Overview
Voriconazole is a broad-spectrum triazole antifungal agent used for the treatment of invasive fungal infections. It is a second-generation synthetic derivative of fluconazole with enhanced activity against Aspergillus species and other molds. Voriconazole is available in oral and intravenous formulations and is considered a first-line agent for invasive aspergillosis.
Mechanism of Action
Voriconazole inhibits fungal cytochrome P450-dependent 14α-lanosterol demethylase, which is essential for ergosterol synthesis in fungal cell membranes. This inhibition leads to depletion of ergosterol and accumulation of toxic sterol precursors, disrupting membrane integrity and inhibiting fungal growth.
Indications
- Invasive aspergillosis
- Candidemia in non-neutropenic patients
- Esophageal candidiasis
- Serious fungal infections caused by Scedosporium apiospermum and Fusarium species
- Prophylaxis in high-risk patients (e.g., hematopoietic stem cell transplant recipients)
Dosage
Loading dose: 6 mg/kg IV every 12 hours for 2 doses, then 4 mg/kg IV every 12 hours. Oral: 200 mg every 12 hours (patients ≥40 kg) or 100 mg every 12 hours (patients <40 kg). Adjust dose based on therapeutic drug monitoring and hepatic function.
Contraindications
- Hypersensitivity to voriconazole or other azole antifungals
- Coadministration with CYP3A4 substrates (e.g., terfenadine, astemizole, cisapride, pimozide, quinidine)
- Coadministration with rifampin, carbamazepine, long-acting barbiturates
- Coadministration with efavirenz, ritonavir, rifabutin
- Coadministration with St. John's wort
Side Effects
- Visual disturbances
- Hepatotoxicity
- Rash
- Nausea
- Vomiting
- Diarrhea
- Headache
- Hallucinations
- Peripheral edema
- Fever
- Chills
- QT prolongation
- Photosensitivity
Interactions
- CYP3A4 inhibitors (e.g., ritonavir) increase voriconazole levels
- CYP3A4 inducers (e.g., rifampin, phenytoin) decrease voriconazole levels
- Voriconazole increases levels of CYP3A4 substrates (e.g., cyclosporine, tacrolimus, warfarin)
- Voriconazole increases levels of CYP2C9 substrates (e.g., phenytoin, sulfonylureas)
- Interacts with omeprazole, NNRTIs, and sirolimus