Prasugrel

⛔ FDA Black Box Warning

WARNING: BLEEDING RISK • Prasugrel tablets can cause significant, sometimes fatal, bleeding [see Warnings and Precautions (5.1 , 5.2) and Adverse Reactions (6.1) ] . • Do not use prasugrel tablets in patients with active pathological bleeding or a history of transient ischemic attack (TIA) or stroke [see Contraindications (4.1 , 4.2) ] . • In patients ≥ 75 years of age, prasugrel tablets are generally not recommended, because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk situations (patients with diabetes or a history of prior myocardial infarction [MI]) where their effect appears to be greater and their use may be considered [see Use in Specific Populations (8.5) ] . • Do not start prasugrel tablets in patients likely to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue prasugrel tablets at least 7 days prior to any surgery [see Warnings and Precautions (5.2) ] . • Additional risk factors for bleeding include: body weight < 60 kg, propensity to bleed, concomitant use of medications that increase the risk of bleeding (e.g., warfarin, heparin, fibrinolytic therapy, chronic use of nonsteroidal anti-inflammatory drugs [NSAIDs]) [see Warnings and Precautions (5.1) ]. • Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, percutaneous coronary intervention (PCI), CABG, or other surgical procedures in the setting of prasugrel tablets [see Warnings and Precautions (5.1) ] . • If possible, manage bleeding without discontinuing prasugrel tablets. Discontinuing prasugrel tablets, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular (CV) events [see Warnings and Precautions (5.3) ] . WARNING: BLEEDING RISK See full prescribing information for complete boxed warning. • Prasugrel tablets can cause significant, sometimes fatal, bleeding ( 5.1 , 5.2 , 6.1 ). • Do not use prasugrel tab

Contraindications

4 CONTRAINDICATIONS • Active pathological bleeding ( 4.1 ). • Prior transient ischemic attack or stroke ( 4.2 ). • Hypersensitivity to prasugrel or any component of the product ( 4.3 ). 4.1 Active Bleeding Prasugrel tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage (ICH) [see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ] . 4.2 Prior Transient Ischemic Attack or Stroke Prasugrel tablets are contraindicated in patients with a history of prior transient ischemic attack (TIA) or stroke. In TRITON-TIMI 38 ( TR ial to Assess I mprovement in T herapeutic Outcomes by O ptimizing Platelet Inhibitio N with Prasugrel), patients with a history of TIA or ischemic stroke (> 3 months prior to enrollment) had a higher rate of stroke on prasugrel tablets (6.5%; of which 4.2% were thrombotic stroke and 2.3% were intracranial hemorrhage [ICH]) than on clopidogrel (1.2%; all thrombotic). In patients without such a history, the incidence of stroke was 0.9% (0.2% ICH) and 1.0% (0.3% ICH) with prasugrel tablets and clopidogrel, respectively. Patients with a history of ischemic stroke within 3 months of screening and patients with a history of hemorrhagic stroke at any time were excluded from TRITON-TIMI 38. Patients who experience a stroke or TIA while on prasugrel tablets generally should have therapy discontinued [see Adverse Reactions (6.1) and Clinical Studies (14) ] . 4.3 Hypersensitivity Prasugrel tablets are contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to prasugrel or any component of the product [see Adverse Reactions (6.2) ] .

Pregnancy & Breastfeeding

8.1 Pregnancy Risk Summary There are no data with prasugrel tablets use in pregnant women to inform a drug-associated risk. No structural malformations were observed in animal reproductive and developmental toxicology studies when rats and rabbits were administered prasugrel during organogenesis at doses of up to 30 times the recommended therapeutic exposures in humans [see Data ] . Due to the mechanism of action of prasugrel tablets, and the associated identified risk of bleeding, consider the benefits and risks of prasugrel tablets and possible risks to the fetus when prescribing prasugrel tablets to a pregnant woman [see Boxed Warning and Warnings and Precautions (5.1 , 5.3) ] . The background risk of major birth defects and miscarriage for the indicated population is unknown. The background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. Data Animal Data In embryo-fetal developmental toxicology studies, pregnant rats and rabbits received prasugrel at maternally toxic oral doses equivalent to more than 40 times the human exposure. A slight decrease in fetal body weight was observed, but there were no structural malformations in either species. In prenatal and postnatal rat studies, maternal treatment with prasugrel had no effect on the behavioral or reproductive development of the offspring at doses greater than 150 times the human exposure.