From the Guidelines
For invasive fungal pneumonia, voriconazole is recommended with a loading dose of 6 mg/kg IV every 12 hours for the first day, followed by a maintenance dose of 4 mg/kg IV every 12 hours, as supported by the 2016 update by the Infectious Diseases Society of America 1.
Key Considerations
- The loading dose is crucial for rapidly achieving therapeutic levels, and the maintenance dose should be adjusted based on patient weight and clinical response.
- Oral voriconazole can be used at 200-300 mg every 12 hours once the patient can tolerate oral medication, with a recommended dose of 200 mg for patients weighing less than 40 kg.
- Treatment duration should be individualized, but typically lasts at least 6-12 weeks, depending on clinical response and immune status.
Important Safety Information
- Therapeutic drug monitoring is essential to ensure efficacy and avoid toxicity, with target trough levels between 2-5.5 μg/mL.
- Dose adjustments may be necessary for patients with hepatic impairment, such as reducing the maintenance dose by 50% in moderate hepatic dysfunction.
- Common side effects include visual disturbances, hepatotoxicity, and skin reactions, and drug interactions are significant due to voriconazole's metabolism by CYP450 enzymes.
Efficacy and Mechanism
- Voriconazole is effective against Aspergillus species and certain other molds that commonly cause invasive fungal pneumonia, working by inhibiting ergosterol synthesis in the fungal cell membrane, as outlined in the guidelines 1.
From the FDA Drug Label
Voriconazole was administered intravenously with a loading dose of 6 mg/kg every 12 hours for the first 24 hours followed by a maintenance dose of 4 mg/kg every 12 hours for a minimum of seven days. Therapy could then be switched to the oral formulation at a dose of 200 mg every 12 hours.
The recommended dosage of Voriconazole for invasive fungal pneumonia (IFP) is:
- Loading dose: 6 mg/kg every 12 hours for the first 24 hours
- Maintenance dose: 4 mg/kg every 12 hours for a minimum of seven days, which can then be switched to an oral formulation at a dose of 200 mg every 12 hours 2.
From the Research
Recommended Dosage of Voriconazole for Invasive Fungal Pneumonia (IFP)
- The recommended dosage of Voriconazole for IFP is not explicitly stated in the provided studies, but the following information can be inferred:
Dosage Regimens
- A study published in 2002 3 used an initial intravenous dose of 6 mg/kg every 12 hours on day 1, followed by 4 mg/kg every 12 hours for more than 7 days, and then switched to oral voriconazole 200 mg every 12 hours.
- A study published in 2018 4 suggested that voriconazole doses of 300-600 mg may maximize the net benefit for patients with Aspergillus spp. infections.
- A study published in 2016 5 recommended 200 mg voriconazole administered intravenously or orally twice daily for Candida infections and 300 mg administered orally or with 200 mg administered intravenously twice daily for Aspergillus infections.
Pharmacokinetic/Pharmacodynamic Analysis
- A study published in 2016 5 found that the cumulative fraction of response was greater than 90% when using the recommended dosage regimens.
- A study published in 2015 6 found that fAUC24:MIC values higher than 25 and fCmin:MIC values higher than 1 may predict clinical response in patients with IFIs.
Clinical Practice
- A study published in 2008 7 found that voriconazole was effective in 61.4% of patients with suspected or proven IFI and 52.4% of patients with empirical treatment, with a mortality rate of 15%.