What is the treatment protocol for Vfend (voriconazole) in patients with serious fungal infections?

Voriconazole (Vfend) Treatment Protocol for Serious Fungal Infections

For patients with serious fungal infections, voriconazole should be administered with a loading dose of 6 mg/kg IV every 12 hours for the first 24 hours, followed by a maintenance dose of 4 mg/kg IV every 12 hours, with transition to oral therapy at 200 mg every 12 hours once the patient is clinically stable and can tolerate oral medication. 1, 2

Dosing Regimen by Infection Type

Invasive Aspergillosis

• Initial therapy (Day 1): IV voriconazole 6 mg/kg every 12 hours for first 24 hours
• Maintenance therapy: IV voriconazole 4 mg/kg every 12 hours
• Oral step-down: 200 mg every 12 hours (for patients ≥40 kg) or 100 mg every 12 hours (for patients <40 kg)
• Duration: Minimum 6-12 weeks, continuing throughout immunosuppression period until lesions resolve 1

Candidemia in Non-neutropenic Patients and Deep Tissue Candida Infections

• Initial therapy (Day 1): IV voriconazole 6 mg/kg every 12 hours for first 24 hours
• Maintenance therapy: IV voriconazole 3-4 mg/kg every 12 hours
• Oral step-down: 200 mg every 12 hours
• Duration: At least 14 days following resolution of symptoms or last positive culture, whichever is longer 1, 2

CNS Aspergillosis

• Primary therapy: Voriconazole (strong recommendation, moderate-quality evidence)
• Alternative: Liposomal amphotericin B
• Additional measures: Surgical resection of infected tissue if feasible
• Caution: Monitor for drug interactions between anticonvulsants and voriconazole 1

Esophageal Candidiasis

• Oral therapy: 200 mg every 12 hours
• Duration: Minimum 14 days and at least 7 days following resolution of symptoms 2

Scedosporiosis and Fusariosis

• Initial therapy (Day 1): IV voriconazole 6 mg/kg every 12 hours for first 24 hours
• Maintenance therapy: IV voriconazole 4 mg/kg every 12 hours
• Oral step-down: 200 mg every 12 hours 2, 3

Administration Guidelines

IV Administration

• Reconstitute voriconazole to 10 mg/mL and subsequently dilute to 5 mg/mL or less
• Administer by IV infusion over 1-2 hours at maximum rate of 3 mg/kg per hour
• Do not administer as IV bolus injection 2

Important Administration Considerations

• IV treatment should be continued for at least 7 days before transitioning to oral therapy
• Transition to oral therapy when patient has clinically improved and can tolerate oral medication
• Correct electrolyte disturbances (hypokalemia, hypomagnesemia, hypocalcemia) before and during therapy
• Do not infuse voriconazole with blood products or concentrated electrolytes, even in separate lines 2

Dose Adjustments

Inadequate Response

• Increase oral maintenance dose from 200 mg to 300 mg every 12 hours
• For patients <40 kg, increase from 100 mg to 150 mg every 12 hours 2

Poor Tolerance

• If unable to tolerate 300 mg orally every 12 hours, reduce by 50 mg steps to minimum of 200 mg every 12 hours
• If unable to tolerate 4 mg/kg IV every 12 hours, reduce to 3 mg/kg every 12 hours 2

Hepatic Impairment

• Dose adjustment required in patients with hepatic dysfunction 2

Therapeutic Monitoring

• Obtain fungal cultures and relevant laboratory studies before initiating therapy
• Monitor clinical symptoms and radiographic imaging (CT) at regular intervals
• Consider therapeutic drug monitoring, especially in patients with poor response or suspected toxicity
• Serial galactomannan assays may be useful for monitoring response in aspergillosis 1

Common Adverse Effects

• Visual disturbances (approximately 30% of patients) - typically transient
• Skin rashes (6%) - may manifest as photosensitivity
• Hepatic enzyme abnormalities
• Drug interactions - high potential for interactions with other medications 4, 5

Clinical Pearls

• Voriconazole has excellent bioavailability in oral form, allowing for effective transition from IV to oral therapy
• For invasive aspergillosis, voriconazole has demonstrated superior outcomes compared to amphotericin B (52.8% vs 31.6% successful outcomes) 4
• Voriconazole is particularly valuable for treating invasive aspergillosis and rare fungal infections including Fusarium and Scedosporium species 3, 6
• Be vigilant about drug interactions, especially with medications metabolized through cytochrome P450 enzymes
• Visual disturbances are common but rarely lead to treatment discontinuation 7

Remember that specimens for fungal culture and other relevant laboratory studies should be obtained prior to therapy to identify causative organisms, though therapy may be initiated before results are available and adjusted once they are known.