Prasugrel Hcl (prasugrel HCl)

Prasugrel hydrochloride, a thienopyridine P2Y12 platelet adenosine diphosphate (ADP)-receptor antagonist, is a platelet-activation and -aggregation inhibitor.

Prasugrel hydrochloride, a thienopyridine derivative structurally and pharmacologically related to clopidogrel, is a platelet-activation and aggregation inhibitor. Like clopidogrel, prasugrel is a prodrug that requires hepatic transformation to an active metabolite (R-138727) in order to exert its pharmacologic effect on the P2Y12 platelet adenosine diphosphate (ADP) receptor. Compared with clopidogrel, prasugrel inhibits ADP-mediated platelet aggregation more rapidly, more consistently, and to a greater extent; inhibition of platelet aggregation is at least 30% greater with prasugrel than with standard dosages of clopidogrel.

The increased potency of prasugrel appears to be a result of more efficient conversion of the prodrug to its active metabolite. Genetic polymorphisms of cytochrome P-450 (CYP) isoenzymes (e.g., CYP2B6, CYP2C9, CYP2C19, CYP3A5) do not appear to affect the pharmacologic or clinical response to prasugrel.

Prasugrel is a P2Y12 platelet ADP-receptor antagonist; the active metabolite binds irreversibly to the P2Y12 class of ADP receptors on the surface of platelets, thereby inhibiting ADP-dependent platelet activation and aggregation for the life of the platelet (approximately 7-10 days). Following a 60-mg loading dose of prasugrel, at least 50% inhibition of platelet aggregation is achieved at 1 hour in approximately 90% of patients. Approximately 70% inhibition of platelet aggregation is achieved at steady state within 3-5 days with prasugrel 10 mg daily.

The maximum inhibition of platelet aggregation attained with a 60-mg loading dose of prasugrel is about 80%. Platelet aggregation gradually returns to baseline values within 5-9 days following discontinuance of the drug. The relationship between inhibition of platelet aggregation and clinical activity of prasugrel has not been established.

Prasugrel is rapidly and completely (at least 79% of a dose) absorbed from the GI tract following oral administration. Once absorbed, the drug is rapidly hydrolyzed by esterases to an inactive thiolactone that is subsequently metabolized to the active metabolite (R-138727) by CYP enzymes (principally by 3A4 and 2B6, and to a lesser extent by 2C9 and 2C19). Compared with clopidogrel, which undergoes a 2-step oxidative process, prasugrel requires only a single step for metabolic activation; this may explain its faster onset of action.

Peak plasma concentrations of the active metabolite of prasugrel are reached approximately 30 minutes after an oral dose, and there is no evidence of accumulation with repeated administration. The active metabolite of prasugrel is approximately 98% bound to human albumin. Administration of a high-fat or high-caloric meal to healthy individuals did not affect exposure to the active metabolite but decreased peak plasma concentrations by 49% and delayed time to peak concentration from 0.5 to 1.5 hours.

The manufacturer states that the elimination half-life of prasugrel's active metabolite (R-138727) averages about 7 hours (range: 2-15 hours), although a half-life of 3.7 hours has been reported in some studies. However, inhibition of platelet aggregation following prasugrel administration persists for about 96 hours. Prasugrel is eliminated principally in urine (68%) and to a lesser extent in feces (27%) as inactive metabolites.

Dialysis is not expected to remove the active metabolite.

USES: Prasugrel is used with aspirin by patients with heart disease (recent heart attack, unstable angina) who undergo a certain heart procedure (angioplasty). This medication helps to prevent other serious heart/blood vessel problems (such as heart attacks, strokes, blood clots in stents). It works by blocking platelets from sticking together and prevents them from forming harmful blood clots.

This "anti-platelet" effect helps to keep blood flowing smoothly in your body.

Generic name: prasugrel HCl
Pronunciation: (PRA-soo-grel)

The following indications are listed for Prasugrel Hcl:

• Myocardial Reinfarction Prevention
• Thrombosis Prevention After Percutaneous Coronary Intervention

Also known as: Maintenance Therapy Of Thrombosis Prevention After Pci, Myocardial Reinfarction Prophylaxis, Thrombosis Prophylaxis After Percutaneous Coronary Intervention, Vascular Thrombosis Prevention After Percutaneous Coronary Intervention.

No ICD codes are available for this drug.