Clopidogrel oral
- Drugs List
- Therapeutic Indications
- Dosage
- Contraindications
- Precautions and Warnings
- Pregnancy and Lactation
- Side Effects
- Monograph
Presentation
Oral formulations of clopidogrel.
Drugs List
Therapeutic Indications
Uses
Minor ischaemic stroke: combination treatment for secondary prevention
Moderate to high-risk TIA: combination treatment for secondary prevention
Prevention of atherothrombotic event in STEMI in combination with aspirin
Prevention of atherothrombotic events in atrial fibrillation with aspirin
Prevention of atherothrombotic events in non-ST elevation ACS with aspirin
Prevention of atherothrombotic events in peripheral arterial disease
Prevention of atherothrombotic events post ischaemic stroke
Prevention of atherothrombotic events post myocardial infarction
Prevention of thromboembolic events in atrial fibrillation with aspirin
Prevention of atherothrombotic events
Clopidogrel is indicated in:
-post myocardial infarction (from a few days after the event until less than 35 days)
-post ischaemic stroke (from 7 days after the event until less than 6 months)
-in established peripheral arterial disease
-in non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction) in combination with aspirin, including patients undergoing a stent placement following percutaneous coronary intervention
-in ST segment elevation acute myocardial infarction, in combination with aspirin in medically treated patients eligible for thrombolytic therapy
In patients with moderate to high-risk transient ischaemic attack (TIA) or minor ischaemic stroke (IS)
Clopidogrel in combination with aspirin is indicated in:
-adult patients with moderate to high-risk TIA (ABCD2 score greater than or equal to 4) or minor IS (NIHSS less than or equal to 3) within 24 hours of either the TIA or IS event.
Prevention of atherothrombotic and thromboembolic events (including stroke) in atrial fibrillation
Clopidogrel in combination with aspirin is indicated in:
-adult patients who have at least one risk factor for vascular events, are not suitable for treatment with vitamin k antagonist and who have a low bleeding risk.
Unlicensed Uses
Initial management of acute ischaemic stroke (with/without thrombolysis)
Transient ischaemic attack
Treatment of transient ischaemic attack in patients with aspirin hypersensitivity or those intolerant of aspirin despite the addition of a proton pump inhibitor.
Initial management of acute ischaemic stroke (with/without thrombolysis) in patients with aspirin hypersensitivity or those intolerant of aspirin despite the addition of a proton pump inhibitor.
Dosage
Adults
The recommended dose is 75mg once daily.
Non-ST segment elevation acute coronary syndrome (unstable angina or non-Q-wave myocardial infarction)
A single loading dose of 300mg should be given and then continued at 75mg once a day (together with low dose aspirin 75mg to 325mg daily). Since higher doses of aspirin were associated with higher bleeding risk it is recommended that the dose of aspirin should not be higher than 100mg.
Some manufacturers recommend an alternative single loading dose for patients aged 18 years to 75 years old of 600mg which may be suitable where percutaneous coronary intervention is intended.
The manufacturer of clopidogrel recommends these doses of aspirin unless contraindicated. See product literature to verify doses of aspirin.
Optimum duration of treatment has not been established. Clinical trial data supports use up to 12 months, and maximum benefit was seen at 3 months.
ST segment elevation acute myocardial infarction
A single loading dose of 300mg should be given and then continued at 75mg once a day in combination with aspirin and with or without thrombolytics. For patients older than 75 years clopidogrel should be initiated without a loading dose. Combined therapy should be started as early as possible after symptoms start and continued for at least four weeks. The benefit of the combination of clopidogrel with aspirin beyond four weeks has not been studied.
Moderate to high-risk TIA (ABCD2 score greater than or equal to 4) or minor IS (NIHSS less than or equal to 3)
A loading dose of 300mg followed by 75mg once daily. Treatment should be started within 24 hours of the event and be continued for 21 days followed by single antiplatelet therapy.
Atrial fibrillation
A single daily dose of 75mg clopidogrel should be given (together with aspirin (75mg to 100mg daily)). The manufacturer of clopidogrel recommends these doses of aspirin unless contraindicated. See product literature to verify doses of aspirin.
