prasugrel 10 MG Oral Tablet

INDICATIONS AND USAGE Prasugrel tablets is a P2Y 12 platelet inhibitor indicated for the reduction of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndrome who are to be managed with percutaneous coronary intervention (PCI) as follows: Patients with unstable angina or non-ST-elevation myocardial infarction (NSTEMI) ( 1.1 ). Patients with ST-elevation myocardial infarction (STEMI) when managed with either primary or delayed PCI ( 1.1 ). 1.1 Acute Coronary Syndrome Prasugrel tablet is indicated to reduce the rate of thrombotic cardiovascular (CV) events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows: Patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI). Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI. Prasugrel tablet has been shown to reduce the rate of a combined endpoint of cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke compared to clopidogrel. The difference between treatments was driven predominantly by MI, with no difference on strokes and little difference on CV death [see Clinical Studies ( 14 )] .

DOSAGE AND ADMINISTRATION Initiate prasugrel tablets treatment as a single 60 mg oral loading dose and then continue at 10 mg orally once daily. Patients taking prasugrel tablets should also take aspirin (75 mg to 325 mg) daily [see Drug Interactions ( 7.4 ) and Clinical Pharmacology ( 12.3 )]. Prasugrel tablets may be administered with or without food [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14 )]. Timing of Loading Dose In the clinical trial that established the efficacy and safety of prasugrel tablets, the loading dose of prasugrel tablets was not administered until coronary anatomy was established in UA/NSTEMI patients and in STEMI patients presenting more than 12 hours after symptom onset. In STEMI patients presenting within 12 hours of symptom onset, the loading dose of prasugrel tablets was administered at the time of diagnosis, although most received prasugrel tablets at the time of PCI [see Clinical Studies ( 14 )] . For the small fraction of patients that required urgent CABG after treatment with prasugrel tablets, the risk of significant bleeding was substantial. Although it is generally recommended that antiplatelet therapy be administered promptly in the management of ACS because many cardiovascular events occur within hours of initial presentation, in a trial of 4033 NSTEMI patients, no clear benefit was observed when prasugrel tablets loading dose was administered prior to diagnostic coronary angiography compared to at the time of PCI; however, risk of bleeding was increased with early administration in patients undergoing PCI or early CABG. Dosing in Low Weight Patients Compared to patients weighing ≥60 kg, patients weighing <60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10 mg once daily maintenance dose. Consider lowering the maintenance dose to 5 mg in patients <60 kg. The effectiveness and safety of the 5 mg dose have not been prospectively studied [see Warnings and Precautions ( 5.1 ), Adverse Reactions ( 6.1 ), and Clinical Pharmacology ( 12.3 )]. • Initiate treatment with a single 60 mg oral loading dose ( 2 ). • Continue at 10 mg once daily with or without food. Consider 5 mg once daily for patients <60 kg ( 2 ). • Patients should also take aspirin (75 mg to 325 mg) daily ( 2 ).

