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.
Section 4.1 Therapeutic Indications
The final paragraph (regarding fibrinolytic treatment of acute ischaemic stroke) has had text both added to and deleted from. The text … as early as possible …,
… 4.5 …, … after … and all that after … imaging techniques … is new.
Section 4.2 Posology and Method of Administration
The Acute ischaemic stroke sub-heading of this section has had both text added to and deleted from.
The text … only …, … under the responsibility and follow-up of …, … trained and experienced …, and … neurovascular … is new in the first paragraph.
The text … as early as possible …, … 4.5 … and the complete final sentence of the third paragraph is new.
Section 4.3 Contraindications
The second paragraph of this section has been added as new text.
The first bullet point of the Additional contraindications in acute ischaemic stroke sub-heading has been amended. The text … 4.5 …, … symptoms for which the …, … time … and … and could potentially be more than 4.5 hours ago (see section 5.1) has been added.
A new sub-heading entitled Use in elderly patients, together with corresponding text, has been added.
Section 4.4 Special Warnings and Precautions for Use
A new first paragraph has been added to this section.
The sub-heading Additional special warnings and precautions in acute ischaemic stroke has had both text added to and deleted from. The text … only …, … under the responsibility and follow-up of a … and … neurovascular … has been added.
A new third bullet point has been added to the Special warnings/conditions with a decreased benefit/risk ratio sub-heading.
A new penultimate paragraph (regarding data available from ECASS III) has been added to this section.
Section 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction
The text … active substances which interfere with … has replaced the text … other agents inhibiting … in the second paragraph of this section.
Section 4.8 Undesirable Effects
The first paragraph of this section (regarding adverse reactions frequency and system organ class) has had text both added to and deleted from.
The text … and without any relevant increase in overall mortality and severe disability combined, i.e. mRS of 5 and 6 … has been added to the common category of the Haemorrhage sub-heading.
The text … ear haemorrhage … has been added to the uncommon category of the Haemorrhage sub-heading.
Section 4.9 Overdose
The text … severe bleeding results, the infusion of fresh frozen plasma or fresh blood is recommended and if necessary, synthetic antifibryinolytics may be administered … has been added to the first paragraph of this section.
Section 5.1 Pharmacodynamic Properties
The text … iv… and … s.c… has been replaced with the text … intravenous … and … subcutaneous … in the fourth paragraph of this section.
The Acute stroke sub-heading of this section has had both text added to and deleted from, including the addition of a new second paragraph regarding the ECASS III trial and the addition of a new third paragraph regarding the safety and efficacy of Actilyse for acute ischaemic stroke treatment.
Section 6.6 Special Precautions for Disposal and Other Handling
Minor editorial changes have been made to this section.
Section 10 Date of Revision of the Text
The date has been amended from November 2009 to October 2011.
Section 2 Qualitative and Quantitative Composition
The text Active ingredient: has been deleted as the first paragraph of this section.
A new second paragraph for this section has been inserted i.e. paragraph commencing with the text: Additional contraindications in acute myocardial infarction, … Section 4.4 Special Warnings and Precautions for Use A new first paragraph for this section has been inserted i.e. paragraph commencing with the text: Special warnings and precautions in acute myocardial infarction, … The word oedama has been corrected to spell oedema in the first sentence of the last paragraph of this section i.e. the one entitled Other special warnings. Section 4.8 Undesirable Effects The first paragraph of this section has been completely reworded i.e. the one regarding adverse reactions according to frequency and system organ class. Text has both been deleted from and added to this paragraph. The word arrythmias has been corrected to spell arrhythmias in the very common paragraph of the Cardiac disorders heading of this section. Section 5.1 Pharmacodynamic Properties A new third paragraph has been added to this section i.e. one commencing with the text: Due to its relative fibrin-specificity alteplase at a dose of 100 mg leads to a modest decrease … This paragraph was originally the first paragraph in section 5.2 (Pharmacokinetic Properties) and has moved location. No changes to the text itself have taken place. Section 5.2 Pharmacokinetic Properties What was originally the first paragraph of this section has been deleted and moved to section 5.1 (Pharmacodynamic Properties) where it has become the third paragraph of this section. Section 6.3 Shelf-Life The text 10 mg, 20 mg and 50 mg pack sizes has been added to now come before the text 3 years. Section 6.4 Special Precautions for Storage The text Do not store above 25ºC has been relocated to become the second sentence of the second paragraph of this section. The text For 10 mg, 20 mg and 50 mg pack sizes: has been added as the first sentence of the second paragraph of this section. Section 6.5 Nature and Contents of Container The text For the 10 mg. 20 mg and 50 mg pack sizes, t has been added to and the capital T of the word the deleted from the beginning of the first sentence under the Solvent heading of this section. The words injection and have been added to the first sentences of each strength pack size details in this section. Section 6.6 Special Precautions for Disposal and Other Handling A new fourth paragraph has been added to this section i.e. one commencing with the text When reconstituting the product from the respective amount of powder and solvent, … Section 10 Date of Revision of the Text The date March 2007 has been replaced with the date April 2010.
