Aspirin + Clopidogrel

Indications

Aspirin + Clopidogrel is used for: Acute coronary syndrome, TIA, Ischaemic events, MI, Stroke

Adult Dose

Adult: PO Prevention of ischaemic events Per tab contains clopidogrel 75 mg and aspirin 75 mg: 1 tab once daily. Acute coronary syndrome Per tab contains clopidogrel 75 mg and aspirin 75 mg: Loading dose: 4 tab; maintenance: 1 tab/day. Hepatic impairment: Severe hepatic impairment: Avoid use.

Child Dose

Renal Dose

Renal impairment: CrCl (ml/min) <10 Avoid use.

Administration

Should be taken with food.

Contra Indications

Hypersensitivity to aspirin, NSAIDs or clopidogrel; active peptic ulceration; children <12 yr; patients with haemophilia or haemorrhagic disorders; gout; severe renal or hepatic impairment; lactation.

Precautions

History of peptic ulcer or those prone to dyspepsia and those with gastric mucosal lesion or heavy ethanol consumption; asthma or allergic disorders; tinnitus; dehydrated patients; uncontrolled hypertension; impaired renal or hepatic function; children and elderly; pregnancy. Patients at risk of increased bleeding from trauma, surgery, or other pathological conditions. 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 7-10 days before surgery.

Pregnancy-Lactation

Interactions

Aspirin: Corticosteroids, phenylbutazone and oxyphenbutazone may increase risk of GI ulceration. Use with coumarins, anagrelide, agatroban, LMWH, bivalirudin, dasatinib, iloprost, lepirudin and tenecteplase may increase the risk of bleeding. Clopidogrel: Co-administration of clopidogrel with NSAIDs may increase the risk of stomach and intestinal bleeding. There is an increased risk of bleeding with coumarins, agatroban, dasatinib, heparin, LMWH, gingko biloba and iloprost. Increased risk of bleeding if clopidogrel and drotrecogin alfa are given within 7 days. May increase bupropion level and side effects (lightheadedness , GI discomfort). Potentially Fatal: Aspirin and clopidogrel: Increased risk of bleeding with dabigatran.

Adverse Effects

Side effects of Aspirin + Clopidogrel : Aspirin: GI disturbances, epigastric discomfort, prolonged bleeding time, rhinitis, urticaria; 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 and pruritus. Potentially Fatal: Aspirin: Gastric erosion, ulceration and bleeding; severe, occasionally fatal exacerbation of airway obstruction in asthma; Reye's syndrome (childn <12 yrs). Hepatotoxicity; CNS depression, which may lead to coma; CV collapse, resp failure; paroxysmal bronchospasm and dyspnoea. Clopidogrel: Bleeding disorders including GI intracranial haemorrhage and thrombotic thrombocytopenic purpura.

Mechanism of Action

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 is a prodrug and is metabolised an active thiol metabolite. The active metabolite 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.