Clopidogrel Bisulfate

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 for oral administration are provided as either white, round, film-coated tablets containing 97.875 mg of clopidogrel bisulfate which is the molar equivalent of 75 mg of clopidogrel base or white, oval, film-coated tablets containing 391.5 mg of clopidogrel bisulfate which is the molar equivalent of 300 mg of clopidogrel base.

Each tablet contains anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium lauryl sulfate and titanium dioxide.

12 CLINICAL PHARMACOLOGY

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.

12.2 Pharmacodynamics

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 P2Y₁₂ 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.

12.3 Pharmacokinetics

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.

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. This metabolic pathway is mediated by CYP2C19, CYP3A, CYP2B6 and CYP1A2. 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 occurs approximately 30 to 60 minutes after dosing. In the 75 mg to 300 mg dose range, the pharmacokinetics of the active metabolite deviates from dose proportionality: increasing the dose by a factor of four results in 2- and 2.7-fold increases in C_max and AUC, respectively.

Elimination

Following an oral dose of ¹⁴C-labeled clopidogrel in humans, approximately 50% of total radioactivity was excreted in urine and approximately 46% in feces over the 5 days post-dosing. After a single, oral dose of 75 mg, clopidogrel has a half-life of approximately 6 hours. The half-life of the active metabolite is about 30 minutes.

Drug Interactions

Clopidogrel is metabolized to its active metabolite in part by CYP2C19. Concomitant use of certain inhibitors of this enzyme results in reduced plasma concentrations of the active metabolite of clopidogrel and a reduction in platelet inhibition.

The effect of proton pump inhibitors (PPI) on the systemic exposure to the clopidogrel active metabolite following multiple doses of clopidogrel 75 mg evaluated in dedicated drug interaction studies is presented in Figure 1.

Pharmacodynamic and pharmacokinetic parameters measured in these studies showed that the interaction was highest with omeprazole and least with dexlansoprazole.

12.5 Pharmacogenomics

CYP2C19 is involved in the formation of both the active metabolite and the 2-oxo-clopidogrel intermediate metabolite. Clopidogrel active metabolite pharmacokinetics and antiplatelet effects, as measured by ex vivo platelet aggregation assays, differ according to CYP2C19 genotype. Genetic variants of other CYP450 enzymes may also affect the formation of clopidogrel’s active metabolite.

The CYP2C19*1 allele corresponds to fully functional metabolism while the CYP2C19*2 and *3 alleles are nonfunctional. CYP2C19*2 and *3 account for the majority of reduced function alleles in white (85%) and Asian (99%) poor metabolizers. Other alleles associated with absent or reduced metabolism are less frequent, and include, but are not limited to, CYP2C19*4, *5, *6, *7, and *8. A patient with poor metabolizer status will possess two loss-of-function alleles as defined above. Published frequencies for poor CYP2C19 metabolizer genotypes are approximately 2% for whites, 4% for blacks and 14% for Chinese. Tests are available to determine a patient’s CYP2C19 genotype.

A crossover study in 40 healthy subjects, ten each in the four CYP2C19 metabolizer groups, evaluated pharmacokinetic and antiplatelet responses using 300 mg followed by 75 mg per day and 600 mg followed by 150 mg per day, each for a total of 5 days. Decreased active metabolite exposure and diminished inhibition of platelet aggregation were observed in the poor metabolizers as compared to the other groups. When poor metabolizers received the 600 mg/150 mg regimen, active metabolite exposure and antiplatelet response were greater than with the 300 mg/75 mg regimen (see Table 3). An appropriate dose regimen for this patient population has not been established in clinical outcome trials.

Some published studies suggest that intermediate metabolizers have decreased active metabolite exposure and diminished antiplatelet effects.

