Pharmacokinetics Dose regime Administration Side-effects Drug interactions Drug resistance
Voriconazole is a triazole medicine used to treat fungal infections. It is effective against a broad spectrum of fungi and is usually reserved for the treatment of serious Candida and mould infections. It is indicated for the treatment of the following infections:
In New Zealand, voriconazole is available as 50 mg and 200 mg tablets, 45 g bottle of powder to make a 40 mg/ml oral suspension, and as 200 mg lyophilised powder for intravenous injection. The trade name for voriconazole is VFEND® and is only available with a doctor’s prescription.
Voriconazole binds to the fungal p450 enzymes and stops the cells making ergosterol, the main component of the cell wall.
Voriconazole is rapidly and almost completely absorbed following oral administration. It is widely distributed in body tissues. The terminal half-life (for half of the medication to be cleared from the bloodstream) of voriconazole is dose-dependent and is approximately 6 hours for a 200 mg oral dose. Because of non-linear pharmacokinetics, the terminal half-life is not useful in the prediction of accumulation or elimination of voriconazole. Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.
Intravenous or oral administration can be given to treat fluconazole-resistant serious invasive Candida infections, invasive aspergillosis, Scedosporium and Fusarium infections and other serious fungal infections. The recommended adult dose is:
Oesophageal candidiasis is normally treated with oral voriconazole using the same oral doses as for other infections above.
If clinical response is inadequate, the oral maintenance dose may be increased to 300 mg twice daily in patients > 40 kg and 150 mg twice daily in patients < 40 kg.
The dosage for children aged 2 to < 12 years is 6 mg/kg every 12 hr (for first 24 hr) followed by 4 mg/kg every 12 hr administered either intravenously or orally.
The more common side effects of voriconazole are usually mild and short-lived. These include:
An increased risk of squamous cell carcinoma has been reported in patients taking voriconazole long term. This is of particular concern in patients at high risk of squamous cell carcinoma, such as elderly white-skinned persons that are immune suppressed (eg, organ transplant recipients).
If any of the following serious side effects occur, voriconazole should be stopped and emergency medical attention sought immediately:
Voriconazole should not be taken in pregnancy except in patients with severe or potentially life-threatening fungal infections and the benefit to the mother clearly outweighs the potential risk to the fetus. Use during breast-feeding is not generally recommended, as it is not known whether voriconazole is excreted in breast milk.
Voriconazole is known to interact with many other medications. Voriconazole is metabolised by cytochrome P450 isoenzymes, hence inhibitors or inducers of these isoenzymes may increase or decrease voriconazole plasma concentrations, respectively. Voriconazole also inhibits cytochrome P450 isoenzyme activity and has the potential to increase the plasma level of drugs also metabolised by these isoenzymes.
Contraindications (do not take with voriconazole)
Adjust dose of voriconazole
Adjust the dose of voriconazole and/or monitor other drugs
No dose adjustment of voriconazole or other drug required
In recent years, both topical and oral allylamine and triazole antifungal drug resistance has become a problem, particularly in the Indian subcontinent.
Extensive therapy-resistant dermatophyte infection should prompt this as a possible problem. Where available, fungal culture and estimation of drug minimum inhibitory concentration determined to guide appropriate medication
For more information, see antifungal drug resistance.
