Voriderm 200 Tablet

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

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. Voriconazole has been shown to be more selective for fungal cytochrome P-450 enzymes than for various mammalian cytochrome P-450 enzyme systems.

Oral-
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.

Injection-
Invasive Aspergillosisd :

• Loading dose: 6 mg/kg 12 hourly for the first 24 hours.
• Maintenance Dose: 4 mg/kg 12 hourly.

Candidemia in nonneutropenic patients and other deep tissue Candida infections:

• Loading dose: 6 mg/kg 12 hourly for the first 24 hours.
• Maintenance Dose: 3-4 mg/kg 12 hourly.

Scedosporiosis and Fusariosis:

• Loading dose: 6 mg/kg 12 hourly for the first 24 hours.
• Maintenance Dose: 4 mg/kg 12 hourly.

Voriconazole film-coated tablets are to be taken at least one hour before, or one hour following a meal. 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).

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.

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. The excretion of voriconazole into breast milk has not been investigated. Breast-feeding must be stopped on initiation of treatment with voriconazole.

Elderly: No dose adjustment is necessary for elderly patients.

Paediatric population: The safety and efficacy of Voriconazole in children below 2 years has not been established.

Renal impairment: The pharmacokinetics of orally administered voriconazole are not affected by renal impairment. Therefore, no adjustment is necessary for oral dosing for patients with mild to severe renal impairment. Voriconazole is haemodialysed with a clearance of 121 ml/min. A 4- hour haemodialysis session does not remove a sufficient amount of voriconazole to warrant dose adjustment.

Hepatic impairment: It is recommended that the standard loading dose regimens be used but that the maintenance dose be halved in patients with mild to moderate hepatic cirrhosis (Child-Pugh A and B) receiving voriconazole. Voriconazole has not been studied in patients with severe chronic hepatic cirrhosis (Child-Pugh C). There is limited data on the safety of Voriconazole in patients with abnormal Liver Function Tests (aspartate transaminase [AST], alanine transaminase [ALT], alkaline phosphatase [ALP], or total bilirubin >5 times the upper limit of normal). Voriconazole has been associated with elevations in liver function tests and clinical signs of liver damage, such as jaundice, and must only be used in patients with severe hepatic impairment if the benefit outweighs the potential risk. Patients with severe hepatic impairment must be carefully monitored for drug toxicity.

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

Keep below 30°C temperature, away from light & moisture. Keep out of the reach of children.