Clopidogrel
Clopidogrel Bisulfate · Tablet, Film Coated · Oral
Uses
Clopidogrel tablets 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 has been shown to reduce the rate of myocardial infarction (MI) and stroke. ( 1.1 ) - For patients with ST-elevation myocardial infarction (STEMI), clopidogrel tablets has been shown to reduce the rate of MI and stroke. ( 1.1 )
• Recent MI, recent stroke, or established peripheral arterial disease. Clopidogrel tablets has been shown to reduce the rate of MI and stroke. ( 1.2 ) 1.1 Acute Coronary Syndrome (ACS)
• Clopidogrel tablets is indicated to reduce the rate of myocardial infarction (MI) and stroke in patients with non-ST-segment elevation ACS (unstable angina [UA]/non-ST-elevation myocardial infarction [NSTEMI]), including patients who are to be managed medically and those who are to be managed with coronary revascularization. Clopidogrel tablets should be administered in conjunction with aspirin.
• Clopidogrel tablets is indicated to reduce the rate of myocardial infarction and stroke in patients with acute ST-elevation myocardial infarction (STEMI) who are to be managed medically. Clopidogrel tablets should be administered in conjunction with aspirin. 1.2 Recent MI, Recent Stroke, or Established Peripheral Arterial Disease In patients with established peripheral arterial disease or with a history of recent myocardial infarction (MI) or recent stroke clopidogrel tablets is indicated to reduce the rate of MI and stroke.
Dosage and administration
• Acute coronary syndrome ( 2.1 ) - Initiate clopidogrel tablets with a single 300 mg oral loading dose and then continue at 75 mg once daily. - Initiating clopidogrel tablets without a loading dose will delay establishment of an antiplatelet effect by several days.
• Recent MI, recent stroke, or established peripheral arterial disease: 75 mg once daily orally without a loading dose. ( 2.2 ) 2.1 Acute Coronary Syndrome In patients who need an antiplatelet effect within hours, initiate clopidogrel tablets with a single 300 mg oral loading dose and then continue at 75 mg once daily. Initiating clopidogrel tablets without a loading dose will delay establishment of an antiplatelet effect by several days [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )] . 2.2 Recent MI, Recent Stroke, or Established Peripheral Arterial Disease 75 mg once daily orally without a loading dose [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.2 )].
Dosage forms and strengths
• 75 mg tablets: Pink colored, biconvex, round shaped, beveled edge, film coated tablets printed "CL 75" on one side and plain on other side. Film-coated tablets: 75 mg ( 3 )
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 tablets is contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage. 4.2 Hypersensitivity Clopidogrel tablets is contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to clopidogrel or any component of the product [see Adverse Reactions ( 6.2 )].
Warnings and precautions
• CYP2C19 inhibitors: Avoid concomitant use of omeprazole or esomeprazole. ( 5.1 )
• Bleeding: Clopidogrel tablets 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]. The metabolism of clopidogrel can also be impaired by drugs that inhibit CYP2C19, such as omeprazole or esomeprazole. Avoid concomitant use of clopidogrel tablets with omeprazole or esomeprazole because both significantly reduce the antiplatelet activity of clopidogrel tablets [see Drug Interactions ( 7.1 )]. 5.2 General Risk of Bleeding P2Y12 inhibitors (thienopyridines), including clopidogrel tablets, increase the risk of bleeding. P2Y12 inhibitors (thienopyridines), inhibit platelet aggregation for the lifetime of the platelet (7 to 10 days). Because the half-life of clopidogrel’s active metabolite is short, it may be possible to restore hemostasis by administering exogenous platelets; however, platelet transfusions within 4 hours of the loading dose or 2 hours of the maintenance dose may be less effective. Use of drugs that induce the activity of CYP2C19 would be expected to result in increased drug levels of the active metabolite of clopidogrel and might potentiate the bleeding risk. As a precaution, avoid concomitant use of strong CYP2C19 inducers [see Drug Interactions ( 7.1 ) and Clinical Pharmacology ( 12.3 )]. Risk factors for bleeding include concomitant use of other drugs that increase the risk of bleeding (e.g., anticoagulants, antiplatelet agents, and chronic use of NSAIDs) [see Drug Interactions ( 7.4 , 7.5 , 7.6 , 7.7 )]. 