Clopidogrel

1 INDICATIONS AND USAGE Clopidogrel is a P2Y 12 platelet inhibitor indicated for: Acute coronary syndrome For patients with non-ST-segment elevation ACS [unstable angina (UA)/non-ST-elevation myocardial infarction (NSTEMI)], clopidogrel tablets have been shown to reduce the rate of myocardial infarction (MI) and stroke. (1.1) For patients with ST-elevation myocardial infarction (STEMI), clopidogrel tablets have been shown to reduce the rate of MI and stroke. (1.1) Recent MI, recent stroke, or established peripheral arterial disease. Clopidogrel tablets have been shown to reduce the rate of MI and stroke.

6 ADVERSE REACTIONS The following serious adverse reactions are discussed below and elsewhere in the labeling: Bleeding [see Warnings and Precautions (5.2) ] Thrombotic thrombocytopenic purpura [see Warnings and Precautions (5.4) ] Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals LLC at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

8.1 Pregnancy Risk Summary Available data from cases reported in published literature and post-marketing surveillance with clopidogrel use in pregnant women have not identified any drug-associated risks for major birth defects or miscarriage [see Data]. There are risks to the pregnant woman and fetus associated with myocardial infarction and stroke [see Clinical Considerations] . No evidence of fetotoxicity was observed when clopidogrel was administered to pregnant rats and rabbits during organogenesis at doses corresponding to 65 and 78 times the recommended daily human dose [see Data] .

WARNING: DIMINISHED ANTIPLATELET EFFECT IN PATIENTS WITH TWO LOSS-OF-FUNCTION ALLELES OF THE CYP2C19 GENE The effectiveness of clopidogrel tablets results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19 [see Warnings and Precautions (5.1) , Clinical Pharmacology (12.3) ] . 5 WARNINGS AND PRECAUTIONS CYP2C19 inhibitors: Avoid concomitant use of omeprazole or esomeprazole. ( 5.1 ) Bleeding: Clopidogrel increases risk of bleeding. ( 5.2 ) Discontinuation: Premature discontinuation increases risk of cardiovascular events. Discontinue 5 days prior to elective surgery that has a major risk of bleeding. ( 5.3 ) Thrombotic thrombocytopenic purpura (TTP) has been reported. ( 5.4 ) Cross-reactivity among thienopyridines has been reported. ( 5.5 ) 5.1 Diminished Antiplatelet Activity in Patients with Impaired CYP2C19 Function Clopidogrel is a prodrug. Inhibition of platelet aggregation by clopidogrel is achieved through an active metabolite. The metabolism of clopidogrel to its active metabolite can be impaired by genetic variations in CYP2C19 [see Boxed Warning ] . 4 CONTRAINDICATIONS Active pathological bleeding, such as peptic ulcer or intracranial hemorrhage. ( 4.1 ) Hypersensitivity to clopidogrel or any component of the product. ( 4.2 ) 4.1 Active Bleeding Clopidogrel is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.