VORICONAZOLE SANDOZ

What it is

VORICONAZOLE is an antifungal medicine . Film-coated tablets are available in 50 mg and 200 mg strengths . A powder for injection is supplied as 200 mg vials that, when reconstituted with 19 mL water for injection, contain 10 mg voriconazole per mL . A powder for oral suspension is available, providing 40 mg voriconazole per mL when reconstituted with water .

Approved indications VORICONAZOLE is indicated for treatment of:

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

Dosing overview

Therapy must be initiated with a specified loading dose regimen of either intravenous or oral VORICONAZOLE to achieve plasma concentrations on Day 1 that are close to steady state . Switching between intravenous and oral administration is appropriate when clinically indicated, based on high oral bioavailability of 96% . For oesophageal candidiasis in patients weighing 40 kg or more, the oral 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. Intravenous administration is not recommended for oesophageal candidiasis. For serious *Candida* infections and invasive aspergillosis in adults, the intravenous loading dose is 6 mg/kg every 12 hours for the first 24 hours, with oral loading dose of 400 mg (or 200 mg for patients under 40 kg) every 12 hours. The intravenous maintenance dose is 3 mg/kg every 12 hours for serious *Candida* infections and 4 mg/kg every 12 hours for invasive aspergillosis, *Scedosporium* and *Fusarium* infections. The oral maintenance dose is 200 mg twice daily (or 100 mg twice daily for patients under 40 kg). For prophylaxis, the intravenous loading dose is 6 mg/kg every 12 hours for the first 24 hours, with oral loading not recommended. The intravenous maintenance dose is 4 mg/kg every 12 hours, and the oral maintenance dose is 200 mg every 12 hours (or 100 mg every 12 hours for patients under 40 kg).

Key safety warnings

Voriconazole 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, hypokalaemia and concomitant medications that may have been contributory. Severe cutaneous adverse reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms, which can be life-threatening or fatal, have been reported. If a patient develops a suspected severe cutaneous adverse reaction, voriconazole should be discontinued immediately. Voriconazole has been associated with photosensitivity skin reaction. It is recommended that patients 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, primarily in patients with serious underlying medical conditions. Patients receiving voriconazole must be carefully monitored for hepatic toxicity. Voriconazole 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, and should not drive at night while taking voriconazole.

Contraindications

VORICONAZOLE is contraindicated in patients with known hypersensitivity to voriconazole or to any of the excipients. Coadministration is contraindicated with medicinal products highly dependent on CYP3A4 for metabolism where elevated plasma concentrations are associated with serious or life-threatening reactions, including terfenadine, pimozide, lurasidone, quinidine, ivabradine, ergot alkaloids, sirolimus, naloxegol, tolvaptan, finerenone, eplerenone, voclosporin and venetoclax (at initiation and during dose titration phase). Coadministration 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 of standard doses of voriconazole with efavirenz 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 is available in the provided source documents.

Regulatory history

VORICONAZOLE multiple generic formulations were first listed on the Australian Register of Therapeutic Goods on 22 July 2016, including 50 mg and 200 mg film-coated tablets in blister and bottle packaging from several sponsors (Arrotex Pharmaceuticals, GenPar, GH and GPPL). The powder for injection (200 mg vial) was registered on 16 September 2016, and the powder for oral suspension (40 mg/mL) formulations were registered on 22 March 2019.