Voriconazole

Author: Vanessa Ngan, Staff Writer, 2005.

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.

Pharmacokinetics of voriconazole

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 blood stream) 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.

Dose regime for voriconazole

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.

How to take voriconazole

Side effects of voriconazole

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.

Drug interactions with voriconazole

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.

The following table list drug interactions with voriconazole and appropriate measures to take when administering medications concomitantly.

Contraindications (do not take with voriconazole)Adjust dose of voriconazoleAdjust dose and/or monitor other drugsNo dose adjustment of voriconazole or other drug required
Rifampicin
Sirolimus
Long acting barbiturates
Carbamazepine
Astemizole
Cisapride
Terfenadine
Pimozide
Quinidine
Ergot alkaloids
Ritonavir
Efavirenz
Phenytoin
Rifabutin
Ciclosporin
Tacrolimus
Omeprazole
Warfarin
Phenytoin
Sulphonylureas
Rifabutin
Statins
Benzodiazepines
Vinca alkaloids
Nevirapine
HIV protease inhibitors (excluding indinavir and ritonavir)
Indinavir
Mycophenolate mofetil
Cimetidine
Ranitidine
Macrolides eg erythromycin
Prednis(ol)one
Digoxin
New Zealand approved datasheets are the official source of information for these prescription medicines, including approved uses and risk information. Check the individual New Zealand datasheet on the Medsafe website.

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