Approved July 10, 2009

PRASUGREL HYDROCHLORIDE
(FDA Category 1P)

EFFIENT(R) (Eli Lilly and Company) is an inhibitor of platelet activation and aggregation mediated by the P2Y12 ADP receptor.

DOSING INFORMATION: Initiate treatment with a single 60 milligrams (mg) oral loading dose and then continue at 10 mg orally once daily with or without food. In patients weighing less than 60 kilograms, the maintenance dose is 5 mg daily. Patients taking prasugrel should also take aspirin 75 mg to 325 mg daily.

PHARMACOKINETICS: Prasugrel is a prodrug and is rapidly hydrolyzed and then metabolized to a pharmacologically active metabolite by CYP3A4 and CYP2B6. Following a 60 mg loading dose of prasugrel, about 90% of patients had at least 50% inhibition of platelet aggregation by 1 hour with maximum platelet inhibition of approximately 80%. The mean steady-state inhibition of platelet aggregation was about 70% after 10 mg daily for 3 to 5 days. Following oral administration, 79% or greater of the dose is absorbed rapidly. The active metabolite is not affected by food; however, food decreases the Cmax by 49% and increase the Tmax from 0.5 to 1.5 hours. The active metabolite is bound approximately 98% to serum albumin; the major inactive metabolites are highly bound to plasma proteins. The apparent Vd of the active metabolite ranged from 44 to 68 L in healthy subjects and patients with stable atherosclerosis. About 68% of the prasugrel dose is excreted in the urine and 27% in the feces as inactive metabolites. The elimination half life of prasugrel active metabolite is 7 to 8 hours (range 2 to 15 hours).

CAUTIONS: Prasugrel is contraindicated in patients with active pathological bleeding, including peptic ulcer and intracranial hemorrhage, and in patients with a history of transient ischemic attack (TIA) or stroke; consider discontinuing if TIA or stroke occurs. However, discontinuation of prasugrel in the first few weeks after acute coronary syndrome increases the risk of subsequent cardiovascular events, so if possible, manage bleeding without discontinuing prasugrel. In patients age 75 years or older, prasugrel is generally not recommended due to fatal and intracranial bleeding with uncertain benefits. Do not start prasugrel in patients likely to undergo urgent coronary artery bypass graft surgery (CABG), and when possible, discontinue prasugrel at least 7 days prior to any surgery. The most common adverse reaction is bleeding related events, particularly in patients age 75 years or older and in those weighing less than 60 kg. Other common non-hemorrhagic adverse events are hypertension, hypercholesterolemia/hyperlipidemia, headache, and back pain.

FDA APPROVED INDICATIONS: Prasugrel is indicated for the reduction of thrombotic cardiovascular events, including stent thrombosis, in patients with acute coronary syndrome (such as unstable angina, non-ST-elevation myocardial infarction, or ST-elevation myocardial infarction) who are to be managed with percutaneous coronary intervention.