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Clopistad
Rx

Clopidogrel inhibits platelet aggregation by selectively inhibiting the binding of adenosine diphosphate (ADP) to its platelet receptor and inhibits platelet aggregation induced by agonists other than ADP by blocking the amplification of platelet activation by released ADP.

Pack size Box of 30 tablets
Shelf-life 36 months
Composition Clopidogrel
Dosage forms and strengths Film-coated tablet: 75 mg
Product code :

PRESCRIBING INFORMATION

Indications

Secondary prevention of atherothrombotic events
Clopistad is indicated in:
+ Adult 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.
+ Adult 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, in combination with acetylsalicylic acid (ASA).
• ST segment elevation acute myocardial infarction, in combination with ASA in medically treated patients eligible for thrombolytic therapy.
In patients with moderate to high-risk transient ischaemic attack (TIA) or minor ischaemic stroke (IS)
Clopidogrel in combination with ASA is indicated in: Adult patients with moderate to high-risk TIA (ABCD2 score ≥ 4) or minor IS (NIHSS ≤ 3) within 24 hours of either the TIA or IS event.
Prevention of atherothrombotic and thromboembolic events in atrial fibrillation
In adult patients with atrial fibrillation who have at least one risk factor for vascular events, are not suitable for treatment with vitamin K antagonists (VKA) and who have a low bleeding risk, clopidogrel is indicated in combination with ASA for the prevention of atherothrombotic and thromboembolic events, including stroke.

Dosage

Adults and elderly

Clopidogrel should be given as a single daily dose of 75 mg.
– 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. A 600 mg loading dose may be considered in patients < 75 years of age when percutaneous coronary intervention is intended. Clopidogrel treatment should be continued at 75 mg once a day (with acetylsalicylic acid (ASA) 75 – 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. Clinical trial data support use up to 12 months, and the maximum benefit was seen at 3 months.
+ ST segment elevation acute myocardial infarction: 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. The benefit of the combination of clopidogrel with ASA beyond four weeks has not been studied in this setting.
– 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 – 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. ASA (75 – 100 mg daily) should be initiated and continued in combination with clopidogrel.
– 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.
Paediatric population
Clopidogrel should not be used in children because of efficacy concerns.
Renal impairment
Therapeutic experience is limited in patients with renal impairment.
Hepatic impairment
Therapeutic experience is limited in patients with moderate hepatic disease who may have bleeding diatheses.

Usage

Clopistad is administered orally with or without food.

  • Known hypersensitivity to clopidogrel or any ingredient in the formulation.
  • Presence of active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage).
  • Severe hepatic impairment.
  • Haematoma.
  • Gastrointestinal haemorrhage, diarrhoea, abdominal pain, dyspepsia.
  • Bruising.
  • Epistaxis.

Bleeding and haematological disorders
Due to the risk of bleeding and haematological adverse reactions, blood cell count determination and/or other appropriate testing should be promptly considered whenever clinical symptoms suggestive of bleeding arise during the course of treatment. 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 non-steroidal anti-inflammatory drugs (NSAIDs) including Cox-2 inhibitors, or selective serotonin reuptake inhibitors (SSRIs), or CYP2C19 strong inducers or other medicinal products associated with bleeding risk such as pentoxifylline. 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. The concomitant administration of clopidogrel with oral anticoagulants is not recommended since it may increase the intensity of bleedings.
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.

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. Patients with a confirmed diagnosis of acquired haemophilia should be managed and treated by specialists, and clopidogrel should be discontinued.

Recent ischaemic stroke
– Initiation of therapy: In acute minor IS or moderate to high-risk TIA patients, dual antiplatelet therapy (clopidogrel and ASA) should be started no later than 24 hours after the event onset. There is no data regarding the benefit-risk of short-term dual antiplatelet therapy in acute minor IS or moderate to high-risk TIA patients, with a history of (non-traumatic) intracranial haemorrhage. In non-minor IS patients, clopidogrel monotherapy should be started only after the first 7 days of the event.
– Non-minor IS patients (NIHSS > 4): In view of the lack of data, use of dual antiplatelet therapy is not recommended.
– Recent minor IS or moderate to high-risk TIA in patients for whom intervention is indicated or planned.
There is no data to support the use of dual antiplatelet therapy in patients for whom treatment with carotid endarterectomy or intravascular thrombectomy is indicated, or in patients planned for thrombolysis or anticoagulant therapy. Dual antiplatelet therapy is not recommended in these situations.

Cytochrome P450 2C19 (CYP2C19)
Pharmacogenetics: In patients who are poor CYP2C19 metabolisers, clopidogrel at recommended doses forms less of the active metabolite of clopidogrel and has a smaller effect on platelet function. Tests are available to identify a patient’s CYP2C19 genotype.
Since clopidogrel is metabolised to its active metabolite partly by CYP2C19, use of medicinal products that inhibit the activity of this enzyme would be expected to result in reduced levels of the active metabolite of clopidogrel. The clinical relevance of this interaction is uncertain. As a precaution concomitant use of strong or moderate CYP2C19 inhibitors should be discouraged.
Use of medicinal products that induce the activity of CYP2C19 would be expected to result in increased drug levels of the active metabolite of clopidogrel and might potentiate the bleeding risk. As a precaution concomitant use of strong CYP2C19 inducers should be discouraged.

CYP2C8 substrates
Caution is required in patients treated concomitantly with clopidogrel and CYP2C8 substrate medicinal products.

Cross-reactions among thienopyridines
Patients should be evaluated for history of hypersensitivity to thienopyridines (such as clopidogrel, ticlopidine, prasugrel) since cross-reactivity among thienopyridines has been reported. Thienopyridines may cause mild to severe allergic reactions such as rash, angioedema, or haematological cross-reactions such as thrombocytopaenia and neutropaenia. Patients who had developed a previous allergic reaction and/or haematological reaction to one thienopyridine may have an increased risk of developing the same or another reaction to another thienopyridine. Monitoring for signs of hypersensitivity in patients with a known allergy to thienopyridines is advised.

Renal impairment: Therapeutic experience with clopidogrel is limited in patients with renal impairment. Therefore clopidogrel should be used with caution in these patients.

Hepatic impairment: Experience is limited in patients with moderate hepatic disease who may have bleeding diatheses. Clopidogrel should therefore be used with caution in this population.

Clopistad contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Clopistad contains hydrogenated castor oil. May cause stomach upset and diarrhoea.

Pregnancy: As no clinical data on exposure to clopidogrel during pregnancy are available, it is preferable not to use clopidogrel during pregnancy as a precautionary measure.

Lactation: It is unknown whether clopidogrel is excreted in human breast milk. Animal studies have shown excretion of clopidogrel in breast milk. As a precautionary measure, breast-feeding should not be continued during treatment with clopidogrel.

Clopidogrel has no or negligible influence on the ability to drive and use machines.