EFFIENT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EFFIENT (EFFIENT).
Prasugrel is a thienopyridine prodrug that irreversibly inhibits the P2Y12 receptor on platelets, reducing ADP-mediated platelet aggregation.
| Metabolism | Prasugrel is a prodrug that is rapidly hydrolyzed by esterases to a thiolactone, then converted to the active metabolite primarily by CYP3A4 and CYP2B6, and to a lesser extent by CYP2C9 and CYP2C19. |
| Excretion | Approximately 68% of the dose is excreted in urine as inactive metabolites, and about 27% in feces. |
| Half-life | The terminal elimination half-life of the active metabolite is about 7.6 hours (range 2-15 hours). Clinically, this supports once-daily dosing. |
| Protein binding | The active metabolite is approximately 98% bound to human serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 44 L (corresponding to about 0.6 L/kg for a 70 kg individual), indicating extensive extravascular distribution. |
| Bioavailability | Bioavailability after oral administration is not applicable as prasugrel is a prodrug; active metabolite exposure is dose-proportional. |
| Onset of Action | Inhibition of platelet aggregation is evident within 30 minutes after a 60 mg loading dose. |
| Duration of Action | Platelet inhibition persists for 3-5 days after the last dose, consistent with the lifespan of irreversibly inhibited platelets. |
| Action Class | P2Y12 inhibitors (ADP receptor) |
| Brand Substitutes | Prasuvix 10mg Tablet, Prasurel 10mg Tablet, Prasusafe 10 Tablet, Efiplat 10 Tablet, Prasudax 10mg Tablet |
Loading dose: 60 mg orally once. Maintenance: 10 mg orally once daily. In patients weighing <60 kg, maintenance dose is 5 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min); use with caution. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Contraindicated in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment required. However, consider lower maintenance dose (5 mg) in elderly patients weighing <60 kg. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EFFIENT (EFFIENT).
| Breastfeeding | It is unknown whether prasugrel or its active metabolite is excreted in human milk. In rat studies, prasugrel and its metabolites were present in milk. The M/P ratio is not established in humans. Due to the potential for serious adverse reactions in nursing infants (e.g., bleeding), breastfeeding is not recommended during therapy and for 7 days after the last dose. |
| Teratogenic Risk | Prasugrel is a thienopyridine antiplatelet agent classified as FDA Pregnancy Category B. Animal studies at doses up to 30 times the human exposure showed no evidence of teratogenicity. In rabbits, reduced fetal body weight and delayed ossification were observed at maternally toxic doses. Human data are limited; however, the risk of maternal hemorrhage and potential fetal hemorrhage during labor and delivery must be weighed. First trimester: no adequate human studies; second and third trimesters: risk of maternal bleeding complications; labor and delivery: increased risk of maternal and neonatal hemorrhage. |
■ FDA Black Box Warning
WARNING: BLEEDING RISK. Prasugrel increases risk of bleeding, sometimes fatal. Do not use in patients with active pathological bleeding or history of transient ischemic attack or stroke. In patients >=75 years, use is generally not recommended due to increased bleeding risk.
| Serious Effects |
["Active pathological bleeding (e.g., peptic ulcer, intracranial hemorrhage)","History of transient ischemic attack (TIA) or stroke","Severe hepatic impairment","Hypersensitivity to prasugrel or any component"]
| Precautions | ["Bleeding risk (including fatal bleeding)","Thrombotic thrombocytopenic purpura (rare)","Hypersensitivity including angioedema","Coronary artery bypass grafting (CABG)-related bleeding (hold at least 7 days prior)","Discontinuation of therapy may increase risk of cardiovascular events"] |
Loading safety data…
| Fetal Monitoring | Monitor maternal complete blood count (CBC) particularly platelet count, hemoglobin, and hematocrit to assess for bleeding. Assess for signs and symptoms of bleeding (e.g., epistaxis, bruising, hematuria, gastrointestinal bleed). Monitor fetal heart rate tracing during labor due to risk of fetal hemorrhage. In neonates, monitor for signs of bleeding and evaluate platelet function if exposure occurred near delivery. |
| Fertility Effects | Animal studies: In male and female rats, prasugrel at doses up to 300 mg/kg/day (335 times human exposure) had no effect on fertility or reproductive performance. Human data are insufficient to determine effects on fertility; however, no adverse effects on fertility are anticipated based on pharmacological profile. |