Clopidogrel 300 mg Tablet, Film Coated
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the P2Y12 Platelet Inhibitor class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
- Clopidogrel keeps platelets — the tiny blood cells that help form clots — from sticking together. That's important when you've had a heart attack, a stroke, or a procedure to open...
- What exactly is clopidogrel supposed to do for me?
- Good news — you can take clopidogrel with or without food, whichever is easier on your stomach. Food doesn't significantly change how well it works, so just pick a consistent time...
- Can I take it with food, or do I need to take it on an empty stomach?
Patient education
Supplement & herbal interactions
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII 3SY5LH9PMK
Anhydrous lactose is a milk sugar with no water content. It acts as a filler and binder in tablets and capsules, adding bulk and helping ingredients stick together.
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UNII 68401960MK
Crospovidone is a synthetic polymer made from polyvinylpyrrolidone. It acts as a disintegrant, helping tablets break apart quickly in the stomach so the medicine dissolves and absorbs into the body.
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UNII 1K09F3G675
Ferric oxide red is an inorganic iron compound used as a colorant in medicines. It gives tablets, capsules, or other dosage forms a red or reddish tint for identification and appearance.
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UNII RFW2ET671P
Hydroxypropyl cellulose is a plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and as a film-former to coat tablets or control how fast the medicine releases.
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UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
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UNII NPU9M2E6L8
Methylcellulose is a plant-derived thickening agent made from cellulose. It acts as a binder to hold tablet ingredients together and a viscosity builder in liquid formulations.
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UNII Q662QK8M3B
Polyethylene glycol 8000 is a synthetic polymer made from ethylene oxide. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and add bulk to the medicine.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII 15FIX9V2JP
Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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UNII H92E6QA4FV
Zinc stearate is a fine white powder made from zinc and stearic acid. It works as a lubricant and glidant to help the tablet or capsule move smoothly through manufacturing equipment and prevents sticking.
10 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $9.221 | $184.42 / 20 tablet |
| Medicaid paysCMS SDUD · 12 mo | $241.85 | $4,837.00 / 20 tablet |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Clopidogrel 300 mgthis 00904-6467-10 | Major | 1 tablet | $9.221 | AB | Availability likely | — |
| Clopidogrel 300 mg 50268-0184-12 | AvPAK | 1 tablet | $9.221 | AB | Availability likely | — |
| Clopidogrel 300 mg 60505-3532-05 | Apotex | 500 tablets | $9.221 | AB | Availability likely | — |
| Clopidogrel bisulfate 300 mg 63739-0178-30 | McKesson | 6 tablets | $9.221 | AB | Availability likely | — |
| Clopidogrel 300 mg 69367-0194-05 | Westminster | 500 tablets | $9.221 | AB | Availability likely | — |
| Plavix 300 mg 00024-1332-30 | Sanofi-Aventis | 10 tablets | — | AB | FDA listed | — |
| Clopidogrel 300 mg 31722-0759-05 | Camber | 500 tablets | — | AB | FDA listed | — |
| Clopidogrel 300 mg 42543-0714-01 | Vensun | 100 tablets | — | AB | FDA listed | — |
| Clopidogrel bisulfate 300 mg 43598-0122-05 | Dr.Reddy's | 500 tablets | — | AB | FDA listed | — |
| Clopidogrel bisulfate 300 mg 50228-0121-05 | ScieGen | 500 tablets | — | AB | FDA listed | — |
| Clopidogrel 300 mg 52605-0083-05 | POLYGEN | 500 tablets | — | AB | FDA listed | — |
| Clopidogrel bisulfate 300 mg 55111-0671-01 | Dr.Reddy's | 100 tablets | — | AB | FDA listed | — |
| Clopidogrel 300 mg 68084-0752-25 | American | 1 tablet | — | AB | FDA listed | — |
| Clopidogrel bisulfate 300 mg 77771-0121-05 | RADHA | 500 tablets | — | AB | FDA listed | — |
| Clopidogrel 300 mg 82804-0986-00 | Proficient | 100 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 00904-6467-07 | 30 BLISTER PACK in 1 CARTON (0904-6467-07) / 1 TABLET, FILM COATED in 1 BLISTER PACK | $9.22 / ea | $276.63 | 2015-04-06 | Active |
| 00904-6467-10 You're viewing this | 20 BLISTER PACK in 1 CARTON (0904-6467-10) / 1 TABLET, FILM COATED in 1 BLISTER PACK | $9.22 / ea | $184.42 | 2015-04-06 | Active |
This pack effectively ties for the lowest per-ea cost of the 2 priced pack sizes ($9.22 NADAC).
