PLAVIX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PLAVIX (PLAVIX).
Clopidogrel is a prodrug that is converted to an active metabolite by CYP450 enzymes. The active metabolite selectively inhibits the P2Y12 component of ADP receptors on the platelet surface, which prevents ADP-mediated activation of the glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet aggregation.
| Metabolism | Clopidogrel is extensively metabolized via two main pathways: one mediated by esterases leading to hydrolysis into an inactive carboxylic acid derivative, and the other mediated by multiple CYP450 enzymes (CYP2C19, CYP1A2, CYP2B6, and CYP3A4) to an active thiol metabolite. CYP2C19 is involved in both the formation of the active metabolite and the intermediate metabolite 2-oxo-clopidogrel. |
| Excretion | Renal: ~50% as inactive metabolites; biliary/fecal: ~50% as inactive metabolites. |
| Half-life | Clopidogrel parent: ~6 hours; active thiol metabolite: ~30 minutes; terminal half-life of inactive metabolite(s): ~8 hours. Clinically, platelet inhibition persists for 5–7 days due to irreversible P2Y12 receptor binding. |
| Protein binding | Parent drug: ~94–98% bound to albumin and alpha-1 acid glycoprotein; active metabolite: ~94% bound similarly. |
| Volume of Distribution | Clopidogrel: ~5 L/kg (suggests extensive tissue distribution); active metabolite: not extensively distributed (Vd not well defined). |
| Bioavailability | Oral: ~50% (parent drug extensively metabolized by intestinal and hepatic CYP450 enzymes; active metabolite bioavailability is ~50% of parent). |
| Onset of Action | Oral: 2 hours (300–600 mg loading dose achieves significant platelet inhibition within 2 hours); maximal effect at 4–6 hours. |
| Duration of Action | Platelet function recovers in 5–7 days after discontinuation due to irreversible receptor blockade; drug elimination half-life does not reflect duration. |
| Action Class | P2Y12 inhibitors (ADP receptor) |
| Brand Substitutes | StayHappi Clopidogrel 75mg Tablet, Clopikind Tablet, Platloc Tablet, Clopact 75 Tablet, Clopivas 75 Tablet |
75 mg orally once daily, with or without food. For acute coronary syndrome, a loading dose of 300 mg (or 600 mg for PCI) is given followed by 75 mg daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for renal impairment (CrCl ≥5 mL/min). Insufficient data for CrCl <5 mL/min; use with caution. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). No dose adjustment for mild to moderate impairment (Child-Pugh A or B); use with caution. |
| Pediatric use | Not recommended for use in pediatric patients (safety and efficacy not established). |
| Geriatric use | No specific dose adjustment required; consider potential for increased bleeding risk due to age-related comorbidities and concomitant medications. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PLAVIX (PLAVIX).
| Breastfeeding | It is not known if clopidogrel is excreted in human breast milk. In animal studies, clopidogrel and its metabolite were present in rat milk. The M/P ratio is unknown. Caution is advised; consider the developmental and health benefits of breastfeeding along with the mother's clinical need for clopidogrel. |
| Teratogenic Risk | Clopidogrel (Plavix) is categorized as FDA Pregnancy Category B. Animal studies did not demonstrate teratogenic effects. There are no adequate and well-controlled studies in pregnant women. Potential fetal risks include hemorrhage, particularly during the third trimester and labor, due to antiplatelet activity. Use only if clearly needed. |
■ FDA Black Box Warning
WARNING: DIMINISHED EFFECTIVENESS IN POOR METABOLIZERS - The effectiveness of Plavix is dependent on its activation to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19. Poor metabolizers treated with Plavix at recommended doses exhibit higher cardiovascular event rates following acute coronary syndrome or percutaneous coronary intervention than patients with normal CYP2C19 function. Tests are available to identify a patient's CYP2C19 genotype; consider alternative treatment strategies in patients identified as CYP2C19 poor metabolizers.
| Serious Effects |
["Active pathological bleeding such as peptic ulcer or intracranial hemorrhage","Hypersensitivity to clopidogrel or any component of the product"]
| Precautions | ["Diminished antiplatelet activity in CYP2C19 poor metabolizers; consider alternative treatment","Risk of bleeding: discontinue 5 days prior to elective surgery if antiplatelet effect is not desired","Thrombotic thrombocytopenic purpura (TTP): rare but serious; requires urgent treatment including plasmapheresis","Reversal of antiplatelet effect: no specific antidote; platelet transfusion may be considered","Cross-reactivity among thienopyridines: patients with prior hypersensitivity to ticlopidine may develop hypersensitivity to clopidogrel","Hepatic impairment: limited data in severe hepatic disease; use with caution"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal and fetal coagulation status, signs of bleeding, hemoglobin, and platelet function. Fetal surveillance with ultrasound may be warranted to detect hemorrhage. Assess for bruising, petechiae, or abnormal bleeding in mother and neonate. |
| Fertility Effects | No human data on fertility effects. Animal studies did not show impaired fertility at doses up to 400 mg/kg/day (clopidogrel) or 300 mg/kg/day (metabolite). Clinical relevance unknown. |