Clopidogrel
CLASS
- anti-platelet agent
MECHANISM OF ACTION
- inhibition of the ADP platelet receptor and subsequent ADP-mediated activation of the glycoprotein IIb/IIIa complex -> inhibits platelet aggregation
PHARMACEUTICS
- PO tablet
- prodrug
DOSE
- load: 300mg
- maintenance: 75mg
- paediatrics: 1.5mg/kg
INDICATIONS
- ACS
- post PCI’s
- prophylaxis of vascular ischaemic events (post stenting)
ADVERSE EFFECTS
- bleeding (stop for 5 days prior to surgery)
- TTP
- neutropenia
- liver dysfunction
PHARMACOKINETICS
- Absorption –
- Distribution
- Metabolism – hepatic to active drug
- Elimination
EVIDENCE
-> in patients with TIA or CVA – combination of aspirin and clopidogrel -> increases bleeding risk and doesn’t change risk of recurrence (CAPRIE and CURE trials)
Deepak, L. et al (2010) “Clopidogrel with or without Omeprazole in Coronary Artery Disease” NEJM, 363:1909-17
- PPI’s are purported to decrease the risk of GIH with anti-platelet therapy but may decrease efficacy of clopidogrel.
- MRCT – double-blind, double-dummy, placebo-controlled, parallel-group
- n = 3761
- dual anti-platelet therapy with clopidogrel vs clopidogrel + omeprazole
- primary gastrointestinal end-point: GIH, symptomatic GU, erosions, obstruction or perforation
- primary cardiovascular end-point: composite death from cardiovascular causes, MI, revascularisation or CVA.
-> GI event rate was 1.1% with omeprazole and 3% without @ 180 days (P<0.001)
-> no significant difference in cardiovascular event rate
Strengths
- large number
- discrete end points
- stratified permuted blocks used (based on Helicobacter serology and used of NSAIDs)
Weaknesses
- not completed due to loss of sponsor funding (loss of power)
- 94% of patients were white
References and Links
CCC Pharmacology Series
Respiratory: Bosentan, Delivery of B2 Agonists in Intubated Patients, Nitric Oxide, Oxygen, Prostacyclin, Sildenafil
Cardiovascular: Adenosine, Adrenaline (Epinephrine), Amiodarone, Classification of Vasoactive drugs, Clevidipine, Digoxin, Dobutamine, Dopamine, Levosimendan, Levosimendan vs Dobutamine, Milrinone, Noradrenaline, Phenylephrine, Sodium Nitroprusside (SNiP), Sotalol, Vasopressin
Neurological: Dexmedetomidine, Ketamine, Levetiracetam, Lignocaine, Lithium, Midazolam, Physostigmine, Propofol, Sodium Valproate, Sugammadex, Thiopentone
Endocrine: Desmopressin, Glucagon Therapy, Medications and Thyroid Function
Gastrointestinal: Octreotide, Omeprazole, Ranitidine, Sucralfate, Terlipressin
Genitourinary: Furosemide, Mannitol, Spironolactone
Haematological: Activated Protein C, Alteplase, Aprotinin, Aspirin, Clopidogrel, Dipyridamole, DOACs, Factor VIIa, Heparin, LMW Heparin, Protamine, Prothrombinex, Tenecteplase, Tirofiban, Tranexamic Acid (TXA), Warfarin
Antimicrobial: Antimicrobial Dosing and Kill Characteristics, Benzylpenicillin, Ceftriaxone, Ciprofloxacin, Co-trimoxazole / Bactrim, Fluconazole, Gentamicin, Imipenem, Linezolid, Meropenem, Piperacillin-Tazobactam, Rifampicin, Vancomycin
Analgesic: Alfentanil, Celecoxib, COX II Inhibitors, Ketamine, Lignocaine, Morphine, NSAIDs, Opioids, Paracetamol (Acetaminophen), Paracetamol in Critical Illness, Tramadol
Miscellaneous: Activated Charcoal, Adverse Drug Reactions, Alkali Therapies, Drug Absorption in Critical Illness, Drug Infusion Doses, Epidural Complications, Epidural vs Opioids in Rib Fractures, Magnesium, Methylene Blue, Pharmacology and Critical Illness, PK and Obesity, PK and ECMO, Sodium Bicarbonate Use, Statins in Critical Illness, Therapeutic Drug Monitoring, Weights in Pharmacology
Toxicology: Digibind, Flumazenil, Glucagon Therapy, Intralipid, N-Acetylcysteine, Naloxone, Propofol Infusion Syndrome
Critical Care
Compendium
Chris is an Intensivist and ECMO specialist at The Alfred ICU, where he is Deputy Director (Education). He is a Clinical Adjunct Associate Professor at Monash University, the Lead for the Clinician Educator Incubator programme, and a CICM First Part Examiner.
He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives. He was one of the founders of the FOAM movement (Free Open-Access Medical education) has been recognised for his contributions to education with awards from ANZICS, ANZAHPE, and ACEM.
His one great achievement is being the father of three amazing children.
On Bluesky, he is @precordialthump.bsky.social and on the site that Elon has screwed up, he is @precordialthump.
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