PRASUGREL- prasugrel_tablet, film coated

Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y 12 Prasugrel produces inhibition of platelet aggregation to 20 muM or 5 muM ADP, as measured by light transmission aggregometry. Following a 60-mg loading dose of Prasugrel tablets, approximately 90% of patients had at least 50% inhibition of platelet aggregation by 1 hour. Maximum platelet inhibition was about 80% (see Figure 2: Inhibition (Mean+/-SD) of 20 muM ADP-induced Platelet Aggregation (IPA) Measured by Light Transmission Aggregometry after Prasugrel 60 mg. 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 a prasugrel 10 mg maintenance dose with or without a prasugrel 60 mg loading dose results in a decrease of 14 percentage points in maximum platelet aggregation (MPA) by Day 7. This decrease in MPA is 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. 5 mg in Low Body Weight Patients Image Prasugrel is a prodrug and is rapidly metabolized to a pharmacologically active metabolite and inactive metabolites. The active metabolite has an elimination half-life of about 7 hours (range 2-15 hours). Healthy subjects, patients with stable atherosclerosis, and patients undergoing PCI show similar pharmacokinetics. Absorption and Binding max max max Metabolism and Elimination Specific Populations Geriatric Patients. [see Warnings and Precautions ( 5. 5 Body Weight [see Dosage and Administration ( 2 5. 6 Male and Female Patients Racial or Ethnic Groups Smoking Patients with Renal Impairment max last [see Warnings and Precautions ( 5. 7 Patients with Hepatic Impairment see Warnings and Precautions ( 5. 8 Drug Interaction Studies Potential for Other Drugs to Affect Prasugrel Inhibitors of CYP3A max max [see Drug Interactions ( 7. 4 Inducers of Cytochromes P450 [see Drug Interactions ( 7. 4 Drugs that Elevate Gastric pH 2 max max 2 [see Drug Interactions ( 7. 4 Statins [see Drug Interactions ( 7. 4 Heparin [see Drug Interactions ( 7. 4 Aspirin [see Drug Interactions ( 7. 4 Warfarin [see Drug Interactions ( 7. 1 Potential for Prasugrel to Affect Other Drugs In vitro Drugs Metabolized by CYP2B6 Effect on Digoxin [see Drug Interactions ( 7. 4 Morphine max max max There is no relevant effect of genetic variation in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 on the pharmacokinetics of prasugrel's active metabolite or its inhibition of platelet aggregation.

Prasugrel tablets is a P2Y 12 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 Prasugrel tablet 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. Prasugrel tablet 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.

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. 3 [see Clinical Pharmacology ( 12. 3 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 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. 3 Initiate treatment with a single 60 mg oral loading dose ( 2 Continue at 10 mg once daily with or without food. Consider 5 mg once daily for patients <60 kg ( 2 Patients should also take aspirin (75 mg to 325 mg) daily ( 2.

The following serious adverse reactions are also discussed elsewhere in the labeling: Bleeding [see Boxed Warning and Warnings and Precautions ( 5. 2 Thrombotic thrombocytopenic purpura [see Warnings and Precautions ( 5. 4 Hypersensitivity including Angioedema [see Warnings and Precautions ( 5. 5 Bleeding, including life-threatening and fatal bleeding, is the most commonly reported adverse reaction ( 6. 1 To report SUSPECTED ADVERSE REACTIONS, contact Apotex Corp. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www. gov/medwatch Safety in patients with ACS undergoing PCI was evaluated in a clopidogrel-controlled study, TRITON-TIMI 38, in which 6741 patients were treated with prasugrel tablets (60 mg loading dose and 10 mg once daily) for a median of 14. 5 months (5802 patients were treated for over 6 months; 4136 patients were treated for more than 1 year). The population treated with prasugrel tablet was 27 to 96 years of age, 25% female, and 92% Caucasian. All patients in the TRITON-TIMI 38 study were to receive aspirin. The dose of clopidogrel in this study was a 300 mg loading dose and 75 mg once daily. Because clinical trials of drug are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials cannot be directly compared with the rates observed in other clinical trials of another drug and may not reflect the rates observed in practice. Drug Discontinuation The rate of study drug discontinuation because of adverse reactions was 7. 