Some sources state that patients selected for percutaneous coronary intervention, with the placement of a coronary stent, will require dual antiplatelet therapy with aspirin and clopidogrel. Aspirin therapy should continue indefinitely. Patients, who are not already taking clopidogrel, should receive a 300mg loading dose prior to the procedure; alternatively, a 600mg (unlicensed) loading dose may produce a greater and more rapid inhibition of platelet aggregation. Clopidogrel is recommended for 1 month following elective percutaneous coronary intervention with placement of a bare-metal stent, and for 12 months if percutaneous coronary intervention with placement of a bare-metal stent was for an acute coronary syndrome; clopidogrel should be given for 12 months following placement of a drug-eluting stent. Clopidogrel should not be discontinued prematurely in patients with a drug-eluting stent as there is an increased risk of stent thrombosis as a result of the eluted drug slowing the re-endothelialisation process. Patients considered to be at high risk of developing late stent thrombosis with a drug-eluting stent may require a longer duration of treatment with clopidogrel.
Treatment of transient ischaemic attack (unlicensed indication)
Clopidogrel 75mg once daily should be given to patients with aspirin hypersensitivity or those intolerant of aspirin despite the addition of a proton pump inhibitor.
Initial management of acute ischaemic stroke (with/without thrombolysis) (unlicensed indication)
Patients with aspirin hypersensitivity or those intolerant of aspirin despite the addition of a proton pump inhibitor: Clopidogrel 75mg once daily.
Elderly
In patients over 75 years, in the treatment of ST segment elevation acute myocardial infarction clopidogrel therapy should be initiated without a loading dose.
(See Dosage; Adult)
Additional Dosage Information
Missed doses
Advise patient if a dose is missed:
-Within less than 12 hours after regular scheduled time: patients should take the dose immediately and then take the next dose at the regular scheduled time.
-For more than 12 hours: patients should take the next dose at the regular scheduled time and should not double the dose.
Contraindications
Children under 18 years
Haemorrhage
Breastfeeding
Intracranial haemorrhage
Peptic ulcer
Pregnancy
Severe hepatic impairment
Precautions and Warnings
Patients over 75 years
Predisposition to haemorrhage
Recent surgery
Recent trauma
CYP2C19 poor metaboliser genotype
Galactosaemia
Glucose-galactose malabsorption syndrome
Lactose intolerance
Moderate hepatic impairment
Renal impairment
Within 7 days of ischaemic cerebrovascular accident
Not all available brands are licensed for all indications
Some brands contain lactose
Monitor for acquired haemophilia
Monitor for bleeding during treatment
Perform blood cell count whenever clinical symptoms suggest bleeding
Refer if thrombotic thrombocytopenic purpura suspected to a specialist
Advise on the need to report unusual bleeding
May cause insulin autoimmune syndrome
May prolong bleeding time
Discontinue 7 days prior to surgery when antiplatelet effect not required
Discontinue treatment if acquired haemophilia is confirmed
Advise patient not to take aspirin unless advised by clinician
Advise patient not to take ginkgo unless advised by clinician
Advise patient not to take NSAIDs unless advised by clinician
Advise patient not to take omeprazole unless advised by a doctor
Advise patient of risk of bleeding
Advise patient to inform physician/dentist of their use of this medication
Patients with genetically reduced CYP2C19 function have lower systemic exposure to the active metabolite of clopidogrel and diminished antiplatelet responses, and generally exhibit higher cardiovascular event rates following myocardial infarction than do patients with normal CYP2C19 function.
Clopidogrel may cause insulin autoimmune syndrome which can lead to severe hypoglycaemia, particularly in patients with human leukocyte antigen DRA4 subtype.
Dual antiplatelet therapy is not recommended in non-minor IS patients (NIHSS greater than 4), or in recent minor IS or moderate to high risk TIA patients for whom carotid endarterectomy or intravascular thrombectomy is indicated, or in patients planned for thrombolysis or anticoagulant therapy.
Pregnancy and Lactation
Pregnancy
Clopidogrel is contraindicated during pregnancy.
The manufacturer recommends clopidogrel is not used during pregnancy as a precautionary measure. Animal studies do not indicate harmful effects on pregnancy, embryonic/foetal development, parturition or postnatal development. It is unknown if clopidogrel crosses the placenta, however due to the drug's molecular weight it is expected to do so. There is insufficient clinical data on exposed human pregnancies. Potential risks are unknown.
Lactation
Clopidogrel is contraindicated during breastfeeding.
The manufacturer recommends that breastfeeding should be discontinued during treatment with clopidogrel as a precautionary measure. Animal studies have shown excretion of clopidogrel and its metabolites in milk, however presence in human breast milk is unknown. Presence of clopidogrel in human milk could inhibit an infant's platelet function for a prolonged period of time and have a slight toxicity effect.
