Vorzol IV® 200 mg Solution

VORZOL IV is a broad spectrum triazole antifungal medicine. The primary mode of action of voriconazole is the inhibition of fungal cytochrome P450 - mediated 14 alpha - lanosterol demethylation, an essential step in fungal ergosterol biosynthesis. The accumulation of 14 alpha - methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell membrane and may be responsible for the antifungal activity of voriconazole.

VORZOL IV is indicated for:

• Treatment of invasive aspergillosis.
• Treatment of serious invasive infections caused by Candida spp. (including C. krusei).
• Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp.
• Prevention of breakthrough of fungal infections in febrile high-risk patients (allogeneic bone marrow transplants, relapsed leukaemia patients) where liposomal amphotericin B cannot be used.

Contraindications

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
• Co-administration of the CYP3A4 substrates, terfenadine, astemizole, cisapride, pimozide, quinidine or ivabradine with VORZOL IV is contraindicated since increased plasma concentrations of these medicinal products can lead to QTc prolongation and occurrences of Torsades de pointes (see section 4.5).
• Co-administration of VORZOL IV with rifampicin, carbamazepine and phenobarbital is contraindicated, since these medicinal products are likely to decrease plasma voriconazole concentrations significantly (see section 4.5).
• Co-administration of standard doses of voriconazole with efavirenz doses of 400 mg once daily or higher is contraindicated, because efavirenz significantly decreases plasma voriconazole concentrations in healthy subjects.
• Co-administration of VORZOL IV with high dose ritonavir (400 mg and above twice daily) is contraindicated because ritonavir significantly decreased plasma VORZOL IV concentrations in healthy subjects at this dose (see section 4.5).

Warnings and precautions

Women of child-bearing potential must always use effective contraception during treatment. Caution should be used in prescribing VORZOL IV to patients with hypersensitivity to other azoles (see also section 4.8).

It is recommended that VORZOL IV be administered at a maximum rate of 3 mg/kg per hour over 1 to 2 hours. For reconstitution directions refer to section 6.6: Special precautions for disposal and other handling.

Dosage adjustment

If patient response is inadequate, the maintenance dose may be increased to 4 mg/kg every 12 hours for intravenous administration. If patients are unable to tolerate treatment at these higher doses, reduce the intravenous dose to the original maintenance dose, 3 mg/kg every 12 hours.

Summary of safety profile

The safety profile of voriconazole in adults is based on an integrated safety database of patients who participated in clinical trials. The most commonly reported adverse reactions were visual impairment, pyrexia, rash, vomiting, nausea, diarrhoea, headache, peripheral oedema, liver function test abnormal, respiratory distress and abdominal pain. The severity of the adverse reactions was generally mild to moderate.

Tabulated list of adverse reactions

Undesirable effects reported in subjects receiving voriconazole:

• Visual impairment
• QT prolongation
• Hepatic failure

Store below 30 °C. Do not freeze. Keep the vial in the outer carton in order to protect from light.

For storage conditions after reconstitution of the medicinal product, see section 6.3.