Category:
Platelet  aggregation inhibitor.                                                                                    (USP DI 2005)                                                                                         
Composition:
Each film-coated tablet contains 75 mg of Clopidogrel.                                                        
Chemistry:
Methyl(+)-(S)-a-(2-Chlorophenyl)-6,7-dihydrothieno [3,2-c] pyridine-5(4H)-acetate sulfate.
C16H16CINO2S,H2SO4               M.W=419.9                 (PDR 2005)
Mechanism of action:
Clopidogrel is an inhibitor of platelet aggregation; doses of 75mg per day inhibit platelet aggregation by 40 to 60% at steady state, which occurs within 3 to 7 days. Clopidogrel inhibits adenosine diphosphate (ADP) binding to its platelet receptor and subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thus inhibiting platelet aggregation. Because clopidogrel irreversibly modifies the ADP receptor, platelets are affected for the remainder of their of lifespan. An active metabolite, not yet isolated, is responsible for the medication’s activity. Platelet aggregation induced by agonists other than ADP is also inhibited by blocking the amplification of platelet activation by released ADP. Clopidogrel dose not inhibit phosphodiesterase activity.                                                                                                                       (USP DI 2005)                                                                                    
Pharmacokinetics:
Clopidogrel is rapidly but incompletely, absorbed after oral administration; absorption appears to be at least 50%. It is a prodrug and is extensively metabolised in the liver, mainly to the inactive carboxylic acid derivative. Clopidogrel and the carboxylic acid derivative are highly protein bound. Clopidogrel and its metabolites are excreted in urine and in faeces, after oral administration, about 50% of a dose is recovered from the urine and about 46% from the faeces.  (Martinade 2005)                                                                                         
Indications:
Indicated for atherosclerotic events as follows:
- Recent MI or stroke or established peripheral arterial disease: For patients with a history of recent MI, recent storke or established peripheral arterial disease, clopidogrel has been shown to reduce the rate of a combined endpoint of new ischemic stroke (fatal or not), new MI (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 coronary artery bypass graft (CABG), clopidogrel has been shown to decrease the rate of a combined endpoint of cardiovascular death, MI or stroke as well as the rate of a combined endpoint of cardiovascular death, MI, storke, or refractory ischemia.                                                                                                                                 (Fact 2005)
Precautions:
Bleeding risk:
As with other antiplatelet agents, use with caution in patients who may be 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, discontinue clopidogrel 5 days prior to surgery.
GI bleeding:
Clopidogrel prolongs the bleeding time. In the clinical trial, clopidogrel was associated with a rate of GI bleeding of 2% vs 2.7%, with aspirin. Use with caution in patients who have lesions with a propensity to bleed (such as ulcers). Cautiously use drugs that might increase such lesions in patients taking clopidogrel.                                                                    (Fact 2005)
Pregnancy:
Adequate and well-controlled studies in humans have not been done.
FDA Pregnancy Category B.                                                                                           (USP DI 2005)
Breast feeding: 
It is not known whether clopidogrel is distributed into human breast milk. Clopidogrel and/or its metabolites are distributed into the milk of lactating rats. Consideration of risk-benefit is recommended in making decisions about using clopidogrel in breast-feeding women or continuing breast - feeding in women taking clopidogrel.                                                                 (USP DI 2005)
Pediatrics:
Appropriate studies on the relationship of age to the effects of clopidogrel have not been performed in the pediatric population.
Safety and efficacy have not been established.                                                             (USP DI 2005)
Geriatrics:
Plasma concentrations of the main circulating metabolite have been found to be significantly higher in elderly individuals (≥ 75 years of age) than in young healthy volunteers but these higher concentrations have not been found to be associated with differences in platelet aggregation and bleeding time. No dosage adjustment is recommended for elderly patients.            (USP DI 2005)
Dental:
Because of the risk of increased surgical blood loss, it is recommended that clopidogrel be discontinued 7 days prior to elective dental surgery if an antiplatelet effect is not desired.
                                                                                                                                                                                     (USP DI 2005)
Surgical:
Because of the risk of increased surgical blood loss, it is recommended that clopidogrel be discontinued 7 days prior to elective surgery if an antiplatelet effect is not desired.   (USP DI 2005)
Drug interactions:
At high concentrations in vitro, clopidogrel inhibits, P450 2C9.
Accordingly, clopidogrel may interfere with the metabolism of phenytoin, tamoxifen, tolbutamide, warfarin, torsemide, fluvastatin and many nonsteroidal anti-inflammatory agents, but there are no data with which to predict the magnitude of these interactions. Use caution when any of these drugs is coadministered with clopidogrel.                                                              (Fact 2005)
Contraindications:
Hypersensitivity to the drug or any component of the product, active pathological bleeding such as peptic ulcer or intracranial hemorrhage.                                                                                                        (Fact 2005)
Warnings:
- Thrombotic thrombocytopenic purpura (TTP): TTP has been reported rarely following use of clopidogrel, sometimes after a short exposure (less than 2 weeks). TTP is a serious condition requiring prompt treatment.
- Hepatic function impairment                                                                                        (Fact 2005)
Adverse reactions:
-Those indicating need for medical attention:
Chest pain, pain, generalized purpura, upper respiratory infection, atrial fibrillation; or palpitations, bronchitis, dyspnea, edema, epistaxis, gastrointestinal hemorrhage, gout, hypertension, syncope, urinary tract infection, intracranial hemorrhage, neutropenia, agranulocytosis, gastric or duodenal ulcer, skin reactions, severe thrombocytopenia.
- Those indicating need for medical attention only if they continue or are bothersome:
Abdominal or stomach pain, arthralgia, back pain, dizziness, dyspepsia, flu-like symptoms, headache, anxiety, asthenia, constipation, cough, diarrhea, fatigue, hypoesthesia or paresthesia, insomnia, itching, leg cramps, mental depression, nausea, rhinitis, skin rash, vomiting.
                                                                                                                                   (USP DI 2005)
Dosage and administration:
-Usual adult dose: 75mg (base) once a day
-Usual pediatric dose: Safety and efficacy have not been established.                              (USP DI 2005)                                                                 
Storage:
Store between 15 and 30°C.                                                                                                                  (USP DI 2005)
How supplied:
Clopidogrel is available as a dirty pink, round, scored, film-coated tablet.      

References:
1-PDR 2005.
2-USP DI 2004.
3-Martindale 2005.
4-Fact 2005.