A new second paragraph for this section has been inserted i.e. paragraph commencing with the text: Additional contraindications in acute myocardial infarction, …
A new first paragraph for this section has been inserted i.e. paragraph commencing with the text: Special warnings and precautions in acute myocardial infarction, … The word oedama has been corrected to spell oedema in the first sentence of the last paragraph of this section i.e. the one entitled Other special warnings. Section 4.8 Undesirable Effects The first paragraph of this section has been completely reworded i.e. the one regarding adverse reactions according to frequency and system organ class. Text has both been deleted from and added to this paragraph. The word arrythmias has been corrected to spell arrhythmias in the very common paragraph of the Cardiac disorders heading of this section. Section 5.1 Pharmacodynamic Properties A new third paragraph has been added to this section i.e. one commencing with the text: Due to its relative fibrin-specificity alteplase at a dose of 100 mg leads to a modest decrease … This paragraph was originally the first paragraph in section 5.2 (Pharmacokinetic Properties) and has moved location. No changes to the text itself have taken place. Section 5.2 Pharmacokinetic Properties What was originally the first paragraph of this section has been deleted and moved to section 5.1 (Pharmacodynamic Properties) where it has become the third paragraph of this section. Section 6.3 Shelf-Life The text 10 mg, 20 mg and 50 mg pack sizes has been added to now come before the text 3 years. Section 6.4 Special Precautions for Storage The text Do not store above 25ºC has been relocated to become the second sentence of the second paragraph of this section. The text For 10 mg, 20 mg and 50 mg pack sizes: has been added as the first sentence of the second paragraph of this section. Section 6.5 Nature and Contents of Container The text For the 10 mg. 20 mg and 50 mg pack sizes, t has been added to and the capital T of the word the deleted from the beginning of the first sentence under the Solvent heading of this section. The words injection and have been added to the first sentences of each strength pack size details in this section. Section 6.6 Special Precautions for Disposal and Other Handling A new fourth paragraph has been added to this section i.e. one commencing with the text When reconstituting the product from the respective amount of powder and solvent, … Section 10 Date of Revision of the Text The date March 2007 has been replaced with the date April 2010.
A new first paragraph for this section has been inserted i.e. paragraph commencing with the text: Special warnings and precautions in acute myocardial infarction, …
The word oedama has been corrected to spell oedema in the first sentence of the last paragraph of this section i.e. the one entitled Other special warnings.
Section 4.8 Undesirable Effects The first paragraph of this section has been completely reworded i.e. the one regarding adverse reactions according to frequency and system organ class. Text has both been deleted from and added to this paragraph. The word arrythmias has been corrected to spell arrhythmias in the very common paragraph of the Cardiac disorders heading of this section. Section 5.1 Pharmacodynamic Properties A new third paragraph has been added to this section i.e. one commencing with the text: Due to its relative fibrin-specificity alteplase at a dose of 100 mg leads to a modest decrease … This paragraph was originally the first paragraph in section 5.2 (Pharmacokinetic Properties) and has moved location. No changes to the text itself have taken place. Section 5.2 Pharmacokinetic Properties What was originally the first paragraph of this section has been deleted and moved to section 5.1 (Pharmacodynamic Properties) where it has become the third paragraph of this section. Section 6.3 Shelf-Life The text 10 mg, 20 mg and 50 mg pack sizes has been added to now come before the text 3 years. Section 6.4 Special Precautions for Storage The text Do not store above 25ºC has been relocated to become the second sentence of the second paragraph of this section. The text For 10 mg, 20 mg and 50 mg pack sizes: has been added as the first sentence of the second paragraph of this section. Section 6.5 Nature and Contents of Container The text For the 10 mg. 20 mg and 50 mg pack sizes, t has been added to and the capital T of the word the deleted from the beginning of the first sentence under the Solvent heading of this section. The words injection and have been added to the first sentences of each strength pack size details in this section. Section 6.6 Special Precautions for Disposal and Other Handling A new fourth paragraph has been added to this section i.e. one commencing with the text When reconstituting the product from the respective amount of powder and solvent, … Section 10 Date of Revision of the Text The date March 2007 has been replaced with the date April 2010.