The relationship between CYP2C19 genotype and clopidogrel treatment outcome was evaluated in retrospective analyses of clopidogrel-treated subjects in CHARISMA (n = 2.428) and TRITON-TIMI 38 (n = 1,477), and in several published cohort studies. In TRITON-TIMI 38 and the majority of the cohort studies, the combined group of patients with either intermediate or poor metabolizer status had a higher rate of cardiovascular events (death, myocardial infarction, and stroke) or stent thrombosis compared to extensive metabolizers. In CHARISMA and one cohort study, the increased event rate was observed only in poor metabolizers.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

There was no evidence of tumorigenicity when clopidogrel was administered for 78 weeks to mice and 104 weeks to rats at dosages up to 77 mg/kg per day, which afforded plasma exposures > 25 times that in humans at the recommended daily dose of 75 mg.

Clopidogrel was not genotoxic in four in vitro tests (Ames test, DNA-repair test in rat hepatocytes, gene mutation assay in Chinese hamster fibroblasts, and metaphase chromosome analysis of human lymphocytes) and in one in vivo test (micronucleus test by oral route in mice).

Clopidogrel was found to have no effect on fertility of male and female rats at oral doses up to 400 mg/kg per day (52 times the recommended human dose on a mg/m² basis).

14 CLINICAL STUDIES

14.1 Acute Coronary Syndrome

CURE

The CURE study included 12,562 patients with ACS without ST-elevation (UA or NSTEMI) and presenting within 24 hours of onset of the most recent episode of chest pain or symptoms consistent with ischemia. Patients were required to have either ECG changes compatible with new ischemia (without ST-elevation) or elevated cardiac enzymes or troponin I or T to at least twice the upper limit of normal. The patient population was largely Caucasian (82%) and included 38% women, and 52% patients ≥ 65 years of age.

Patients were randomized to receive clopidogrel (300 mg loading dose followed by 75 mg once daily) or placebo, and were treated for up to one year. Patients also received aspirin (75 mg to 325 mg once daily) and other standard therapies such as heparin. The use of GPIIb/IIIa inhibitors was not permitted for 3 days prior to randomization.

The number of patients experiencing the primary outcome (CV death, MI, or stroke) was 582 (9.3%) in the clopidogrel-treated group and 719 (11.4%) in the placebo-treated group, a 20% relative risk reduction (95% CI of 10% to 28%; p < 0.001) for the clopidogrel-treated group (see Table 4).

Most of the benefit of clopidogrel occurred in the first 2 months, but the difference from placebo was maintained throughout the course of the trial (up to 12 months) (see Figure 2 ).

In CURE, the use of clopidogrel was associated with a lower incidence of CV death, MI or stroke in patient populations with different characteristics, as shown in Figure 3. The benefits associated with clopidogrel were independent of the use of other acute and long-term cardiovascular therapies, including heparin/LMWH, intravenous glycoprotein IIb/IIIa (GPIIb/IIIa) inhibitors, lipid-lowering drugs, beta-blockers, and ACE-inhibitors. The efficacy of clopidogrel was observed independently of the dose of aspirin (75 mg to 325 mg once daily). The use of oral anticoagulants, non-study anti-platelet drugs, and chronic NSAIDs was not allowed in CURE.

The use of clopidogrel in CURE was associated with a decrease in the use of thrombolytic therapy (71 patients [1.1%] in the clopidogrel group, 126 patients [2%] in the placebo group; relative risk reduction of 43%), and GPIIb/IIIa inhibitors (369 patients [5.9%] in the clopidogrel group, 454 patients [7.2%] in the placebo group, relative risk reduction of 18%). The use of clopidogrel in CURE did not affect the number of patients treated with CABG or PCI (with or without stenting), (2,253 patients [36%] in the clopidogrel group, 2,324 patients [36.9%] in the placebo group; relative risk reduction of 4%).

COMMIT

In patients with STEMI, the safety and efficacy of clopidogrel were evaluated in the randomized, placebo-controlled, double-blind study, COMMIT. COMMIT included 45,852 patients presenting within 24 hours of the onset of the symptoms of myocardial infarction with supporting ECG abnormalities (i.e., ST-elevation, ST-depression or left bundle-branch block). Patients were randomized to receive clopidogrel (75 mg once daily) or placebo, in combination with aspirin (162 mg per day), for 28 days or until hospital discharge, whichever came first.

