AstraZeneca UK Limited

SPC Changes

Accolate 20mg Tablets

Section 4.2

Changes to the Elderly paragraph, now reads as,

“Elderly:

The clearance of zafirlukast is reduced in elderly patients (> 65 years old), such that C_max 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.”

Changes to the Renal impairment paragraph, now reads as,

” Renal impairment:

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.”

Section 4.4

Deletion of second paragraph.

Additional text in third paragraph, now reads as,

“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. ”

Additional final paragraph, reads as,

” 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.”

Section 4.8

Changes to table, now reads as,

1 These events have usually resolved following cessation of therapy.

2 Frequency is based on post-marketing data.

Deletion of text in paragraph on Hepatic Effects, now reads as,

” Hepatic Effects:

Elevated serum transaminase levels have been observed in clinical trials with Accolate. The changes usually 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.

Hyperbilirubinemia without elevated liver function tests has also been associated with the use of Accolate.

During post-marketing experience there have been rare reports of symptomatic hepatitis, with and without hyperbilirubinemia, associated with the use of Accolate. These cases have usually resolved following cessation of therapy with Accolate. The predominate majority of cases have been reported in females. (See also section 4.4).”

Section 4.9

Text deleted and additional text inserted in second paragraph, now reads as,

” Management should be supportive. Gastric lavage and/or installation of charcoal may be considered in selected cases of the excessive overdose of Accolate.”

Section 10

10 February 2011

SPC Changes, Accolate UK

Section 1

Format change, now reads, “Accolate™ 20 mg Film-coated Tablets”

Section 4.4

Significant additional text and deletions, now reads, ” Accolate should be taken regularly to achieve benefit, even during symptom free periods. Accolate therapy should normally be continued during acute exacerbations of asthma.

Accolate should not be substituted abruptly for inhaled or oral corticosteroids.

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.

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.

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.”

Section 4.8

Significant additional text and deletions, now reads, ” Administration of Accolate may be associated with the following undesirable effects. The reactions are classified according to frequency (very common ≥1/10, common ≥1/100 to <1/10; uncommon ≥1/1000 to <1/100; rare ≥1/10000 to <1/1000; very rare <1/10000; not known (cannot be estimated from available data)).

1 These events have usually resolved following cessation of therapy.

Hepatic Effects:

Elevated serum transaminase levels have been observed in clinical trials with Accolate. The changes usually 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.

Hyperbilirubinemia without elevated liver function tests has also been associated with the use of Accolate.

During post-marketing experience there have been rare reports of symptomatic hepatitis, with and without hyperbilirubinemia, associated with the use of Accolate. These cases have usually resolved following cessation of therapy with Accolate. The predominate majority of cases have been reported in females. Very rarely, fulminant hepatitis and hepatic failure have been reported, sometimes with a fatal outcome (see also section 4.4).

Infection:

In placebo-controlled clinical trials, an increased incidence of infection has been observed in elderly patients given Accolate. Infections were usually mild, predominantly affecting the respiratory tract and not necessitating withdrawal from therapy with Accolate.

Section 10

20 July 2010

Section 1

Tradename change to:

Accolate™ 20 mg Film-coated Tablets