Voriconazole

The introduction of voriconazole represented a significant improvement in the treatment of mould infections. It is also a broad-spectrum antifungal like itraconazole, with good activity against  Candida species and many moulds. Unlike itraconazole,  voriconazole is well absorbed and available in both highly bioavailable oral formulations and an IV ad-mixture. Perhaps most important, voriconazole was shown to be superior to amphotericin B deoxy-cholate for invasive aspergillosis and has become the drug of choice for that disease.

Spectrum

Good: Candida albicans, Candida lusitaniae, Candida parapsilosis, Candida tropicalis, Candida krusei, Cryptococcus neoformans, Aspergillus species, many other moulds

Moderate: Candida glabrata (can be susceptible dose-dependent, or resistant), Candida albicans that are fluconazole-resistant, Fusarium species

Poor: Zygomycetes

Adverse Effects

In addition to the hepatotoxicity, rash, and drug interactions that are common with this class, voriconazole has some agent-specific adverse effects worth watching. Visual effects such as seeing wavy lines or flashing are very common and dose-related;  they tend to go away with continued use. Visual hallucinations can also occur but are less common.

Dosing Issues

Voriconazole has highly variable interpatient pharmacokinetics and nonlinear elimination, making it difficult to dose correctly. Some centers monitor voriconazole trough concentrations, but tests are not yet widely available. If you are committing your patient to an extended course of therapy for voriconazole, consider checking a trough.

Important Facts

• Voriconazole is active against many fluconazole-resistant strains of Candida albicans, but it is less active against them than fluconazole-susceptible strains. An echinocandin is a better choice, but consider susceptibility testing if you need to use voriconazole for an oral option.

• Voriconazole is a potent inhibitor and a substrate of the cytochrome P450 system. The list of drugs that interact with voriconazole is long and varied. Some of them are contraindicated,  such as rifampin, while others, such as calcineurin inhibitors (e.g., cyclosporine), require dose adjustments. This is significant, because many of the patients who require voriconazole are immunosuppressed.

• The IV form of voriconazole contains a cyclodextrin vehicle that accumulates in renal dysfunction and may be nephrotoxic. It is contraindicated with a creatinine clearance of less than 50 ml/min. The oral formulations avoid this issue.

• Voriconazole is eliminated hepatically and is un-likely to be useful in the treatment of candiduria.

 What It’s Good For

Voriconazole is the drug of choice for invasive aspergillosis and is frequently used in the treatment of infections caused by other moulds. It can be used for candidiasis as well, but fluconazole and echino-candins are more frequently used for these infections. Some clinicians use voriconazole in the empiric treatment of febrile neutropenia.

Don’t Forget!

Watch for drug interactions with voriconazole, and consider checking drug concentrations if you are using it for an extended course of therapy.

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.