In the PRISM-PLUS study, using the Aggrastat 0.4 microgram/kg/min infusion regimen, the incidence of TIMI major bleeding was 1.4% for Aggrastat in combination with heparin and 0.8% for heparin alone. The incidence of TIMI minor bleeding was 10.5% for Aggrastat in combination with heparin and 8.0% for heparin alone. The percentage of patients who received a transfusion was 4.0% for Aggrastat in combination with heparin and 2.8% for heparin alone.

With the Aggrastat 25 microgram/kg dose bolus regimen, data from the ADVANCE study suggest that the number of bleeding events is low and does not seem to be significantly increased compared to placebo. There were no TIMI major bleedings and no transfusions in either group. TIMI minor bleeding with the Aggrastat 25 microgram/kg dose bolus regimen was 4% as compared with 1% in the placebo arm p=0.19).

In the On-TIME 2 study, there were no significant differences in the incidence of TIMI major bleeding (3.4% vs. 2.9% p =0.58) and TIMI minor bleeding (5.9% vs. 4.4%; p=0.206) between the Aggrastat 25 microgram/kg dose bolus regimen and the control arm.

The rates of TIMI major (2.4% vs. 1.6%; p=0.44) 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

4.9 Overdose
Inadvertent overdose with tirofiban hydrochloride occurred in the clinical studies, up