tions) [see Adverse Reactions (6.2)].
A history of thrombocytopenia following prior exposure to AGGRASTAT [see Adverse Reactions (6.1)].
Active internal bleeding or a history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month [see Adverse Reactions (6.1)].
5 WARNINGS AND PRECAUTIONS
5.1 General Risk of Bleeding
Bleeding is the most common complication encountered during therapy with AGGRASTAT. Most bleeding associated with AGGRASTAT occurs at the arterial access site for cardiac catheterization. Minimize the use of traumatic or potentially traumatic procedures such as arterial and venous punctures, intramuscular injections, nasotracheal intubation, etc.
Concomitant use of fibrinolytics, anticoagulants and antiplatelet drugs increases the risk of bleeding.
5.2 Thrombocytopenia
Profound thrombocytopenia has been reported with AGGRASTAT. Monitor platelet counts beginning about 6 hours after treatment initiation and daily thereafter. If the platelet count decreases to <90,000/mm3, monitor platelet counts to exclude pseudothrombocytopenia. If thrombocytopenia is confirmed, discontinue AGGRASTAT and heparin. Previous exposure to a glycoprotein (GP) IIb/IIIa receptor antagonist may increase the risk of developing thrombocytopenia [see Adverse Reactions (6.1)].
6 ADVERSE REACTIONS
6.1 Clinical Trial Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
In the PRISM (Platelet Receptor Inhibition for Ischemic Syndrome Management), PRISM-PLUS (Platelet Receptor Inhibition for Ischemic Syndrome Management — Patients Limited by Unstable Signs and Symptoms) and RESTORE (Randomized Efficacy Study of Tirofiban for Outcomes and Restenosis) trials, 1946 patients received AGGRASTAT in combination with heparin and 2002 patients received AGGRASTAT alone for about 3 days. Forty-three percent of the population was >65 years of age and approximately 30% of patients were female. In clinical studies with the recommended regimen (25 mcg/kg bolus followed by a 0.15 mcg/kg/min maintenance infusion), AGGRASTAT was administered in combination with aspirin, clopidogrel and heparin or bivalirudin to over 8000 patients for typically ≤24 hours. Approximately 30% of the population was >65 years of age and approximately 25% were female.
Bleedin
PRISM-PLUS Regimen
The incidences of major and minor bleeding using the TIMI criteria in the PRISM-PLUS study are shown below.
Table 2 TIMI Major and Minor Bleeding in PRISM-PLUS
* Major = Hemoglobin drop of >5.0 g/dL with or without an identified site, intracranial hemorrhage, or cardiac tamponade. † Minor = Hemoglobin drop of >3.0 g/dL with bleeding from a known site, spontaneous gross hematuria, hematemesis or hemoptysis. ‡ 0.4 mcg/kg/min initial infusion; 0.10 mcg/kg/min maintenance infusion.
PRISM-PLUS
(NSTE-ACS)
Bleeding
(TIMI Criteria)*†
AGGRASTAT‡+ Heparin
(n=773)
Heparin alone
(n=797)
Major Bleeding
1.4%
0.8%
Minor Bleeding
10.5%
8.0%
Transfusions
4.0%
2.8%
The incidence rates of TIMI major bleeding in patients undergoing percutaneous proced |