2% for Prasugrel tablets and 6. 3% for clopidogrel. Bleeding was the most common adverse reaction leading to study drug discontinuation for both drugs (2. 5% for prasugrel tablets and 1. 4% for clopidogrel). Bleeding Bleeding Unrelated to CABG Surgery Table 1 Table 1: Non-CABG-Related Bleeding * * dagger Prasugrel tablets (%) (N=6741) Clopidogrel (%) (N=6716) TIMI Major or Minor bleeding 4. 4 TIMI Major bleeding dagger 2. 7 Life-threatening 1. 1 Symptomatic intracranial hemorrhage (ICH) 0. 3 Requiring inotropes 0. 1 Requiring surgical intervention 0. 3 Requiring transfusion (>=4 units) 0. 5 TIMI Minor bleeding dagger 2. 9 Figure 1 demonstrates non-CABG related TIMI Major or Minor bleeding. The bleeding rate is highest initially, as shown in Figure 1 (inset: Days 0 to 7) [see Warnings and Precautions ( 5. 1 Bleeding by Weight and Age Table 2 Table 2: Bleeding Rates for Non-CABG-Related Bleeding by Weight and Age (TRITON-TIMI 38) * dagger Major/Minor Fatal Prasugrel tablets * (%) Clopidogrel dagger Prasugrel tablets * (%) Clopidogrel dagger (%) Weight <60 kg (N=308 Prasugrel tablets, N=356 clopidogrel) 10. 3 Weight >=60 kg (N=6373 Prasugrel tablets, N=6299 clopidogrel) 4. 1 Age <75 years (N=5850 Prasugrel tablets, N=5822 clopidogrel) 3. 1 Age >=75 years (N=891 Prasugrel tablets, N=894 clopidogrel) 9. 1 Bleeding Related to CABG (see Table 3: CABG-Related Bleeding * * Prasugrel tablets (%) (N=213) Clopidogrel (%) (N=224) TIMI Major or Minor bleeding 14. 5 TIMI Major bleeding 11. 9 0 Reoperation 3. 5 Transfusion of >=5 units 6. 2 Intracranial hemorrhage 0 0 TIMI Minor bleeding 2. 9 Bleeding Reported as Adverse Reactions - Malignancies During TRITON-TIMI 38, newly-diagnosed malignancies were reported in 1. 2% of patients treated with prasugrel and clopidogrel, respectively. The sites contributing to the differences were primarily colon and lung. In another Phase 3 clinical study of ACS patients not undergoing PCI, in which data for malignancies were prospectively collected, newly-diagnosed malignancies were reported in 1. 7% of patients treated with prasugrel and clopidogrel, respectively. The site of malignancies was balanced between treatment groups except for colorectal malignancies. The rates of colorectal malignancies were 0. 3% prasugrel, 0. 1% clopidogrel and most were detected during investigation of GI bleed or anemia. It is unclear if these observations are causally-related, are the result of increased detection because of bleeding, or are random occurrences. Other Adverse Events In TRITON-TIMI 38, common and other important non-hemorrhagic adverse events were, for prasugrel tablets and clopidogrel, respectively: severe thrombocytopenia (0. 04%), anemia (2. 0%), abnormal hepatic function (0. 27%), allergic reactions (0. 36%), and angioedema (0. Table 4 summarizes the adverse events reported by at least 2. 5% of patients. Table 4: Non-Hemorrhagic Treatment Emergent Adverse Events Reported by at Least 2. 5% of Patients in Either Group * Prasugrel tablets (%) (N=6741) Clopidogrel (%) (N=6716) Hypertension 7. 1 Hypercholesterolemia/Hyperlipidemia 7. 4 Headache 5. 3 Back pain 5. 5 Dyspnea 4. 3 Dizziness 4. 1 Hypotension 3. 8 Fatigue 3. 8 Non-cardiac chest pain 3. 5 Atrial fibrillation 2. 1 Bradycardia 2. 4 Leukopenia (<4 x 10 9 * 2. 4 Pyrexia 2. 2 Peripheral edema 2. 0 Pain in extremity 2. 6 Diarrhea 2. 6 The following adverse reactions have been identified during post approval use of prasugrel tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and lymphatic system disorders - [see Warnings and Precautions ( 5. 4 17 Immune system disorders - [see Contraindications ( 4.

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 Prasugrel tablet is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage [see Warnings and Precautions ( 5. 1 Prasugrel tablet is contraindicated in patients with a history of prior transient ischemic attack (TIA) or stroke. In TRITON-TIMI 38 ( TR I T O N [see Adverse Reactions ( 6. 1 14 Prasugrel tablet is contraindicated in patients with hypersensitivity (e. , anaphylaxis) to prasugrel or any component of the product [see Adverse Reactions ( 6.

