What is the dosage and treatment duration for voriconazole (antifungal medication) tablets in adults with serious fungal infections?

Voriconazole Tablet Dosage and Treatment Duration for Serious Fungal Infections in Adults

For adults with serious fungal infections, voriconazole tablets should be administered at a loading dose of 400 mg (6 mg/kg) every 12 hours for the first 24 hours, followed by a maintenance dose of 200 mg every 12 hours, taken at least one hour before or after meals. 1

Dosing Regimens by Infection Type

Invasive Aspergillosis

• Initial treatment requires IV loading dose of 6 mg/kg every 12 hours for the first 24 hours 1
• Switch to oral tablets after at least 7 days of IV therapy when clinically improved 1
• Maintenance dose: 200 mg every 12 hours orally 1
• Treatment duration: Continue until resolution or stabilization of all clinical and radiographic manifestations 2
• Median duration in clinical trials: 76 days (range 2-232 days) for oral therapy 1

Candidemia in Non-neutropenic Patients and Deep Tissue Candida Infections

• Initial treatment requires IV loading dose of 6 mg/kg every 12 hours for the first 24 hours 1
• Maintenance dose: 200 mg every 12 hours orally 1
• Treatment duration: At least 14 days following resolution of symptoms or following last positive culture, whichever is longer 1, 2

Esophageal Candidiasis

• Maintenance dose: 200 mg every 12 hours orally 1
• Treatment duration: Minimum of 14 days and for at least 7 days following resolution of symptoms 1
• Typical treatment course: 14-21 days until clinical improvement is seen 2

Scedosporiosis and Fusariosis

• Initial treatment requires IV loading dose of 6 mg/kg every 12 hours for the first 24 hours 1
• Maintenance dose: 200 mg every 12 hours orally 1
• Treatment duration: Similar to invasive aspergillosis, until resolution of clinical and radiographic manifestations 2

Dose Adjustments

Based on Response

• If response is inadequate, oral maintenance dose may be increased from 200 mg to 300 mg every 12 hours 1
• For patients weighing less than 40 kg, oral maintenance dose may be increased from 100 mg to 150 mg every 12 hours 1
• If patient cannot tolerate 300 mg every 12 hours, reduce by 50 mg steps to minimum of 200 mg every 12 hours (or 100 mg for patients <40 kg) 1

Special Populations

• For CNS infections (aspergillosis, candidiasis): Voriconazole is a preferred agent due to good CNS penetration 2
• For patients with hepatic impairment: Dose reduction may be necessary 1
• Be aware of drug interactions, particularly with anticonvulsants in CNS infections 2

Administration Considerations

• Administer voriconazole tablets at least one hour before or after meals 1
• Tablets can be crushed if necessary for patients unable to swallow whole tablets (bioequivalent to whole tablets) 3
• Switching between IV and oral formulations is appropriate due to high oral bioavailability 1, 4

Monitoring

• Follow-up blood cultures should be obtained for all patients with candidemia to ensure clearance 2
• Consider therapeutic drug monitoring in cases of treatment failure or toxicity concerns 5
• Target trough concentrations between 1-5.5 mg/L are generally recommended, though not definitively established 6, 5

Common Pitfalls and Caveats

• Voriconazole has numerous drug interactions due to CYP450 metabolism that may require dose adjustments 4, 5
• Visual disturbances are common (approximately 30% of patients) but typically transient 7
• Genetic polymorphism of CYP2C19 can lead to significant variability in drug exposure between patients 5
• Standard dosing may be inadequate for Aspergillus infections compared to Candida infections, potentially requiring higher doses (300-600 mg) in some patients 6