Pack size FAQ
What quantity is in NDC 00904-6467-10?
What NDC number is used to bill for this package of Clopidogrel 300 mg Tablet, Film Coated?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🚨 Boxed Warning ▾
WARNING: DIMINISHED ANTIPLATELET EFFECT IN PATIENTS WITH TWO LOSS-OF-FUNCTION ALLELES OF THE CYP2C19 GENE WARNING: DIMINISHED ANTIPLATELET EFFECT IN PATIENTS WITH TWO LOSS-OF-FUNCTION ALLELES OF THE CYP2C19 GENE See full prescribing information for complete boxed warning. • Effectiveness of clopidogrel tablets depends on conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. ( 5.1, 12.3 ) • Tests are available to identify patients who are CYP2C19 poor metabolizers. ( 12.5 ) • Consider use of another platelet P2Y 12 inhibitor in patients identified as CYP2C19 poor metabolizers.
( 5.1 ) 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 )] . Clopidogrel tablets at recommended doses forms less of the active metabolite and so has a reduced effect on platelet activity in patients who are homozygous for nonfunctional alleles of the CYP2C19 gene, (termed "CYP2C19 poor metabolizers").
Tests are available to identify patients who are CYP2C19 poor metabolizers [see Clinical Pharmacology ( 12.5 )] . Consider use of another platelet P2Y 12 inhibitor in patients identified as CYP2C19 poor metabolizers.
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Clopidogrel tablets are 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 )
1.1Acute Coronary Syndrome (ACS) • Clopidogrel tablets are 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 should be administered in conjunction with aspirin. • Clopidogrel tablets are 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.
1.2Recent 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 are indicated to reduce the rate of MI and stroke.
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Acute coronary syndrome ( 2.1 ) o Initiate clopidogrel with a single 300 mg oral loading dose and then continue at 75 mg once daily. o Initiating clopidogrel 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 )
2.1Acute 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 without a loading dose will delay establishment of an antiplatelet effect by several days [see Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.1 )] .
2.2Recent 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 ▾
3 DOSAGE FORMS AND STRENGTHS Clopidogrel tablets, USP 75 mg are pink, round, biconvex, film coated tablets, engraved "APO" on one side and "CL" over "75" on the other side. Clopidogrel tablets, USP 300 mg are pink, oblong, biconvex, film coated tablets, engraved "APO" on one side and "CL 300" on the other side. Film-coated tablets: 75 mg, 300 mg ( 3 )
⛔ Contraindications ▾
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 )
4.1Active Bleeding Clopidogrel tablets are contraindicated in patients with active pathological bleeding such as peptic ulcer or intracranial hemorrhage.
4.2Hypersensitivity Clopidogrel tablets are contraindicated in patients with hypersensitivity (e.g., anaphylaxis) to clopidogrel or any component of the product [see Adverse Reactions ( 6.2 )] .
⚠️ Warnings and Cautions ▾
5 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 )
5.1Diminished 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 with omeprazole or esomeprazole because both significantly reduce the antiplatelet activity of clopidogrel [see Drug Interactions ( 7.2 )] .
5.2General 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 )] .
5.3Discontinuation of Clopidogrel Tablets Discontinuation of clopidogrel tablets increases the risk of cardiovascular events. If clopidogrel 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 for five days prior to such surgery. Resume clopidogrel as soon as hemostasis is achieved.
5.4Thrombotic Thrombocytopenic Purpura (TTP) TTP, sometimes fatal, has been reported following use of clopidogrel tablets, sometimes after a short exposure (<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 )].
5.5Cross-Reactivity among Thienopyridines Hypersensitivity including rash, angioedema or hematologic reaction has been reported in patients receiving clopidogrel, including patients with a history of hypersensitivity or hematologic reaction to other thienopyridines [see Contraindications ( 4.2 ) and Adverse Reactions ( 6.2 )] .
5.5Cross-Reactivity among Thienopyridines Hypersensitivity including rash, angioedema or hematologic reaction has been reported in patients receiving clopidogrel, including patients with a history of hypersensitivity or hematologic reaction to other thienopyridines [see Contraindications ( 4.2 ) and Adverse Reactions ( 6.2 )] .
🤒 Adverse Reactions ▾
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 Apotex Inc. at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 plus aspirin to placebo plus aspirin and trials comparing clopidogrel alone to aspirin alone are discussed below.
