PRASUGREL

Clinical summary

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 ). Standard dosing 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 )]. Dose forms and strengths 30 1 MANNITOL 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 ) Key warnings CABG-related bleeding: Risk increases in patients receiving prasugrel tablets who undergo CABG ( 5.2 ). CABG-related bleeding: Risk increases in patients receiving prasugrel tablets who undergo CABG ( 5.2 ). Discontinuation of prasugrel tablets: Premature discontinuation increases risk of stent thrombosis, MI, and death ( 5.3 ). Thrombotic thrombocytopenic purpura (TTP): TTP has been reported with prasugrel tablets ( 5.4 ). Hypersensitivity: Hypersensitivity including angioedema has been reported with prasugrel tablets including in patients with a history of hypersensitivity reaction to other thienopyridines ( 5.5 ). Drug interactions Opioids: Decreased exposure to prasugrel. Consider use of parenteral anti-platelet agent ( 7.3 ). Pregnancy guidance Risk Summary There are no data with prasugrel tablets use in pregnant women to inform a drug-associated risk. No structural malformations were observed in animal reproductive and developmental toxicology studies when rats and rabbits were administered prasugrel during organogenesis at doses of up to 30 times the recommended therapeutic exposures in humans [see Data ]. Due to the mechanism of action of prasugrel tablets, and the associated identified risk of bleeding, consider the benefits and risks of prasugrel tablets and possible risks to the fetus when prescribing Prasugrel tablets to a pregnant woman [see Boxed Warning , and Warnings and Precautions ( 5.1 , 5.3 )]. The background risk of major birth defects and miscarriage for the indicated population is unknown. The background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies. Data Animal Data In embryo fetal developmental toxicology studies, pregnant rats and rabbits received prasugrel at maternally toxic oral doses equivalent to more than 40 times the human exposure.A slight decrease in fetal body weight was observed; but, there were no structural malformations in either species. In prenatal and postnatal rat studies, maternal treatment with prasugrel had no effect on the behavioral or reproductive development of the offspring at doses g