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 [see Boxed Warning 5. 3 The background risk of major birth defects and miscarriage for the indicated population is unknown. The background risk in the U. 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 greater than 150 times the human exposure. Risk Summary There is no information regarding the presence of prasugrel in human milk, the effects on the breastfed infant, or the effects on milk production. Metabolites of prasugrel were found in rat milk [see Data Data Animal Data Following a 5 mg/kg oral dose of [ 14 Safety and effectiveness in pediatric patients have not been established. In a randomized, placebo-controlled trial, the primary objective of reducing the rate of vaso-occlusive crisis (painful crisis or acute chest syndrome) in pediatric patients, aged 2 to less than 18 years, with sickle cell anemia was not met. In TRITON-TIMI 38, 38. 5% of patients were >=65 years of age and 13. 2% were >=75 years of age. The risk of bleeding increased with advancing age in both treatment groups, although the relative risk of bleeding (prasugrel tablets compared with clopidogrel) was similar across age groups. Patients >=75 years of age who received prasugrel tablets 10 mg had an increased risk of fatal bleeding events (1. 0%) compared to patients who received clopidogrel (0. In patients >=75 years of age, symptomatic intracranial hemorrhage occurred in 7 patients (0. 8%) who received prasugrel tablets and in 3 patients (0. 3%) who received clopidogrel. Because of the risk of bleeding, and because effectiveness is uncertain in patients >=75 years of age [see Clinical Studies ( 14 [see Warnings and Precautions ( 5. 3 14 In TRITON-TIMI 38, 4. 6% of patients treated with prasugrel tablets had body weight <60 kg. Individuals with body weight <60 kg had an increased risk of bleeding and an increased exposure to the active metabolite of prasugrel [see Dosage and Administration ( 2 5. 3 [see Dosage and Administration ( 2 12. 3 No dosage adjustment is necessary for patients with renal impairment. There is limited experience in patients with end-stage renal disease, but such patients are generally at higher risk of bleeding [see Warnings and Precautions ( 5. 3 No dosage adjustment is necessary in patients with mild to moderate hepatic impairment (Child-Pugh Class A and B). The pharmacokinetics and pharmacodynamics of prasugrel in patients with severe hepatic disease have not been studied, but such patients are generally at higher risk of bleeding [see Warnings and Precautions ( 5. 3 In healthy subjects, patients with stable atherosclerosis, and patients with ACS receiving prasugrel, there was no relevant effect of genetic variation in CYP2B6, CYP2C9, CYP2C19, or CYP3A5 on the pharmacokinetics of prasugrel's active metabolite or its inhibition of platelet aggregation.

Opioids: Decreased exposure to prasugrel. Consider use of parenteral anti-platelet agent ( 7. 3 Coadministration of prasugrel tablets and warfarin increases the risk of bleeding [see Warnings and Precautions ( 5. 3 Coadministration of prasugrel tablets and NSAIDs (used chronically) may increase the risk of bleeding [see Warnings and Precautions ( 5. 1 As with other oral P2Y 12 [see Clinical Pharmacology ( 12. 3 Prasugrel tablets can be administered with drugs that are inducers or inhibitors of cytochrome P450 enzymes [see Clinical Pharmacology ( 12. 3 Prasugrel tablets can be administered with aspirin (75 mg to 325 mg per day), heparin, GPIIb/IIIa inhibitors, statins, digoxin, and drugs that elevate gastric pH, including proton pump inhibitors and H 2 [see Clinical Pharmacology ( 12.

OVERDOSAGE
Platelet inhibition by prasugrel is rapid and irreversible, lasting for the life of the platelet, and is unlikely to be increased in the event of an overdose. In rats, lethality was observed after administration of 2000 mg/kg. Symptoms of acute toxicity in dogs included emesis, increased serum alkaline phosphatase, and hepatocellular atrophy. Symptoms of acute toxicity in rats included mydriasis, irregular respiration, decreased locomotor activity, ptosis, staggering gait, and lacrimation. Platelet transfusion may restore clotting ability. The prasugrel active metabolite is not likely to be removed by dialysis.