5.3 Discontinuation of clopidogrel tablets Discontinuation of clopidogrel tablets increases the risk of cardiovascular events. If clopidogrel tablets must be temporarily discontinued (e.g., to treat bleeding or for surgery with a major risk of bleeding), restart it as soon as possible. When possible, interrupt therapy with clopidogrel tablets for five days prior to such surgery. Resume clopidogrel tablets as soon as hemostasis is achieved. 5.4 Thrombotic Thrombocytopenic Purpura (TTP) TTP, sometimes fatal, has been reported following use of clopidogrel tablets, sometimes after a short exposure (less than 2 weeks). TTP is a serious condition that requires urgent treatment including plasmapheresis (plasma exchange). It is characterized by thrombocytopenia, microangiopathic hemolytic anemia (schistocytes [fragmented RBCs] seen on peripheral smear), neurological findings, renal dysfunction, and fever [see Adverse Reactions ( 6.2 )]. 5.5 Cross-Reactivity among Thienopyridines Hypersensitivity including rash, angioedema or hematologic reaction has been reported in patients receiving clopidogrel tablets, including patients with a history of hypersensitivity or hematologic reaction to other thienopyridines [see Contraindications ( 4.2 ) and Adverse Reactions ( 6.2 )].
Side effects
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 Ascend Laboratories, LLC at 1-877-272-7901 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions and durations of follow-up, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Clopidogrel tablets has been evaluated for safety in more than 54,000 patients, including over 21,000 patients treated for one year or more. The clinically important adverse reactions observed in trials comparing clopidogrel tablets plus aspirin to placebo plus aspirin and trials comparing clopidogrel tablets alone to aspirin alone are discussed below. Bleeding CURE In CURE, clopidogrel tablets use with aspirin was associated with an increase in major bleeding (primarily gastrointestinal and at puncture sites) compared to placebo with aspirin (see Table 1). The incidence of intracranial hemorrhage (0.1%) and fatal bleeding (0.2%) were the same in both groups. Other bleeding events that were reported more frequently in the clopidogrel group were epistaxis, hematuria, and bruise. The overall incidence of bleeding is described in Table 1. Table 1: CURE Incidence of Bleeding Complications (% patients) Event Clopidogrel tablets (+ aspirin) (n=6259) Placebo (+ aspirin) (n=6303) Major bleeding * 3.7 2.7 Life-threatening bleeding 2.2 1.8 Fatal 0.2 0.2 5 g/dL hemoglobin drop 0.9 0.9 Requiring surgical intervention 0.7 0.7 Hemorrhagic strokes 0.1 0.1 Requiring inotropes 0.5 0.5 Requiring transfusion (≥4 units) 1.2 1.0 Other major bleeding 1.6 1.0 Significantly disabling 0.4 0.3 Intraocular bleeding with significant loss of vision 0.05 0.03 Requiring 2-3 units of blood 1.3 0.9 Minor bleeding † 5.1 2.4 * Life-threatening and other major bleeding. † Led to interruption of study medication. COMMIT In COMMIT, similar rates of major bleeding were observed in the clopidogrel tablets and placebo groups, both of which also received aspirin (see Table 2). Table 2: Incidence of Bleeding Events in COMMIT (% patients) Type of Bleeding Clopidogrel tablets (+ aspirin) (n=22961) Placebo (+ aspirin) (n=22891) p-value Major* noncerebral or cerebral bleeding 0.6 0.5 0.59 Major noncerebral 0.4 0.3 0.48 Fatal 0.2 0.2 0.90 Hemorrhagic stroke 0.2 0.2 0.91 Fatal 0.2 0.2 0.81 Other noncerebral bleeding (nonmajor) 3.6 3.1 0.005 Any noncerebral bleeding 3.9 3.4 0.004 * Major bleeds were cerebral bleeds or noncerebral bleeds thought to have caused death or that required transfusion. CAPRIE (Clopidogrel tablets vs Aspirin) In CAPRIE, gastrointestinal hemorrhage occurred at a rate of 2.0% in those taking clopidogrel tablets versus 2.7% in those taking aspirin; bleeding requiring hospitalization occurred in 0.7% and 1.1%, respectively. The incidence of intracranial hemorrhage was 0.4% for clopidogrel tablets compared to 0.5% for aspirin. Other bleeding events that were reported more frequently in the clopidogrel tablets group were epistaxis and hematoma. Other Adverse Events In CURE and CHARISMA, which compared clopidogrel tablets plus aspirin to aspirin alone, there was no difference in the rate of adverse events (other than bleeding) between clopidogrel tablets and placebo. In CAPRIE, which compared clopidogrel tablets to aspirin, pruritus was more frequently reported in those taking clopidogrel tablets. No other difference in the rate of adverse events (other than bleeding) was reported. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of clopidogrel tablets. Because these reactions are reported voluntarily from a population of an unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hemorrhages, including those with fatal outcome, have been reported in patients treated with clopidogrel tablets.