Bleeding CURE In CURE, clopidogrel 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 (+aspirin) (n=6,259) Placebo (+ aspirin) (n=6,303) Major bleeding* 3.7
2.7Life-threatening bleeding 2.2
1.8Fatal 0.2 0.2 5 g/dL hemoglobin drop 0.9
0.9Requiring surgical intervention 0.7
0.7Hemorrhagic strokes 0.1
0.1Requiring inotropes 0.5
0.5Requiring transfusion (≥4 units) 1.2 1 Other major bleeding 1.6 1 Significantly disabling 0.4
0.3Intraocular bleeding with significant loss of vision 0.05
0.03Requiring 2 to 3 units of blood 1.3
0.9Minor 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 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 (+ aspirin) (n=22,961) Placebo (+ aspirin) (n=22,891) p-value Major* noncerebral or cerebral bleeding 0.6 0.5
0.59Major noncerebral 0.4 0.3
0.48Fatal 0.2 0.2
0.90Hemorrhagic stroke 0.2 0.2
0.91Fatal 0.2 0.2
0.81Other 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 vs Aspirin) In CAPRIE, gastrointestinal hemorrhage occurred at a rate of 2% in those taking clopidogrel 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 compared to 0.5% for aspirin.
Other bleeding events that were reported more frequently in the clopidogrel group were epistaxis and hematoma. Other Adverse Events In CURE and CHARISMA, which compared clopidogrel plus aspirin to aspirin alone, there was no difference in the rate of adverse events (other than bleeding) between clopidogrel and placebo. In CAPRIE, which compared clopidogrel to aspirin, pruritus was more frequently reported in those taking clopidogrel.
No other difference in the rate of adverse events (other than bleeding) was reported.
6.2Postmarketing 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 unk…
🔄 Drug Interactions ▾
7 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 )
7.1CYP2C19 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 with omeprazole or esomeprazole.
In clinical studies, omeprazole was shown to reduce significantly the antiplatelet activity of clopidogrel when given concomitantly or 12 hours apart. A similar reduction in antiplatelet activity was observed with esomeprazole when given concomitantly with clopidogrel. Dexlansoprazole, lansoprazole, and pantoprazole had less effect on the antiplatelet activity of clopidogrel than did omeprazole or esomeprazole [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.3) ].
7.3Opioids As with other oral P2Y 12 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.
7.4Nonsteroidal Anti-inflammatory Drugs (NSAIDs) Coadministration of clopidogrel and NSAIDs increases the risk of gastrointestinal bleeding.
7.5Warfarin (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 with warfarin increases the risk of bleeding because of independent effects on hemostasis. However, at high concentrations in vitro , clopidogrel inhibits CYP2C9.
7.6SSRIs 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.
7.7Other 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 )].
7.8Repaglinide (CYP2C8 Substrates) The acyl-β-glucuronide metabolite of clopidogrel is a strong inhibitor of CYP2C8. Clopidogrel can increase the systemic exposure to drugs that are primarily cleared by CYP2C8, thereby needing dose adjustment and appropriate monitoring. Clopidogrel increased repaglinide exposures by 3.9-fold to 5.1-fold [see Clinical Pharmacology ( 12.3 )] . Avoid co…
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy 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.
8.2Lactation 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 and any potential adverse effects on the breastfed infant from clopidogrel or from underlying maternal condition.
8.4Pediatric 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.
8.5Geriatric Use Of the total number of subjects in the CAPRIE and CURE controlled clinical studies, approximately 50% of patients treated with clopidogrel were 65 years of age and older, and 15% were 75 years and older. In COMMIT, approximately 58% of the patients treated with clopidogrel were 60 years and older, 26% of whom were 70 years and older. The observed risk of bleeding events with clopidogrel plus aspirin versus placebo plus aspirin by age category is provi…
🤰 Pregnancy ▾
8.1Pregnancy 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 ▾
8.4Pediatric 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 ▾
8.5Geriatric Use Of the total number of subjects in the CAPRIE and CURE controlled clinical studies, approximately 50% of patients treated with clopidogrel were 65 years of age and older, and 15% were 75 years and older. In COMMIT, approximately 58% of the patients treated with clopidogrel were 60 years and older, 26% of whom were 70 years and older. The observed risk of bleeding events with clopidogrel 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 ▾
10 OVERDOSAGE Platelet inhibition by clopidogrel 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 1,500 or 2,000 mg/kg was lethal to mice and to rats and at 3,000 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Clopidogrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y 12 class of ADP receptors on platelets.
