Trade name(s): Arrow-clopid Drug Class:Antiplatelet


Theraputic use: Clopidogrel is used as an antiplatelet

Pharmacological action: Clopidogrel, a P2Y12 antagonist, is metabolised to an active derivative that irreversibly inhibits ADP binding to the P2Y12 receptor on platelets.

This inhibits fibrinogen-platelet binding

Pharmacokinetics:

  • Absorption Clopidogrel is rapidly absorbed, mean unchanged clopidogrel concentration is about 45 minutes after dosing. Absorption is at least 50%.

  • Distribution clopidogrel and main circulating metabolite binds reversably to human plasme proteins at a ratio od 98% and 94% respectively

  • Metabolism clopidogrel is extensively metabolisded by 2 main pathways leading to an inactive carboxylic acid derivatives and one mediated by cytochrome p450 derivatives to a thiol derivative of clopidogrel. the active thiol metabolite binds rapidly and irreversibly to the platelet receptors.

  • Excretion Clopidogrel has a half life of approximately 6 hours the half life of the active metabolite is about 30 mins. After an oral dose of clopidogrel 50% was excreted in urine and 46% in faeces.


Indications: TIA or stroke not associated with atrial fibrillation prevention of vascular ischaemic events in patients with symptomatic atherosclerosis prevention of atherothrombotic events in acute coronary syndrome and MI

Contraindications: severe hepatic impairment; active bleeding; breast-feeding

Precautions: Risk of increased bleeding from trauma, surgery, or other pathological conditions;  Discontinue 5 days before elective surgery Risk of treatment failure with slow CYP2C19 metabolisers


Adverse reactions: Dyspepsia, abdominal pain, diarrhoea, bleeding disorders less commonly nausea, vomiting, gastritis, flatulence, constipation, gastric and duodenal ulcers, headache, dizziness, paraesthesia, leucopenia, decreased platelets

Interactions: a great number of interactions with grapefruit juice and (anti-HIV)antivirals. Visit stockley interactions for all of them


Dosing/Current guidelines: TIA or stroke not associated with atrial fib Start 24 hours after thrombolysis or immediately if thrombolysis not given. if not taking 300 mg clopidogrel as loading dose use 75 mg daily

Prevention of vascular ischaemic events if not taking 300 mg clopidogrel as loading dose use 75 mg daily

Acute coronary syndrome and acute MI if not taking 300 mg clopidogrel as loading dose use 75 mg daily (with aspirin)


Overdose: Effects of clopidogrel overdose relate to overcooking the dose.

additionally oral doses equal or greater then 1500 mg/kg caused a great deal of inflammation of the gi tract and kidney damage

Treatment of OD: supportive care and possible platelet transfusion


Pregnancy

What to tell patients: avoid grapefruit, grapefruit juice or food containing grapefruit.

Subsidised? arrow clopid is subsudised

Comments/Observations/notes: