Each film coated tablet contains: Clopidogrel Bisulfate, Equivalent to Clopidogrel 75 mg.
Clopidogrel bisulfate is an inhibitor of ADP-induced platelet aggregation acting by direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex. Chemically it is methyl (+)-(S)-a- (2-chlorophenyl)-6, 7-dihydrothienio [3,2-c] pyridine-5 (4H)-acetate sulfate (1:1). The empirical formula of Clopidogrel bisulfate is C16H16ClNO2S·H2SO4 and its molecular weight is 419.9.
Pharmacology: Pharmacodynamics: Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its 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 aggregation induced by agonist other than ADP by blocking the amplification of platelet activation by released 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.
Dose dependent inhibition of platelet aggregation can be seen 2 hours after single oral doses of Clopidogrel. Repeated doses of 75 mg Clopidogrel per day inhibits ADP-induced platelet aggregation on the first day, and inhibition reaches steady state between day 3 and day 7. At steady state, the average inhibition level observed with a dose of 75 mg Clopidogrel per day was between 40% and 60%. Platelet aggregation and bleeding time gradually return to baseline values after treatment is discontinued, generally in about 5 days.
Pharmacokinetics: Clopidogrel is rapidly absorbed after oral administration of repeated doses of 75 mg Clopidogrel (base), with peak plasma levels (approx. 3 mg/mL) of the main circulating metabolite occurring approximately 1 hour after dosing. Clopidogrel is extensively metabolized by the liver. The main circulating metabolite is the carboxylic acid derivative and both the parent compound and the carboxylic acid derivative have no effect on platelet aggregation. Clopidogrel and the main circulating metabolite bind reversibly in vitro to human plasma proteins (98% and 94%, respectively). Following an oral dose of 1C-labeled Clopidogrel in humans, approximately 50% was excreted in the urine and approximately 46% in the feces in the 5 days after dosing. The elimination half-life of the main circulating metabolite was 8 hours after single and repeated administration. Administration of Clopidogrel with meals did not significantly modify the bioavailability of Clopidogrel as assessed by the pharmacokinetics of the main circulating metabolite.
Clopidogrel is indicated for the prevention of atherosclerosis events in peripheral arterial disease or within 35 days of myocardial infarction, or within 6 months of ischemic stroke, or (given with aspirin) in acute coronary syndrome without ST-segment-elevation.
The recommended dose of Clopidogrel is 75 mg once daily with or without food. No dosage adjustment is necessary for elderly patients or patients with renal disease.
One case of deliberate overdosage with Clopidogrel has been reported. A 34 year old woman took a single 1,050 mg dose of Clopidogrel (equivalent to 14 standard 75 mg tablets). There were no associated adverse events. No special therapy was instituted, and she recovered without sequelae.
However, based on biological plausibility, platelet transfusion may be appropriate to reverse the pharmacological effects of Clopidogrel if quick reversal is required.
The use of Clopidogrel is contraindicated in the following conditions: Hypersensitivity to Clopidogrel or any component of the product.
Active pathological bleeding such us peptic ulcer or intracranial hemorrhage.
As with other anti-platelet agents, Clopidogrel should be used with caution in patients who may at risk of increased bleeding from trauma, surgery, or other pathological conditions. If a patient is to undergo elective surgery and an antiplatelet effect is not desired, Clopidogrel should be discontinued 7 days prior to surgery. Clopidogrel should be used with caution in patients who have lesions with a propensity to bleed (such as ulcers). Drugs that might induce such lesions such as aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) should be with caution in patients taking Clopidogrel.
Experience is limited in patients with severe hepatic disease, who may have bleeding diatheses. Clopidogrel should be administered with caution in this population. Safety and effectiveness of the drug in pediatric population has not been established. Clopidogrel should be used in pregnant and lactating mothers only when clearly needed.
Clopidogrel should be used in pregnant and lactating mothers only when clearly needed.
The overall tolerability of Clopidogrel is similar to that of aspirin regardless of age, gender and race. The clinically important adverse events reported with the drug include the following: hemorrhage (GI, Intracranial); neutropenia/agranulocytosis, GIT disturbances (abdominal pain, dyspepsia, gastritis, constipation, diarrhea and ulceration), skin rashes and pruritis. Other reported side effects include chest pain, accidental injury, influenza like symptoms, headache, dizziness, arthalgia and back pain.
Concomitant used of Clopidogrel with aspirin, other NSAIDs, heparin and warfarin should be undertaken with caution for the fear of causing increased bleeding. No clinically significant pharmacodynamic interactions were observed when Clopidogrel was co-administered with atenolol, nifedipine, digoxin or theophylline. The pharmacodynamic activity of Clopidogrel was also not significantly influenced by the co-administration of phenobarbital, cimetidine or estrogen.
Clopidogrel may interfere with the metabolism of phenytoin, tamoxifen, tolbutamide, warfarin, torsemide, fluvastatin and many non-steriodal anti-inflammatory agents, but there are no data with to predict the magnitude of these interactions. Caution should be used when any of these drugs is co-administered with Clopidogrel. In addition to the above specific interaction studies, patients entered into CAPRIE received a variety of concomitant medication including diuretics, beta-blocking agents, angiotensin converting enzyme inhibitors, calcium antagonist, cholesterol lowering agents, coronary vasodilators, antidiabetic agents, anti-epileptic agents and hormone replacement therapy without evidence of clinically significant adverse interactions.
Store at temperatures not exceeding 30°C.
Protect from light.
B01AC04 - clopidogrel ; Belongs to the class of platelet aggregation inhibitors excluding heparin. Used in the treatment of thrombosis.
Noklot film-coated tab 75 mg
30's (P776.7/pack, P25.89/film-coated tab)
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