Ticagrelor

BRILINTA is a P2Y 12 platelet inhibitor indicated • to reduce the risk of cardiovascular (CV) death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of MI. For at least the first 12 months following ACS, it is superior to clopidogrel. BRILINTA also reduces the risk of stent thrombosis in patients who have been stented for treatment of ACS. • to reduce the risk of a first MI or stroke in patients with coronary artery disease (CAD) at high risk for such events. While use is not limited to this setting, the efficacy of BRILINTA was established in a population with type 2 diabetes mellitus (T2DM). • to reduce the risk of stroke in patients with acute ischemic stroke (NIH Stroke Scale score ≤5) or high-risk transient ischemic attack (TIA).

Ticagrelor and its major metabolite reversibly interact with the platelet P2Y 12 ADP-receptor to prevent signal transduction and platelet activation. Ticagrelor and its active metabolite are approximately equipotent.

• ACS or History of MI • Initiate treatment with 180 mg oral loading dose of BRILINTA. Then administer 90 mg twice daily during the first year. After one year, administer 60 mg twice daily. • Patients with CAD and No Prior Stroke or MI • Administer 60 mg BRILINTA twice daily. • Acute Ischemic Stroke • Initiate treatment with a 180 mg loading dose of BRILINTA then continue with 90 mg twice daily for up to 30 days. Use BRILINTA with a daily maintenance dose of aspirin of 75-100 mg. However, in patients who have undergone PCI, consider single antiplatelet therapy with BRILINTA based on the evolving risk for thrombotic versus bleeding events.

• History of intracranial hemorrhage. • Active pathological bleeding. • Hypersensitivity to ticagrelor or any component of the product.

Boxed warning (bleeding risk • brilinta): like other antiplatelet agents, can cause significant, sometimes fatal bleeding. • Do not use BRILINTA in patients with active pathological bleeding or a history of intracranial hemorrhage •. • Do not start BRILINTA in patients undergoing urgent coronary artery bypass graft surgery (CABG) ( 5.1, • 6.1 ). • If possible, manage bleeding without discontinuing BRILINTA. • Dyspnea was reported more frequently with BRILINTA than with control agents in clinical trials. Dyspnea from BRILINTA is self-limiting. • Severe Hepatic Impairment: Likely increase in exposure to ticagrelor. • Laboratory Test Interference: False negative platelet functional test results have been reported for Heparin Induced Thrombocytopenia (HIT). BRILINTA is not expected to impact PF4 antibody testing for HIT.

The following adverse reactions are also discussed elsewhere in the labeling: • Bleeding • Dyspnea Most common adverse reactions (>5%) are bleeding and dyspnea.

• Avoid use with strong CYP3A inhibitors or CYP3A inducers. • Opioids: Decreased exposure to ticagrelor. Consider use of parenteral anti-platelet agent. • Patients receiving more than 40 mg per day of simvastatin or lovastatin may be at increased risk of statin-related adverse effects. • Rosuvastatin plasma concentrations may increase. Monitor for statin-related adverse effects. • Monitor digoxin levels with initiation of or any change in BRILINTA.

Store at 25°C (77°F), excursions permitted to 15 to 30°C (59 to 86°F).