Voriconazole

Voriconazole is a broad-spectrum triazole antifungal agent used to treat serious fungal infections. It works by inhibiting fungal lanosterol 14-α-demethylase (ERG11), an enzyme in the ergosterol synthesis pathway. Inhibition of ergosterol production disrupts fungal cell membranes and impairs growth, providing a fungistatic or fungicidal effect depending on the organism and drug exposure.

The drug has activity against a range of fungi, most notably Aspergillus species and many Candida species, and it also shows activity against some Fusarium and Scedosporium species. Activity against Zygomycetes is limited, and voriconazole is not the preferred agent for mucormycosis. Clinically, it is indicated for invasive aspergillosis and other serious fungal infections when alternatives are unsuitable, including esophageal candidiasis and certain mold infections. It is also used as prophylaxis in high-risk immunocompromised patients in some settings, depending on local guidelines.

Pharmacokinetically, voriconazole is well absorbed orally with high bioavailability and can be given by IV or oral administration with generally comparable systemic exposure. It is extensively metabolized in the liver by cytochrome P450 enzymes, particularly CYP2C19, with contributions from CYP2C9 and CYP3A4. Genetic polymorphisms in CYP2C19 can cause marked interindividual variability in drug levels. Because of its metabolism, voriconazole has numerous potential drug interactions with CYP inhibitors or inducers. It is not primarily cleared renally, and dose adjustments are usually guided by hepatic function rather than renal function.

Common adverse effects include hepatotoxicity, visual disturbances (such as blurred vision and photophobia), and central nervous system effects (headache, confusion, or hallucinations). Other possible effects are rash and photosensitivity with prolonged use. Monitoring of liver function, consideration of drug interactions, and, where available, therapeutic drug monitoring are recommended to maintain efficacy while minimizing toxicity.