Clopidogrel Acino Pharma GmbH

Posology  Adults and elderly Clopidogrel should be given as a single daily dose of 75 mg. If a dose is missed: - Within less than 12 hours after regular scheduled time: patients should take the dose immediately and then take the next dose at the regular scheduled time.

- For more than 12 hours: patients should take the next dose at the regular scheduled time and should not double the dose. 1). 4). 4). 2Medicinal product no longer authorised Method of administration For oral use It may be given with or without food.

Clopidogrel has been evaluated for safety for 1 year or more. The clinically relevant adverse reactions observed in the CAPRIE study are discussed below. Overall, clopidogrel 75 mg/day was comparable to ASA 325 mg/day in CAPRIE regardless of age, gender and race.

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. 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).

Within each system organ class, adverse reactions are presented in order of decreasing seriousness. 4), aplastic anaemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anaemia Immune system disorders Serum sickness, anaphylactoid reactions Psychiatric disorders Hallucinations, confusion 6Medicinal product no longer authorised Nervous system disorders Intracranial bleeding (some cases were reported with fatal outcome), headache, paraesthesia, dizziness Taste disturbances Eye disorders Eye bleeding (conjunctival, ocular, retinal) Ear and labyrinth disorders Vertigo Vascular disorders Haematoma Serious haemorrhage, haemorrhage of operative wound, vasculitis, hypotension Respiratory, thoracic and mediastinal disorders Epistaxis Respiratory tract bleeding (haemoptysis, pulmonary haemorrhage), bronchospasm, interstitial pneumonitis Gastrointestinal disorders Gastrointestinal haemorrhage, diarrhoea, abdominal pain, dyspepsia Gastric ulcer and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence Retroperitoneal haemorrhage Gastrointestinal and retroperitoneal haemorrhage with fatal outcome, pancreatitis, colitis (including ulcerative or lymphocytic colitis), stomatitis Hepato-biliary disorders Acute liver failure, hepatitis, abnormal liver function test Skin and subcutaneous tissue disorders Bruising Rash, pruritus, skin bleeding (purpura) Bullous dermatitis (toxic epidermal necrolysis, Stevens Johnson Syndrome, erythema multiforme), angioedema, rash erythematous, urticaria, eczema, lichen planus Musculoskeletal , connective tissue and bone disorders Musculo-skeletal bleeding (haemarthrosis), arthritis, arthralgia, myalgia 7Medicinal product no longer authorised Renal and urinary disorders Haematuria Glomerulonephritis, blood creatinine increased General disorders and administration site conditions Bleeding at puncture site Fever Investigations Bleeding time prolonged, neutrophil count decreased, platelet count decreased

8). As with other antiplatelet agents, clopidogrel should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery or other pathological conditions and in patients receiving treatment with ASA, heparin, glycoprotein IIb/IIIa inhibitors or nonsteroidal anti-inflammatory drugs (NSAIDs) including Cox-2 inhibitors.

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, and that they should report any unusual bleeding (site or duration) to their 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.

Recent ischaemic stroke In view of the lack of data, clopidogrel cannot be recommended during the first 7 days after acute ischaemic stroke.

Cytochrome P450 2C19 (CYP2C19) Pharmacogenetics:

 Hypersensitivity to the active substance or to any of the excipients.  Severe hepatic impairment.  Active pathological bleeding such as peptic ulcer or intracranial haemorrhage.