Clopidogrel

Registered South African indications:

• Reduction of atherosclerotic events

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Severe hepatic impairment
• Active pathological bleeding
• Peptic ulcer
• Intracranial haemorrhage

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Mild to moderate hepatic impairment
• Patients at an increased risk of bleeding from trauma, surgery or other pathological conditions
• Invasive cardiac procedures
• Recent ischaemic stroke (the first 7 days)
• Chronic diarrhoea
• Poor CYP2C19 metabolisers
• History of hypersensitivity to thienopyridines
• Lactose allergy
• Galactose intolerance
• Lapp lactase deficiency
• Glucose-galactose malabsorption

Forms avail. in SA and covered in this monograph: tab

Recent myocardial infarction (< 35 days)
Ischaemic stroke (from 7 days until less than 6 months)
Established peripheral arterial disease

• Oral (tab): 75mg, dly; Max: 75mg/24hrs; Max treatment duration: 12 months

Acute coronary syndrome
-Non-ST segment elevation acute coronary syndrome
-Stent placement following percutaneous coronary intervention

• Oral (tab): Loading dose: 300mg, Then 75mg, dly; Max: 75mg/24hrs; Max duration: 12 months

ST-segment elevation acute myocardial infarction

Younger than 75 years

• Oral (tab): Loading dose: 300mg, then 75mg, dly, for 4 weeks; Max: 75mg/24hrs; Max duration: 4 weeks

Older than 75 years

• Oral (tab): 75mg, dly, for 4 weeks; Max: 75mg/24hrs; Max duration: 4 weeks

Prevention of atherothrombotic and thromboembolic events in atrial fibrillation

• Oral (tab): 75mg, dly; Max: 75mg/24hrs 

Not established for use in children below 18 years

Pregnancy

• Caution; no evidence of risk in studies
• As no clinical data on exposure to clopidogrel during pregnancy are available, it is preferable not to use clopidogrel during pregnancy as a precautionary measure. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development

Breastfeeding

• Caution; not recommended
• It is unknown whether clopidogrel is excreted in human breast milk. Animal studies have shown excretion of clopidogrel in breast milk. As a precautionary measure, breastfeeding should not be continued during treatment with clopidogrel

Fertility

• Clopidogrel was not shown to alter fertility in animal studies

Renal Impairment

• Caution; no dose adjustment recommended

Hepatic Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated

Elderly

• No dose adjustment recommended

Porphyria Information

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Hallucinations
• Confusion
• Intracranial bleeding
• Headache
• Paraesthesia
• Dizziness

Cardiovascular Disorders

• Haematoma
• Serious haemorrhage
• Haemorrhage of operative wound
• Vasculitis
• Hypotension
• Kounis syndrome
• Vasospastic allergic anigna
• Allergic myocardial infarction

Respiratory Disorders

• Epistaxis
• Respiratory tract bleeding
• Haemoptysis
• Pulmonary haemorrhage
• Bronchospasm
• Interstitial pneumonitis
• Eosinophilic pneumonia

Gastrointestinal Disorders

• Gastrointestinal haemorrhage
• Diarrhoea
• Abdominal pain
• Dyspepsia
• Gastric and duodenal ulcer
• Gastritis
• Nausea and vomiting
• Constipation
• Flatulence
• Retroperitoneal haemorrhage
• Pancreatitis
• Colitis
• Stomatitis

Hepatobiliary Disorders

• Acute hepatic failure
• Hepatitis
• Abnormal hepatic function test

Genitourinary Disorders

• Haematuria
• Glomerulonephritis
• Increased blood creatinine
• Gynaecomastia

Musculoskeletal Disorders

• Musculoskeletal bleeding
• Arthritis
• Arthralgia
• Myalgia

Skin and Subcutaneous Tissue Disorders

• Bruising
• Rash
• Pruritus
• Skin bleeding
• Bullous dermatitis
• Toxic epidermal necrolysis
• Stevens-Johnson syndrome
• Erythema multiforme
• Acute generalised exanthematous pustulosis
• Angioedema drug-induced hypersensitivity syndrome
• Drug rash with eosinophilia and systemic symptoms (DRESS)
• Urticaria
• Eczema
• Lichen planus
• Bleeding at puncture site

Immune, Blood and Lymphatic System Disorders

• Serum sickness
• Anaphylactoid reactions
• Cross-reactive drug hypersensitivity among thienopyridines
• Thrombocytopenia
• Leucopenia
• Eosinophilia
• Neutropenia
• Thrombotic thrombocytopenic purpura
• Aplastic anaemia
• Pancytopenia
• Agranulocytosis
• Acquired haemophilia A
• Granulocytopenia
• Anaemia
• Insulin autoimmune syndrome
• Fever
• Prolonged bleeding time
• Decreased neutrophil count
• Decreased platelet count

Sensory Disorders

• Eye bleeding
• Vertigo
• Taste disturbances

• Oral anticoagulants
• Glycoprotein IIb/IIIa inhibitors
• Acetylsalicylic acid
• Heparin
• Thrombolytics
• Non-steroidal anti-inflammatory drugs
• Selective serotonin reuptake inhibitors
• CYP2C19 inhibitors
• Omeprazole
• Esomeprazole
• Fluvoxamine
• Fluoxetine
• Moclobemide
• Voriconazole
• Fluconazole
• Ticlopidine
• Carbamazepine
• Efavirenz
• CYP2C8 substrates
• Opioids
• Morphine
• Antiretroviral-boosted (ritonavir-based) therapies
• Proton pump inhibitors
• Repaglinide
• Thienopyridines

None routine. Special cases may require

• Platelet function
• Hepatic function
• Haemoglobin
• Haematocrit

Clopidogrel is a prodrug, which is metabolised by CYP450 enzymes to produce an active metabolite. This metabolite selectively inhibits the binding of adenosine diphosphate (ADP) to its platelet (P2Y12) receptor and the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation. Due to the irreversible binding, platelets exposed are affected for the remainder of their lifespan (approximately 7-10 days) and recovery of normal platelet function occurs at a rate consistent with platelet turnover. 

Tablet 75mg

• Acticlop 75
• Arrow Clopidogrel (Arrow) (Discontinued: 06/12/2021)
• Clopidogrel 75 Biotech (Biotech)
• Clopindogrel Unicorn 75 (Unicorn)
• Clopidogrel Zydus 75 (Zydus)
• Clopivas (Cipla Medpro)
• Clopiwin 75 fct (Sanofi)
• Closolve (Ranbaxy)
• Clovexa (Accord)
• Deplatt (Trinity Pharma)
• Mistro (Dr Reddy's)
• Pharma Dynamics Clopidogrel (Pharma Dynamics)
• Plagrol (Adcock)
• Plavix (Sanofi) originator
• Spec Clopidogrel (Specpharm) originator
• Zyklot 75 (Zydus)

Tablet 300mg

• Clopiwin (Zentiva)

COMBINATION PREPARATIONS

Clopidogrel/ Acetylsalicylic acid

Tablet 75mg/75mg 

• Clopiwin plus 75/75 (Sanofi)