CLOPIDOGREL WINTHROP

What it is

Clopidogrel hydrogen sulfate is the active ingredient. Each tablet contains 75 mg clopidogrel hydrogen sulfate. The tablets are pink coloured, round, biconvex, film coated tablets. Clopidogrel is a specific and potent inhibitor of platelet aggregation. The active metabolite selectively inhibits the binding of ADP to its platelet P2Y12 receptor and the subsequent ADP-mediated activation of the GPIIb/IIIa complex, thereby inhibiting platelet aggregation.

Approved indications —

Prevention of vascular ischaemia associated with atherothrombotic events (myocardial infarction, stroke and vascular death) in patients with a history of symptomatic atherosclerotic disease. — Unstable angina or non-ST-elevation myocardial infarction in combination with aspirin in order to prevent early and long-term atherothrombotic events (myocardial infarction, stroke, vascular death or refractory ischaemia). — ST-segment elevation acute myocardial infarction in order to prevent atherothrombotic events.

Dosing overview

Clopidogrel should be taken once a day with or without food. Generally, clopidogrel should be given as a single daily dose of 75 mg. In patients with unstable angina or non-ST-elevation myocardial infarction, clopidogrel treatment should be initiated with a single 300 mg loading dose and then continued long-term at 75 mg once a day (with aspirin 75 mg–325 mg daily). In patients with ST segment elevation acute myocardial infarction, clopidogrel treatment should be given as a single daily dose of 75 mg initiated with or without a 300 mg loading dose in combination with aspirin and with or without thrombolytics. No dosage adjustment is necessary for either elderly patients or patients with renal impairment.

Key safety warnings

As with other anti-platelet agents, clopidogrel prolongs bleeding time and 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 acetylsalicylic acid, heparin, glycoprotein IIb/IIIa inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), selective serotonin reuptake inhibitors (SSRIs), or CYP2C19 strong inducers. If a patient is to undergo elective surgery and an anti-platelet effect is not desired, clopidogrel should be discontinued at least 5 days prior to surgery. 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 (plasma exchange). Due to the risk of bleeding and haematological undesirable effects, 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. CYP2C19 poor metaboliser status is associated with diminished antiplatelet response to clopidogrel. Although a higher dose regimen in poor metabolisers increases antiplatelet response, an appropriate dose regimen for this patient population has not been established in clinical outcome trials. Consider alternative treatment or treatment strategies in patients identified as CYP2C19 poor metabolisers.

Contraindications

Hypersensitivity to clopidogrel or any of the excipients. Severe liver impairment. Active pathological bleeding such as peptic ulcer and intracranial haemorrhage. Breastfeeding.

Regulatory history

CLOPIDOGREL WINTHROP clopidogrel (as hydrogen sulfate) 75 mg tablet was first listed on the ARTG on 2008-08-05. An AusPAR approval for a fixed-dose combination product was dated 2009-09-01, intended as continuation of therapy in patients with acute coronary syndrome already initiated with separate clopidogrel and aspirin products. The submission for extension of indications for prevention of atherothrombotic and thromboembolic events in atrial fibrillation was withdrawn by the sponsor on 11 March 2011, with subsequent amendments made to the Product Information.