When a pharmaceutical company changes an SPC or PIL, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.
SPC changes, Accolate 20mg
Section 4.2
Elderly
Third line, the word zafirlukast replaced with “Accolate”.
Children
As above
Renal Impairment
Text changed, now reads as,
“Renal impairment:
Experience is limited in patients with mild to severe renal impairment, so clear dose recommendations cannot be given. Therefore, Accolate should be used with caution in these patients.”
Section 4.3
Second paragraph deleted.
Third paragraph (now second) changed to read,
” Accolate is contraindicated for patients with hepatic impairment including hepatic cirrhosis.”
Section 4.4
Section changed extensively, now reads as,
” 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 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, pruritis 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 liver function testing. Periodic serum transaminase testing has not proven to prevent serious injury but it is generally believed that early detection of drug-induced hepatic injury along with immediate withdrawal of the suspect drug may enhance the likelihood for recovery. Patients in whom Accolate was withdrawn because of hepatotoxicity with no other attributable cause 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.” Section 4.8 First sentence deleted (Assolcate is well tolerated). Table 1 updated, now reads as, Infections and infestations: Very common: Infection Blood and the lymphatic system disorders: Rare: Bleeding disorders1 Very rare: Agranulocytosis1,2. Immune system disorders: Uncommon:Hypersensitivity1 Rare: Angioedema1. Psychiatric disorder: Uncommon: Insomnia1 Nervous system disorder: Common: Headache Gastrointestinal disorders: Common: Nausea, vomiting, diarrhoea and abdominal pain Hepatobiliary disorders: Common: Elevations in transaminase levels Uncommon: Hyperbilirubinemia Rare: Hepatitis Very rare: 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 Second to last paragraph updated, now reads as, ” 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 Second paragraph updated, now reads as, ” Gastric lavage and/or installation of charcoal may be considered in selected cases of the excessive overdose of Accolate. Management should be supportive. ” Section 10 15th February 2011
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
First sentence deleted (Assolcate is well tolerated).
Table 1 updated, now reads as,
Infections and infestations:
Very common: Infection
Blood and the lymphatic system disorders:
Rare: Bleeding disorders1
Very rare: Agranulocytosis1,2.
Immune system disorders:
Uncommon:Hypersensitivity1
Rare: Angioedema1.
Psychiatric disorder:
Uncommon: Insomnia1
Nervous system disorder:
Common: Headache
Gastrointestinal disorders:
Common: Nausea, vomiting, diarrhoea and abdominal pain
Hepatobiliary disorders:
Common: Elevations in transaminase levels
Rare: Hepatitis
Very rare: 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
Second to last paragraph updated, now reads as,
” 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
Second paragraph updated, now reads as,
” Gastric lavage and/or installation of charcoal may be considered in selected cases of the excessive overdose of Accolate. Management should be supportive. ”
Section 10
15th February 2011
SPC Changes – Accolate 20mg Film-coated Tablets
Addition of fourth paragraph, text reads as,
“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.
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 whom no previous clinical signs or symptoms suggestive of liver dysfunction were reported.”
Formatting amendment to second to last paragraph, two occurrences of ACCOLATE is now ’Accolate’.
Significant changes to section and table, now reads as,
” Accolate is well tolerated. 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).
Table 1
Vascular disorders:
1 These events have usually resolved following cessation of therapy.
2 Frequency is based on post-marketing data.
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.”
’25 March 2010’