Progil^®

Progil^® is the preparation of Voriconazole which is a broad spectrum, triazole systemic antifungal agent. The primary mode of action of Voriconazole is the inhibition of fungal cytochrome P-450 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.

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Progil® is indicated for the treatment of following fungal infections-

• Invasive aspergillosis
• Candidemia (non-neutropenics) and disseminated candidiasis in skin, abdomen, kidney, bladder wall and wounds
• Esophageal candidiasis
• Serious infections caused by Scedosporium apiospermum and Fusarium species including Fusarium solani, in patients intolerant of or refractory to other therapy

Route of administration: Progil^® tablet and powder for suspension should be taken orally at least one hour before or one hour following a meal.

• At or over 40 kg body weight: Loading dose regimen is 400 mg or 10 ml every 12 hours (for the first 24 hours) and maintenance dose (after first 24 hours) is 200 mg or 5 ml twice daily.

. Below 40 kg body weight: Loading dose regimen is 200 mg or 5 ml every 12 hours (for the first 24 hours) and maintenance dose (after first 24 hours) is 100 mg or 2.5 ml twice daily or as directed by the registered physician.

Direction of preparation for suspension: Shake the bottle well before mixing the water. To prepare 40 ml suspension add 25 ml (5 teaspoonfuls) boiled and cooled water in two portions and shake well after each addition till powder is completely mixed with water. After reconstitution, store below 30°C and discard unused portion after 14 days. Use the supplied spoon for water measurement.

Pregnancy: There are no adequate and well-controlled studies in pregnant women. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is not known whether it is excreted in human milk. So a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Use in children and adolescents

Safety and effectiveness of voriconazole have not been established in pediatric patients below the age of 2 years.

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 (SCC) of the skin 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.

The most common side effects of voriconazole are abdominal pain, anaemia, blurred vision, headache, chest pain, nausea and diarrhea.

Voriconazole is contraindicated in patient with known history of hypersensitivity to voriconazole or any other components of this product. Co-administration with terfenadine, astemizole, cisapride, pimozide or quinidine, sirolimus is also contraindicated due to risk of serious adverse reactions. Co-administration with rifampin, carbamazepine, long-acting barbiturates, efavirenz, ritonavir, rifabutin, ergot alkaloids and St. John's Wort is also contraindicated due to risk of loss of efficacy.

Drug interaction with medication

• 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 doses of these other drugs and monitor for adverse reactions.

■ Phenytoin or efavirenz: With co-administration, increase maintenance dosage of voriconazole.

Drug interaction with food and others: Not applicable.

In clinical trials there were 3 cases of accidental overdose. All occurred in pediatric 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.

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Storage

Store Progil^® tablet in a cool (below 30°C) and dry place protected from light. Store Progil^® powder for suspension in a refrigerator at 2°C-8°C, protected from light. Keep away from the reach of children.

Packing

Progil^® 50 tablet: Carton of 20 tablets in blister pack.

Progil^® 200 tablet: Carton of 10 tablets in blister pack.

Progil^® powder for suspension: Each bottle contains 40 ml powder for suspension.