What is the recommended treatment regimen for Isavuconazole (Isavuconazonium sulfate) in patients with invasive fungal infections?

Isavuconazole Treatment Regimen for Invasive Fungal Infections

For patients with invasive fungal infections, isavuconazole should be administered as a loading dose of 200 mg intravenously every 8 hours for 2 days (6 doses), followed by a maintenance dose of 200 mg intravenously or orally once daily. 1

Dosing Protocol

Initial Loading Dose

• Intravenous formulation: 200 mg every 8 hours for 2 days (total of 6 doses)
• Alternative loading regimen: 400 mg every 12 hours for 1 day (total of 2 doses) 1

Maintenance Dose

• Standard maintenance: 200 mg once daily (IV or oral) 1
• Duration: Continue until resolution of clinical and radiographic manifestations, typically minimum 6-12 weeks for invasive aspergillosis 2
• No dose adjustment needed for renal impairment 1

Specific Indications and Considerations

Invasive Aspergillosis

• First-line therapy option with strong recommendation (high-quality evidence) 2
• Particularly beneficial for patients with:
  • Renal insufficiency (no dose adjustment needed)
  • Risk of hepatic toxicity
  • Polypharmacy concerns
  • Risk of QTc prolongation
  • Predisposition to visual or cutaneous adverse effects 1

Mucormycosis

• Recommended dosage: 3 × 200 mg on days 1-2, followed by 1 × 200 mg per day from day 3 2
• Strongly recommended for patients with pre-existing renal compromise 2
• Can be used as primary therapy or after failure of other antifungal agents 3

Multiple Fungal Species Infections

• Same dosing regimen applies for mixed infections 4
• Median treatment duration in complex cases may be longer (97 days reported in studies) 4

Monitoring and Safety

Therapeutic Drug Monitoring

• Recommended in cases of:
  • Treatment failure
  • Suspected drug interactions
  • Suspected toxicity 1

Safety Profile

• Better safety profile compared to voriconazole:
  • Fewer treatment-related adverse events (42% vs 60%)
  • Lower frequencies of hepatobiliary, ocular, and cutaneous disorders
  • Shortens QTc interval rather than prolonging it 1
  • Well-tolerated with only 4% discontinuation rate due to adverse events in real-world studies 5

Common Adverse Events

• Gastrointestinal disorders (nausea, vomiting, diarrhea) 6
• Monitor for serious adverse events, which occurred in approximately 80% of patients in clinical studies 4

Treatment Response Assessment

• Evaluate clinical and radiological response at 6 weeks and 12 weeks 5
• For stable disease or partial response, continue treatment
• For progressive disease despite adequate therapy, consider:
  • Testing antifungal susceptibility
  • Reviewing potential drug interactions
  • Performing therapeutic drug monitoring
  • Reducing doses of immunosuppression if feasible
  • Surgical intervention if appropriate
  • Switching to a different class of antifungal or combination therapy 2

Special Considerations

• Isavuconazole has excellent bioavailability with no food effect for oral formulation 6
• For patients with successfully treated invasive aspergillosis who require subsequent immunosuppression, secondary prophylaxis should be initiated to prevent recurrence 2
• No significant difference in outcomes between isavuconazole monotherapy and combination therapy in real-world studies 5

Isavuconazole represents an important treatment option for invasive fungal infections with comparable efficacy to traditional agents but with improved safety and tolerability profiles, especially in patients with renal impairment or those at risk for drug interactions.