• Blood and lymphatic system disorders: Agranulocytosis, aplastic anemia/pancytopenia, thrombotic thrombocytopenic purpura (TTP), acquired hemophilia A
• Gastrointestinal disorders: Colitis (including ulcerative or lymphocytic colitis), pancreatitis, stomatitis, gastric/duodenal ulcer, diarrhea
• General disorders and administration site condition: Fever
• Hepatobiliary disorders: Acute liver failure, hepatitis (noninfectious), abnormal liver function test
• Immune system disorders: Hypersensitivity reactions, anaphylactoid reactions, serum sickness, insulin autoimmune syndrome, which can lead to severe hypoglycemia
• Musculoskeletal, connective tissue and bone disorders: Myalgia, arthralgia, arthritis
• Nervous system disorders: Taste disorders, headache, ageusia
• Psychiatric disorders: Confusion, hallucinations
• Respiratory, thoracic and mediastinal disorders: Bronchospasm, interstitial pneumonitis, eosinophilic pneumonia
• Renal and urinary disorders: Increased creatinine levels
• Skin and subcutaneous tissue disorders: Maculopapular, erythematous or exfoliative rash, urticaria, bullous dermatitis, eczema, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis (AGEP), angioedema, drug-induced hypersensitivity syndrome, drug rash with eosinophilia and systemic symptoms (DRESS), erythema multiforme, lichen planus, generalized pruritus
• Vascular disorders: Vasculitis, hypotension
Drug interactions
• CYP2C19 inducers: Increases levels of clopidogrel active metabolite and increases platelet inhibition. ( 7.1)
• Opioids: Decreased exposure to clopidogrel. Consider use of parenteral antiplatelet agent.( 7.3 )
• Nonsteroidal anti-inflammatory drugs (NSAIDs), warfarin, selective serotonin and serotonin norepinephrine reuptake inhibitors (SSRIs, SNRIs): Increases risk of bleeding. ( 7.4 , 7.5 , 7.6 ) Other Antiplatelet Agents: Increases the risk of bleeding due to an additive effect. ( 7.7 )
• Repaglinide (CYP2C8 substrates): Increases substrate plasma concentrations. ( 7.8 ) 7.1 CYP2C19 Inducers Since clopidogrel is metabolized to its active metabolite partly by CYP2C19, use of drugs that induce the activity of this enzyme would be expected to result in increased drug levels of the active metabolite of clopidogrel. Rifampin strongly induces CYP2C19 resulting to both an increase level of clopidogrel active metabolite and platelet inhibition, which in particular might potentiate the risk of bleeding. As a precaution, avoid concomitant use of strong CYP2C19 inducers [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )]. 7.2CYP2C19 Inhibitors Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of drugs that inhibit the activity of this enzyme results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition [see Warnings and Precautions (5.1)]. Omeprazole or Esomeprazole Avoid concomitant use of clopidogrel tablets with omeprazole or esomeprazole. In clinical studies, omeprazole was shown to reduce significantly the antiplatelet activity of clopidogrel tablets when given concomitantly or 12 hours apart. A similar reduction in antiplatelet activity was observed with esomeprazole when given concomitantly with clopidogrel tablets. Dexlansoprazole, lansoprazole, and pantoprazole had less effect on the antiplatelet activity of clopidogrel tablets than did omeprazole or esomeprazole [see Warnings and Precautions ( 5.1 ) and Clinical Pharmacology ( 12.3 )]. 7.3 Opioids As with other oral P2Y12 inhibitors, coadministration of opioid agonists delay and reduce the absorption of clopidogrel, presumably because of slowed gastric emptying, resulting in reduced exposure to its metabolites [ see Clinical Pharmacology ( 12.3 ) ]. Consider the use of a parenteral antiplatelet agent in acute coronary syndrome patients requiring coadministration of morphine or other opioid agonists. 7.4 Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Coadministration of clopidogrel tablets and NSAIDs increases the risk of gastrointestinal bleeding. 