The first paragraph of this section has been completely reworded i.e. the one regarding adverse reactions according to frequency and system organ class. Text has both been deleted from and added to this paragraph.
The word arrythmias has been corrected to spell arrhythmias in the very common paragraph of the Cardiac disorders heading of this section.
A new third paragraph has been added to this section i.e. one commencing with the text: Due to its relative fibrin-specificity alteplase at a dose of 100 mg leads to a modest decrease …
This paragraph was originally the first paragraph in section 5.2 (Pharmacokinetic Properties) and has moved location. No changes to the text itself have taken place.
Section 5.2 Pharmacokinetic Properties
What was originally the first paragraph of this section has been deleted and moved to section 5.1 (Pharmacodynamic Properties) where it has become the third paragraph of this section.
Section 6.3 Shelf-Life
The text 10 mg, 20 mg and 50 mg pack sizes has been added to now come before the text 3 years.
Section 6.4 Special Precautions for Storage The text Do not store above 25ºC has been relocated to become the second sentence of the second paragraph of this section. The text For 10 mg, 20 mg and 50 mg pack sizes: has been added as the first sentence of the second paragraph of this section. Section 6.5 Nature and Contents of Container The text For the 10 mg. 20 mg and 50 mg pack sizes, t has been added to and the capital T of the word the deleted from the beginning of the first sentence under the Solvent heading of this section. The words injection and have been added to the first sentences of each strength pack size details in this section. Section 6.6 Special Precautions for Disposal and Other Handling A new fourth paragraph has been added to this section i.e. one commencing with the text When reconstituting the product from the respective amount of powder and solvent, … Section 10 Date of Revision of the Text The date March 2007 has been replaced with the date April 2010.
Section 6.4 Special Precautions for Storage
The text Do not store above 25ºC has been relocated to become the second sentence of the second paragraph of this section.
The text For 10 mg, 20 mg and 50 mg pack sizes: has been added as the first sentence of the second paragraph of this section.
Section 6.5 Nature and Contents of Container
The text For the 10 mg. 20 mg and 50 mg pack sizes, t has been added to and the capital T of the word the deleted from the beginning of the first sentence under the Solvent heading of this section.
The words injection and have been added to the first sentences of each strength pack size details in this section.
A new fourth paragraph has been added to this section i.e. one commencing with the text When reconstituting the product from the respective amount of powder and solvent, …
The date March 2007 has been replaced with the date April 2010.
Changes to section 4.2 - Posology and method of administration, Change to section 4.3 – Contraindications, Change to section 4.4 – Special warnings and special precautions for use, Change to section 4.5 – Interaction with other medicinal products and other forms of interaction, Change to section 4.8 – Undesirable effects.
Change details:
Section 4.2 Posology and method of administration.
The section on adjunctive therapy has been updated to incorporate current recommendations. It now states “Antithrombotic adjunctive therapy is recommended according to the current international guidelines for the management of patients with ST-elevation myocardial infarction”
Acitylase is contraindicated in cases where there is a high risk of haemorrhage in a number of situations; this now includes patients with a “significant bleeding disorder at present or within the past 6 months”.
An additional contraindication for use in acute myocardial infarction and acute pulmonary embolism was any history of stroke. This has now been changed to include
“any known history of haemorrhagic stroke or stroke of unknown origin”
and “any known history of ischaemic stroke if transient ischaemic attack in the preceding 6 months, except current acute ischaemic stroke in the last 3 hours”.
Section 4.4 Special warnings and special precautions for use
This section now notes that the concomitant use of GPIIb/IIIa antagonists increases the risk of bleeding.
Section 4.5 Interaction with other medicinal products and other forms of interaction
Section 4.8 – Undesirable effects
Corrections in the frequency classification of some undesirable effects. The following effects have been reclassified from uncommon to common:
Respiratory tract haemorrhage (such as pharyngeal haemorrhage, epistaxis, haemoptysis)
Gastrointestinal haemorrhage (such as gastric haemorrhage, gastric ulcer haemorrhage, haemorrhage rectum, haematemesis, melaena, mouth haemorrhage)
As with other thrombolytic agents some cardiac disorders have been reported as sequelae of myocardial infarction and / or thrombolytic treatment. Reperfusion arrythmias are now classified as a very common undesirable effect.
Gastrointestinal disorders: Nausea and vomiting have been reclassified from a rare to a common undesirable effect.
The following effect has been added
Injury and poisoning and procedural complications:
rare: fat embolism (cholesterol crystal embolisation), which may lead to corresponding consequences in the organs concerned