Clopidogrel Tablets USP 75mg.
Each film coated tablet contains:
Clopidogrel Bisulfate USP
eq. to Clopidogrel 75mg
Colour: Red Oxide of Iron
Mechanism of Action: Clopidogrel is an inhibitor of platelet aggregation. A variety of drugs that inhibit platelet function have been shown to decrease morbid events in people with established cardiovascular atherosclerotic disease as evidenced by stroke or transient ischemic attacks, myocardial infarction, unstable angina or the need for vascular bypass or angioplasty. This indicates that platelets participate in the initiation and/or evolution of these events and that inhibiting them can reduce the event rate.
Pharmacodynamic Properties: Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GPllb/llla 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 aggregation induced by agonists other than ADP by blocking the amplification of platelet activation by released ADP. Clopidogrel does not inhibit phosphodiesterase activity.
PHARMACOKINETICS AND METABOLISM
After repeated 75 mg oral doses of clopidogrel (base); plasma concentrations of the parent compound, which has no platelet inhibiting effect, are very low and are generally below the quantification limit (0.00025 mg/L) beyond 2 hours after dosing. Clopidogrel is extensively metabolized by the liver. The main circulating metabolite is the carboxylic acid derivative and it too has no effect on platelet aggregation. It represents about 85% of the circulating drug-related compounds in plasma.
Effect of Food: Administration of clopidogrel bisulfate with meals did not significantly modify the bioavailability of clopidogrel as assessed by the pharmacokinetics of the main circulating metabolite.
Absorption and Distribution: Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75mg clopidogrel (base), with peak plasma levels (≈3 mg/L) of the main circulating metabolite occurring approximately 1 hour after dosing. The pharmacokinetics of the main circulating metabolite are linear (plasma concentrations increased in proportion to dose) in the dose range of 50 to 150 mg of clopidogrel. Absorption is at least 50% based on urinary excretion of clopidogrel-related metabolites.
Clopidogrel and the main circulating metabolite bind reversibly in vitro to human plasma proteins (98% and 94%, respectively), the binding is nonsaturable in vitro up to a concentration of 100 µg/mL.
Metabolism and Elimination: In vitro and in vivo, clopidogrel undergoes rapid hydrolysis into its carboxylic acid derivative. In plasma and urine, the glucuronide of the carboxylic acid derivative is also observed.
INDICATIONS AND USAGE
Clopidogrel bisulfate is indicated for the reduction of atherothrombotic events as follows:
• Recent MI, Recent Stroke or Established Peripheral Arterial Disease.
For patients with a history of recent myocardial infarction (Ml), recent stroke or established peripheral arterial disease, clopidogrel bisulfate has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new Ml (fatal or not) and other vascular death.
• Acute Coronary Syndrome
For patients with acute coronary syndrome (unstable angina/non-Q-wave MI) including patients who are to be managed medically and those who are to be managed with percutaneous coronary intervention (with or without stent) or CABG, clopidogrel bisulfate has been shown to decrease the rate of a combined endpoint of cardiovascular health, MI or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, stroke or refractory ischemia.
The use of clopidogrel bisulfate is contraindicated in the following conditions:
• Hypersensitivity to the drug substance or any component of the product.
• Active pathological bleeding such as peptic ulcer or intracranial haemorrhage.
Thrombotic thrombocytopenic purpura (TTP)
TTP has been reported rarely following use of clopidogrel bisulfate, sometimes after a short exposure (<2 weeks). Urgent treatment including plasma pheresis (plasma exchange). It is characterized by thrombocytopenia, microangiopathic haemolytic anemia (schistocytes [fragmented RBCs] seen on peripheral smear), neurological findings, renal dysfunction and fever.
General: Clopidogrel Bisulfate prolonged the bleeding time and therefore should be used with caution in patients who may be at risk of increased bleeding from trauma, surgery or other intraocular. If a patient is to undergo elective surgery and an antiplatelet effect is not desired, clopidogrel bisulfate should be discontinued 5 days prior to surgery.
GI Bleeding: Clopidogrel bisulfate was associated with a rate of gastrointestinal bleeding of 2% vs 2.7% on aspirin. Clopidogrel bisulfate should be used with caution in patients who have lesions with a propensity to bleed (such as ulcers). Drugs that might induce such lesions should be used with caution in patients taking clopidogrel bisulfate.
Use in Hepatically Impaired Patients: Experience is limited in patients with severe hepatic disease, who may have bleeding diathesis. Clopidogrel bisulfate should be used with caution in this population.
Use in Renally Impaired Patients: Experience is limited in patients with severe renal impairment. Clopidogrel bisulfate should be used with caution in this population.
Information for Patients: Patients should be told that it may take them longer than usual to stop bleeding, that they may bruise and/or bleed more easily when they take clopidogrel bisulfate or clopidogrel bisulfate combined with aspirin and that they should report any unusual bleeding to their physician. Patients should inform physicians and dentists that they are taking clopidogrel bisulfate and/or any other product.
Pregnancy: Pregnancy category B. Reproduction studies performed in rats and rabbits at doses up to 500 and 300 mg/kg/day (respectively, 65 and 78 times the recommended daily human dose on a mg/m2 basis), revealed no evidence of impaired fertility or fetotoxicity due to clopidogrel. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of a human response, clopidogrel bisulfate should be used during pregnancy only if clearly needed.
Clopidogrel bisulfate has been evaluated for safety in more than 17500 patients, including over 9000 patients treated for 1 year or more. The overall tolerability of clopidogrel bisulfate was similar to that of aspirin regardless of age, gender and race, with an approximately equal incidence (13%) of patients withdrawing from treatment because of adverse reactions. The clinically important adverse events are discussed below.
Overdose following clopidogrel administration may lead to prolonged bleeding time and subsequent bleeding complications.
DOSAGE AND ADMINISTRATION
Recent MI, Recent stroke or established peripheral arterial disease: The recommended daily dose of clopidogrel tablets is 75mg once daily.
Acute Coronary Syndrome: For patients with acute coronary syndrome (unstable angina/non-Q-wave MI), clopidogrel bisulfate should be initiated with a single 300mg loading dose and then continued at 75mg once daily.
Protect from moisture. Store at a temperature, not exceeding 25°C.
KEEP OUT OF REACH OF CHILDREN.
3 x 10 Tablets in a Carton.
NAFDAC Reg. No.: A4-6556
BHARAT PARENTERALS LTD.
Vill. Haripura, Ta. Savli,
Dist. Vadodara – 391 520 (Gujarat), India.
Zolun Healthcare Limited
37 Isolo way, Isolo, Lagos,