Package Leaflet: Information for the User

Plavix 75 mg Film-Coated Tablets

clopidogrel

Read this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, talk to your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What isPlavixand what it is used for

2. What you need to know before you start takingPlavix

3. How to takePlavix

4. Possible side effects

5. Storage ofPlavix

6. Contents of the pack and additional information

Plavix contains clopidogrel and belongs to a group of medications called antiplatelet agents. Platelets are very small cells found in the blood, and they aggregate when the blood clots. Antiplatelet agents, by preventing this aggregation, reduce the likelihood of blood clots (a process known as thrombosis) forming.

Plavix is administered to adults to prevent blood clots (thrombi) from forming in hardened blood vessels (arteries), a process known as atherothrombosis, which can cause atherothrombotic effects (such as cerebral infarction, myocardial infarction, or death).

You have been prescribed Plavix to help prevent blood clots from forming and reduce the risk of these severe events because:

• you have a process that produces the hardening of the arteries (also known as atherosclerosis), and
• you have previously experienced a myocardial infarction, a cerebral infarction, or suffer from a disease known as peripheral arterial disease, or
• you have experienced a severe chest pain, known as “unstable angina” or “myocardial infarction”. Your doctor may need to place a stent in the blocked or narrowed artery to restore adequate blood flow. It is possible that your doctor has also prescribed acetylsalicylic acid (a substance found in many medications used to relieve pain and reduce fever, as well as to prevent blood clots from forming).
• you have experienced symptoms of a transient ischemic attack that disappear in a short period of time (also known as a transient ischemic attack) or a mild ischemic stroke. Your doctor may also administer acetylsalicylic acid during the first 24 hours.
• you have an irregular heartbeat, a disease known as “atrial fibrillation”, and cannot take medications known as “oral anticoagulants” (vitamin K antagonists) that prevent the formation of new clots and prevent the growth of existing clots. You have been told that “oral anticoagulants” are more effective than acetylsalicylic acid or the combined use of Plavix and acetylsalicylic acid for this disease. Your doctor has prescribed Plavix in combination with acetylsalicylic acid if you cannot take “oral anticoagulants” and do not have a high risk of severe bleeding.

Do not take Plavix

• If you are allergic (hypersensitive) to clopidogrel or to any of the other components of this medication (listed in section 6).
• If you have an active bleeding, such as a stomach ulcer or brain hemorrhage.
• If you have a severe liver disease.

If you think this may affect you, or if you have any doubts, consult your doctor before taking Plavix.

Warnings and precautions

Before starting treatment with Plavix, inform your doctor if you are in any of the following situations:

• If you have a risk of bleeding (bleeding) because:

• You have a disease that involves a risk of internal bleeding (such as a stomach ulcer).
• You have a blood disorder that predisposes you to internal bleeding (bleeding in tissues, organs, or joints of the body).
• You have recently suffered a serious injury.
• You have recently undergone surgery (including dental surgery).
• You are scheduled to undergo surgery (including dental surgery) in the next seven days.

• If you have had a blood clot in a cerebral artery (ischemic stroke) in the last 7 days.
• If you have liver or kidney diseases.
• If you have had an allergy or reaction to any medication used to treat your disease.
• If you have a history of non-traumatic cerebral hemorrhage.

During treatment with Plavix:

Children and adolescents

This medication should not be administered to children because it is not effective.

Plavix with other medications

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication, including those purchased without a prescription.

Some medications may affect the use of Plavix or vice versa.

You must inform your doctor explicitly if you are taking:

- medications that may increase the risk of bleeding such as:

• oral anticoagulants, medications used to reduce blood coagulation,
• non-steroidal anti-inflammatory drugs, medications used to treat pain and/or inflammation of muscles or joints,
• heparin, or any other injectable medication used to reduce blood coagulation,
• ticlopidine, another antiplatelet agent,
• an SSRI (such as fluoxetine or fluvoxamine and other medications of the same type), medications used to treat depression,
• rifampicin (used for serious infections)

- omeprazole or esomeprazole, medications to treat stomach discomfort,

- fluconazole or voriconazole, medications to treat fungal infections,

- efavirenz, or other antiretroviral medications (used to treat HIV infections),

- carbamazepine, a medication to treat certain forms of epilepsy,

- moclobemide, a medication for depression,

- repaglinide, a medication to treat diabetes,

- paclitaxel, a medication to treat cancer,

- opioids: if you are taking clopidogrel, inform your doctor before they prescribe any opioid (used to treat intense pain),

- rosuvastatin (used to reduce cholesterol levels).

