Clopidogrel

Chemical

A thienopyridine

Use

↓atherothrombotic events in patients with atherosclerotic disease

Presentation

Tablets

Dose

Prophylactic: 75mg PO

ACS + aspirin: 300mg PO

Route

PO

Onset

2 hrs

DoA

Platelet aggregation returns to normal 5 days after Tx withdrawal → requires new platelet synthesis

MoA

PRODRUG – requires activation – absorbed in intestine & activated in liver through two sequential oxidative steps

  • Inhibits binding of ADP to P2Y12 receptor
  • ∴ prevents ADP-mediated activation of GP IIb/IIIa
  • Irreversible

PD

CVS: platelet aggregation inhibition

PK

A

OBA 50%

D

98% PPB

M

85% hepatic esterases → INACTIVE

15% by Cytochrome P450 → ACTIVE DRUG

E

Metabolites excreted in urine & faeces

Adverse Effects

  • ↑risk GI bleeding
  • TTP

INTERACTIONS

  • + any anti-clotting drug = HUGE risk of bleeding
  • CYP2C19 poor metabolisers → ↓response with Clopidogrel
  • AVOID OMEPRAZOLE because metabolised by CYP2C19

Monitoring

  • Generally not performed, but platelet aggregometry can be used
  • PF100 (not available everywhere) – formally know as the Dade Behring platelet function analyzer Second Life Marketplace - Prince (Symbol)

Reversal

  • Platelet transfusion