7.5 Warfarin (CYP2C9 Substrates) Although the administration of clopidogrel 75 mg per day did not modify the pharmacokinetics of S-warfarin (a CYP2C9 substrate) or INR in patients receiving long-term warfarin therapy, coadministration of clopidogrel tablets with warfarin increases the risk of bleeding because of independent effects on hemostasis. However, at high concentrations in vitro, clopidogrel inhibits CYP2C9. 7.6 SSRIs and SNRIs Since selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs) affect platelet activation, the concomitant administration of SSRIs and SNRIs with clopidogrel may increase the risk of bleeding. 7.7 Other Antiplatelet Agents Coadministration of antiplatelet agents increase the risk of bleeding due to an additive effect. Promptly evaluate any signs or symptoms of blood loss if patients are treated concomitantly with other antiplatelet agents [see Warnings and Precautions ( 5.2) ]. 7.8 Repaglinide (CYP2C8 Substrates) The acyl-β-glucuronide metabolite of clopidogrel is a strong inhibitor of CYP2C8. Clopidogrel tablets can increase the systemic exposure to drugs that are primarily cleared by CYP2C8, thereby needing dose adjustment and appropriate monitoring. Clopidogrel tablets increased repaglinide exposures by 3.9-fold to 5.1-fold [see Clinical Pharmacology ( 12.3 )]. Avoid concomitant use of repaglinide with clopidogrel tablets. If concomitant use cannot be avoided, initiate repaglinide at 0.5 mg before each meal and do not exceed a total daily dose of 4 mg. Increased frequency of glucose monitoring may be required during concomitant use.
Use in specific populations
8.1 Pregnancy Risk Summary Available data from cases reported in published literature and postmarketing 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]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Myocardial infarction and stroke are medical emergencies. Therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of clopidogrel on the fetus. Labor or delivery Clopidogrel use during labor or delivery will increase the risk of maternal bleeding and hemorrhage. Avoid neuraxial blockade during clopidogrel use because of the risk of spinal hematoma. When possible, discontinue clopidogrel 5 to 7 days prior to labor, delivery, or neuraxial blockade. Data Human data The available data from published case reports over two decades of postmarketing use have not identified an association with clopidogrel use in pregnancy and major birth defects, miscarriage, or adverse fetal outcomes. Animal data Embryo-fetal developmental toxicology studies were performed in pregnant rats and rabbits with doses up to 500 and 300 mg/kg/day, respectively, administered during organogenesis. These doses, corresponding to 65 and 78 times the recommended daily human dose, respectively, on a mg/m 2 basis, revealed no evidence of impaired fertility or fetotoxicity due to clopidogrel. 8.2 Lactation Risk Summary There are no data on the presence of clopidogrel in human milk or the effects on milk production. No adverse effects on breastfed infants have been observed with maternal clopidogrel use during lactation in a small number of postmarketing cases. Studies in rats have shown that clopidogrel and/or its metabolites are present in the milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for clopidogrel tablets and any potential adverse effects on the breastfed infant from clopidogrel tablets or from underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness in pediatric populations have not been established. A randomized, placebo-controlled trial (CLARINET) did not demonstrate a clinical benefit of clopidogrel in neonates and infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary arterial shunt. Possible factors contributing to this outcome were the dose of clopidogrel, the concomitant administration of aspirin, and the late initiation of therapy following shunt palliation. It cannot be ruled out that a trial with a different design would demonstrate a clinical benefit in this patient population. 