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EFFIENT (prasugrel) tablets
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use Effient safely and effectively. See full prescribing information for Effient.
EFFIENT (prasugrel) tablets
Initial U.S. Approval: 2009
WARNING: BLEEDING RISK
See full prescribing information for complete boxed warning
Effient can cause significant, sometimes fatal, bleeding (5.1, 5.2, and 6.1).
Do not use Effient in patients with active pathological bleeding or a history of transient ischemic attack or stroke (4.1 and 4.2).
In patients ≥ 75 years of age, Effient is generally not recommended because of the increased risk of fatal and intracranial bleeding and uncertain benefit, except in high-risk patients (diabetes or prior MI), where its effect appears to be greater and its use may be considered (8.5).
Do not start Effient in patients likely to undergo urgent coronary artery bypass graft surgery (CABG). When possible, discontinue Effient at least 7 days prior to any surgery.
Additional risk factors for bleeding include:
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body weight < 60 kg
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propensity to bleed
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concomitant use of medications that increase the risk of bleeding
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 Effient.
If possible, manage bleeding without discontinuing Effient. Stopping Effient, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events (5.3).
RECENT MAJOR CHANGES
Contraindications, Hypersensitivity (4.3) 12/2010
Warnings and Precautions, Thrombotic Thrombocytopenic Purpura (5.4) 12/2010
INDICATIONS AND USAGE
Effient is a P2Y12 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 PCI as follows:
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Patients with unstable angina or, non-ST-elevation myocardial infarction (NSTEMI) (1.1).
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Patients with ST-elevation myocardial infarction (STEMI) when managed with either primary or delayed PCI (1.1).
DOSAGE AND ADMINISTRATION
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Initiate treatment with a single 60 mg oral loading dose (2).
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Continue at 10 mg once daily with or without food. Consider 5 mg once daily for patients <60 kg (2).
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Patients should also take aspirin (75 mg to 325 mg) daily (2).
DOSAGE FORMS AND STRENGTHS
5 mg and 10 mg tablets (3)
CONTRAINDICATIONS
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Active pathological bleeding (4.1)
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Prior transient ischemic attack or stroke (4.2)
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Hypersensitivity to prasugrel or any component of the product (4.3)
WARNINGS AND PRECAUTIONS
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CABG-related bleeding: Risk increases in patients receiving Effient who undergo CABG (5.2).
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Discontinuation of Effient: Premature discontinuation increases risk of stent thrombosis, MI, and death (5.3).
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Thrombotic thrombocytopenic purpura (TTP): TTP has been reported with Effient (5.4).
ADVERSE REACTIONS
Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Eli Lilly and Company at 1-800-545-5979 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.
Revised: 3/2011
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
1.1 Acute Coronary Syndrome
Effient™ 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:
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Patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI).
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Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI.
Effient 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)].
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 the clinical trial that established the efficacy of Effient, Effient and the control drug were not administered to UA/NSTEMI patients until coronary anatomy was established. For the small fraction of patients that required urgent CABG after treatment with Effient, the risk of significant bleeding was substantial [see Warnings and Precautions (5.2)]. Because the large majority of patients are managed without CABG, however, treatment can be considered before determining coronary anatomy if need for CABG is considered unlikely. The advantages of earlier treatment with Effient must then be balanced against the increased rate of bleeding in patients who do need to undergo urgent CABG.
2 DOSAGE AND ADMINISTRATION
Initiate Effient treatment as a single 60 mg oral loading dose and then continue at 10 mg orally once daily. Patients taking Effient should also take aspirin (75 mg to 325 mg) daily [see Drug Interactions (7) and Clinical Pharmacology (12.3)]. Effient may be administered with or without food [see Clinical Pharmacology (12.3) and Clinical Studies (14)].
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.
3 DOSAGE FORMS AND STRENGTHS
Effient 5 mg is a yellow, elongated hexagonal, film-coated, non-scored tablet debossed with “5 MG” on one side and “4760” on the other side.
Effient 10 mg is a beige, elongated hexagonal, film-coated, non-scored tablet debossed with “10 MG” on one side and with “4759” on the other side.
4 CONTRAINDICATIONS
4.1 Active Bleeding
Effient 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
Effient is contraindicated in patients with a history of prior transient ischemic attack (TIA) or stroke. In TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel), patients with a history of TIA or ischemic stroke (> 3 months prior to enrollment) had a higher rate of stroke on Effient (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 Effient 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 Effient generally should have therapy discontinued [see Adverse Reactions (6.1) and Clinical Studies (14)].
4.3 Hypersensitivity
Effient is contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to prasugrel or any component of the product [see Adverse Reactions (6.2)].
5 WARNINGS AND PRECAUTIONS
5.1 General Risk of Bleeding
Thienopyridines, including Effient, 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 Effient 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).
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 Effient in patients with active bleeding, prior TIA or stroke [see Contraindications (4.1 and 4.2)].
Other risk factors for bleeding are:
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Age ≥ 75 years. Because of the risk of bleeding (including fatal bleeding) and uncertain effectiveness in patients ≥ 75 years of age, use of Effient 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 Trials (14)].
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CABG or other surgical procedure [see Warnings and Precautions (5.2)].
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Body weight < 60 kg. Consider a lower (5 mg) maintenance dose [see Dosage and Administration (2), Adverse Reactions (6.1), Use in Specific Populations (8.6)].
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Propensity to bleed (e.g., recent trauma, recent surgery, rec
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