Accolate ZafirlukastTabs 20MG
dults 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 zafirlukast, Accolate should not be taken with meals.
The clearance of zafirlukast is reduced in elderly patients (> 65 years old), such that Cmax and AUC are approximately twice those of younger adults. However, accumulation of Accolate is not evident in elderly patients. In clinical trials, elderly patients receiving a dose of 20 mg twice daily were not associated with an increase in the overall incidence of adverse events or withdrawals because of adverse events. Therapy may be initiated at 20 mg twice daily and adjusted according to clinical response.
There is no clinical experience of the use of Accolate in children under 12 years of age.
Until safety information is available, the use of Accolate in children is contraindicated.
Experience is limited in patients with mild to severe renal impairment (see section 5.2) so clear dose recommendations cannot be given; therefore Accolate should be used with caution in this patient group.
Accolate should not be given to patients who have previously experienced hypersensitivity to the product or any of its ingredients.
Accolate 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.
Accolate is contraindicated in children under 12 years of age until safety information is available.
4.4 Special warnings and precautions for use
Accolate should be taken regularly to achieve benefit, even during symptom free periods. Accolate therapy should normally be continued during acute exacerbations of asthma.
As with inhaled steroids and cromones (disodium cromoglycate, nedocromil sodium), Accolate is not indicated for use in the reversal of bronchospasm in acute asthma attacks.
Accolate has not been evaluated in the treatment of labile (brittle) or unstable asthma. Inhaled and oral corticosteroids should not be stopped abruptly after initiation of Accolate.
Rarely, patients with asthma on anti-leukotriene medications, including Accolate, may present with systemic eosinophilia, eosinophilic pneumonia or with clinical features of systemic vasculitis, consistent with Churg-Strauss syndrome. Presentations may involve various body systems including vasculitic rash, worsening pulmonary symptoms, cardiac complications or neuropathy. These events have usually, but not always, been associated with reductions and/or withdrawal of steroid therapy. The possibility that leukotriene receptor antagonists, including Accolate, may be associated with emergence of Churg-Strauss syndrome can neither be excluded nor established. If a patient develops an eosinophilic condition, or a Churg-Strauss Syndrome type illness, Accolate should be stopped. A rechallenge test should not be performed and treatment should not be restarted.
Elevations in serum transaminases can occur during treatment with Accolate. These are usually asymptomatic and transient but could represent early evidence of hepatotoxicity, and have very rarely been associated with more severe hepatocellular injury, fulminant hepatitis and liver failure, some of which resulted in a fatal outcome. Extremely rarely, cases of fulminant hepatitis and liver failure have been reported in patients in whom no previous clinical signs or symptoms suggestive of liver dysfunction were reported (see also section 4.8).
If clinical symptoms or signs suggestive of liver dysfunction occur (e.g. anorexia, nausea, vomiting, right upper quadrant pain, fatigue, lethargy, flu-like symptoms, enlarged liver, pruritus and jaundice), Accolate should be discontinued. The serum transaminases, in particular serum ALT, should be measured immediately and the patient managed accordingly.
Physicians may consider the value of routine liver function testing. Periodic serum transaminase testing has not proven to prevent serious injury but is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug may enhance the likelihood of recovery. If liver function testing shows evidence of hepatotoxicity Accolate should be discontinued immediately and the patient managed accordingly.
Patients in whom Accolate was withdrawn because of hepatotoxicity should not be re-exposed to Accolate.
Accolate 20 mg contains 45 mg lactose monohydrate in each tablet. Patients with rare hereditary problems of galactose intolerance, the Lapp Lactase deficiency or glucose-galactose malabsorption, should not take this medicine.
4.5 Interaction with other medicinal products and other forms of interaction
Accolate 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 Accolate without adverse interaction.
Accolate 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 Accolate is co-administered with warfarin, prothrombin time should be closely monitored. The interaction is probably due to an inhibition by zafirlukast of the cytochrome P450 2C9 isoenzyme system.
In clinical trials co-administration with theophylline resulted in decreased plasma levels of zafirlukast, by approximately 30%, but with no effect on plasma theophylline levels. However, during post-marketing surveillance, there have been rare cases of patients experiencing increased theophylline levels when co-administered Accolate.
Co-administration with terfenadine resulted in a 54% decrease in AUC for zafirlukast, but with no effect on plasma terfenadine levels.
Co-administration with acetylsalicylic acid ("aspirin", 650 mg four times a day) may result in increased plasma levels of zafirlukast, by approximately 45%.
Co-administration with erythromycin will result in decreased plasma levels of zafirlukast, by approximately 40%.
Co-administration with fluconazole, a moderate CYP2C9 inhibitor, resulted in increased plasma levels of zafirlukast, by approximately 60%. The clinical significance of this interaction is unknown.
Co-administration with itraconazole, a strong CYP3A4 inhibitor, caused no change in plasma levels of zafirlukast.
The clearance of zafirlukast in smokers may be increased by approximately 20%.
At concentrations of 10 microgram/ml and above, zafirlukast causes increases in the assay value for bilirubin in animal plasma. However, zafirlukast has not been shown to interfere with the 2,5-dichlorophenyl diazonium salt method of bilirubin analysis of human plasma.
4.6 Pregnancy and lactation
The safety of Accolate in human pregnancy has not been established. In animal studies, zafirlukast 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 Accolate should be used during pregnancy only if clearly needed.
Zafirlukast is excreted in human breast milk. Accolate should not be administered to mothers who are breast-feeding.
4.7 Effects on ability to drive and use machines
There is no evidence that Accolate affects the ability to drive and use machinery.
Accolate ZafirlukastTabs 20MG
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