EFFIENT™ (prasugrel) tablets

DESCRIPTION
Effient contains prasugrel, a thienopyridine class inhibitor of platelet activation and aggregation mediated by the P2Y12 ADP receptor. Effient is formulated as the hydrochloride salt, a racemate, which is chemically designated as 5-[(1RS)-2-cyclopropyl-1-(2-fluorophenyl)-2-oxoethyl]-4,5,6,7-tetrahydrothieno[3,2-c]pyridin-2-yl acetate hydrochloride. Prasugrel hydrochloride has the empirical formula C20H20FNO3S•HCl representing a molecular weight of 409.90.

Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y12 class of ADP receptors on platelets.

Pharmacodynamics
Prasugrel produces inhibition of platelet aggregation to 20 µM or 5 µM ADP, as measured by light transmission aggregometry. Following a 60-mg loading dose of Effient, approximately 90% of patients had at least 50% inhibition of platelet aggregation by 1 hour. Maximum platelet inhibition was about 80%. Mean steady-state inhibition of platelet aggregation was about 70% following 3 to 5 days of dosing at 10 mg daily after a 60-mg loading dose of Effient.

Platelet aggregation gradually returns to baseline values over 5-9 days after discontinuation of prasugrel, this time course being a reflection of new platelet production rather than pharmacokinetics of prasugrel. Discontinuing clopidogrel 75 mg and initiating prasugrel 10 mg with the next dose resulted in increased inhibition of platelet aggregation, but not greater than that typically produced by a 10 mg maintenance dose of prasugrel alone. The relationship between inhibition of platelet aggregation and clinical activity has not been established.

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)].

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.

-- Active pathological bleeding
-- Prior transient ischemic attack or stroke
-- Hypersensitivity to prasugrel or any component of the product

--CABG-related bleeding: Risk increases in patients receiving Effient who undergo CABG.
--Discontinuation of Effient: Premature discontinuation increases risk of stent thrombosis, MI, and death.
--Thrombotic thrombocytopenic purpura (TTP): TTP has been reported with Effient.
--Hypersensitivity: Hypersensitivity including angioedema has been reported with Effient including in patients with a history of hypersensitivity reaction to other thienopyridines

Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction.
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

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. Effient may be administered with or without food].

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.

Effient (prasugrel) 5 mg is supplied as a yellow, elongated hexagonal, film-coated, non-scored tablet debossed with "5 MG" on one side and with "4760" on the other side.

5 mg tablets are supplied as follows:
Bottles of 7 - NDC 0002-4760-76
Bottles of 30 - NDC 0002-4760-30

Effient (prasugrel) 10 mg is supplied as a beige, elongated hexagonal, film-coated, non-scored tablet debossed with "10 MG" on one side and "4759" on the other side.

10 mg tablets are supplied as follows:
Bottles of 30 – NDC 0002-4759-30
Blisters ID 90* NDC 0002-4759-77

(*Identi Dose®, unit dose medication, Lilly)
Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F).

Dispense and keep product in original container. Keep container closed and do not remove desiccant from bottle. Do not break the tablet.