VIERA

VORICONAZOLE

Voriconazole is a broad-spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows: Treatment of invasive aspergillosis. Treatment of candidaemia in non-neutropenic patients. Treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei). Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp. Voriconazole should be administered primarily to patients with progressive, possibly life-threatening infections. Prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (HSCT) recipients.

Other Antifungal preparations

Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine. Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine. Inhibition of these enzyme systems reduces the rate of digestion of complex carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in hemoglobin-A1c level.

Therapy must be initiated with the specified loading dose regimen of either intravenous or oral voriconazole 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. Detailed information on dosage recommendations is provided in the following table: Loading dose regimen (first 24 hours)- Patients 40 kg and above: 400 mg every 12 hours Patients less than 40 kg: 200 mg every 12 hours Maintenance dose (after first 24 hours)- Patients 40 kg and above: 200 mg twice daily Patients less than 40 kg: 100 mg twice daily.Method of Administration: Voriconazole film-coated tablets are to be taken at least one hour before, or one hour following a meal. Duration of treatment: Treatment duration should be as short as possible depending on the patient's clinical and mycological response. Long term exposure to voriconazole greater than 180 days (6 months) requires careful assessment of the benefit risk balance. Prophylaxis in adults and children Prophylaxis should be initiated on the day of transplant and may be administered for up to 100 days. Prophylaxis should be as short as possible depending on the risk for developing invasive fungal infection (IFI) as defined by neutropenia or immunosuppression. It may only be continued up to 180 days after transplantation in case of continuing immunosuppression or graft versus host disease (GvHD).

CYP3A4, CYP2C9 and CYP2C19 inhibitors and inducers: Adjust Voriconazole dosage and monitor for adverse reactions or lack of efficacy. Voriconazole may increase the concentrations and activity of drugs that are CYP3A4, CYP2C9 and CYP2C19 substrates. Reduce dosage of these other drugs and monitor for adverse reactions. Phenytoin or Efavirenz: with co-administration, increase maintenance oral and intravenous dosage of Voriconazole.

Voriconazole is contraindicated in patients with known hypersensitivity to the drug or other azoles.

Most common adverse reactions: visual disturbances, fever, nausea, rash, vomiting, chills, headache, liver function test abnormal, tachycardia, hallucinations.

Pregnancy: There are no adequate data on the use of voriconazole in pregnant women available. Voriconazole must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus. Lactation: The excretion of voriconazole into breast milk has not been investigated. Breast-feeding must be stopped on initiation of treatment with voriconazole.

In clinical trials there were 3 cases of accidental overdose. All occurred in paediatric patients, who received up to five times the recommended intravenous dose of voriconazole. A single adverse reaction of photophobia of 10 minutes duration was reported. There is no known antidote to voriconazole. Voriconazole is haemodialysed with a clearance of 121 ml/min. The intravenous vehicle, SBECD, is haemodialysed with a clearance of 55 ml/min. In an overdose, haemodialysis may assist in the removal of voriconazole and SBECD from the body

Long-term treatment: Long term exposure (treatment or prophylaxis) greater than 180 days (6 months) requires careful assessment of the benefit-risk balance and physicians should therefore consider the need to limit the exposure to voriconazole. Squamous cell carcinoma of the skin (SCC) has been reported in relation with long-term voriconazole treatment. Non-infectious periostitis with elevated fluoride and alkaline phosphatase levels has been reported in transplant patients. If a patient develops skeletal pain and radiologic findings compatible with periostitis voriconazole discontinuation should be considered after multidisciplinary advice.

Store at temperature not exceeding 308 C in a dry place