prasugrel (Effient)
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Introduction
FDA approved 2009
Genetics
- reduced-function CYP polymorphisms do not attenuate antiplatelet effects of prasugrel[5]
Indications
- cardiovascular risk reduction (more effective than clopidogrel*, less so in elderly)[1]
- 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
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]
Adverse effects
bleeding risk > clopidogrel (hazzard ratio 1.3)
- drug adverse effects of antiplatelet agents
- drug adverse effects of antithrombotic agent(s)
- drug adverse effects of P2Y12 receptor inhibitor(s)
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)
More general terms
References
- ↑ 1.0 1.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/17982182 <Internet> http://dx.doi.org/10.1056/NEJMoa0706482
- ↑ Prescriber's Letter 15(4): 2008 Investigational Drug: Prasugrel (Effient) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=240403&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/18030066
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/19249633
Stone GW. Ischaemia versus bleeding: The art of clinical decision-making. Lancet 2009 Feb 28; 373:695. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19249613 - ↑ 5.0 5.1 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: https://www.ncbi.nlm.nih.gov/pubmed/19414633
- ↑ 6.0 6.1 Prescriber's Letter 16(8): 2009 New Drug: Effient (Prasugrel) Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=250804&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22920930 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1205512 - ↑ 8.0 8.1 Prescriber's Letter 21(6): 2014 Oral Meds to Keep in Original Containers Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=300622&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 9.0 9.1 Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018
- ↑ 10.0 10.1 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: https://www.ncbi.nlm.nih.gov/pubmed/31475799 https://www.nejm.org/doi/10.1056/NEJMoa1908973
- ↑ 11.0 11.1 11.2 11.3 Medscape: Praugrel Rx https://reference.medscape.com/drug/effient-prasugrel-999200