days
Special Considerations for Young Children
- Higher dosing (15 mg/kg) may be needed for patients aged 1-<3 years to achieve adequate drug exposure 2
Treatment Duration
- Invasive Aspergillosis: Treatment should continue until resolution or stabilization of all clinical and radiographic manifestations 1
- Mucormycosis: Longer treatment courses are typically required, often 3-6 months or until resolution of infection 1
Efficacy and Evidence
Invasive Aspergillosis
- Isavuconazole is recommended as first-line therapy for invasive aspergillosis, with efficacy comparable to voriconazole 1
- In the SECURE trial, isavuconazole demonstrated non-inferiority to voriconazole for primary treatment of invasive mold disease (primarily aspergillosis) 3
Mucormycosis
- Isavuconazole showed similar efficacy to amphotericin B in a matched case-control analysis 4
- Day-42 crude all-cause mortality was 33% for isavuconazole vs 39% for amphotericin B-treated matched controls 4
- Isavuconazole can be used as an option for patients with mucormycosis who are refractory to or intolerant of amphotericin B 1
Safety Profile and Advantages
- Better tolerated than voriconazole with fewer drug-related adverse events 3
- Most common adverse events: gastrointestinal disorders (nausea, vomiting, diarrhea) 3
- Excellent bioavailability with oral formulation
- No cyclodextrin in IV formulation, making it suitable for patients with renal impairment 3
- Predictable pharmacokinetics with fewer drug-drug interactions compared to other triazoles 5
Monitoring
- Therapeutic drug monitoring may be beneficial, although specific target levels are not as well established as for other azoles
- Regular liver function tests should be performed
- Monitor for breakthrough infections, especially in patients previously exposed to other antifungal agents
Special Populations
- Safe to use in patients with renal impairment
- No dose adjustment required for mild to moderate hepatic impairment
- Limited data in severe hepatic impairment
Clinical Pearls and Pitfalls
- Isavuconazole has a broad spectrum of activity against clinically important fungi including Aspergillus species and Mucorales
- The prodrug (isavuconazonium sulfate) is water-soluble, allowing for IV administration without cyclodextrin
- Oral and IV formulations are interchangeable with 98% bioavailability
- In real-world studies, isavuconazole has shown promising clinical response whether used as first-line therapy or after failure of other antifungal agents 6
- Combination therapy with other antifungals has not been shown to improve outcomes compared to isavuconazole monotherapy 6
By following these dosing guidelines and monitoring recommendations, isavuconazole provides an effective treatment option for invasive aspergillosis and mucormycosis with a favorable safety profile compared to alternative therapies.