8.5 Geriatric Use Of the total number of subjects in the CAPRIE and CURE controlled clinical studies, approximately 50% of patients treated with clopidogrel tablets were 65 years of age and older, and 15% were 75 years and older. In COMMIT, approximately 58% of the patients treated with clopidogrel tablets were 60 years and older, 26% of whom were 70 years and older. The observed risk of bleeding events with clopidogrel tablets plus aspirin versus placebo plus aspirin by age category is provided in Table 1 and Table 2 for the CURE and COMMIT trials, respectively [ see Adverse Reactions ( 6.1 ) ]. No dosage adjustment is necessary in elderly patients. 8.6 Renal Impairment Experience is limited in patients with severe and moderate renal impairment [ see Clinical Pharmacology ( 12.2 ) ]. 8.7 Hepatic Impairment No dosage adjustment is necessary in patients with hepatic impairment [ see Clinical Pharmacology ( 12.2 ) ].
Pregnancy
8.1 Pregnancy Risk Summary Available data from cases reported in published literature and postmarketing 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]. The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defects, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Disease-associated maternal and/or embryo/fetal risk Myocardial infarction and stroke are medical emergencies. Therapy for the pregnant woman should not be withheld because of potential concerns regarding the effects of clopidogrel on the fetus. Labor or delivery Clopidogrel use during labor or delivery will increase the risk of maternal bleeding and hemorrhage. Avoid neuraxial blockade during clopidogrel use because of the risk of spinal hematoma. When possible, discontinue clopidogrel 5 to 7 days prior to labor, delivery, or neuraxial blockade. Data Human data The available data from published case reports over two decades of postmarketing use have not identified an association with clopidogrel use in pregnancy and major birth defects, miscarriage, or adverse fetal outcomes. Animal data Embryo-fetal developmental toxicology studies were performed in pregnant rats and rabbits with doses up to 500 and 300 mg/kg/day, respectively, administered during organogenesis. These doses, corresponding to 65 and 78 times the recommended daily human dose, respectively, on a mg/m 2 basis, revealed no evidence of impaired fertility or fetotoxicity due to clopidogrel.
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric populations have not been established. A randomized, placebo-controlled trial (CLARINET) did not demonstrate a clinical benefit of clopidogrel in neonates and infants with cyanotic congenital heart disease palliated with a systemic-to-pulmonary arterial shunt. Possible factors contributing to this outcome were the dose of clopidogrel, the concomitant administration of aspirin, and the late initiation of therapy following shunt palliation. It cannot be ruled out that a trial with a different design would demonstrate a clinical benefit in this patient population.
Geriatric use
8.5 Geriatric Use Of the total number of subjects in the CAPRIE and CURE controlled clinical studies, approximately 50% of patients treated with clopidogrel tablets were 65 years of age and older, and 15% were 75 years and older. In COMMIT, approximately 58% of the patients treated with clopidogrel tablets were 60 years and older, 26% of whom were 70 years and older. The observed risk of bleeding events with clopidogrel tablets plus aspirin versus placebo plus aspirin by age category is provided in Table 1 and Table 2 for the CURE and COMMIT trials, respectively [ see Adverse Reactions ( 6.1 ) ]. No dosage adjustment is necessary in elderly patients.
Overdosage
Platelet inhibition by clopidogrel tablets is irreversible and will last for the life of the platelet. Overdose following clopidogrel administration may result in bleeding complications. A single oral dose of clopidogrel at 1500 or 2000 mg/kg was lethal to mice and to rats and at 3000 mg/kg to baboons. Symptoms of acute toxicity were vomiting, prostration, difficult breathing, and gastrointestinal hemorrhage in animals. Based on biological plausibility, platelet transfusion may restore clotting ability.