Side Effects
Abdominal pain
Abnormal liver function tests
Acquired haemophilia
Acute generalised exanthematous pustulosis
Acute hepatic failure
Ageusia
Agranulocytosis
Anaemia
Anaphylactoid reaction
Angioedema
Aplastic anaemia
Arthralgia
Arthritis
Bleeding
Bronchospasm
Bruising
Bullous dermatoses
Confusion
Conjunctival haemorrhage
Constipation
Diarrhoea
Dizziness
Drug rash with eosinophilia and systemic symptoms (DRESS)
Duodenal ulcer
Dyspepsia
Eczema
Eosinophilia
Eosinophilic pneumonia
Epistaxis
Erythema multiforme
Erythematous rash
Fever
Flatulence
Gastric ulceration
Gastritis
Gastrointestinal bleeding
Glomerulonephritis
Granulocytopenia
Gynaecomastia
Haemarthrosis
Haematoma
Haematuria
Haemoptysis
Hallucinations
Headache
Hepatitis
Hypersensitivity reactions
Hypotension
Insulin autoimmune syndrome
Interstitial pneumonitis
Intracranial bleeding
Kounis syndrome
Leucopenia
Lichen-planus type reaction
Lymphocytic colitis
Myalgia
Nausea
Neutropenia
Ocular haemorrhage
Pancreatitis
Pancytopenia
Paraesthesia
Prolonged bleeding
Pruritus
Pulmonary haemorrhage
Purpura
Rash
Reduced platelet count
Retinal haemorrhage
Retroperitoneal bleeding
Serum creatinine increased
Serum sickness
Stevens-Johnson syndrome
Stomatitis
Taste disturbances
Thrombocytopenia
Thrombotic thrombocytopenic purpura
Toxic epidermal necrolysis
Ulcerative colitis
Urticaria
Vasculitis
Vertigo
Vomiting
Wound haemorrhage
Overdosage
It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.
The following number will direct the caller to the relevant local centre (0844) 892 0111
Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).
Further Information
Last Full Review Date: September 2019
Reference Sources
Medications and Mothers' Milk, Sixteenth Edition (2014) Hale, T and Rowe, H, Hale Publishing, Plano, Texas.
Summary of Product Characteristics: Clopidogrel 75mg Film-coated Tablets. Accord Healthcare Ltd. Revised June 2018.
Summary of Product Characteristics: Clopidogrel 75mg Film-coated Tablets. Aurobindo Pharma Ltd. Revised June 2019.
Summary of Product Characteristics: Clopidogrel 75mg Film-coated Tablets. Consilient Health Ltd. Revised July 2019.
Summary of Product Characteristics: Clopidogrel Mylan 75mg Film-coated Tablets. Mylan. Revised March 2019.
Summary of Product Characteristics: Clopidogrel Winthrop 75mg Film-coated Tablets. Zentiva. Revised June 2019.
Summary of Product Characteristics: Clopidogrel Zentiva 75mg Film-coated Tablets. Zentiva. Revised September 2018.
Summary of Product Characteristics: Grepid (clopidogrel) 75mg tablets. Kent Pharma UK Ltd. Revised April 2014.
Summary of Product Characteristics: Plavix 75mg tablets. Sanofi-aventis. Revised June 2022.
Summary of Product Characteristics: Plavix 300mg tablets. Sanofi-aventis. Revised June 2022.
The Renal Drug Handbook. 3rd edition. (2009) ed. Ashley, C and Currie, Radcliffe Publishing Ltd, Abingdon.
MHRA Drug Safety Update December 2013
Available at: https://www.mhra.gov.uk
Last accessed: December 14, 2014
National electronic Library for Medicines (NeLM) Q&A 91.4: Can a person on low dose aspirin take ginkgo? Issue date: August 2014
Available at: https://www.sps.nhs.uk/wp-content/uploads/2014/09/SW_QA91_4_GinkgoAspirin_August2014.doc?UNLID=105103475120189618815
Last accessed: September 06, 2019
National Institute for Health and Care Excellence (NICE) technology appraisal guidance 210: Clopidogrel and modified-release dipyridamole for the prevention of occlusive vascular events (Review of TA90). Issue date December 2010
Available at: https://guidance.nice.org.uk/TA210/Guidance/doc/English
Last accessed: September 06, 2019
NICE Evidence Services Available at: www.nice.org.uk Last accessed: 07 September 2022
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