VORCON

What it is

Vorcon is voriconazole, available as tablets and intravenous powder for injection. The tablet formulation is supplied in 50 mg and 200 mg strengths. The intravenous formulation is supplied as 200 mg powder for injection.

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

Therapy must be initiated with a specified loading dose regimen of either intravenous or oral Vorcon 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. Dosing varies by indication and patient weight. Intravenous administration is not recommended for the treatment of oesophageal candidiasis. For oesophageal candidiasis, the oral loading dose is 400 mg every 12 hours for the first 24 hours (or 200 mg every 12 hours for patients weighing less than 40 kg), with maintenance dosing of 200 mg twice daily (or 100 mg twice daily for patients less than 40 kg). For indications other than oesophageal candidiasis, the intravenous loading dose is 6 mg/kg every 12 hours for the first 24 hours, with maintenance dosing of 3 mg/kg every 12 hours for serious Candida infections and 4 mg/kg every 12 hours for invasive aspergillosis and other serious mould infections. The oral loading dose is 400 mg every 12 hours (or 200 mg every 12 hours for patients less than 40 kg), with maintenance dosing of 200 mg twice daily (or 100 mg twice daily for patients less than 40 kg). Oral tablets must be taken at least one hour before, or one hour following, a meal. The intravenous formulation is administered at a maximum rate of 3 mg/kg per hour over 1 to 2 hours.

Key safety warnings

Voriconazole has been associated with QT interval prolongation, and 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. Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected, if necessary, 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, which can be life-threatening or fatal, have been reported with voriconazole use. If a patient develops a suspected severe cutaneous adverse reaction, voriconazole should be discontinued immediately and an alternative treatment should be considered. Patients, including children, should avoid exposure to direct sunlight during voriconazole treatment and use measures such as protective clothing and sunscreen with high sun protection factor. Cases of serious hepatic reactions including clinical hepatitis, cholestasis and fulminant hepatic failure have been reported, occurring primarily in patients with serious underlying medical conditions (predominantly haematological malignancy), although transient hepatic reactions have occurred in patients with no other identifiable risk factors. Liver dysfunction has usually been reversible on discontinuation of therapy. Laboratory evaluation of hepatic function (specifically AST and ALT) is recommended at the initiation of treatment and at least weekly for the first month of treatment. If treatment is continued, monitoring frequency can be reduced to monthly if there are no changes in the liver function tests. In patients with photosensitivity skin reactions and additional risk factors (including immunosuppression), squamous cell carcinoma of the skin (including cutaneous squamous cell carcinoma in situ, or Bowen's disease) and melanoma have been reported during long-term therapy.

Contraindications

Vorcon 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. These include terfenadine, pimozide, lurasidone, quinidine, ivabradine, ergot alkaloids, sirolimus, naloxegol, tolvaptan, finerenone, eplerenone, voclosporin, and venetoclax (at initiation and during dose titration phase). Coadministration of voriconazole is contraindicated with medicinal products that induce CYP450 and significantly reduce plasma concentrations of voriconazole: rifabutin, rifampicin, carbamazepine and 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.

Regulatory history

Vorcon voriconazole 200 mg tablets, 50 mg tablets, and 200 mg powder for injection were first registered on the ARTG on 27 July 2016.