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prasugrel (Effient)

FDA approved 2009 Indications: - cardiovascular risk reduction (more effective than clopidogrel*, less so in elderly) [1] - secondary prevention in patients with cardiovascular disease - for use with aspirin 81-325 mg QD after angioplasty (percutaneous coronary intervention) [6] - prasugrel for STEMI prior to PCI but deferred until after PCI for NSTEMI & other acute coronary syndromes (superior to routine ticagrelor) [10] * no better than clopidogrel in patients with acute coronary syndrome who do not undergo revascularization [7] Contraindications: - elderly > 74 years of age - low body weight (< 60 kg, 132 lbs) - history of stroke, history of TIA [9] Dosage: - 7.5, 10 or 15 mg PO QD, loading dose 40-60 mg Storage: - store in orginal container - original container has a desiccant - must be used within 30 days once original container is opened [8] Pharmacokinetics: - must be metabolized to active metabolite(s) for activity - converted to its active metabolite via 2 steps - first it is hydrolyzed, then undergoes a single cytochrome P-450 (CYP3A4 & CYP2B6)-dependent step by enzymes located in the gut lumen & liver [11] - onset of action 15 minutes - 98% protein-bound - volume of distribution: 44-68 L (active metabolite) - 1/2life 7 hours (range 2-15 hours) [11] - excreted in urine (68%), feces (27%) [11] Genetics: - reduced-function CYP polymorphisms do not attenuate antiplatelet effects of prasugrel [5] Adverse effects: bleeding risk > clopidogrel (hazzard ratio 1.3) Mechanism of action: - inhibits platelet aggregation by irreversibly binding the platelet ADP receptor - about 10-fold more potent that clopidogrel (Plavix) Notes: Cost is about $180/month (2009)

Interactions

drug adverse effects of antiplatelet agents

General

thienopyridine P2Y12-receptor inhibitor

Database Correlations

PUBCHEM cid=6918456

References

  1. Wiviott SD et al for the TRITON-TIMI 38 Investigators Prasugrel versus clopidogrel in patients with acute coronary syndrome. N Engl J Med 2007, 357:2001 PMID: 17982182 http://dx.doi.org/10.1056/NEJMoa0706482
  2. Prescriber's Letter 15(4): 2008 Investigational Drug: Prasugrel (Effient) Detail-Document#: 240403 (subscription needed) http://www.prescribersletter.com
  3. Payne CD, Li YG, Small DS, Ernest CS 2nd, Farid NA, Jakubowski JA, Brandt JT, Salazar DE, Winters KJ. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol. 2007 Nov;50(5):555-62. PMID: 18030066
  4. Montalescot G et al Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): Double-blind, randomised controlled trial. Lancet 2009 Feb 28; 373:723 PMID: 19249633 - Stone GW. Ischaemia versus bleeding: The art of clinical decision-making. Lancet 2009 Feb 28; 373:695. PMID: 19249613
  5. Mega JL et al Cytochrome P450 genetic polymorphisms and the response to prasugrel: Relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 2009 May 19; 119:2553. PMID: 19414633
  6. Prescriber's Letter 16(8): 2009 New Drug: Effient (Prasugrel) Detail-Document#: 250804 (subscription needed) http://www.prescribersletter.com
  7. Physician's First Watch, Aug 27 2012 Massachusetts Medical Society http://www.jwatch.org - Roe MT et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012 Aug 26 PMID: 22920930 http://www.nejm.org/doi/full/10.1056/NEJMoa1205512
  8. Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: 300622 (subscription needed) http://www.prescribersletter.com
  9. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018
  10. Schupke S, Neumann FJ, Menichelli M et al. Ticagrelor or prasugrel in patients with acute coronary syndromes. N Engl J Med 2019 Sep 1 PMID: 31475799 https://www.nejm.org/doi/10.1056/NEJMoa1908973
  11. Medscape: Praugrel Rx https://reference.medscape.com/drug/effient-prasugrel-999200