12.2Pharmacodynamics Clopidogrel must be metabolized by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. The active metabolite of clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet P2Y 12 receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. This action is irreversible.
Consequently, platelets exposed to clopidogrel's active metabolite are affected for the remainder of their lifespan (about 7 to 10 days). Platelet aggregation induced by agonists other than ADP is also inhibited by blocking the amplification of platelet activation by released ADP. Dose-dependent inhibition of platelet aggregation can be seen 2 hours after single oral doses of clopidogrel.
Repeated doses of 75 mg clopidogrel per day inhibit ADP-induced platelet aggregation on the first day, and inhibition reaches steady state between Day 3 and Day 7. At steady state, the average inhibition level observed with a dose of 75 mg clopidogrel per day was between 40% and 60%. Platelet aggregation and bleeding time gradually return to baseline values after treatment is discontinued, generally in about 5 days.
Geriatric Patients Elderly (≥75 years) and young healthy subjects had similar effects on platelet aggregation. Renally Impaired Patients After repeated doses of 75 mg clopidogrel per day, patients with severe renal impairment (creatinine clearance from 5 to 15 mL/min) and moderate renal impairment (creatinine clearance from 30 to 60 mL/min) showed low (25%) inhibition of ADP-induced platelet aggregation. Hepatically Impaired Patients After repeated doses of 75 mg clopidogrel per day for 10 days in patients with severe hepatic impairment, inhibition of ADP-induced platelet aggregation was similar to that observed in healthy subjects.
Gender In a small study comparing men and women, less inhibition of ADP-induced platelet aggregation was observed in women.
12.3Pharmacokinetics Clopidogrel is a prodrug and is metabolized to a pharmacologically active metabolite and inactive metabolites. Absorption After single and repeated oral doses of 75 mg per day, clopidogrel is rapidly absorbed. Absorption is at least 50%, based on urinary excretion of clopidogrel metabolites.
Effect of food Clopidogrel can be administered with or without food. In a study in healthy male subjects when clopidogrel 75 mg per day was given with a standard breakfast, mean inhibition of ADP-induced platelet aggregation was reduced by less than 9%. The active metabolite AUC 0–24 was unchanged in the presence of food, while there was a 57% decrease in active metabolite C max .
Similar results were observed when a clopidogrel 300 mg loading dose was administered with a high-fat breakfast. Metabolism Clopidogrel is extensively metabolized by two main metabolic pathways: one mediated by esterases and leading to hydrolysis into an inactive carboxylic acid derivative (85% of circulating metabolites) and one mediated by multiple cytochrome P450 enzymes. Cytochromes first oxidize clopidogrel to a 2-oxo-clopidogrel intermediate metabolite.
Subsequent metabolism of the 2-oxo-clopidogrel intermediate metabolite results in formation of the active metabolite, a thiol derivative of clopidogrel. The active metabolite is formed mostly by CYP2C19 with contributions from several other CYP enzymes, including CYP1A2, CYP2B6 and CYP3A. The active thiol metabolite binds rapidly and irreversibly to platelet receptors, thus inhibiting platelet aggregation for the lifespan of the platelet.
The C max of the active metabolite is twice as high following a single 300 mg clopidogrel loading dose as it is after four days of 75 mg maintenance dose. C max occ…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Clopidogrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y 12 class of ADP receptors on platelets.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Clopidogrel tablets, USP 300 mg are pink, oblong, biconvex, film coated tablets, engraved "APO" on one side and "CL 300" on the other side. They are supplied as follows: Cartons of 20 film coated tablets (10 film coated tablets each blister pack x 2), NDC 0904-6467-10 Cartons of 30 film coated tablets (10 film coated tablets each blister pack x 3), NDC 0904-6467-07 WARNING: These Unit Dose packages are not child resistant and are Intended for Institutional Use Only. Keep this and all drugs out of the reach of children.
Store at 25°C(77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) [See USP Controlled Room Temperature]. Dispense in a tight container [see USP]. Protect from moisture.
📋 Description ▾
11 DESCRIPTION Clopidogrel tablets, USP 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(4 H )-acetate sulfate (1:1). The molecular formula of clopidogrel bisulfate is C 16 H 16 ClNO 2 S•H 2 SO 4 and its molecular weight is 419.9.
The structural formula is as follows: Clopidogrel bisulfate, USP 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 75 mg for oral administration are provided as pink, round, biconvex, film coated tablets, engraved “APO” on one side, “CL” over “75” on the other side. The tablets contain 97.875 mg of clopidogrel bisulfate, which is the molar equivalent of 75 mg of clopidogrel base.