The primary endpoints were death from any cause and the first occurrence of re-infarction, stroke or death.

The patient population included 28% women, 58% age ≥ 60 years (26% age ≥ 70 years), 55% patients who received thrombolytics, 68% who received ACE-inhibitors, and only 3% who underwent PCI.

As shown in Table 5 and Figure 4 and Figure 5 below, clopidogrel significantly reduced the relative risk of death from any cause by 7% (p = 0.029), and the relative risk of the combination of re-infarction, stroke or death by 9% (p = 0.002).

The effect of clopidogrel did not differ significantly in various pre-specified subgroups as shown in Figure 6. The effect was also similar in non-prespecified subgroups including those based on infarct location, Killip class or prior MI history (see Figure 7). Such subgroup analyses should be interpreted cautiously.

14.2 Recent Myocardial Infarction, Recent Stroke, or Established Peripheral Arterial Disease

CAPRIE

The CAPRIE trial was a 19,185 patient, 304 center, international, randomized, double-blind, parallel-group study comparing clopidogrel (75 mg daily) to aspirin (325 mg daily). The patients randomized had: 1) recent histories of myocardial infarction (within 35 days); 2) recent histories of ischemic stroke (within 6 months) with at least a week of residual neurological signs; or 3) established peripheral arterial disease. Patients received randomized treatment for an average of 1.6 years (maximum of 3 years).

The trial's primary outcome was the time to first occurrence of new ischemic stroke (fatal or not), new myocardial infarction (fatal or not), or other vascular death. Deaths not easily attributable to nonvascular causes were all classified as vascular.

As shown in Table 6, clopidogrel was associated with a lower incidence of outcome events, primarily MI. The overall relative risk reduction (9.8% vs. 10.6%) was 8.7%, p = 0.045. Similar results were obtained when all-cause mortality and all-cause strokes were counted instead of vascular mortality and ischemic strokes (risk reduction 6.9%). In patients who survived an on-study stroke or myocardial infarction, the incidence of subsequent events was lower in the clopidogrel group.

The curves showing the overall event rate are shown in Figure 8. The event curves separated early and continued to diverge over the 3-year follow-up period.

The statistical significance favoring clopidogrel over aspirin was marginal (p = 0.045). However, because aspirin is itself effective in reducing cardiovascular events in patients with recent myocardial infarction or stroke, the effect of clopidogrel is substantial.

The CAPRIE trial included a population that was randomized on the basis of three entry criteria. The efficacy of clopidogrel relative to aspirin was heterogeneous across these randomized subgroups (p = 0.043). It is not clear whether this difference is real or a chance occurrence. Although the CAPRIE trial was not designed to evaluate the relative benefit of clopidogrel over aspirin in the individual patient subgroups, the benefit appeared to be strongest in patients who were enrolled because of peripheral vascular disease (especially those who also had a history of myocardial infarction) and weaker in stroke patients. In patients who were enrolled in the trial on the sole basis of a recent myocardial infarction, clopidogrel was not numerically superior to aspirin.

14.3 Lack of Established Benefit of Clopidogrel Plus Aspirin in Patients with Multiple Risk Factors or Established Vascular Disease

CHARISMA

The CHARISMA trial was a 15,603 subject, randomized, double-blind, parallel group study comparing clopidogrel (75 mg daily) to placebo for prevention of ischemic events in patients with vascular disease or multiple risk factors for atherosclerosis. All subjects were treated with aspirin 75 mg to 162 mg daily. The mean duration of treatment was 23 months. The study failed to demonstrate a reduction in the occurrence of the primary endpoint, a composite of CV death, MI, or stroke. A total of 534 (6.9%) patients in the clopidogrel group versus 573 (7.4%) patients in the placebo group experienced a primary outcome event (p = 0.22). Bleeding of all severities was more common in the subjects randomized to clopidogrel.

