Clopidogrel

WARNING: DIMINISHED ANTIPLATELET EFFECT IN PATIENTS WITH TWO LOSS-OF-FUNCTION ALLELES OF THE CYP2C19 GENE

BOXED WARNING SECTION

The effectiveness of clopidogrel 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 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 P2Y12 inhibitor in patients identified as CYP2C19 poor metabolizers.

1 INDICATIONS AND USAGE

INDICATIONS & USAGE SECTION

2 DOSAGE AND ADMINISTRATION

DOSAGE & ADMINISTRATION SECTION

3 DOSAGE FORMS AND STRENGTHS

DOSAGE FORMS & STRENGTHS SECTION

Clopidogrel Tablets, USP 75 mg tablets: Pink colored, Round shaped, biconvex, film coated tablets de-bossed on one side with SG and 124 on other side. Clopidogrel Tablets, USP 300 mg tablets: Pink colored, Modified oval shaped, film coated tablets de-bossed on one side with SG and 121 on other side.

4 CONTRAINDICATIONS

CONTRAINDICATIONS SECTION

5 WARNINGS AND PRECAUTIONS

WARNINGS AND PRECAUTIONS SECTION

6 ADVERSE REACTIONS

ADVERSE REACTIONS SECTION

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) ]

7 DRUG INTERACTIONS

DRUG INTERACTIONS SECTION

8 USE IN SPECIFIC POPULATIONS

USE IN SPECIFIC POPULATIONS SECTION

10 OVERDOSAGE

OVERDOSAGE SECTION

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 1500 or 2000 mg/kg was lethal to mice and to rats and at 3000 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.

11 DESCRIPTION

DESCRIPTION SECTION

Clopidogrel bisulfate 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 empirical 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 freely soluble in methanol, practically insoluble in ether. It has a specific optical rotation of about +56°. Clopidogrel for oral administration is provided as either pink colored, round shaped, biconvex, de-bossed, film coated tablets containing 97.875 mg of clopidogrel bisulfate which is the molar equivalent of 75 mg of clopidogrel base or pink colored, modified oval shaped, de-bossed film coated tablets containing 391.5 mg of clopidogrel bisulfate which is the molar equivalent of 300 mg of clopidogrel base. Each tablet contains microcrystalline cellulose, mannitol, croscarmellose sodium, hydroxy propyl cellulose, hydroxy propyl methyl cellulose and hydrogenated castor oil as inactive ingredients. The film coating contains hypromellose, titanium dioxide, polyethylene glycol and red iron oxide.

12 CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

NONCLINICAL TOXICOLOGY SECTION

14 CLINICAL STUDIES

CLINICAL STUDIES SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

HOW SUPPLIED SECTION

Clopidogrel tablets, USP 75 mg are available as pink colored, round shaped, biconvex, film coated tablets de-bossed on one side with SG and 124 on other side. Clopidogrel tablets, USP 300 mg are available as pink colored, modified oval shaped, film coated tablets de-bossed on one side with SG and 121 on other side. Tablets are provided as follows: NDC 50268-184-12 (5 tablets per card, 4 cards per carton)

17 PATIENT COUNSELING INFORMATION

INFORMATION FOR PATIENTS SECTION

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

SPL UNCLASSIFIED SECTION

SPL UNCLASSIFIED SECTION

The brands listed are trademarks of their respective owners and are not trademarks of AvKARE. The makers of these brands are not affiliated with and do not endorse AvKARE or its products. Manufactured for: AvKARE Pulaski, TN 38478 Mfg Rev. 07/23 AV Rev. 06/25 (M) AvPAK

Medication Guide Clopidogrel Tablets, USP (kloe pid' oh grel)

SPL MEDGUIDE SECTION

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 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 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 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 herbal supplements. Clopidogrel tablets may affect the way other medicines work, and other medicines may affect how clopidogrel tablets works. See " What is the most important information I should know about clopidogrel tablets? " Clopidogrel tablets 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 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 ® ) 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 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. 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). 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 G...

PRINCIPAL DISPLAY PANEL - 300 mg Tablet Bottle Label

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL