Plavix (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 Plavix (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
PatientsPlavixn=9599Aspirinn=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, Plavix 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 Plavix group.

The curves showing the overall event rate are shown in Figure 7. The event curves separated early and continued to diverge over the 3-year follow-up period.

Figure 7: Fatal or Nonfatal Vascular Events in the CAPRIE Study

Figure
(click image for full-size original)

The statistical significance favoring Plavix 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 Plavix is substantial.

The CAPRIE trial enrolled a population that had recent MI, recent stroke, or PAD. The efficacy of Plavix 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 Plavix 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, Plavix was not numerically superior to aspirin.

Figure 8: Hazard Ratio and 95% CI by Baseline Subgroups in the CAPRIE Study

Figure
(click image for full-size original)

14.3 No Demonstrated Benefit of Plavix 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 Plavix (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 75–162 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 Plavix 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 Plavix.

16 HOW SUPPLIED/STORAGE AND HANDLING

Plavix (clopidogrel tablets) 75 mg are available as pink, round, biconvex, film-coated tablets debossed with “75” on one side and “1171” on the other. Tablets are provided as follows:

NDC 63653-1171-6 Bottles of 30
NDC 63653-1171-1 Bottles of 90
NDC 63653-1171-3 Blisters of 100

Plavix (clopidogrel tablets) 300 mg are available as pink, oblong, film-coated tablets debossed with “300” on one side and “1332” on the other. Tablets are provided as follows:

NDC 63653-1332-2 Unit-dose packages of 30

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

17 PATIENT COUNSELING INFORMATION

Advise patients to read FDA approved patient labeling (Medication Guide).

Discontinuation

Advise patients not to discontinue Plavix 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 Plavix 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 Plavix. Dexlansoprazole, lansoprazole, and pantoprazole had less pronounced effects on the antiplatelet activity of Plavix than did omeprazole or esomeprazole [see Drug Interactions (7.1)].

Medication Guide
Plavix® (PLAV-iks)
(clopidogrel
tablets)

Read this Medication Guide before you start taking Plavix 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 Plavix?

  1. Plavix may not work as well in people who:
    • have certain genetic factors that affect how the body breaks down Plavix. Your doctor may do genetic tests to make sure Plavix 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 Plavix.
  2. Plavix can cause bleeding which can be serious and can sometimes lead to death. Plavix is a blood thinner medicine that lowers the chance of blood clots forming in your body. While you take Plavix:
    • 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 Plavix without talking to the doctor who prescribes it for you. People who stop taking Plavix too soon have a higher risk of having a heart attack or dying. If you must stop Plavix because of bleeding, your risk of a heart attack may be higher.

What is Plavix?

Plavix is 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

Plavix 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. Plavix helps to prevent platelets from sticking together and forming a clot that can block an artery.

It is not known if Plavix is safe and effective in children.

Who should not take Plavix?

Do not take Plavix if you:

  • currently have a condition that causes bleeding, such as a stomach ulcer
  • are allergic to clopidogrel or other ingredients in Plavix. See the end of this leaflet for a complete list of ingredients in Plavix.

What should I tell my doctor before taking Plavix?

Before you take Plavix, 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 Plavix?
  • are pregnant or plan to become pregnant. It is not known if Plavix will harm your unborn baby.
  • are breastfeeding or plan to breastfeed. It is not known if Plavix passes into your breast milk. A decision should be made with your healthcare provider to avoid or discontinue breastfeeding when continuing Plavix 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 Plavix. They should talk to the doctor who prescribed Plavix 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.

Plavix may affect the way other medicines work, and other medicines may affect how Plavix works. See “What is the most important information I should know about Plavix?

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

Taking Plavix 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 Plavix 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 Plavix?

  • Take Plavix exactly as your doctor tells you.
  • Do not change your dose or stop taking Plavix without talking to your doctor first. Stopping Plavix may increase your risk of heart attack or stroke.
  • Take Plavix with aspirin as instructed by your doctor.
  • If you miss a dose, take Plavix 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 Plavix at the same time unless your doctor tells you to.
  • If you take too much Plavix, call your doctor or go to the nearest emergency room right away.
  • Talk with your doctor about stopping your Plavix before you have surgery. Your doctor may tell you to stop taking Plavix at least 5 days before you have surgery to avoid excessive bleeding during surgery.

What are the possible side effects of Plavix?

Plavix can cause serious side effects including:

  • See What is the most important information I should know about Plavix?
  • A blood clotting problem called Thrombotic Thrombocytopenic Purpura (TTP). TTP can happen with Plavix, 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 cannot 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
    • persistent low blood sugar symptoms

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 Plavix.

These are not all the possible side effects of Plavix. 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 Plavix?

  • Store Plavix at 59°F to 86°F (15°C to 30°C).

Keep Plavix and all medicines out of the reach of children.

General information about Plavix

Medicines are sometimes used for purposes other than those listed in a Medication Guide. Do not take Plavix for a condition for which it was not prescribed. Do not give Plavix 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 Plavix. If you would like more information, talk to your doctor. Ask your doctor or pharmacist for information about Plavix that was written for healthcare professionals.

For more information, go to www.sanofi-aventis.us or www.bms.com or call 1-800-321-1335.

What are the ingredients in Plavix?

Active ingredient: clopidogrel bisulfate

Inactive ingredients:

Tablet: hydrogenated castor oil, hydroxypropyl cellulose, mannitol, microcrystalline cellulose, polyethylene glycol 6000

Film coating: ferric oxide, hypromellose 2910, lactose monohydrate, titanium dioxide, triacetin, Carnauba wax

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

Revised: April 2020

Distributed by:
Bristol-Myers Squibb/Sanofi Pharmaceuticals Partnership
Bridgewater, NJ 08807

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