16 HOW SUPPLIED/STORAGE AND HANDLING

Clopidogrel Tablets, USP are available as tablets containing clopidogrel bisulfate, USP equivalent to 75 mg or 300 mg of clopidogrel.

The 75 mg tablet is a white film-coated, round, unscored tablet debossed with M on one side of the tablet and C27 on the other side. They are available as follows:

NDC 51079-557-20 - Unit dose blister packages of 100 (10 cards of 10 tablets each).

The 300 mg tablet is a white film-coated, oval, unscored tablet debossed with M C28 on one side of the tablet and blank on the other side. They are available as follows:

NDC 51079-558-03 - Unit dose blister packages of 30 (5 cards of 6 tablets each).

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

PHARMACIST: Dispense a Medication Guide with each prescription.

17 PATIENT COUNSELING INFORMATION

[See Medication Guide (17.6).]

17.1 Benefits and Risks

• •Summarize the effectiveness features and potential side effects of clopidogrel.
• •Tell patients to take clopidogrel exactly as prescribed.
• •Remind patients not to discontinue clopidogrel without first discussing it with the physician who prescribed clopidogrel.

17.2 Bleeding

Inform patients that they:

• •will bruise and bleed more easily.
• •will take longer than usual to stop bleeding.
• •should report any unanticipated, prolonged, or excessive bleeding, or blood in their stool or urine.

17.3 Other Signs and Symptoms Requiring Medical Attention

• •Inform patients that TTP is a rare but serious condition that has been reported with clopidogrel and other drugs in this class of drugs.
• •Instruct patients to get prompt medical attention if they experience any of the following symptoms that cannot otherwise be explained: fever, weakness, extreme skin paleness, purple skin patches, yellowing of the skin or eyes, or neurological changes.

17.4 Invasive Procedures

Instruct patients to:

• •inform physicians and dentists that they are taking clopidogrel before any invasive procedure is scheduled.
• •tell the doctor performing the invasive procedure to talk to the prescribing health care professional before stopping clopidogrel.

17.5 Concomitant Medications

Ask patients to list all prescription medications, over-the-counter medications, or dietary supplements they are taking or plan to take, including prescription or over-the-counter proton pump inhibitors (e.g., omeprazole), warfarin, or NSAIDs [see Warnings and Precautions (5)].

17.6 Medication Guide

MEDICATION GUIDE
CLOPIDOGREL TABLETS, USP
(kloe pid′ oh grel)
75 mg and 300 mg

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 tablets are 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 tablets are 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 are treated with a stent, and stop taking clopidogrel tablets too soon, have a higher risk of getting a blood clot on the stent, 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 tablets are 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 tablets help 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 tablets will harm your unborn baby
• •are breast-feeding or plan to breast-feed. It is not known if clopidogrel passes into your breast milk. You and your doctor should decide if you will take clopidogrel tablets or breast-feed. You should not do both without talking to your doctor.

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 herbal supplements.

Clopidogrel tablets may affect the way other medicines work, and other medicines may affect how clopidogrel tablets work. See “What is the most important information I should know about clopidogrel tablets?”

Taking clopidogrel tablets with certain other medicines may increase your risk of bleeding.

Especially tell your doctor if you take:

• •aspirin, especially if you have had a stroke. Always talk to your doctor about whether you should take aspirin along with clopidogrel tablets to treat your condition.
• •Non-steroidal anti-inflammatory drugs (NSAIDs). Ask your doctor or pharmacist for a list of NSAID medicines if you are not sure.
• •warfarin (Coumadin^®*, Jantoven^®*)

Know the medicines you take. Keep a list of them to show your doctor or pharmacist when you get a new medicine.

How should I take clopidogrel tablets?

