Clopidogrel
Regulatory sources consulted
- openfda-label-ff58c1f3-4875-4d10-aca7-c622af163cef
- ema-epar-EMEA/H/C/000975
- aemps-cima-71622
- ansm-bdpm-68348757
- PubMed PMID:35034351 ↗
- PubMed PMID:40174599 ↗
- PubMed PMID:40902613 ↗
- PubMed PMID:35094598 ↗
- PubMed PMID:38157499 ↗
- OpenFDA · B01AC04
- RxNorm rxcui 32968 ↗
Approved indications
- Acute Coronary Syndrome (ACS): For patients with non-ST-segment elevation ACS (unstable angina/non-ST-elevation myocardial infarction), in combination with acetylsalicylic acid (ASA). For patients with ST-elevation myocardial infarction (STEMI), in combination with ASA in medically treated patients eligible for thrombolytic therapy.
- Secondary prevention of atherothrombotic events in patients suffering from myocardial infarction (from a few days until less than 35 days), ischaemic stroke (from seven days until less than six months) or established peripheral arterial disease.
- Prevention of atherothrombotic and thromboembolic events in atrial fibrillation, in combination with ASA, in patients who are not suitable for treatment with vitamin K antagonists (VKA) and who have a low bleeding risk.
Contraindications
Absolute
- Active pathological bleeding, such as peptic ulcer or intracranial hemorrhage.
- Hypersensitivity to clopidogrel or any component of the product.
- Severe hepatic impairment.
Clinical warnings
- Boxed warning · Diminished antiplatelet effect in patients with two loss-of-function alleles of the CYP2C19 gene (CYP2C19 poor metabolizers). Effectiveness depends on conversion to an active metabolite by the CYP system, principally CYP2C19. Consider use of another platelet P2Y12 inhibitor in these patients. — FDA
- Major warning · Clopidogrel increases the risk of bleeding. It can cause significant and, sometimes, fatal bleeding. — FDA
- Major warning · Thrombotic Thrombocytopenic Purpura (TTP) has been reported, sometimes after a short exposure. It is a serious condition that requires urgent treatment. — EMA SPC
Drug interactions
- ModerateOmeprazole / EsomeprazoleA02BC01
Mechanism: Inhibition of CYP2C19, a key enzyme for the bioactivation of clopidogrel to its active metabolite. Significantly reduces antiplatelet efficacy.
Recommendation: Avoid concomitant use. Consider using proton pump inhibitors with less inhibitory effect on CYP2C19 (e.g., pantoprazole, lansoprazole).
FDA label
- HighRifampinJ04AB02
Mechanism: Strong induction of CYP2C19, increasing conversion to the active metabolite and platelet inhibition.
Recommendation: Avoid concomitant use due to potentiated risk of bleeding.
FDA labelEMA SPC
- ModerateOpioidsN02A
Mechanism: Delay and reduce the absorption of clopidogrel, presumably because of slowed gastric emptying, resulting in reduced exposure to its active metabolite.
Recommendation: In acute coronary syndrome patients requiring opioids, consider the use of a parenteral antiplatelet agent.
FDA label
- HighOral anticoagulantsB01A
Mechanism: Additive effect on hemostasis, significantly increasing the risk of bleeding.
Recommendation: Concomitant administration of clopidogrel and oral anticoagulants is not recommended.
EMA SPC
Adverse events
Common (≥1%)
bleeding · bruising · epistaxis · hematuria
Rare but serious
thrombotic thrombocytopenic purpura (TTP) · intracranial hemorrhage · acquired hemophilia · severe gastrointestinal bleeding
Pregnancy and lactation
FDA category: N/A
Available data have not identified drug-associated risks for major birth defects or miscarriage. However, treatment for emergencies such as myocardial infarction should not be withheld in a pregnant woman. Increased risk of maternal and/or fetal bleeding during labor and delivery.
Recent literature (PubMed)
Actualización de la guía CPIC que refuerza la recomendación de usar terapia antiplaquetaria alternativa al clopidogrel en metabolizadores intermedios y pobres de CYP2C19, debido a la reducción de la formación del metabolito activo y el aumento del riesgo de eventos cardiovasculares y cerebrovasculares adversos.
En pacientes de alto riesgo que completaron DAPT tras una ICP, la monoterapia con clopidogrel redujo significativamente el compuesto de muerte, IM o ictus en comparación con la monoterapia con aspirina a 3 años (4.4% vs 6.6%, HR 0.71), sin un aumento significativo en el sangrado mayor.
Metaanálisis de datos de pacientes individuales (N=28,982) que muestra que la monoterapia con clopidogrel es superior a la monoterapia con aspirina para la prevención secundaria en pacientes con enfermedad coronaria establecida, reduciendo los eventos cardiovasculares adversos mayores (MACCE) (HR 0.86) sin un aumento en el sangrado mayor.
En pacientes con ictus isquémico menor o AIT de alto riesgo, iniciar doble antiagregación (clopidogrel + aspirina) dentro de las 72 horas posteriores al inicio de los síntomas redujo el riesgo de un nuevo ictus a 90 días en comparación con aspirina sola (7.3% vs 9.2%), a costa de un ligero aumento en el sangrado moderado a severo (0.9% vs 0.4%).
Revisión sobre el uso de antiagregantes en la prevención del ictus isquémico. Destaca la evidencia para la doble antiagregación a corto plazo (21 días) post-ictus, y discute el fracaso del tratamiento debido a la falta de adherencia y polimorfismos genéticos (resistencia al clopidogrel).