Last Updated on eMC 31-03-2016 View medicine  | AstraZeneca UK Limited Contact details

When a pharmaceutical company changes an SPC or PIL, a new version is published on the eMC.  For each version, we show the dates it was published on the eMC and the reasons for change.

Reasons for adding or updating:

  • Change to section 4.8 - Undesirable effects
  • Change to section 5.3 - Preclinical safety data
  • Change to section 10 - Date of revision of the text
  • Improved presentation of SPC

Date of revision of text on the SPC:18-03-2016

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



QRD changes throughout SmPC.

Section 4.8 add the information on reporting a side effect, implement the outcome of the PBRER work-sharing procedure, i.e. -  psychiatric disorders: include the term ‘nightmares’, nervous system disorders: include the terms ‘Hypoaesthesia) / Paraesthesia’, ‘Dizziness’

Section 5.3 QRD update and clarification that effects in non-clinical studies were at exposures in excess of the maximum human exposure indicating little relevance to clinical use and additional information re liver findings


Section 10 date of revision

Reasons for adding or updating:

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 10 - Date of revision of the text

Date of revision of text on the SPC:23-12-2013

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 4.5 -  addition of fluconazole and itraconazole interaction.

Section 10 – date of revision.

Reasons for adding or updating:

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:10-02-2011

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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 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.”

 

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,

 

Infections and infestations:

Very common: Infection

Blood and the lymphatic system disorders

Rare: Bleeding disorders including menorrhagia, thrombocytopenia1

Not known: Agranulocytosis1,2.

Immune system disorders:

Uncommon:Hypersensitivity1

Rare: Angioedema1.

Psychiatric disorder:

Uncommon: Insomnia1

Nervous system disorder:

Common: Headache

Gastrointestinal disorders:

Common: Nausea, vomiting, abdominal pain

Hepatobiliary disorders:

Common: Elevations in transaminase levels

Uncommon: Hyperbilirubinemia

Rare: Hepatitis

Not known: Fulminant hepatitis2, hepatic failure2

Skin and subcutaneous disorder:

Common: Rash1

Uncommon: Urticaria1, pruritus1.

Rare: Blister1

Musculoskeletal and connective tissue disorder:

Common : Myalgia

Uncommon: Arthralgia

General disorders and administration site conditions:

Uncommon: Oedema1, malaise1

Injury, Poisoning and Procedural Complications:

Rare: Bruising1

 

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

 

 

Reasons for adding or updating:

  • Change to section 1 -Name of the Medicinal product
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:20-07-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



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)).

 

Infections and infestations:

Very common: Infection

Blood and the lymphatic system disorders

Not known: Agranulocytosis1,.

Immune system disorders:

Uncommon:Hypersensitivity1

Rare: Angioedema1.

Psychiatric disorder:

Uncommon: Insomnia1

Nervous system disorder:

Common: Headache

Vascular disorders:

Rare: Bleeding disorders including menorrhagia, thrombocytopenia1

Gastrointestinal disorders:

Common: Nausea, vomiting, abdominal pain

Hepatobiliary disorders:

Common: Elevations in transaminase levels

Uncommon: Hyperbilirubinemia

Rare: Hepatitis

Not known: Fulminant hepatitis, hepatic failure

Skin and subcutaneous disorder:

Common: Rash1

Uncommon: Urticaria1, pruritus1.

Rare: Blister1

Musculoskeletal and connective tissue disorder:

Common : Myalgia

Uncommon: Arthralgia

General disorders and administration site conditions:

Uncommon: Oedema1, malaise1

Injury, Poisoning and Procedural Complications:

Rare: Bruising1

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

Reasons for adding or updating:

  • Change to section 1 -Name of the Medicinal product
  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:11-05-2010

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:



Section 1

Tradename change to:

 

Accolate™ 20 mg Film-coated Tablets

 

Section 4.4

 

Deletion of text:

Accolate’ does not allow a reduction in existing steroid treatment.

 

Additional text:

Accolate should not be substituted abruptly for inhaled or oral corticosteroids

 

 

Additional/deleted text:

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. Cases of eosinophilic conditions, including Churg-Strauss Syndrome and eosinophilic pneumonia have been reported in association with Accolate usage. Presentations may involve various body systems including vasculitic rash, worsening pulmonary symptoms, cardiac complications or neuropathy. A causal relationship has neither been confirmed nor refuted

 

 

Section 10

Revision date of text: 11 May 2010

Reasons for adding or updating:

  • Change to section 4.4 - Special warnings and precautions for Use
  • Change to section 4.8 - Undesirable Effects
  • Change to section 10 date of revision of the text

Date of revision of text on the SPC:02-05-2008

Legal Category:POM

Black Triangle (CHM): NO

Free-text change information supplied by the pharmaceutical company:

Section 4.4
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. (see section 4.8). In extremely rare post-marketing cases, no prior clinical symptoms or signs suggestive of liver dysfunction preceded the severe hepatic injury. 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.

Section 4.8
Hepatobiliary: Symptomatic hepatitis with and without hyperbilirubinaemia (rare), hyperbilirubinaemia, without elevated liver function tests (rare), hepatic failure (very rare),and  fulminant hepatitis, sometimes with a fatal outcome (see section 4.4) (very rare)

Section 10
Date changed to 2nd May 2008


Reasons for adding or updating:

  • Change to section 4.8 - Undesirable Effects
  • Change to section 4.9 - Overdose
  • Change to section 10 (date of (partial) revision of the text

Reasons for adding or updating:

  • Change to section 4.4 - Special Warnings and Precautions for Use
  • Change to section 4.8 - Undesirable Effects

Reasons for adding or updating:

  • Change to section 4.4 - Special Warnings and Precautions for Use

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder

Reasons for adding or updating:

  • Change to section 7 - Marketing Authorisation Holder
  • Change to section 8 - MA number
  • Change to section 10 (date of (partial) revision of the text
  • Removal of Black Triangle

Reasons for adding or updating:

  • No reasons supplied

Reasons for adding or updating:

  • No reasons supplied

Reasons for adding or updating:

  • No reasons supplied