Clopidogrel tablets, USP 300 mg for oral administration are provided as pink, oblong, biconvex, film coated tablets engraved "APO" on one side and "CL 300" on the other side. The tablets contain 392 mg of clopidogrel bisulfate, which is the molar equivalent of 300 mg of clopidogrel base. Each tablet contains anhydrous lactose, colloidal silicon dioxide, crospovidone, methylcellulose and zinc stearate as inactive ingredients.
The pink film coating contains ferric oxide red, hydroxypropyl cellulose, hypromellose, polyethylene glycol and titanium dioxide. clopiodgrel-01.jpg
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise patients to read FDA approved patient labeling (Medication Guide). Discontinuation Advise patients not to discontinue clopidogrel 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 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. Dexlansoprazole, lansoprazole, and pantoprazole had less pronounced effects on the antiplatelet activity of clopidogrel than did omeprazole or esomeprazole [see Drug Interactions ( 7.1 )] .
Dispense with Medication Guide available at https://www.apotex.com/products/us/mg.as p APOTEX INC. CLOPIDOGREL TABLETS, USP 75 mg and 300 mg Manufactured by Manufactured for Apotex Inc. Apotex Corp.
Toronto, Ontario Weston, Florida Canada M9L 1T9 USA, 33326 Packaged and Distributed by: MAJOR® PHARMACEUTICALS Indianapolis, IN 46268 USA Refer to package label for Distributor's NDC Number Rev. 30
💬 Medication Guide ▾
Medication Guide Clopidogrel (kloe pid’ oh grel) Tablets, USP Medication Guide available at https://www.apotex.com/products/us/mg.asp Read this Medication Guide before you start taking clopidogrel tablets and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking with your doctor about your medical condition or your treatment.
What is the most important information I should know about clopidogrel tablets? 1. Clopidogrel tablets may not work as well in people who: • have certain genetic factors that affect how the body breaks down clopidogrel.
Your doctor may do genetic tests to make sure clopidogrel is right for you. • take certain medicines, especially omeprazole (Prilosec ® ) or esomeprazole (Nexium ® ). Your doctor may change the medicine you take for stomach acid problems while you take clopidogrel tablets. 2.
Clopidogrel tablets can cause bleeding which can be serious and can sometimes lead to death. Clopidogrel is a blood thinner medicine that lowers the chance of blood clots forming in your body. While you take clopidogrel tablets: • you may 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 • blood in your urine (pink, red or brown urine) • red or black stools (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 clopidogrel tablets without talking to the doctor who prescribes it for you.
People who stop taking clopidogrel tablets too soon have a higher risk of having a heart attack or dying. If you must stop clopidogrel tablets because of bleeding, your risk of a heart attack may be higher. What are clopidogrel tablets?
Clopidogrel tablets are a prescription medicine used to treat people who have any of the following: • chest pain due to heart problems • poor circulation in their legs (peripheral arterial disease) • a heart attack • a stroke Clopidogrel is used alone or with aspirin to lower your chance of having another serious problem with your heart or blood vessels such as heart attack, stroke, or blood clot that can lead to death. Platelets are blood cells that help your blood clot normally. Clopidogrel helps to prevent platelets from sticking together and forming a clot that can block an artery.
It is not known if clopidogrel tablets are safe and effective in children. Who should not take clopidogrel tablets? Do not take clopidogrel tablets if you: • currently have a condition that causes bleeding, such as a stomach ulcer • are allergic to clopidogrel or other ingredients in clopidogrel tablets.
See the end of this leaflet for a complete list of ingredients in clopidogrel tablets. What should I tell my doctor before taking clopidogrel tablets? Before you take clopidogrel tablets, tell your doctor if you: • have a history of bowel (gastrointestinal) or stomach ulcers. • have a history of bleeding problems. • plan to have surgery or a dental procedure.
See " How should I take clopidogrel tablets? " • are pregnant or plan to become pregnant. It is not known if clopidogrel will harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if clopidogrel passes into your breast milk.
A decision should be made with your healthcare provider to avoid or discontinue breastfeeding when continuing clopidogrel is needed. • have had an allergy or reaction to any medicine used to treat your disease. Tell all of your doctors and your dentist that you are taking clopidogrel tablets. They should talk to the doctor who prescribed clopidogrel tablets for you before you have any surgery or invasive procedure.
Tell your doctor about all the medicines you take , including prescription, non-prescription medicines, vitamins and h…