Contents

Search

vorapaxar (Zontivity)

FDA-approval May 2014 [3,4,5] Indications: - prevention of atherothrombotic events (myocardial infarction, stroke, TIA) in high-risk patients [5] - peripheral artery disease [7] * FDA-approved for use in combination with low-dose aspirin or clopidogrel [6] * do not use alone [7] Contraindications: - history of intracranial hemorrhage, stroke or TIA - secondary prevention of myocardial infarction in conjunction with dual anti-platelet therapy [1] Dose: - 2.5 mg PO QD [4,7] * each tablet contains 2.5 mg of vorapaxar sulfate, providing 2.08 mg of vorapaxar [7] Pharmacokinetics: - long half life - platelet inhibition can last at least 4 weeks after discontinuation [7] Adverse effects: - hemorrhage - intracranial hemorrhage - moderate or severe bleeding 4.2% vs 2.5% for placebo [4] - comment: seems very high incidence of bleeding in placebo group - risk of hemorrage mitigates its benefit in preventing atheroembolic events [2] * no antidote [6,7] Drug interactions: - interaction with prasugrel (Effient) not studied - interaction with ticagrelor (Brilinta) not studied [7] - avoid using with strong CYP3A4 inhibitors - clarithromycin ... - avoid using with strong CYP3A4 inducers - phenytoin ... Mechanism of action: - protease-activated receptor-1 antagonist [7] - inhibits thrombin-induced platelet activation Notes: - cost: $267 for 30 day supply (2014)

Interactions

drug adverse effects of antiplatelet agents

General

antiplatelet agent thrombin inhibitor receptor antagonist

Database Correlations

PUBCHEM cid=10077129

References

  1. Tricoci P et al for the TRACER Investigators. Thrombin-receptor antagonist vorapaxar in acute coronary syndromes. N Engl J Med 2011 Nov 13; PMID: 22077816 http://www.nejm.org/doi/full/10.1056/NEJMoa1109719
  2. Morrow DA et al. for the TRA 2P-TIMI 50 Steering Committee and Investigators. Vorapaxar in the secondary prevention of atherothrombotic events. N Engl J Med 2012 Mar 24 PMID: 22443427 http://www.nejm.org/doi/full/10.1056/NEJMoa1200933
  3. N Engl J Med Journal Watch. Jan 21, 2014 http://www.jwatch.org (subscription required) - Clarke T FDA advisory panel backs Merck's blood clot-preventing drug. Reuters. Jan 15, 2014 http://www.reuters.com/article/2014/01/15/us-merck-vorapaxar-idUSBREA0E1KV20140115
  4. Wood S Medcape. May 8, 2014 FDA Approves PAR-1 Antagonist Zontivity (Vorapaxar) to Reduce MI, Stroke Risk http://www.medscape.com/viewarticle/824886
  5. FDA News Release: May 8, 2014 FDA approves Zontivity to reduce the risk of heart attacks and stroke in high-risk patients. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm396585.htm
  6. Prescriber's Letter 21(8): 2014 No Detail Document. (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 21(9): 2014 Comparison of Oral Antiplatelets Detail-Document#: 300909 (subscription needed) http://www.prescribersletter.com