Description
Clopidogrel is a thienopyridine class inhibitor of P2Y 12 ADP platelet receptors. Chemically it is methyl (+)-(S)-α-(2- chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (1:1). The empirical formula of clopidogrel bisulfate is C 16 H 16 CINO 2 S
• H 2 SO 4 and its molecular weight is 419.9. The structural formula is as follows: Clopidogrel bisulfate is a white to off-white powder. It is practically insoluble in water at neutral pH but freely soluble at pH 1. It also dissolves freely in methanol, dissolves sparingly in methylene chloride, and is practically insoluble in ethyl ether. It has a specific optical rotation of about +56°. Clopidogrel tablets, USP for oral administration is provided as either pink colored, biconvex, round shaped, beveled edge, film coated tablets printed "CL 75" on one side and plain on other side containing 97.875 mg of clopidogrel bisulfate which is the molar equivalent of 75 mg of clopidogrel base. Each tablet contains colloidal silicon dioxide, hydrogenated castor oil, low substituted hydroxypropyl cellulose, mannitol, microcrystalline cellulose, and polyethylene glycol 6000 as inactive ingredients. The pink film coating contains hypromellose 2910, lactose monohydrate, red iron oxide, titanium dioxide, and triacetin. The imprinting ink contains ammonium hydroxide, black iron oxide, propylene glycol and shellac. FDA approved dissolution test and specification differ from USP. clop_01
Mechanism of action
12.1 Mechanism of Action Clopidogrel 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.
How supplied
Clopidogrel tablets, USP 75 mg are available as pink colored, biconvex, round shaped, beveled edge, film coated tablets printed "CL 75" on one side and plain on other side. Tablets are provided as follows: NDC 67877-276-30 Bottles of 30 NDC 67877-276-90 Bottles of 90 NDC 67877-276-05 Bottles of 500 Store at 25°C (77°F); excursions permitted to 15° C to 30° C (59°F to 86° F) [see USP Controlled Room Temperature].
Patient information
Advise patients to read FDA approved patient labeling (Medication Guide). Discontinuation Advise patients not to discontinue clopidogrel tablets without first discussing it with the healthcare provider who prescribed it [see Warnings and Precautions ( 5.3 )]. Bleeding Advise patients that they:
• will bruise and bleed more easily
• will take longer than usual to stop bleeding
• must report any unanticipated, prolonged, or excessive bleeding, or blood in their stool or urine [see Warnings and Precautions ( 5.2 )] Thrombotic Thrombocytopenic Purpura Instruct patients to get prompt medical attention if they experience symptoms of TTP that cannot otherwise be explained [see Warnings and Precautions ( 5.4 )]. Invasive Procedures Advise patients to inform physicians and dentists that they are taking clopidogrel tablets before any surgery or dental procedure [see Warnings and Precautions ( 5.2 , 5.3 )]. Proton Pump Inhibitors Advise patients not to take omeprazole or esomeprazole while taking clopidogrel tablets. Dexlansoprazole, lansoprazole, and pantoprazole had less pronounced effects on the antiplatelet activity of clopidogrel tablets than did omeprazole or esomeprazole [see Drug Interactions ( 7.1 )]. Manufactured by: Alkem Laboratories Ltd., Mumbai - 400 013, INDIA. Distributed by: Ascend Laboratories, LLC Bedminster, NJ 07921
Label text from the FDA structured product label by Ascend Laboratories, LLC (revised Jun 1, 2026). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Clopidogrel Bisulfate in 41 products
- Clopidogrel in 2 products
Clopidogrel NDC products (43)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-7467 | Clopidogrel Bisulfate 75 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-7466 | Clopidogrel Bisulfate 75 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-6568 | Clopidogrel Bisulfate 75 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-6567 | Clopidogrel Bisulfate 75 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-5868 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 50090-2082 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | A-S Medication Solutions | ANDA |
| 50090-5781 | Clopidogrel Bisulfate 75 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 68084-536 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | American Health Packaging | ANDA |
