Accolate - International abbreviated prescribing information

International abbreviated prescribing information

Accolate™ tablets, 10 mg, 20 mg and 40 mg

See local Prescribing Information for full details, as Prescribing Information may vary from country to country.

Indications: Prophylaxis and chronic treatment of asthma

Dosage: Adults and children 12 years of age and older, 20 mg twice daily. Additional benefit may be gained by increasing the dose up to a maximum of 40 mg twice daily. The maximum recommended dose should not be exceeded.

Children 5 - 11 years 10 mg twice daily.

Should not be taken with meals.

Contraindications: Hypersensitivity to the product or any of its ingredients.

Warnings and precautions: Should be taken regularly and normally be continued during acute exacerbations of asthma. ACCOLATE is not indicated for use in reversal of bronchospasm in acute asthma attacks. Not evaluated in labile (brittle) or unstable asthma. Should not be substituted abruptly for inhaled corticosteroids.

Caution is required in treating patients with severe asthma when steroid reduction is being considered. Rarely, such patients 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 been associated with reductions in oral steroid therapy. A causal relationship with ACCOLATE has not been established.

Elevations in serum transaminases 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 of liver dysfunction were reported.

If clinical symptoms or signs suggestive of liver dysfunction occur, ACCOLATE should be discontinued. Serum transaminases should be measured immediately and the patient managed accordingly (See full Prescribing Information).

Patients in whom ACCOLATE was withdrawn because of hepatotoxicity with no other attributable cause should not be re-exposed to ACCOLATE.

ACCOLATE is not recommended for patients with hepatic impairment including hepatic cirrhosis.

The safety and efficacy of ACCOLATE in children under 5 years has not yet been established.

Interactions: Possible pharmacokinetic interactions with warfarin, acetylsalicylic acid (‘aspirin’), erythromycin, terfenadine and theophylline.

Pregnancy and lactation: The safety of ACCOLATE in human pregnancy has not been established. The potential risks should be weighed against the benefits of continuing therapy during pregnancy and used only if clearly needed.

Zafirlukast is excreted in human breast milk. ACCOLATE should not be administered to mothers who are breast-feeding.

Undesirable effects:

Adults and children 12 years of age and older;

Headache and gastrointestinal disturbance may be associated with ACCOLATE administration. These side effects are mostly mild.

The following have been reported in association with the administration of ACCOLATE:

Insomnia, malaise (common)
rashes, including blistering, pruritus, oedema (uncommon)
hypersensitivity reactions including urticaria and angioedema (rare)
bruising, bleeding disorders (rare)
agranulocytosis (very rare)

The above events have usually resolved following cessation of therapy.

Infrequently, elevated serum transaminase levels have been observed in clinical trials with ACCOLATE. The changes resolved during continued treatment or following cessation of therapy. Rarely the transaminase profile has been consistent with a drug-induced hepatitis which resolved following cessation of ACCOLATE therapy.

During post-marketing experience there have been rare reports of symptomatic hepatitis, associated with the use of ACCOLATE. These cases have usually resolved following cessation of therapy with ACCOLATE. Very rarely, fulminant hepatitis and hepatic failure have been reported, sometimes with a fatal outcome.

Rarely hyperbilirubinemia without other elevated liver function tests has also been associated with the use of ACCOLATE.

Increased incidence of infection (usually mild) was observed in elderly patients in placebocontrolled trials and did not necessitate withdrawal of therapy.

Rarely non-specific arthralgia and non-specific myalgia have been reported in association with ACCOLATE.

The safety profile in clinical trials in 5 - 11 year olds was similar to the safety profile in older children and adults. The pattern of post-marketing reports in this age group is similar to that seen in adults, including increases in liver enzymes and other hepatic events.

Further information is available on request from AstraZeneca address or local AstraZeneca subsidiaries.

Date: August 2007