ANTITHROMBOTIC
(PLATELET AGGREGATION INHIBITORS)

 

FORMULATION:
Each film-coated tablet contains:
Clopidogrel (as Bisulfate) USP ......................................................75 mg

PRODUCT DESCRIPTION:
A reddish brown colored, round, biconvex, film-coated tablet.

PHARMACODYNAMIC PROPERTIES:
Pharmacotherapeutic group: platelet aggregation inhibitors excl. heparin.

Mechanism of action:
Clopidogrel is a prodrug, one of whose metabolites is an inhibitor of platelet aggregation. Clopidogrel must be metabolized by CYP450 enzymes to produce the active metabolite that inhibits platelet aggregation. The active metabolite of Clopidogrel 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. Platelet aggregation induced by agonists other than ADP is also inhibited by blocking the amplification of platelet activation by released ADP. Because the active metabolite is formed by CYP450 enzymes, some of which are polymorphic or subject to inhibition by other medicinal products, not all patients will have adequate platelet inhibition.

Pharmacodynamic effects:
Repeated doses of 75 mg per day produced substantial inhibition of ADP-induced platelet aggregation from the first day; this increased progressively and reached steady state between Day 3 and Day 7. At steady state, the average inhibition level observed with a dose of 75 mg per day was between 40% and 60%. Platelet aggregation and
bleeding time gradually returned to baseline values, generally within 5 days after treatment was discontinued.