WARNINGS AND PRECAUTIONS CABG-related bleeding: Risk increases in patients receiving prasugrel who undergo CABG (5.2) . Discontinuation of prasugrel: Premature discontinuation increases risk of stent thrombosis, MI, and death (5.3) . Thrombotic thrombocytopenic purpura (TTP): TTP has been reported with prasugrel (5.4) . Hypersensitivity: Hypersensitivity including angioedema has been reported with prasugrel including in patients with a history of hypersensitivity reaction to other thienopyridines (5.5) . 5.1 General Risk of Bleeding Thienopyridines, including prasugrel, increase the risk of bleeding. With the dosing regimens used in TRITON-TIMI 38, TIMI (Thrombolysis in Myocardial Infarction) Major (clinically overt bleeding associated with a fall in hemoglobin ≥ 5 g/dL, or intracranial hemorrhage) and TIMI Minor (overt bleeding associated with a fall in hemoglobin of ≥ 3 g/dL but < 5 g/dL), bleeding events were more common on prasugrel than on clopidogrel [see Adverse Reactions (6.1) ] . The bleeding risk is highest initially, as shown in Figure 1 (events through 450 days; inset shows events through 7 days). Figure 1: Non-CABG-Related TIMI Major or Minor Bleeding Events Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or other surgical procedures even if the patient does not have overt signs of bleeding. Do not use prasugrel in patients with active bleeding, prior TIA or stroke [see Contraindications (4.1, 4.2) ] . Other risk factors for bleeding are: Age ≥ 75 years. Because of the risk of bleeding (including fatal bleeding) and uncertain effectiveness in patients ≥ 75 years of age, use of prasugrel is generally not recommended in these patients, except in high-risk situations (patients with diabetes or history of myocardial infarction) where its effect appears to be greater and its use may be considered [see Adverse Reactions (6.1) , Use in Specific Populations (8.5) , Clinical Pharmacology (12.3) and Clinical Studies (14) ] . CABG or other surgical procedure [see Warnings and Precautions (5.2) ] . Body weight < 60 kg. Consider a lower (5 mg) maintenance dose [see Dosage and Administration (2) , Adverse Reactions (6.1) and Use in Specific Populations (8.6) ] . Propensity to bleed (e.g., recent trauma, recent surgery, recent or recurrent gastrointestinal (GI) bleeding, active peptic ulcer disease, severe hepatic impairment, or moderate to severe renal impairment) [see Adverse Reactions (6.1) and Use in Specific Populations (8.7, 8.8) ] . Medications that increase the risk of bleeding (e.g., oral anticoagulants, chronic use of nonsteroidal anti-inflammatory drugs [NSAIDs], and fibrinolytic agents). Aspirin and heparin were commonly used in TRITON-TIMI 38 [see Drug Interactions (7.1, 7.2, 7.4) and Clinical Studies (14) ] . Thienopyridines inhibit platelet aggregation for the lifetime of the platelet (7 to 10 days), so withholding a dose will not be useful in managing a bleeding event or the risk of bleeding associated with an invasive procedure. Because the half-life of prasugrel’s active metabolite is short relative to the lifetime of the platelet, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 6 hours of the loading dose or 4 hours of the maintenance dose may be less effective. Figure 1 5.2 Coronary Artery Bypass Graft Surgery-Related Bleeding The risk of bleeding is increased in patients receiving prasugrel who undergo CABG. If possible, prasugrel should be discontinued at least 7 days prior to CABG. Of the 437 patients who underwent CABG during TRITON-TIMI 38, the rates of CABG-related TIMI Major or Minor bleeding were 14.1% in the prasugrel group and 4.5% in the clopidogrel group [see Adverse Reactions (6.1) ] . The higher risk for bleeding events in patients treated with prasugrel persisted up to 7 days from the most recent dose of study drug. For patients receiving a thienopyridine within 3 days prior to CABG, the frequencies of TIMI Major or Minor bleeding were 26.7% (12 of 45 patients) in the prasugrel group, compared with 5.0% (3 of 60 patients) in the clopidogrel group. For patients who received their last dose of thienopyridine within 4 to 7 days prior to CABG, the frequencies decreased to 11.3% (9 of 80 patients) in the prasugrel group and 3.4% (3 of 89 patients) in the clopidogrel group. Do not start prasugrel in patients likely to undergo urgent CABG. CABG-related bleeding may be treated with transfusion of blood products, including packed red blood cells and platelets; however, platelet transfusions within 6 hours of the loading dose or 4 hours of the maintenance dose may be less effective. 5.3 Discontinuation of Prasugrel Discontinue thienopyridines, including prasugrel, for active bleeding, elective surgery, stroke, or TIA. The optimal duration of thienopyridine therapy is unknown. In patients who are managed with PCI and stent placement, premature discontinuation of any antiplatelet medication, including thienopyridines, conveys an increased risk of stent thrombosis, myocardial infarction, and death. Patients who require premature discontinuation of a thienopyridine will be at increased risk for cardiac events. Lapses in therapy should be avoided, and if thienopyridines must be temporarily discontinued because of an adverse event(s), they should be restarted as soon as possible [see Contraindications (4.1, 4.2) and Warnings and Precautions (5.1) ] . 5.4 Thrombotic Thrombocytopenic Purpura (TTP) TTP has been reported with the use of prasugrel. TTP can occur after a brief exposure (< 2 weeks). TTP is a serious condition that can be fatal and requires urgent treatment, including plasmapheresis (plasma exchange). TTP is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragment red blood cells] seen on peripheral smear), neurological findings, renal dysfunction, and fever [see Adverse Reactions (6.2) ] . 5.5 Hypersensitivity Including Angioedema Hypersensitivity including angioedema has been reported in patients receiving prasugrel, including patients with a history of hypersensitivity reaction to other thienopyridines [see Contraindications (4.3) and Adverse Reactions (6.2) ] . 5.1 General Risk of Bleeding Thienopyridines, including prasugrel, increase the risk of bleeding. With the dosing regimens used in TRITON-TIMI 38, TIMI (Thrombolysis in Myocardial Infarction) Major (clinically overt bleeding associated with a fall in hemoglobin ≥ 5 g/dL, or intracranial hemorrhage) and TIMI Minor (overt bleeding associated with a fall in hemoglobin of ≥ 3 g/dL but < 5 g/dL), bleeding events were more common on prasugrel than on clopidogrel [see Adverse Reactions (6.1) ] . The bleeding risk is highest initially, as shown in Figure 1 (events through 450 days; inset shows events through 7 days). Figure 1: Non-CABG-Related TIMI Major or Minor Bleeding Events Suspect bleeding in any patient who is hypotensive and has recently undergone coronary angiography, PCI, CABG, or other surgical procedures even if the patient does not have overt signs of bleeding. Do not use prasugrel in patients with active bleeding, prior TIA or stroke [see Contraindications (4.1, 4.2) ] . Other risk factors for bleeding are: Age ≥ 75 years. Because of the risk of bleeding (including fatal bleeding) and uncertain effectiveness in patients ≥ 75 years of age, use of prasugrel is generally not recommended in these patients, except in high-risk situations (patients with diabetes or history of myocardial infarction) where its effect appears to be greater and its use may be considered [see Adverse Reactions (6.1) , Use in Specific Populations (8.5) , Clinical Pharmacology (12.3) and Clinical Studies (14) ] . CABG or other surgical procedure [see Warnings and Precautions (5.2) ] . Body weight < 60 kg. Consider a lower (5 mg) maintenance dose [see Dosage and Administration (2) , Adverse Reactions (6.1) and Use in Spec

CONTRAINDICATIONS Active pathological bleeding ( 4.1 ) 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 tablet is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage [see Warnings and Precautions ( 5.1 ) and Adverse Reactions ( 6.1 )] . 4.2 Prior Transient Ischemic Attack or Stroke Prasugrel tablet is 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 tablet is contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to prasugrel or any component of the product [see Adverse Reactions ( 6.2 )] .

Mechanism of Action Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y 12 class of ADP receptors on platelets.