NONCLINICAL TOXICOLOGY
Carcinogenesis Mutagenesis in vitro in vivo Impairment of Fertility
CLINICAL STUDIES
The clinical evidence for the effectiveness of Prasugrel tablet is derived from the TRITON-TIMI 38 ( TR I T O N Patients with UA/NSTEMI presenting within 72 hours of symptom onset were to be randomized after undergoing coronary angiography. Patients with STEMI presenting within 12 hours of symptom onset could be randomized prior to coronary angiography. Patients with STEMI presenting between 12 hours and 14 days of symptom onset were to be randomized after undergoing coronary angiography. Patients underwent PCI, and for both UA/NSTEMI and STEMI patients, the loading dose was to be administered anytime between randomization and 1 hour after the patient left the catheterization lab. If patients with STEMI were treated with thrombolytic therapy, randomization could not occur until at least 24 hours (for tenecteplase, reteplase, or alteplase) or 48 hours (for streptokinase) after the thrombolytic was given. Patients were randomized to receive prasugrel tablets (60 mg loading dose followed by 10 mg once daily) or clopidogrel (300 mg loading dose followed by 75 mg once daily), with administration and follow-up for a minimum of 6 months (actual median 14. Patients also received aspirin (75 mg to 325 mg once daily). Other therapies, such as heparin and intravenous glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, were administered at the discretion of the treating physician. Oral anticoagulants, other platelet inhibitors, and chronic NSAIDs were not allowed. The primary outcome measure was the composite of cardiovascular death, nonfatal MI, or nonfatal stroke in the UA/NSTEMI population. Success in this group allowed analysis of the same endpoint in the overall ACS and STEMI populations. Nonfatal MIs included both MIs detected solely through analysis of creatine kinase muscle-brain (CK-MB) changes and clinically apparent (investigator-reported) MIs. The patient population was 92% Caucasian, 26% female, and 39% >=65 years of age. The median time from symptom onset to study drug administration was 7 hours for patients with STEMI and 30 hours for patients with UA/NSTEMI. Approximately 99% of patients underwent PCI. The study drug was administered after the first coronary guidewire was placed in approximately 75% of patients. Prasugrel tablets significantly reduced total endpoint events compared to clopidogrel ( see [see Adverse Reactions ( 6. 1 The treatment effect of prasugrel tablet was apparent within the first few days, and persisted to the end of the study ( see Figure 3: Time to first event of CV Death, MI, or Stroke (TRITON-TIMI 38). The Kaplan-Meier curves ( see Prasugrel tablets reduced the occurrence of the primary composite endpoint compared to clopidogrel in both the UA/NSTEMI and STEMI populations ( see Table 5: Patients with Outcome Events (CV Death, MI, Stroke) in TRITON-TIMI 38 * Patients with events From Kaplan-Meier analysis Prasugrel tablets (%) Clopidogrel (%) Relative Risk Reduction (%) * (95% CI) p-value UA/NSTEMI N=5044 N=5030 CV death, nonfatal MI, or nonfatal stroke 9. 002 CV death 1. 885 Nonfatal MI 7. 001 Nonfatal Stroke 0. 922 STEMI N=1769 N=1765 CV death, nonfatal MI, or nonfatal stroke 9. 019 CV death 2. 129 Nonfatal MI 6. 016 Nonfatal Stroke 1. 77 The effect of Prasugrel tablets in various subgroups is shown in Figures 4 and 5. Results are generally consistent across pre-specified subgroups, with the exception of patients with a history of TIA or stroke [see Contraindications ( 4. 2 [see Adverse Reactions ( 6. 1 Figure 4: Subgroup analyses for time to first event of CV Death, MI, or Stroke (HR and 95% CI; TRITON-TIMI 38) en dash UA/NSTEMI Patients. Figure 5: Subgroup analyses for time to first event of CV Death, MI, or Stroke (HR and 95% CI; TRITON-TIMI 38) en dash STEMI Patients. Prasugrel tablet is generally not recommended in patients >=75 years of age, except in high-risk situations (diabetes mellitus or prior MI) where its effect appears to be greater and its use may be considered. These recommendations are based on subgroup analyses ( see Table 6: Subgroup Analyses for Time to First Event of CV Death, MI, or Stroke: Patients < or >=75 Years of Age, +/- Diabetes, +/- Prior History of MI, All ACS Patient Population Prasugrel tablets Clopidogrel Hazard Ratio (95% CI) N % with eventsN % with events Age >=75 Diabetes - yes 249 14. 97) Diabetes - no 652 16. 43) Age <75 Diabetes - yes 1327 10. 89) Diabetes - no 4585 7. 94) Age >=75 Prior MI - yes 220 17. 09) Prior MI - no 681 15. 37) Age <75 Prior MI - yes 1006 12. 99) Prior MI - no 4906 7. 90) There were 50% fewer stent thromboses (95% C. 32% - 64%; p<0. 001) reported among patients randomized to Prasugrel tablets (0. 9%) than among patients randomized to clopidogrel (1. The difference manifested early and was maintained through one year of follow-up. Findings were similar with bare metal and drug-eluting stents. In TRITON-TIMI 38, prasugrel reduced ischemic events (mainly nonfatal MIs) and increased bleeding events [see Adverse Reactions ( 6. 1 [see Clinical Pharmacology ( 12. 2 Image Image Image Image.
