EFFIENT- prasugrel hydrochloride tablet, film coated
Eli Lilly and Company
WARNING: BLEEDING RISK
Effient can cause significant, sometimes fatal, bleeding [see Warnings and Precautions (5.1, 5.2) and Adverse Reactions (6.1)] .
Do not use Effient in patients with active pathological bleeding or a history of transient ischemic attack or stroke [see Contraindications (4.1, 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 situations (patients with diabetes or a history of prior MI) where its effect appears to be greater and its use may be considered [see Use in Specific Populations (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 [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 non-steroidal 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 Effient [see Warnings and Precautions (5.1)].
If possible, manage bleeding without discontinuing Effient. Discontinuing Effient, particularly in the first few weeks after acute coronary syndrome, increases the risk of subsequent cardiovascular events [see Warnings and Precautions (5.3)] .
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:
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.
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)].
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 (7.3) and Clinical Pharmacology (12.3)]. Effient 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 Effient, the loading dose of Effient 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 Effient was administered at the time of diagnosis, although most received Effient at the time of PCI [see Clinical Studies (14)]. For the small fraction of patients that required urgent CABG after treatment with Effient, 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 Effient 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)].
