Clopidogrel Zentiva (Previously Clopidogrel Winthrop)

Posology Adults and elderly Clopidogrel Zentiva 75 mg film-coated tablets Clopidogrel should be given as a single daily dose of 75 mg. Clopidogrel Zentiva 300 mg film-coated tablets This 300 mg tablet of clopidogrel is intended for use as a loading dose.

In patients suffering from acute coronary syndrome: • Non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction): clopidogrel treatment should be initiated with a single 300 mg or 600 mg loading dose.

4). Clopidogrel treatment should be continued at 75 mg once a day (with acetylsalicylic acid (ASA) 75 mg-325 mg daily). Since higher doses of ASA were associated with higher bleeding risk it is recommended that the dose of ASA should not be higher than 100 mg.

The optimal duration of treatment has not been formally established. 1). • ST segment elevation acute myocardial infarction: - For medically treated patients eligible for thrombolytic/fibrinolytic therapy clopidogrel should be given as a single daily dose of 75 mg initiated with a 300 mg loading dose in combination with ASA and with or without thrombolytics.

For medically treated patients over 75 years of age clopidogrel should be initiated without a loading dose. Combined therapy should be started as early as possible after symptoms start and continued for at least four weeks. 1). - When percutaneous coronary intervention (PCI) is intended: ▪ Clopidogrel should be initiated at a loading dose of 600 mg in patients undergoing primary PCI and in patients undergoing PCI more than 24 hours of receiving fibrinolytic therapy.

4). ▪ Clopidogrel 300 mg loading dose should be given in patients undergoing PCI within 24 hours of receiving fibrinolytic therapy. Clopidogrel treatment should be continued at 75 mg once a day with ASA 75 mg – 100 mg daily. 1). 1 Age, Blood pressure, Clinical features, Duration, and Diabetes mellitus diagnosis 2 National Institutes of Health Stroke Scale 4 Adult patients with moderate to high-risk TIA or minor IS: Adult patients with moderate to high-risk TIA (ABCD2 score ≥4) or minor IS (NIHSS ≤3) should be given a loading dose of clopidogrel 300 mg followed by clopidogrel 75 mg once daily and ASA (75 mg -100 mg once daily).

Treatment with clopidogrel and ASA should be started within 24 hours of the event and be continued for 21 days followed by single antiplatelet therapy. In patients with atrial fibrillation, clopidogrel should be given as a single daily dose of 75 mg.

Summary of the safety profile Clopidogrel has been evaluated for safety in more than 44,000 patients who have participated in clinical studies, including over 12,000 patients treated for 1 year or more. Overall, clopidogrel 75 mg/day was comparable to ASA 325 mg/day in CAPRIE regardless of age, gender and race.

The clinically relevant adverse reactions observed in the CAPRIE, CURE, CLARITY, COMMIT and 10 ACTIVE-A studies are discussed below. In addition to clinical studies experience, adverse reactions have been spontaneously reported. Bleeding is the most common reaction reported both in clinical studies as well as in post-marketing experience where it was mostly reported during the first month of treatment.

3%. The incidence of severe cases was similar for clopidogrel and ASA. In CURE, there was no excess in major bleeds with clopidogrel plus ASA within 7 days after coronary bypass graft surgery in patients who stopped therapy more than five days prior to surgery.

3% for placebo plus ASA. In CLARITY, there was an overall increase in bleeding in the clopidogrel plus ASA group vs. the placebo plus ASA group. The incidence of major bleeding was similar between groups. This was consistent across subgroups of patients defined by baseline characteristics, and type of fibrinolytic or heparin therapy.

In COMMIT, the overall rate of noncerebral major bleeding or cerebral bleeding was low and similar in both groups. 3%). 5% vs. 8%). 8%, respectively). 6%, respectively) between groups. 0001). Tabulated list of adverse reactions Adverse reactions that occurred either during clinical studies or that were spontaneously reported are presented in the table below.

Their frequency is defined using the following conventions: common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data). Within each system organ class, adverse reactions are presented in order of decreasing seriousness.

8). 5). 8). Patients should be followed carefully for any signs of bleeding including occult bleeding, especially during the first weeks of treatment and/or after invasive cardiac procedures or surgery. 5). If a patient is to undergo elective surgery and antiplatelet effect is temporarily not desirable, clopidogrel should be discontinued 7 days prior to surgery.

Patients should inform physicians and dentists that they are taking clopidogrel before any surgery is scheduled and before any new medicinal product is taken. Clopidogrel prolongs bleeding time and should be used with caution in patients who have lesions with a propensity to bleed (particularly gastrointestinal and intraocular).

Patients should be told that it might take longer than usual to stop bleeding when they take clopidogrel (alone or in combination with ASA), and that they should report any unusual bleeding (site or duration) to their physician. The use of clopidogrel 600 mg loading dose is not recommended in patients with non-ST segment elevation acute coronary syndrome and ≥75 years of age due to increased bleeding risk in this population.

Due to the limited clinical data in patients ≥75 years old with STEMI PCI, and increased risk of bleeding, the use of clopidogrel 600 mg loading dose should be considered only after an individual assessment of the bleeding risk of the patient by the physician.

Thrombotic Thrombocytopenic Purpura (TTP) Thrombotic Thrombocytopenic Purpura (TTP) has been reported very rarely following the use of clopidogrel, sometimes after a short exposure. It is characterised by thrombocytopenia and microangiopathic haemolytic anaemia associated with either neurological findings, renal dysfunction or fever.

TTP is a potentially fatal condition requiring prompt treatment including plasmapheresis. Acquired haemophilia Acquired haemophilia has been reported following use of clopidogrel. In cases of confirmed isolated activated Partial Thromboplastin Time (aPTT) prolongation with or without bleeding, acquired haemophilia should be considered.

1. • Severe hepatic impairment. • Active pathological bleeding such as peptic ulcer or intracranial hemorrhage.