MEDICATION GUIDE
Prasugrel tablets USP (PRA-soo-grel tablets) What is the most important information I should know about prasugrel tablets? Prasugrel tablet is used to lower your chance of having a heart attack or other serious problems with your heart or blood vessels. But, prasugrel tablets can cause bleeding, which can be serious, and sometimes lead to death. You should not start to take prasugrel tablets if it is likely that you will have heart bypass surgery (coronary artery bypass graft surgery or CABG) right away. You have a higher risk of bleeding if you take prasugrel tablets and then have heart bypass surgery. What is Prasugrel tablet? Prasugrel tablet is a prescription medicine used to treat people who: have had a heart attack or severe chest pain that happens when your heart does not get enough oxygen, and have been treated with a procedure called "angioplasty" (also called balloon angioplasty). Prasugrel tablet is used to lower your chance of having another serious problem with your heart or blood vessels, such as another heart attack, a stroke, blood clots in your stent, or death. Platelets are blood cells that help with normal blood clotting. Prasugrel tablets helps prevent platelets from sticking together and forming a clot that can block an artery or a stent. It is not known if Prasugrel tablet is safe and works in children. Who should not take prasugrel tablets? Do not take prasugrel tablets if you: currently have abnormal bleeding, such as stomach or intestinal bleeding, or bleeding in your head have had a stroke or "mini-stroke" (also known as transient ischemic attack or TIA) are allergic to prasugrel or any of the ingredients in prasugrel tablets. See the end of this Medication Guide for a list of ingredients in prasugrel tablets. Get medical help right away if you think you may be having a stroke or TIA. Symptoms that you may be having a stroke or TIA include: sudden slurring of speech, sudden weakness or numbness in one part of your body, sudden blurry vision, or sudden severe headache. If you have a stroke or TIA while taking prasugrel tablets, your doctor will probably stop your prasugrel tablets. Follow your doctor''s instructions about stopping prasugrel tablets. Do not stop taking prasugrel tablets unless your doctor tells you to. Before having any surgery you should talk to your doctor about stopping prasugrel tablets. If possible, prasugrel tablets should be stopped at least 1 week (7 days) before any surgery, as instructed by the doctor who prescribed prasugrel tablets for you. Your risk of bleeding while taking prasugrel tablets may be higher if you also: have had trauma, such as an accident or surgery have stomach or intestine bleeding that is recent or keeps coming back, or you have a stomach ulcer have severe liver problems have moderate to severe kidney problems weigh less than 132 pounds take other medicines that increase your risk of bleeding, including: warfarin sodium (Coumadin*, Jantoven*) a medicine that contains heparin other medicines to prevent or treat blood clots regular daily use of nonsteroidal anti-inflammatory drugs (NSAIDs) Tell your doctor if you take any of these medicines. Ask your doctor if you are not sure if your medicine is one listed above. Prasugrel tablets increases your risk of bleeding because it lessens the ability of your blood to clot. While you take prasugrel tablets: you will bruise and bleed more easily you are more likely to have nose bleeds it will take longer for any bleeding to stop Call your doctor right away if you have any of these signs or symptoms of bleeding: unexpected bleeding or bleeding that lasts a long time bleeding that is severe or you cannot control pink or brown urine red or black stool (looks like tar) bruises that happen without a known cause or get larger cough up blood or blood clots vomit blood or your vomit looks like "coffee grounds" Do not stop taking prasugrel tablets without talking to the doctor who prescribes it for you. People who are treated with angioplasty and have a stent, and stop taking prasugrel tablets too soon, have a higher risk of a blood clot in the stent, having a heart attack, or dying. If you must stop prasugrel tablets because of bleeding, your risk of a heart attack may be higher. See "What are the possible side effects of Prasugrel tablets?" for more information about side effects. What should I tell my doctor before taking prasugrel tablets? Before you take Prasugrel tablets, tell your doctor about all of your medical conditions, including if you: have any bleeding problems have had a stroke or "mini-stroke" (also known as transient ischemic attack or TIA) are allergic to any medicines, including clopidogrel (Plavix*) or ticlopidine hydrochloride have a history of stomach ulcers, colon polyps, diverticulosis have liver problems have kidney problems have had any recent severe injury or surgery plan to have surgery or a dental procedure. See "What is the most important information I should know about prasugrel tablets?" are pregnant, or are planning to get pregnant. It is not known if Prasugrel tablets will harm your baby. are breast-feeding. It is not known if prasugrel tablets passes into your breast-milk. You and your doctor should decide if you will take prasugrel tablets or breastfeed. You should not do both without talking with your doctor. Tell all of your doctors and dentists that you are taking prasugrel tablets. They should talk to the doctor who prescribed prasugrel tablets for you, before you have any Tell your doctor about all the medicines you take Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. How should I take prasugrel tablets? Take prasugrel tablets exactly as prescribed by your doctor. Take prasugrel tablets one time each day. You can take prasugrel tablets with or without food. Do not split Prasugrel tablets. Take prasugrel tablets with aspirin as instructed by your doctor. Your doctor will decide how long you should take prasugrel tablets. Do not stop taking prasugrel tablets without first talking to the doctor who prescribed it for you. See "What is the most important information I should know about prasugrel tablets?" If you miss a dose, take prasugrel tablets as soon as you remember. If it is almost time for your next dose, skip the missed dose. Just take the next dose at your regular time. Do not take two doses at the same time unless your doctor tells you to. If you take too much prasugrel tablets, call your local emergency room or poison control center right away. Call your doctor or healthcare provider right away if you fall or injure yourself, especially if you hit your head. Your doctor or healthcare provider may need to check you. What are the possible side effects of prasugrel tablets? Prasugrel tablets can cause serious side effects, including: See "What is the most important information I should know about prasugrel tablets?" A blood clotting problem called thrombotic thrombocytopenic purpura (TTP). purplish spots called purpura on the skin or mucous membranes (such as on the mouth) due to bleeding under the skin paleness or jaundice (a yellowish color of the skin or eyes) feeling tired or weak fever fast heart rate or feeling short of breath headache, speech changes, confusion, coma, stroke, or seizure low amount of urine or urine that is pink-tinged or has blood in it stomach area (abdominal) pain, nausea, vomiting, or diarrhea visual changes Serious allergic reactions Get medical help right away if you get any of these symptoms of a severe allergic reaction while taking prasugrel tablets. swelling or hives of your face, lips, in or around your mouth, or throat trouble breathing or swallowing chest pain or pressure dizziness or fainting Tell your doctor if you have any side effect that bothers you or that does not go away. These are not all of the possible side effects of prasugrel tablets. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store prasugrel tablets? Keep prasugrel tablets at room temperature between 59°F to 86°F (15°C to 30°C). Keep and dispense only in original container. Keep the container closed tightly with the gray cylinder inside. Protect prasugrel tablets from moisture. Keep prasugrel tablets and all medicines out of the reach of children. General Information about safe and effective use of prasugrel tablets Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use prasugrel tablets for a condition for which it was not prescribed. Do not give your prasugrel tablets to other people, even if they have the same symptoms you have. It may harm them. This Medication Guide summarizes the most important information about prasugrel tablets. If you would like more information about prasugrel tablets, talk with your doctor or pharmacist. For more information, call Apotex Corp. at 1-800-706-5575 What are the ingredients in prasugrel tablets? Active Ingredient: prasugrel hydrochloride, USP Inactive Ingredients: microcrystalline cellulose, mannitol, low-substituted hydroxypropyl cellulose, hypromellose, stearic acid, and glyceryl behenate. The color coatings contain lactose monohydrate, hypromellose, titanium dioxide, triacetin, iron oxide yellow, and iron oxide red (only in prasugrel 10 mg tablet). Revised : Manufactured by : Panacea Biotec Pharma Limited Malpur, Baddi, District Solan (H.P.) - 173205, India. Mfg. Lic. No.: Manufactured for : Apotex Corp. Weston, Florida 33326 This Medication Guide has been approved by the U.S. Food and Drug Administration. *

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