Prasugrel 10 mg · Tablets

Prasugrel is an inhibitor of platelet activation and aggregation through the irreversible binding of its active metabolite to the P2Y 12class of ADP receptors on platelets.

Prasugrel is a prodrug and is rapidly metabolized to a pharmacologically active metabolite and inactive metabolites. The active metabolite has an elimination half-life of about 7 hours (range 2-15 hours). Healthy subjects, patients with stable atherosclerosis, and patients undergoing PCI show similar pharmacokinetics.

Absorption and Binding- Following oral administration, ≥79% of the dose is absorbed. The absorption and metabolism are rapid, with peak plasma concentrations (C max) of the active metabolite occurring approximately 30 minutes after dosing. The active metabolite's exposure (AUC) increases slightly more than proportionally over the dose range of 5 to 60 mg. Repeated daily doses of 10 mg do not lead to accumulation of the active metabolite. In a study of healthy subjects given a single 15 mg dose, the AUC of the active metabolite was unaffected by a high fat, high calorie meal, but C maxwas decreased by 49% and T maxwas increased from 0.5 to 1.5 hours. Prasugrel tablets can be administered without regard to food. The active metabolite is bound about 98% to human serum albumin.

Metabolism and Elimination- Prasugrel is not detected in plasma following oral administration. It is rapidly hydrolyzed in the intestine to a thiolactone, which is then converted to the active metabolite by a single step, primarily by CYP3A4 and CYP2B6 and to a lesser extent by CYP2C9 and CYP2C19. The estimates of apparent volume of distribution of prasugrel's active metabolite ranged from 44 to 68 L and the estimates of apparent clearance ranged from 112 to 166 L/hr in healthy subjects and patients with stable atherosclerosis. The active metabolite is metabolized to two inactive compounds by S-methylation or conjugation with cysteine. The major inactive metabolites are highly bound to human plasma proteins. Approximately 68% of the prasugrel dose is excreted in the urine and 27% in the feces as inactive metabolites.

Specific Populations — Geriatric Patients- In a study of 32 healthy subjects between the ages of 20 and 80 years, age had no significant effect on pharmacokinetics of prasugrel's active metabolite or its inhibition of platelet aggregation. In TRITON-TIMI 38, the mean exposure (AUC) of the active metabolite was 19% higher in patients ≥75 years of age than in patients <75 years of age. In a study in subjects with stable atherosclerosis, the mean exposure (AUC) to the active metabolite of prasugrel in subjects ≥75 years old taking a 5 mg maintenance dose was approximately half that seen in subjects 45 to 64 years old taking a 10 mg maintenance dose . [see Warnings and Precautions ( 5.1) and Use in Specific Populations ( 8.5)].

Body Weight- The mean exposure (AUC) to the active metabolite is approximately 30 to 40% higher in subjects with a body weight of <60 kg than in those weighing ≥60 kg. In a study in subjects with stable atherosclerosis, the AUC of the active metabolite on average was 38% lower in subjects <60 kg taking 5-mg (N=34) than in subjects ≥60 kg taking 10 mg (N=38) [see Dosage and Administration ( 2), Warnings and Precautions ( 5.1), Adverse Reactions ( 6.1), and Use in Specific Populations ( 8.6)].

Male and Female Patients- Pharmacokinetics of prasugrel's active metabolite is similar in men and women.

Racial or Ethnic Groups- Exposure in subjects of African and Hispanic descent is similar to that in Caucasians. In clinical pharmacology studies, after adjusting for body weight, the AUC of the active metabolite was approximately 19% higher in Chinese, Japanese, and Korean subjects than in Caucasian subjects.

Smoking- Pharmacokinetics of prasugrel's active metabolite is similar in smokers and nonsmokers.