VFEND

What it is

VFEND is voriconazole , an antifungal medicine. Film-coated tablets contain 50 mg or 200 mg of voriconazole. The powder for injection contains 200 mg voriconazole per vial and, after reconstitution with 19 mL water for injection, contains 10 mg of voriconazole per mL. The powder for oral suspension contains 40 mg of voriconazole per mL when reconstituted with water.

Approved indications

VFEND is indicated for treatment of 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; and prophylaxis in patients who are at high risk of developing invasive fungal infections.

Dosing overview

Therapy must be initiated with the specified loading dose regimen of either intravenous or oral VFEND to achieve plasma concentrations on Day 1 that are close to steady state. On the basis of the high oral bioavailability (96%), switching between intravenous and oral administration is appropriate when clinically indicated. Intravenous administration is not recommended for the treatment of oesophageal candidiasis. Adolescents aged 12 to 16 years should be dosed as adults. Voriconazole is not recommended for children less than 2 years of age.

Key safety warnings

Voriconazole has been associated with QT interval prolongation, and there have been rare cases of torsades de pointes in patients who had risk factors such as history of cardiotoxic chemotherapy, cardiomyopathy, hypokalaemia and concomitant medications that may have been contributory. Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected prior to initiation of and during voriconazole therapy. Severe cutaneous adverse reactions such as Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms have been reported with voriconazole, and if a patient develops a suspected reaction, voriconazole should be discontinued immediately and an alternative treatment should be considered. Voriconazole has been associated with photosensitivity skin reaction, and 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 been reported during treatment, primarily in patients with serious underlying medical conditions such as haematological malignancy, and transient hepatic reactions have occurred among patients with no other identifiable risk factors. Laboratory evaluation of hepatic function (specifically AST and ALT) should be performed at the initiation of treatment and at least weekly for the first month of treatment, and if treatment is continued, monitoring frequency can be reduced to monthly if there are no changes in the liver function tests. Anaphylactoid-type reactions including flushing, fever, sweating, tachycardia, chest tightness, dyspnoea, faintness, nausea, pruritus and rash have occurred during administration of the intravenous formulation, and depending on the severity of symptoms, consideration should be given to stopping treatment.

Contraindications

VFEND is contraindicated in patients with known hypersensitivity to voriconazole or to any of the excipients. Coadministration of voriconazole 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 (contraindicated at initiation and during venetoclax dose titration phase). Coadministration is contraindicated with medicinal products that induce CYP3A4 and significantly reduce plasma concentrations of voriconazole, including rifabutin, rifampicin, carbamazepine, long-acting barbiturates (including 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

VFEND powder for oral suspension 40 mg per mL is listed on the PBS in 70 mL bottles with authority required restriction and an ex-manufacturer price of A$439.14.

Regulatory history

VFEND voriconazole tablets (50 mg and 200 mg) and powder for injection (200 mg) were first registered on the ARTG on 3 September 2002. VFEND powder for oral suspension (40 mg/mL) was registered on the ARTG on 9 January 2004.