VZOLE

What it is

VZOLE is a medicine containing voriconazole. Film-coated tablets are available in strengths of 50 mg or 200 mg. Powder for oral suspension is also available, which when reconstituted with water contains 40 mg of voriconazole per mL.

Approved indications —

Invasive aspergillosis. — Serious *Candida* infections (including *C. krusei*), including oesophageal and systemic *Candida* infections (hepatosplenic candidiasis, disseminated candidiasis, candidaemia). — Serious fungal infections caused by *Scedosporium spp* and *Fusarium spp*. — Other serious fungal infections, in patients intolerant of, or refractory to, other therapy. — Prophylaxis in patients who are at high risk of developing invasive fungal infections.

Dosing overview

VZOLE therapy must be initiated with a loading dose regimen to achieve plasma concentrations on Day 1 that are close to steady state. Dosing varies by indication and patient weight. For oesophageal candidiasis in patients weighing 40 kg or more, the loading dose is 400 mg every 12 hours for the first 24 hours, followed by a maintenance dose of 200 mg twice daily. For patients weighing less than 40 kg, the loading dose is 200 mg every 12 hours for the first 24 hours, followed by a maintenance dose of 100 mg twice daily. For other indications including invasive aspergillosis and serious *Candida* infections, intravenous loading dose is 6 mg/kg every 12 hours for the first 24 hours, with maintenance doses of 3–4 mg/kg every 12 hours depending on the infection type. Oral maintenance doses are 200 mg twice daily for patients 40 kg or more, and 100 mg twice daily for patients under 40 kg.

Key safety warnings

VZOLE has been associated with QT interval prolongation. Rare cases of *torsades de pointes* have occurred in patients taking voriconazole who had risk factors such as history of cardiotoxic chemotherapy, cardiomyopathy, or hypokalaemia. Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected prior to initiation of and during VZOLE therapy. Severe cutaneous adverse reactions including Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms have been reported with VZOLE use. If a patient develops a suspected severe cutaneous adverse reaction, voriconazole should be discontinued immediately and alternative treatment should be considered. VZOLE has been associated with photosensitivity skin reaction. Patients should avoid exposure to direct sunlight during treatment and use protective clothing and sunscreen with high sun protection factor. Serious hepatic reactions including clinical hepatitis, cholestasis and fulminant hepatic failure have occurred during treatment with VZOLE, primarily in patients with serious underlying medical conditions. Transient hepatic reactions have also occurred in patients with no other identifiable risk factors. Liver function tests should be evaluated at the initiation of treatment and at least weekly for the first month. If treatment continues, monitoring frequency can be reduced to monthly if there are no changes in liver function tests. VZOLE may cause changes to vision, including blurring, altered or enhanced visual perception and photophobia. Patients must avoid potentially hazardous tasks such as driving or operating machinery whilst experiencing these symptoms. Patients should not drive at night while taking VZOLE.

Contraindications

VZOLE is contraindicated in patients with known hypersensitivity to voriconazole or to any of the excipients. Coadministration of VZOLE is contraindicated with medicinal products that are highly dependent on CYP3A4 for metabolism and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions, including terfenadine, pimozide, lurasidone, quinidine, ivabradine, ergot alkaloids, sirolimus, naloxegol, tolvaptan, finerenone, eplerenone, voclosporin, and venetoclax at initiation and during venetoclax dose titration phase. VZOLE is contraindicated with medicinal products that induce CYP3A4 and significantly reduce voriconazole plasma concentrations, including rifabutin, rifampicin, carbamazepine, long-acting barbiturates such as phenobarbital, and St John's Wort. Coadministration with efavirenz at standard doses of 400 mg once daily or higher is contraindicated. Coadministration with high doses of ritonavir (400 mg and higher twice daily) is contraindicated.

PBS listing

No information regarding PBS listing status, item numbers, restriction type or ex-manufacturer price is available in the provided source documents.

Regulatory history

VZOLE film-coated tablets 50 mg and 200 mg were first listed on the Australian Register of Therapeutic Goods on 22 July 2016. Powder for oral suspension 40 mg/mL was first listed on 22 March 2019.