BRIEF SUMMARY OF PRESCRIBING INFORMATION
Non-Bleeding
For full prescribing information visit www.medicure.com/aggrastat/pi.pdf
The incidences of non-bleeding adverse events that occurred at an incidence of >1% and numerically
higher than control, regardless of drug relationship, are shown below:
You are encouraged to report negative side effects of prescription drugs to the FDA.
To report SUSPECTED ADVERSE REACTIONS, contact Medicure at 1-800-509-0544
or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Table 3: Non-bleeding Adverse Reactions in PRISM-PLUS
INDICATIONS AND USAGE
AGGRASTAT + heparin (N=1953) %
AGGRASTAT is indicated to reduce the rate of thrombotic cardiovascular events (combined
endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients
with non-ST elevation acute coronary syndrome (NSTE-ACS).
®
Heparin alone (N=1887) %
AGGRASTAT is contraindicated in patients with:
▪ Severe hypersensitivity reaction to AGGRASTAT (i.e., anaphylactic reactions).
▪ A history of thrombocytopenia following prior exposure to AGGRASTAT.
▪ Active internal bleeding or a history of bleeding diathesis, major surgical procedure or severe
physical trauma within the previous month.
Body as a Whole
Edema/swelling
Pain, pelvic
Reaction, vasovagal
Cardiovascular System
Bradycardia
Dissection, coronary artery
Musculoskeletal System
Pain, leg
Nervous System/Psychiatric
Dizziness
Skin & Skin Appendage
Sweating
WARNINGS AND PRECAUTIONS
Thrombocytopenia
General Risk of Bleeding
Patients treated with AGGRASTAT plus heparin, were more likely to experience decreases in platelet
counts than were those on heparin alone. These decreases were reversible upon discontinuation of
AGGRASTAT. The percentage of patients with a decrease of platelets to <90,000/mm3 was 1.5%,
compared with 0.6% in the patients who received heparin alone. The percentage of patients with a
decrease of platelets to <50,000/mm3 was 0.3%, compared with 0.1% of the patients who received
heparin alone.
DOSAGE AND ADMINISTRATION
Refer to package insert for administration & dosing instructions by weight and creatinine clearance.
CONTRAINDICATIONS
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,
oral anticoagulants and antiplatelet drugs increases the risk of bleeding.
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].
ADVERSE REACTIONS
Clinical Trial Experience
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.
Bleeding
PRISM-PLUS Regimen
The incidences of major and minor bleeding using the TIMI criteria in the PRISM-PLUS study are
shown below.
Table 1: TIMI Major and Minor Bleeding in PRISM-PLUS
Bleeding (TIMI Criteria)‡ §
Major Bleeding
Minor Bleeding
Transfusions
*
AGGRASTAT* + heparin (N=773)
1.4%
10.5%
4.0%
Heparin alone (N=797)
0.8%
8.0%
2.8%
2
6
2
1
5
1
4
5
3
4
3
2
3
2
2
1
Post-Marketing Experience
The following additional adverse reactions have been identified during post-approval use of
AGGRASTAT. Because these reactions are reported voluntarily from a population of uncertain size,
it is not always possible to reliably estimate their frequency or establish a causal relationship to the
drug exposure.
Hypersensitivity: Severe allergic reactions including anaphylactic reactions have occurred during
the first day of AGGRASTAT infusion, during initial treatment, and during readministration of
AGGRASTAT. Some cases have been associated with severe thrombocytopenia (platelet counts
<10,000/mm3). No information is available on the formation of antibodies to tirofiban.
USE IN SPECIFIC POPULATIONS
Pregnancy Pregnancy Category B: There are no adequate and well-controlled studies in pregnant
women. Tirofiban has been shown to cross the placenta in pregnant rats and rabbits. Studies
with tirofiban HCl at intravenous doses up to 5 mg/kg/day (about 5 and 13 times the maximum
recommended daily human dose for rat and rabbit, respectively, when compared on a body surface
area basis) have revealed no harm to the fetus.
Nursing Mothers It is not known whether tirofiban is excreted in human milk. However, significant
levels of tirofiban were shown to be present in rat