What is the recommended treatment for a Voriconazole-sensitive infection?

Treatment for Voriconazole-Sensitive Infections

Voriconazole is the recommended first-line treatment for voriconazole-sensitive infections, particularly for invasive aspergillosis and other serious fungal infections. 1

Recommended Dosing Regimen

For Adults:

• Loading dose: 6 mg/kg IV every 12 hours for the first 24 hours
• Maintenance dose:
  • IV: 4 mg/kg every 12 hours
  • Oral: 200 mg every 12 hours (for patients ≥40 kg) or 100 mg every 12 hours (for patients <40 kg) 2

For Children (12-14 years weighing ≥50 kg and ≥15 years regardless of weight):

• Same dosing as adults 2

Treatment by Specific Infection Type

Invasive Aspergillosis

• Voriconazole is strongly recommended as primary therapy 1
• Treatment should begin with IV formulation for at least 7 days, then transition to oral therapy when clinically improved 2
• Duration: Typically 6-12 weeks, depending on severity and response 1

Candidiasis

• For esophageal candidiasis: Oral voriconazole 200 mg twice daily for 14-21 days 1
• For candidemia in non-neutropenic patients: Begin with IV therapy, then transition to oral when clinically stable 1, 2
• Minimum treatment duration: 14 days after resolution of symptoms or last positive culture 2

Scedosporiosis and Fusariosis

• Voriconazole is recommended for patients intolerant of or refractory to other therapy 2
• Same dosing regimen as for invasive aspergillosis 2

Other Site-Specific Infections

• CNS aspergillosis: Voriconazole is the preferred treatment 1
• Aspergillus endophthalmitis: Systemic voriconazole plus intravitreal voriconazole 1
• Aspergillus endocarditis: Early surgical intervention plus voriconazole 1
• Aspergillus osteomyelitis/arthritis: Surgical intervention plus voriconazole 1
• Cutaneous aspergillosis: Voriconazole plus evaluation for primary focus 1
• Peritoneal aspergillosis: Prompt catheter removal plus voriconazole 1

Pharmacokinetic Considerations

• Voriconazole has excellent bioavailability (>90%) when taken orally 3
• Administer at least one hour before or after meals 2
• Achieves good penetration into CSF and vitreous body 1, 3
• Exhibits nonlinear pharmacokinetics with dose-dependent elimination 3
• Reaches steady state within 24 hours with IV loading dose 3

Monitoring and Adjustments

• If response is inadequate, oral maintenance dose may be increased from 200 mg to 300 mg every 12 hours 2
• If patient cannot tolerate 300 mg orally, reduce by 50 mg steps to minimum of 200 mg every 12 hours 2
• Consider therapeutic drug monitoring in special populations (children, liver dysfunction) due to wide inter-individual variability 4

Common Adverse Effects

• Transient visual disturbances (approximately 30% of patients) 5, 6
• Skin rashes and photosensitivity 6
• Hepatic enzyme elevations 6

Important Considerations

• High potential for drug-drug interactions due to CYP450 metabolism 3, 6
• Intravenous formulation contains cyclodextrin and should be avoided in patients with creatinine clearance <50 mL/min 1
• For patients with mild-to-moderate hepatic impairment, dosage reduction is required 1
• Switching between IV and oral formulations is appropriate due to high bioavailability 2

Voriconazole has become the drug of choice for serious infections with Aspergillus and other filamentous fungi due to its excellent efficacy profile and availability in both oral and IV formulations 7, 6.