PLAVISTAD 75 Tablet

Clopidogrel is indicated in adults for the prevention of atherothrombotic events in:

- Patients suffering from myocardial infarction (from a few days until less than 35 days), ischaemic stroke (from 7 days until less than 6 months) or established peripheral arterial disease.

- Patients suffering from acute coronary syndrome:

+ Non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction), including patients undergoing a stent placement following percutaneous coronary intervention.

+ ST segment elevation acute myocardial infarction, in medically treated patients eligible for thrombolytic therapy.

DOSAGE AND ADMINISTRATION

Plavistad 75 is administered orally with or without food.

- Adults and elderly: A single daily dose: 75mg.

- Non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction): Clopidogrel treatment should be initiated with a single 300mg loading dose and then continued at 75mg once a day (with acetylsalicylic acid (ASA) 75mg-325mg daily).

- ST segment elevation acute myocardial infarction: Clopidogrel should be given as a single daily dose of 75mg initiated with a 300mg loading dose in combination with ASA and with or without thrombolytics.

- For 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.

- Known hypersensitivity to clopidogrel or any ingredient in the formulation.

- Severe liver impairment.

- Presence of active pathological bleeding (e.g. peptic ulcer, intracranial hemorrhage).

- The incidence of adverse effects, particularly blood dyscrasias, is lower with clopidogrel, although fatalities have been reported.

- Common: haematoma, epistaxis, gastrointestinal haemorrhage, diarrhoea, abdominal pain, dyspepsia, bruising and bleeding at puncture site.

- Uncommon: thrombocytopenia, leucopenia, eosinophilia, intracranial bleeding, headache, paraesthesia, dizziness, eye bleeding, gastric ulcer and duodenal ulcer, gastritis, vomiting, nausea, constipation, flatulence, rash, pruritus, skin bleeding (purpura) and haematuria.

- Rare: neutropenia including severe neutropenia, vertigo and retroperitoneal haemorrhage.

- Very rare: thrombotic thrombocytopenic purpura (TTP), aplastic anaemia, pancytopenia, agranulocytosis, severe thrombocytopenia, granulocytopenia, anaemia, serum sickness, anaphylactoid reactions, hallucinations, confusion, taste disturbances, serious haemorrhage, haemorrhage of operative wound, vasculitis, hypotension, respiratory tract bleeding, bronchospasm, interstitial pneumonitis, gastrointestinal and retroperitoneal haemorrhage with fatal outcome, pancreatitis, colitis, stomatitis, acute liver failure, hepatitis, abnormal liver function test, bullous dermatitis, angioedema, rash erythematous, urticaria, eczema, lichen planus, musculo-skeletal bleeding, arthritis, arthralgia, myalgia, glomerulonephritis blood creatinine increase and fever.

(See the package insert for details.)

- Aspirin

- Heparin

- Thrombolytics

- Other NSAIDs

- Warfarin

Pregnancy

There are no adequate and well-controlled studies in pregnant women, clopidogrel should be used during pregnancy only if clearly needed.

Lactation

Not known whether the drug is distributed into milk in humans. Discontinue nursing or the drug because of potential for severe adverse effects in infants.

- Prolongs bleeding time. Use with caution in patients at increased risk of bleeding from trauma, surgery, ulcers, or other pathology, particularly gastrointestinal or intraocular conditions. If bleeding or hematologic disorders are suspected, promptly consider determining blood cell counts or other appropriate monitoring. Discontinue clopidogrel 5-7 days prior to elective surgery or coronary artery bypass graft (CABG), if antiplatelet effect is undesirable. Drugs (e.g. aspirin, other NSAIDs) that might induce such lesions should be used with caution in patients receiving clopidogrel.

- Use with caution because of possibility of bleeding diatheses in patients with severe hepatic disease.

- Experience is limited in patients with severe renal impairment (creatinine clearance of 5-15mL/minute); use with caution.

- Pharmacogenetics: Based on literature data, patients with genetically reduced CYP2C19 function (intermediate or poor metabolisers) have lower systemic exposure to the active metabolite of clopidogrel and diminished antiplatelet responses, and generally exhibit higher cardiovascular event rates following myocardial infarction than do patients with normal CYP2C19 function.

Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to tis platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPⅡb/Ⅲa complex, thereby inhibiting platelet aggregation. Biotransformation of clopidogrel is necessary to produce inhibition of platelet aggregation, but an active metabolite responsible for the activity of the drug has not been isolated. Clopidogrel also inhibits platelet ADP. Clopidogrel does not inhibit phosphodiesterase activity.

Clopidogrel acts by irreversibly modifying the platelet ADP receptor. Consequently, platelets exposed to clopidogrel are affected for the remainder of their lifespan.