If you have had severe chest pain (unstable angina or myocardial infarction), transient ischemic attack, or mild ischemic stroke, you may have been prescribed Plavix in combination with aspirin, a substance present in many medications used to relieve pain and reduce fever. A single dose of aspirin administered sporadically (not exceeding 1,000 mg in 24 hours) generally should not cause any problems, but prolonged use in other circumstances should be consulted with your doctor.

Plavix with food and drinks

Plavix can be taken with or without food.

Pregnancy and breastfeeding

It is preferable not to take this medication during pregnancy.

If you are pregnant or think you may be, inform your doctor or pharmacist before taking Plavix. If you become pregnant while taking Plavix, consult your doctor immediately since clopidogrel is not recommended during pregnancy.

You should not breastfeed while taking this medication.

If you are breastfeeding or plan to do so, inform your doctor before taking this medication.

Consult your doctor or pharmacist before using any medication.

Driving and operating machinery

It is unlikely that Plavix will affect your ability to drive or operate machinery.

Plavix contains lactose

If your doctor has told you that you have an intolerance to certain sugars (e.g. lactose), consult with him before taking this medication.

Plavix contains hydrogenated ricin oil

This may cause stomach discomfort and diarrhea.

Follow exactly the administration instructions of this medication indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The recommended dose, even for patients with a disease called “atrial fibrillation” (an irregular heart rhythm), is one 75 mg Plavix tablet per day, taken orally with or without food and at the same time every day.

If you have experienced severe chest pain (unstable angina or myocardial infarction),your doctor may prescribe 300 mg or 600 mg of Plavix (1 or 2 300 mg tablets or 4 or 8 75 mg tablets) to be taken once at the beginning of treatment. After that, the recommended dose is one 75 mg Plavix tablet per day as described above.

If you have experienced symptoms of a stroke that disappear in a short period of time (also known as transient ischemic attack) or a mild ischemic stroke, your doctor may prescribe 300 mg of Plavix (1 300 mg tablet or 4 75 mg tablets) once at the beginning of treatment. After that, the recommended dose is one 75 mg Plavix tablet per day as described above with acetylsalicylic acid for 3 weeks. After that, your doctor will prescribe either Plavix alone or acetylsalicylic acid alone.

You should take Plavix for the time your doctor continues to prescribe it.

If you take more Plavix than you should

Contact your doctor or go to the nearest hospital emergency department, as there is a higher risk of bleeding.

If you forget to take Plavix

If you forget to take a Plavix dose, but remember before 12 hours have passed sincethe time when you should have taken the medication,take the tablet immediately and the next one at the usual time.

If you forget for more than 12 hours, simply take the next dose at the usual time. Do not take a double dose to compensate for a missed tablet.

In the 7, 14, 28, and 84 tablet formats, you can check the last day you took a Plavix tablet by looking at the calendar printed on the blister pack.

If you interrupt treatment with Plavix

Do not stop your treatment unless your doctor tells you to. Contact your doctor or pharmacist before stopping this medication.

If you have any other questions about the use of this medication, ask your doctor or pharmacist.

Like all medicines, Plavix can have side effects, although not everyone will experience them.

Contact your doctor immediately if you experience:

• Fever, signs of infection, or extreme fatigue. These symptoms may be due to a rare decrease in some blood cells.
• Signs of liver problems, such as yellowing of the skin and/or eyes (jaundice), associated or not with bleeding that appears under the skin as red spots and/or confusion (see section 2 “Warnings and precautions”).
• Swelling of the mouth or skin disorders such as hives and itching, blisters on the skin. These may be signs of an allergic reaction.

The most frequent side effect reported with Plavixis bleeding. Bleeding can occur in the stomach or intestine, bruises, hematomas (abnormal bleeding or bruises under the skin), nasal bleeding, blood in urine. Also, a reduced number of cases of: bleeding of the blood vessels of the eyes, intracranial, pulmonary, or joint bleeding have been reported.

