Magazine article Drug Topics

Health-System Edition: P&T Portfolio

Magazine article Drug Topics

Health-System Edition: P&T Portfolio

Article excerpt

Generic name

Voriconazole

Proprietary name/manufacturer

Vfend/Pfizer

FDA-approved indication

Treatment of invasive aspergillosis; treatment of serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani in patients intolerant of, or refractory to, other therapy

Pharmacology

Voriconazole is a broad-spectrum triazole antifungal agent. Its primary mechanism of action is the inhibition of fungal cytochrome P450-dependent ergosterol synthesis mediated via 14-alpha-sterol demethylase. The accumulation of 14-alpha-methyl sterols correlates with the subsequent reduction of normal ergosterol in the fungal cell wall and may be responsible for the antifungal activity of voriconazole.

Efficacy

A limited number of clinical trials and case reports demonstrated that voriconazole is effective for the primary therapy of invasive aspergillosis and for the treatment of patients with invasive aspergillosis who were refractory to, or intolerant of, other antifungal therapy. Voriconazole appears to be more effective than conventional amphotericin B in the treatment of acute invasive aspergillosis, but comparative studies with other antifungal agents are not available. Pooled analyses of patient study data also indicate that voriconazole is effective against additional fungal pathogens, including Scedosporium apiospermum and Fusarium spp., with response rates of 63% (15/24) and 43% (9/21), respectively.

Pharmacokinetics

Contraindications

*Hypersensitivity to voriconazole or its excipients

*Coadministration of the CYP3A4 substrates, terfenadine, astemizole, cisapride, pimozide, or quinidine, which can lead to QT prolongation and rare occurrences of torsade de pointes

*Coadministration with sirolimus, which can cause a significant increase in sirolimus concentrations

*Coadministration with rifampin, carbamazepine, and long-acting barbiturates, which can significantly decrease plasma voriconazole concentrations

*Coadministration with rifabutin, which can significantly increase rifabutin plasma concentrations and significantly decrease voriconazole plasma concentrations

* Coadministration with ergot alkaloids (ergotamine and dihydroergotamine), which can lead to ergotism

Warnings

* Accumulation of the intravenous vehicle, SBECD, may occur in patients with renal dysfunction; oral voriconazole is preferred.

*Dosage adjustment is required in patients with hepatic insufficiency. …

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