Triazole antifungal agent used to treat Aspergillus infections.
A third generation broad-spectrum triazole commonly used to treat invasive aspergillosis and Candida albicans infections.
Metabolized in the liver by cytochrome P450 system and has nonlinear pharmacokinetics.
Higher plasma levels associated with ocular toxicity.
An association exists between improved therapeutic outcome in Aspergillus infections and higher plasma levels of the drug have been reported.
Poorly soluble.
Following oral administration, as either tablet or solution, bioavailability is 96%.
Oral absorption is reduced by 22% when taken with food.
Is 56% bound to serum proteins.
Metabolized in the liver, mainly by CYP2C19 and CYP3A4 and to a lesser extent by CYP2C9.
Steady-state concentration without a loading dose is achieved within 5 to 6 days of treatment.
Prnetrates the blood-brain barrier, and CSF level is ∼46% of the serum level.
Only 2% of the active drug can be found in urine.
Active against most Candida and Aspergillus spp, has significant activity against Scedosporium apiospermum (Pseudallescheria boydii) and is also active against fusariosis.
Voriconazole is reasonably active in vitro against the endemic fungi (Blastomyces dermatitidis, Coccidioides spp., and Histoplasma capsulatum) as well as Cryptococcus neoformans, Trichosporon spp., and Acremonium kilensii.
Approved for the treatment of invasive aspergillosis and has subsequently replaced amphotericin B for this indication.
Small increases in dose result in exponential increases in blood levels, as the drug exhibits nonlinear pharmokinetics.
Nineteen percent of the Asian and 2% of the Caucasian population are poor metabolizers in terms of CYP2C19 activity resulting in high voriconazole blood levels.
Higher percentages of patients are heterozygous for the CYP2C19 allele, leading to an intermediate metabolizer phenotype with moderately increased voriconazole blood levels.
Patients with mild to moderate hepatic disease should get 50% of the usual maintenance dose.
It should be used with caution in patients with creatinine clearance of < 50 mL/min.
Usually well tolerated; the most common adverse events are visual changes, with an incidence of 20 to 23%.
Typically, patients report blurred vision, photopsias, photophobia, and color changes 30 minutes to 1 hour after dosing.
Visual symptoms are transient and reversible, almost never lead to drug discontinuation, and tend to dissipate after repeated dosing.
As with all azoles, can cause hepatotoxicity, mainly manifested by elevation of AST/ALT, which, on rare occasion, can be serious or lethal.
Hallucinations are most often reported with the intravenous formulation and tend to disappear with the oral drug or with continued treatment.
Skin rashes and cheilitis can occur after prolonged treatment, mainly due to photosensitivity.
Pseudoporphyria, toxic epidermal necrolysis, and multifocal facial squamous cell carcinomas have also been reported.
Use of sunscreen is advised, and appropriate guidance for sun exposure avoidance should be given in chronically treated patients.
Q-Tc prolongation and torsades de pointes should be a consideration in patients with predisposing factors.
Acutely painful extremities and peripheral neuropathy have been described.
With continued use may be associated with bone pain or swelling.
Fluoride is a constituent of voriconazole and long-term use can lead to high fluoride concentrations in serum and plasma.
The prescribing information for voriconazole advises discontinuation of voriconazole if skeletal fluorosis or periostitis develops.
Teratogenic in animals and should not be used during pregnancy (class D).
Its efficacy of voriconazole for the treatment of esophageal candidiasis compared with fluconazole was evaluated by a large, randomized, double-blind, multicenter trial in immunocompromised patients, at a dose of 200 mg twice daily was as effective as fluconazole but was associated with more adverse event-related discontinuation of treatment.
This dose is also indicated for the treatment of candidemia and other deep Candida infections in nonneutropenic patients.