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 4.9 Overdose
The third paragraph of the Symptoms sub-heading of this section has had both text deleted from and added to. The sentence A drop in blood pressure and tachycardia might be observed has been added.
A final paragraph has been added to the Symptoms sub-heading of this section which reads:
Dizziness and tinnitus can, particularly in elderly patients, be symptoms of overdose.
Section 5.1 Pharmacodynamic Properties
The third paragraph of this section has had a new first sentence regarding platelet aggregation in response to various stimuli added.
In the Clinical Trials sub-heading of this section, several figures in the ESPS2 paragraph have been updated.
In the Clinical Trials sub-heading of this section, the text regarding individuals who were ≥ 55 years of age and who had had an ischemic stroke within 90 days of entry to the study has been deleted from the PRoFESS paragraph. The word previously has been added to the first sentence of this paragraph.
Section 5.2 Pharmacokinetic Properties
New first, second, third and final sentences have been added to the Distribution sub-heading of this section.
Section 10 Date of Revision of the Text
The date has been updated from March 2009 to March 2011.
The following information has been added to Sections 4.5 and 5.1:
Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.
Section 4.4 - Asasantin should be used with caution in patients at increased bleeding risk, including patients receiving concomitant medication which may increase the risk of bleeding. Headache or migraine-like headache which may occur should not be treated with analgesic doses of acetylsalicylic acid.
Section 4.5 - Acetylsalicylic acid has been shown to enhance the effect of phenytoin.
Section 4.8 - Updated to include data from the PRoFESS (Prevention Regimen For Effectively Avoiding Second Strokes) trial. New undesirable effects are: Intracranial haemmorrhage, anaemia, syncope, epistaxis, abdominal pain, Gastrointestinal haemmorrhage.
Section 5.1 - Addition of information from the PRoFESS trial. The primary endpoint was the time to recurrent stroke of any type and the incidence was similar in the Asasantin and clopidogrel groups. No significant differences were detected for other pre-specified endpoints.
Change details:
Section 5.1 Pharmacodynamic properties
This section has been updated to include more extensive and detailed information on the pharmacodynamic properties of the two components of ASASANTIN Retard® (acetylsalicylic acid and dipyridamole).
In addition, a section detailing clinical trials of ASASANTIN Retard® in secondary stroke prevention has been added:
“ASASANTIN Retard® was studied in a double-blind, placebo-controlled, 24-month study (European Stroke Prevention Study 2, ESPS2) in which 6602 patients had an ischemic stroke or transient ischemic attack (TIA) within three months prior to entry. Patients were randomized to one of four treatment groups: ASASANTIN Retard (ASA /extended-release dipyridamole) 25 mg/200 mg; extended-release dipyridamole (ER-DP) 200 mg alone; ASA 25 mg alone; or placebo. Patients received one capsule twice daily (morning and evening). Efficacy assessments included analyses of stroke (fatal or nonfatal) and death (from all causes) as confirmed by a blinded morbidity and mortality assessment group. In ESPS-2 ASASANTIN Retard reduced the risk of stroke by 22.1% compared to ASA.
50 mg/day alone (p =0.008) and reduced the risk of stroke by 24.4% compared to extended-release dipyridamole 400 mg/day alone (p = 0.002). ASASANTIN Retard reduced the risk of stroke by 36.8% compared to placebo (p <0.001).
The results of the ESPS-2 study are supported by the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT) study [112] which studied a combination treatment of diypridamole 400 mg daily (83% of patients treated with the extended-release dipyridamole formulation) and ASA 30-325 mg daily. A total of 2739 patients after ischaemic stroke of arterial origin were enrolled in the ASA-alone (n = 1376) and combination ASA plus dipyridamole (n = 1363) arm. The primary outcome event was the composite of death from all vascular causes, non-fatal stroke, non-fatal myocardial infarction (MI), or major bleeding complications. Patients in the ASA plus dipyridamole group showed a 20% risk reduction (p<0.05) for the primary composite endpoint compared with those in the ASA alone group (12.7% vs. 15.7%; hazard ratio [HR] 0.80, 95% CI 0.66–0.98).”
Section 5.2 Pharmacokinetic properties
This section has been updated to include more detailed information on the pharmacokinetic properties of ASASANTIN Retard®, including information on both acetylsalicylic acid and extended-release dipyridamole.
Section 4.2 Posology and Method of Administration
Details of an alternative treatment regimen in case of intolerable headaches have been added:
“In the event of intolerable headaches during treatment initiation, switch to one capsule at bedtime and low-dose acetylsalicylic acid (ASA) in the morning. Because there are no outcome data with this regimen and headaches become less of a problem as treatment continues, patients should return to the usual regimen as soon as possible, usually within one week.”
Section 4.4 Special Warnings and Precautions for Use
Information on a small number of cases in which unconjugated dipyridamole was shown to be incorporated into gallstones has been added. All patients in these cases were elderly, had evidence of ascending cholangitis and had been treated with oral dipyridamole for a number of years. There is no evidence to suggest that dipyridamole was the initiating factor in causing gallstones in these patients.
Section 4.6 Pregnancy and Lactation
It had previously been stated that Asasantin Retard should be used with caution in the first and second trimester. It is now noted that Asasantin Retard should only be used with caution in the first and second trimester “if considered essential by the physician in terms of benefit and risk”.
Section 4.4 (Special warnings and precautions for use) has been updated to include the following statement: "Caution should be advised in patients receiving concomitant medication which may increase the risk of bleeding, such as anti-platelet agents (e.g. clopidogrel, ticlopidine) or selective serotonin reuptake inhibitors (SSRIs)."
Section 4.5 (Interactions with other medicaments and other forms of interaction) has been updated to include the following information: "Acetylsalicylic acid has been shown to enhance the effect of anticoagulants (e.g. coumarin derivatives and heparin), antiplatelet drugs (e.g clopidogrel, ticlopidine) and valproic acid which may result in an increased risk of side effects. Selective serotonin reuptake inhibitors (SSRIs) may increase the risk of bleeding. Gastrointestinal side effects also increase when acetylsalicylic acid is administered concomitantly with NSAIDs, corticosteroids, or chronic alcohol use."
Section 4.8 (Undesirable effects) has been updated to state that "Skin haemorrhages such as contusion, ecchymosis and haematoma may occur with ASASANTIN retard."
Section 1: The trade name for this product has been updated to "ASASANTIN Retard 200 mg/25 mg Modified Release Hard Capsules"
Section 4.3: The following has been added to the list of contraindications:
"In certain rare hereditary conditions the product is contraindicated owing to the prescence of certain excipients in the product."
Section 4.4: The following has been added to the list of special warnings and special precautions for use:
"This product contains 106 mg of lactose and 22.5 mg sucrose per maximum recommended daily dose. Patients with rare hereditary problems of fructose intolerance and/or galactose intolerance e.g. galactosaemia should not take this medicine."
In addition, the generic name for one of the products constituents has been changed from aspirin to acetylsalicylic acid through out the document.