If you experience prolonged bleeding while taking Plavix

If you cut or get a wound, it is possible that bleeding may take a little longer than usual to stop. This is related to the mechanism of action of the medication, as it prevents the blood's ability to form clots. For minor cuts or wounds, such as cutting during shaving, this usually does not matter. However, if you are concerned about your bleeding, consult your doctor immediately (see section 2 “Warnings and precautions”).

Other side effects include:

Frequent side effects (may affect up to 1 in 10 people):

Diarrhea, abdominal pain, indigestion, or heartburn.

Rare side effects (may affect up to 1 in 100 people):

Headache, stomach ulcer, vomiting, nausea, constipation, excessive gas in the stomach or intestine, rashes, itching, dizziness, numbness, and tingling.

Rare side effects (may affect up to 1 in 1,000 people):

Dizziness, breast enlargement in men.

Very rare side effects (may affect up to 1 in 10,000 people):

Jaundice; severe abdominal pain with or without back pain; fever, difficulty breathing, sometimes associated with cough; generalized allergic reactions (e.g., feeling of general heat with sudden general discomfort until fainting); swelling of the mouth; blisters on the skin; skin allergy; inflammation of the mucous membrane of the mouth (stomatitis); decreased blood pressure; confusion; hallucinations; joint pain; muscle pain; changes in taste or loss of taste of food.

Side effects of unknown frequency (cannot be estimated from available data): Hypersensitivity reactions with chest or abdominal pain, persistent symptoms of low blood sugar levels.

Your doctor may also observe changes in your blood or urine test results.

Reporting side effects

If you experienceany type of side effect, consult your doctor or pharmacist, even if it is apossibleside effect that does not appear in this prospectus.You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the packaging and in the blister pack, after CAD. The expiration date is the last day of the month indicated.

See storage conditions on the packaging.

Store below30°Cwhen Plavix is presented in PVC/PVDC/aluminum blisters.

When Plavix is presented in any aluminum blister, no special storage conditions are required.

Do not use this medication if you observe any visible signs of deterioration.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. This will help protect the environment.

Composition of Plavix

The active ingredient is clopidogrel. Each tablet contains 75 mg of clopidogrel (as hydrogen sulfate).

The other components are (see section 2 "Plavix contains lactose" and "Plavix contains hydrogenated ricin oil"):

• Tablet core: mannitol (E421), hydrogenated ricin oil, microcrystalline cellulose, macrogol 6000, and partially substituted hydroxypropylcellulose.
• Tablet coating: lactose monohydrate (milk sugar), hypromellose (E464), triacetin (E1518), iron oxide red (E172), and titanium dioxide (E171).
• Coating: carnauba wax.

Appearance of the product and contents of the package

Plavix 75 mg coated tablets are round, biconvex, pink in color, and have the number "75" engraved on one face and the number "1171" on the other. Plavix is presented in cartons containing:

- 7, 14, 28, 30, 84, 90, and 100 tablets in PVC/PVDC/Aluminum or Aluminum/Aluminum blisters.

- 50 x 1 tablets in PVC/PVDC/Aluminum or single-dose aluminum blisters.

Only some package sizes may be marketed.

Marketing authorization holder and manufacturer

Marketing authorization holder:

Sanofi Winthrop Industrie

82 avenue Raspail

94250 Gentilly

France

Manufacturers:

Sanofi Winthrop Industrie

1, Rue de la Vierge, Ambarès & Lagrave, F- 33565 Carbon Blanc cedex , France.

or

Delpharm Dijon

6, Boulevard de l’Europe, F - 21800 Quétigny, France

or

Sanofi S.r.l.

Strada Statale 17, Km 22

67019 Scoppito (AQ) – Italy

or

Sanofi Winthrop Industrie

30-36 avenue Gustave Eiffel

37100 Tours

France

For more information about this medicine, please contact the local representative of the marketing authorization holder.

Last update of this leaflet:

The detailed information on this medicine is available on the website of the European Medicines Agency: http://www.ema.europa. eu/