• •Take clopidogrel tablets exactly as your doctor tells you.
• •Do not change your dose or stop taking clopidogrel tablets without talking to your doctor first. Stopping clopidogrel tablets may increase your risk of heart attack or stroke.
• •Take clopidogrel tablets with aspirin as instructed by your doctor.
• •You can take clopidogrel tablets with or without food.
• •If you miss a dose, take clopidogrel tablets as soon as you remember. If it is almost time for your next dose, skip the missed dose. Take the next dose at your regular time. Do not take two doses of clopidogrel tablets at the same time unless your doctor tells you to.
• •If you take too much clopidogrel tablets, call your doctor or go to the nearest emergency room right away.
• •Talk with your doctor about stopping your clopidogrel tablets before you have surgery. Your doctor may tell you to stop taking clopidogrel tablets at least 5 days before you have surgery to avoid excessive bleeding during surgery.

What are the possible side effects of clopidogrel tablets?

Clopidogrel tablets can cause serious side effects including:

• •See “What is the most important information I should know about clopidogrel tablets?”
• • A blood clotting problem called Thrombotic Thrombocytopenic Purpura (TTP). TTP can happen with clopidogrel tablets, sometimes after a short time (less than 2 weeks). TTP is a blood clotting problem where blood clots form in blood vessels; and can happen anywhere in the body. TTP needs to be treated in a hospital right away, because it may cause death. Get medical help right away if you have any of these symptoms and they can not be explained by another medical condition:
• •purplish spots (called purpura) on the skin or in the mouth (mucous membranes) due to bleeding under the skin
• •your skin or the whites of your eyes are yellow (jaundice)
• •you feel tired or weak
• •your skin looks very pale
• •fever
• •fast heart rate or feeling short of breath
• •headache
• •speech changes
• •confusion
• •coma
• •stroke
• •seizure
• •low amount of urine, or urine that is pink or has blood in it
• •stomach area (abdominal) pain
• •nausea, vomiting, or diarrhea
• •vision changes

Tell your doctor if you have any side effect that bothers you or that does not go

away.

These are not all the possible side effects of clopidogrel 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 clopidogrel tablets?

• •Store clopidogrel tablets at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Keep clopidogrel tablets and all medicines out of the reach of children.

General information about clopidogrel tablets

Medicines are sometimes used for purposes other than those listed in a Medication Guide. Do not take clopidogrel tablets for a condition for which it was not prescribed. Do not give clopidogrel tablets to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about clopidogrel tablets. If you would like more information, talk to your doctor. Ask your doctor or pharmacist for information about clopidogrel tablets that was written for healthcare professionals.

For more information, call 1-877-446-3679 (1-877-4-INFO-RX).

What are the ingredients in clopidogrel tablets?

Active ingredient: clopidogrel bisulfate

Inactive ingredients: anhydrous lactose, colloidal silicon dioxide, croscarmellose sodium, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, sodium lauryl sulfate and titanium dioxide

This Medication Guide has been approved by the U.S. Food and Drug Administration.

*The brands listed are trademarks of their respective owners.

Manufactured by:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Distributed by:
Mylan Institutional Inc.
Rockford, IL 61103 U.S.A.

S-11223 R1
12/12

PRINCIPAL DISPLAY PANEL - 75 mg

NDC 51079-557-20

Clopidogrel
Tablets, USP
75 mg*

100 Tablets (10 x 10)

*Each film-coated tablet
contains 97.875 mg of
clopidogrel bisulfate, USP
equivalent to 75 mg of
clopidogrel base.

Usual Dosage: See accompanying
prescribing information and Medication Guide.

Store at 20° to 25°C (68° to 77°F).
[See USP Controlled Room
Temperature.]

Manufactured by:
Mylan Pharmaceuticals Inc.
Morgantown, WV 26505 U.S.A.

Rx only

S-11224 R2

Packaged and Distributed by:

Mylan Institutional Inc.

Rockford, IL 61103 U.S.A.

This unit dose package is not child resistant.

For institutional use only.

Keep this and all drugs out of the reach of children.

This container provides light-resistance.

See window for lot number and expiration date.