or minor bleeding (4.8% vs. 6.2%; p=0.4) were also not significantly different between the Aggrastat 25 microgram/kg dose and the standard dose of abciximab, which were compared in the MULTISTRATEGY study.
Based upon an assessment of haemorrhagic complications performed in the context of a meta-analysis (n=4076 ACS patients), the Aggrastat 25 microgram/kg dose bolus regimen does not significantly increase the rates of major bleeding, or thrombocytopenia, when compared to placebo. When considering the trials of the Aggrastat 25 microgram/kg bolus regimen compared with abciximab, individual study results do not demonstrate a significant difference in major bleeding between the two treatments.
Thrombocytopenia
During Aggrastat therapy, acute decreases in platelet count or thrombocytopenia occurred more frequently than in the placebo group. These decreases were reversible upon discontinuation of Aggrastat. Acute and severe platelet (platelet counts <20,000/mm3) decreases have been observed in patients with no prior history of thrombocytopenia upon re-administration of GPIIb/IIIa receptor antagonists and may be associated with chills, low-grade fever or bleeding complications.
Analysis of the studies comparing the 25 microgram/kg dose bolus regimen against abciximab yielded a significantly lower rate of thrombocytopenia for Aggrastat (0.45% vs. 1.7%; OR=0.31; p=0.004).
Allergic reactions
Severe allergic reactions (e.g., bronchospasm, urticaria) including anaphylactic reactions have occurred during initial treatment (also on the first day) and during readministration of Aggrastat. Some cases have been associated with severe thrombocytopenia (platelet counts <10,000/mm3).
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via:
United Kingdom
Yellow Card Scheme
Website: www.mhra.gov.uk/yellowcard
Inadvertent overdose with tirofiban hydrochloride occurred in the clinical studies, up to 50 microgram/kg as a three minute bolus or 1.2 microgram/kg/min as an initial infusion. Overdose with up to 1.47 microgram/kg/min as a maintenance infusion rate has also occurred.
a) Symptoms of overdose
The symptom of overdose most commonly reported was bleeding, usually mucosal bleeding and localised bleeding at the arterial puncture site for cardiac catheterisation but also single cases of intracranial haemorrhages and retroperitoneal bleedings (see sections 4.4 and 5.1).
b) Measures
Overdose with tirofiban hydrochloride should be treated in accordance with the patient's condition and the attending physician's assessment. If treatment of haemorrhage is necessary, the Aggrastat infusion should be discontinued. Transfusions of blood and/or thrombocytes should also be considered. Aggrastat can be removed by haemodialysis.
Pharmacotherapeutic group: Blood and blood forming organs – antithrombotic agents –antithrombotic agents – Platelet aggregation inhibitors excl. heparin
ATC-Code: B01A C17
