Clopidogrel + Aspirin information from DrugsUpdate
L - Contraindicated in lactation
FI - Food *
LI - Lab *
Clopidogrel selectively inhibits the binding of adenosine diphosphate 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 agonists 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 bisulfate. Repeated doses of 75 mg Clopidogrel bisulfate per day inhibit 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 bisulfate 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.
Aspirin inhibits the formation of thromboxane A2 in the platelets. This inhibits platelet aggregation and coagulation. This action lasts until the enzyme cyclo-oxygenase is regenerated in the platelets. Clopidogrel selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet receptor and the subsequent ADP-mediated activation of the glycoprotein GP IIb/IIIa complex, thereby inhibiting platelet aggregation.
Aspirin: GI disturbances; prolonged bleeding time, rhinitis, urticaria and epigastric discomfort; angioedema, salicylism, tinnitus.
Clopidogrel: Dyspepsia, abdominal pain, nausea, vomiting, flatulence, constipation, gastritis, gastric and duodenal ulcers. Serious events include bleeding and GI haemorrhage. GI upset, diarrhoea, paraesthesia, vertigo, headache, dizziness, leucopaenia, eosinophilia, rash; pruritus and rashes.
Potentially Fatal: Aspirin: Gastric erosion, ulceration and bleeding; severe, occasionally fatal exacerbation of airway obstruction in asthma; Reye's syndrome (children <12 years). Hepatotoxicity; CNS depression, which may lead to coma; CV collapse, respiratory failure; paroxysmal bronchospasm and dyspnoea.
Clopidogrel: Bleeding disorders including GI intracranial haemorrhage.
Clopidogrel bisulfate prolongs 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 pathological conditions (particularly gastrointestinal and 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.
Due to the risk of bleeding and undesirable hematological effects, blood cell count determination and/or other appropriate testing should be promptly considered, whenever such suspected clinical symptoms arise during the course of treatment.
In patients with recent TIA or stroke who are at high risk for recurrent ischemic events, the combination of aspirin and Clopidogrel bisulfate has not been shown to be more effective than Clopidogrel bisulfate alone, but the combination has been shown to increase major bleeding.
In caprie, Clopidogrel bisulfate was associated with a rate of gastrointestinal bleeding of 2%, vs. 2.7% on aspirin. In CURE, the incidence of major gastrointestinal bleeding was 1.3% vs 0.7% (Clopidogrel bisulfate + aspirin vs. placebo + aspirin, respectively). 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 diatheses. 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.
History of peptic ulcer or those prone to dyspepsia and those with gastric mucosal lesion; asthma or allergic disorders; dehydrated patients; uncontrolled hypertension; impaired renal or hepatic function; elderly; pregnancy. Patients at risk of increased bleeding from trauma, surgery, or other pathological conditions.
Use of clopidogrel may lead to thrombotic thrombocytopenic purpura which is characterised by thrombocytopenia, microangiopathic haemolytic anaemia, neurological findings, renal dysfunction and fever. Increased risk of Reye's syndrome when used in patients with chicken pox, influenza or flu symptoms. Caution when used in patients with nasal allergies or nasal polyps. For patients undergoing elective surgery and an antiplatelet effect is not needed, clopidogrel should be discontinued 7 days before surgery.
Aspirin: Alcohol, corticosteroids, analgin, phenylbutazone and oxyphenbutazone may increase risk of GI ulceration. Aspirin increases phenytoin levels. May antagonize actions of uricosurics and spironolactone.
Clopidogrel: Co-administration of clopidogrel with NSAIDs may increase the risk of stomach and intestinal bleeding. At high conc in the blood, clopidogrel inhibits the activity of enzyme metabolising warfarin leading to an increased warfarin levels thus increasing the risk of bleeding due to over-thinning of the blood. High doses of clopidogrel inhibit cytochrome P-450 (CYP2C9). Clopidogrel may interfere with the metabolism of phenytoin, tamoxifen, torasemide, fluvastatin and some NSAIDs.
Potentially Fatal: Aspirin may potentiate effects of anticoagulants, methotrexate and oral hypoglycaemics.
Increased risk of GI bleeding when used with alcohol.
Prevention of ischaemic events
Adult: Each tablet contains clopidogrel 75 mg and aspirin 75 mg: 1 tablet once daily.
Acute coronary syndrome
Adult: Each tablet contains clopidogrel 75 mg and aspirin 75 mg: Loading dose: 4 tablets; maintenance: 1 tablet daily.
List of Contraindications
Caution when used during pregnancy
Contraindicated in lactation
Safety and effectiveness in the pediatric population have not been established.
Of the total number of subjects in controlled clinical studies, approximately 50% of patients treated with Clopidogrel bisulfate were 65 years of age and over. Approximately 16% of patients treated with Clopidogrel bisulfate were 75 years of age and over.
Hypersensitivity; active peptic ulceration; children <12 years; patients with haemophilia or haemorrhagic disorders; gout; severe renal or hepatic impairment; lactation, admin within 7 days after ischaemic stroke.
Interferes with thyroid function tests
Clopidogrel + Aspirin brands in India
C-Grel Plus 75
Clopivas AP 75
Ecosprin Gold Forte