Zafir20 mg

Zafir 20 mg is indicated for the prophylaxis and chronic treatment of asthma in adults and children 5 years of age and older.

Leukotriene receptor antagonists

Zafir 20 mg is a selective and competitive leukotriene-receptor antagonist (LTRA) of leukotriene D4 and E4 (LTD4 and LTE4), components of slow-reacting substance of anaphylaxis (SRSA). Cysteinyl leukotriene production and receptor occupation have been correlated with the pathophysiology of asthma, including airway oedema, smooth muscle constriction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

Zafir 20 mg should be taken continuously. Children under 7 years of age: There is no clinical experience of the use of Zafir 20 mg in children under 7 years of age until safety information is available.Children over 7 years through 11 years of age: The recommended dose of Zafir 20 mg in this age group is 10 mg twice daily.Adult and children aged 12 years and over: The dosage is one 20 mg tablet twice daily. This dosage should not be exceeded. Higher doses may be associated with elevations of one or more liver enzymes consistent with hepatotoxicity. As food may reduce the bioavailability of Zafir 20 mg, Zafir 20 mg should not be taken with mealsElderly: The clearance of Zafir 20 mg is significantly reduced in elderly patients (over 65 years old), and Cmax and AUC are approximately double than those of younger adults. However, accumulation of Zafir 20 mg is not greater than that seen in multiple dose trials conducted in adult subjects with asthma and the consequences of the altered kinetic in the elderly are unknown. Clinical experience with Zafir 20 mg in the elderly (over 65 years) is limited and caution is recommended until further information is available.Renal impairment: No dosage adjustment is necessary in patients with mild renal impairment.

Zafir 20 mg may be administered with other therapies routinely used in the management of asthma and allergy. Inhaled steroids, inhaled and oral bronchodilator therapy, antibiotics and antihistamines are examples of agents which have been co-administered with Zafir 20 mg without adverse interaction.Zafir 20 mg may be administered with oral contraceptives without adverse interaction. Co-administration with Warfarin results in an increase in maximum prothrombin time by approximately 35%. It is therefore recommended that if Zafir 20 mg is co-administered with Warfarin, prothrombin time should be closely monitored. The interaction is probably due to an inhibition by Zafir 20 mg of the cytochrome P450 2C9 enzyme system. In clinical trials co-administration with Theophylline resulted in decreased plasma levels of Zafir 20 mg, by approximately 30%, but with no effect on plasma Theophylline levels. However, during postmarketing surveillance, there have been rare cases of patients experiencing increased Theophylline levels when co-administered with Zafir 20 mg.Co-administration with Terfenadine resulted in a 54% decrease in AUC for Zafir 20 mg, but with no effect on plasma Terfenadine levels. Coadministration with Acetylsalicylic acid (650 mg four times a day) may result in increased plasma levels of Zafir 20 mg, by approximately 45%.Co-administration with Erythromycin will result in decreased plasma levels of Zafir 20 mg, by approximately 40%. The clearance of Zafir 20 mg in smokers may be increased by approximately 20%

Zafir 20 mg should not be given to patients who have previously experienced hypersensitivity to the product or any of its ingredients. Zafir 20 mg is contraindicated in patients with a history of moderate or severe renal impairment. Zafir 20 mg is contraindicated in patients with hepatic impairment or cirrhosis; it has not been studied in patients with hepatitis or in long term studies of patients with cirrhosis. Zafir 20 mg is contraindicated in children under 7 years of age until safety information is available.

Effect on ability to drive or operate machinery: There is no evidence that Zafir 20 mg affects the ability to drive and use machinery. Administration of Zafir 20 mg in clinical trials against placebo has been associated with headache (9.9% vs. 9.0%) or gastrointestinal disturbance (nausea 2.6% vs. 2.2%, vomiting 1.2% vs. 1.0%, diarrhoea 2.3% vs. 1.8%, abdominal pain 1.6% vs. 1.2%). These symptoms are usually mild and do not necessitate withdrawal from therapy. During post-marketing experience, bruising, bleeding disorders, including menorrhagia (rare), thrombocytopaenia and agranulocytosis (very rare) have also been reported.Hypersensitivity reactions, including urticaria and angio-oedema have been reported. Rashes, including blistering, have also been reported. The above events have usually resolved during continued treatment or following cessation of therapy. Infrequently, elevated serum transaminase levels have been observed in clinical trials against placebo with Zafir 20 mg (increased AST 1.0% vs. 0.9%, increased AST 0.6% vs. 0.6%); at recommended doses the incidence was equivalent to placebo. Rarely the transaminase profile has been consistent with drug-induced hepatitis, which resolved following cessation of Zafir 20 mg therapy. During post-marketing experience there have been rare reports of hepatitis, with or without elevated bilirubin levels. These cases were usually reversible.In placebo controlled clinical trials, an increased incidence of infection has been observed in elderly patients given Zafir 20 mg (7.8% vs. 1.4%). Infections were usually mild, predominantly affecting the respiratory tract.

Pregnancy: The safety of Zafir 20 mg in human pregnancy has not been established. In animal studies, Zafir 20 mg did not have any apparent effect on fertility and did not appear to have any teratogenic or selective toxic effect on the foetus. The potential risks should be weighed against the benefits of continuing therapy during pregnancy and Zafir 20 mg should be used during pregnancy only if clearly needed.Lactation: Zafir 20 mg is excreted in human breast milk. Zafir 20 mg should not be administered to nursing mothers.

Zafir 20 mg should be taken regularly to achieve benefit, even during symptom free periods. Zafir 20 mg therapy should normally be continued during acute exacerbations of asthma. Zafir 20 mg does not allow a reduction in existing steroid treatment. As with inhaled steroids and hormones (disodium cromoglycate, nedocromil sodium), Zafir 20 mg is not indicated for use in the reversal of bronchospasm in acute asthma attacks. Zafir 20 mg has not been evaluated in the treatment of labile (brittle) or unstable asthma.Cases of Churg Strauss syndrome have been reported in association with Zafir 20 mg usage. A causal relationship has neither been confirmed nor refuted. If a patient develops a Churg Strauss syndrome type illness, Zafir 20 mg should be stopped, a re-challenge test should not be performed and treatment should not be restarted.Elevations in serum transaminases can occur during treatment with Zafir 20 mg. These are usually asymptomatic and transient but could represent early evidence of hepatotoxicity.If clinical symptoms or signs suggestive of liver dysfunction occur (e.g., nausea, vomiting, right upper quadrant pain, fatigue, lethargy, flu-like symptoms, enlarged liver, pruritus and jaundice), the serum transaminases, in particular serum ALT, should be measured and the patient managed accordingly. A decision to discontinue Zafir 20 mg should be individualized to the patient’s condition, weighing the risk of hepatic dysfunction against the clinical benefit of Zafir 20 mg to the patient.

Store between 20-25° C. Protect from light and moisture.