| 68084-752 | Clopidogrel Bisulfate 300 mg/1 Tablet, Film Coated | American Health Packaging | ANDA |
| 65162-414 | Clopidogrel Bisulfate 75 mg/1 Tablet | Amneal Pharmaceuticals LLC | ANDA |
| 71610-527 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Aphena Pharma Solutions - Tennessee, LLC | ANDA |
| 60505-0253 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Apotex Corp. | ANDA |
| 60505-3532 | Clopidogrel Bisulfate 300 mg/1 Tablet, Film Coated | Apotex Corp. | ANDA |
| 67877-276 | Clopidogrel Bisulfate 75 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 65862-357 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Aurobindo Pharma Limited | ANDA |
| 50268-184 | Clopidogrel Bisulfate 300 mg/1 Tablet, Film Coated | AvPAK | ANDA |
| 71335-0080 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Bryant Ranch Prepack | ANDA |
| 71335-0581 | Clopidogrel Bisulfate 75 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 31722-759 | Clopidogrel 300 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-758 | Clopidogrel 75 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 55154-2149 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Cardinal Health 107, LLC | ANDA |
| 68645-590 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Legacy Pharmaceutical Packaging, LLC | ANDA |
| 33342-060 | Clopidogrel Bisulfate 75 mg/1 Tablet | Macleods Pharmaceuticals Limited | ANDA |
| 0904-6467 | Clopidogrel Bisulfate 300 mg/1 Tablet, Film Coated | Major Pharmaceuticals | ANDA |
| 16714-052 | Clopidogrel Bisulfate 75 mg/1 Tablet | NorthStar RxLLC | ANDA |
| 72205-199 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Novadoz Pharmaceuticals LLC | ANDA |
| 68071-3319 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-4023 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals,Inc. | ANDA |
| 68071-4138 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | NuCare Pharmaceuticals,Inc. | ANDA |
| 72789-469 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | PD-Rx Pharmaceuticals, Inc. | ANDA |
| 68788-4173 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Preferred Pharmaceuticals Inc. | ANDA |
| 82804-986 | Clopidogrel Bisulfate 300 mg/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 71205-073 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 63187-362 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Proficient Rx LP | ANDA |
| 67296-2266 | Clopidogrel Bisulfate 75 mg/1 Tablet | Redpharm Drug | ANDA |
| 70518-1898 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | REMEDYREPACK INC. | ANDA |
| 70518-4373 | Clopidogrel Bisulfate 75 mg/1 Tablet | REMEDYREPACK INC. | ANDA |
| 0093-7314 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Teva Pharmaceuticals USA, Inc. | ANDA |
| 13668-141 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Torrent Pharmaceuticals Limited | ANDA |
| 42543-713 | Clopidogrel Bisulfate 75 mg/1 Tablet | Vensun Pharmaceuticals, Inc. | ANDA |
| 42543-714 | Clopidogrel Bisulfate 300 mg/1 Tablet | Vensun Pharmaceuticals, Inc. | ANDA |
| 69367-200 | Clopidogrel Bisulfate 75 mg/1 Tablet, Film Coated | Westminster Pharmaceuticals, LLC | ANDA |
| 69367-194 | Clopidogrel Bisulfate 300 mg/1 Tablet, Film Coated | Westminster Pharmaceuticals, LLC | ANDA |
Clopidogrel recalls
- D-0787-2021 Sep 8, 2021 · Class II · Terminated
Presence of foreign matter
Frequently asked questions
What is Clopidogrel used for?
Clopidogrel tablets 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 has been shown to reduce the rate of myocardial infarction (MI) and stroke. ( 1.1 ) - For patients with ST-elevation myocardial infarction (STEMI), clopidogrel tablets…
What are the side effects of Clopidogrel?
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 Ascend Laboratories,… See the full label for the complete list.
Who makes Clopidogrel?
Clopidogrel is listed by 26 labelers in the FDA NDC directory, including A-S Medication Solutions, American Health Packaging, Amneal Pharmaceuticals LLC, Aphena Pharma Solutions - Tennessee, LLC.
Has Clopidogrel been recalled?
The FDA enforcement database lists 1 recall for Clopidogrel, most recently D-0787-2021 (class ii): Presence of foreign matter