Clopidogrel Kit (Page 5 of 6)

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). To be eligible to enroll, patients had to have: 1) recent history of myocardial infarction (within 35 days); 2) recent histories of ischemic stroke (within 6 months) with at least a week of residual neurological signs; and/or 3) established peripheral arterial disease (PAD). 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.

Table 6: Outcome Events in the CAPRIE Primary Analysis
Clopidogrel Aspirin
Patients n=9599 n=9586

Ischemic stroke (fatal or not)

438 (4.6%)

461 (4.8%)

MI (fatal or not)

275 (2.9%)

333 (3.5%)

Other vascular death

226 (2.4%)

226 (2.4%)

Total

939 (9.8%)

1020 (10.6%)

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.

Figure7.jpg
(click image for full-size original)

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 enrolled a population that had recent MI, recent stroke, or PAD. The efficacy of clopidogrel relative to aspirin was heterogeneous across these subgroups (p=0.043) (see Figure 8). Nonetheless this difference may be a chance occurrence because the CAPRIE trial was not designed to evaluate the relative benefit of clopidogrel over aspirin in the individual patient subgroups. The benefit was most apparent in patients who were enrolled because of peripheral arterial disease and less apparent 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.

Figure8.jpg
(click image for full-size original)

14.3 No Demonstrated 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 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 75 mg are pink, round, biconvex, film coated tablets, engraved “APO” on one side and “CL” over “75” on the other side. They are supplied as follows:

NDC 70882-116-30, Adherence Packages of 30 Tablets

Store at 25°C(77°F); excursions permitted from 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature]. Protect from moisture.

17 PATIENT COUNSELING INFORMATION

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 [see Warnings and Precautions (5) and Drug Interactions (7)].

CLOPIDOGREL TABLETS, USP
75 mg

Manufactured by Apotex, Inc.
Toronto, Ontario
Canada M9L 1T9

Distributed by Cambridge Therapeutic Technologies, LLC
Teaneck, NJ 07666

Packaged by Legacy Pharmaceutical Packaging, LLC
Earth City, MO 63045

Revised: December 2016
20551

Medication Guide

Clopidogrel Bisulfate Tablets, USP 75 mg and 300 mg

(kloe pid’ oh grel bye sul’ fate)

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 bisulfate 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. You and your doctor should decide if you will take clopidogrel tablets or breastfeed. You should not do both without talking to your doctor
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 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?

Clopidogrel may increase blood levels of other medicines such as repaglinide (Prandin®).

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 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®)
selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). Ask your doctor or pharmacist for a list of SSRI or SNRI medicines if you are not sure.

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.
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 2 doses of clopidogrel tablets at the same time unless your doctor tells you to.
If you take too much clopidogrel, 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, 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.

Tell your doctor if you develop an allergic reaction including skin reactions while taking clopidogrel tablets.

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 59°F to 86°F (15°C to 30°C). Protect from moisture.

Keep clopidogrel 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 that was written for healthcare professionals.

What are the ingredients in clopidogrel tablets?

Active Ingredient: clopidogrel bisulfate

Inactive Ingredients:

Tablet: anhydrous lactose, colloidal silicon dioxide, crospovidone, methylcellulose and zinc stearate

Film coating: hydroxypropyl cellulose, hypromellose, polyethylene glycol, red ferric oxide and titanium dioxide.

All registered trademarks in this document are the property of their respective owners.

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

CLOPIDOGREL TABLETS, USP
75 mg

Manufactured by Apotex, Inc.
Toronto, Ontario
Canada M9L 1T9

Distributed by
Cambridge Therapeutic Technologies, LLC
Teaneck, NJ 07666

Packaged by
Legacy Pharmaceutical Packaging, LLC
Earth City, MO 63045

Revised: December 2016

Coumadin® is a registered trademark of Bristol-Myers Squibb Pharma Company.
Prilosec® is a registered trademark of AstraZeneca.Jantoven® is a registered trademark of USL Pharma.

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