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drotrecogin alpha (Xigris); recombinant protein C, activated

Tradename: Xigris Withdrawn from US Market Oct 2011 Indications: 1) FDA approved 12/01 for sepsis* a) septic shock requiring vasopressors despite fluid resuscitation b) sepsis-induced ARDS requiring mechanical ventilation with at least two dysfunctional organs [8] 2) systemic inflammatory response syndrome * does NOT improve mortality in low-risk patients with severe sepsis; recommended only for patients with APACHE II scores > 25 [5] * not helpful in children with severe sepsis [6] Contraindications: - no survival benefit; withdrawn from US market [9] Adverse effects: - bleeding, increased risk of serious bleeding [7] - death in patients with sepsis & baseline bleeding risk factors [7] Mechanism of action: 1) recombinant activated protein C 2) anti-inflammatory 3) anti-coagulant Notes: Manufacturer: Lilly

Interactions

drug adverse effects of antithrombotic agent(s)

Related

sepsis systemic inflammatory response syndrome (SIRS)

General

protein C, activated recombinant protein; chimer

References

  1. Journal Watch 21(8):61, 2001 Bernar et al, NEJM 344:699, 2001 Mathat, NEJM 344:759, 2001
  2. Prescriber's Letter 8(12):72 2001
  3. Prescriber's Letter 9(1):4 2002
  4. Journal Watch 22(23):174, 2002 Warren HS et al, N Engl J Med 347:1027, 2002 Siegel JP, N Engl J Med 347:1030, 2002 Manns BJ et al, N Engl J Med 347:993, 2002
  5. Abraham E, Laterre PF, Garg R, Levy H, Talwar D, Trzaskoma BL, Francois B, Guy JS, Bruckmann M, Rea-Neto A, Rossaint R, Perrotin D, Sablotzki A, Arkins N, Utterback BG, Macias WL; Administration of Drotrecogin Alfa (Activated) in Early Stage Severe Sepsis (ADDRESS) Study Group. Drotrecogin alfa (activated) for adults with severe sepsis and a low risk of death. N Engl J Med. 2005 Sep 29;353(13):1332-41. PMID: 16192478
  6. Nadel S, Goldstein B, Williams MD, Dalton H, Peters M, Macias WL, Abd-Allah SA, Levy H, Angle R, Wang D, Sundin DP, Giroir B; REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective (RESOLVE) study group. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet. 2007 Mar 10;369(9564):836-43. PMID: 17350452
  7. FDA Medwatch http://www.fda.gov/medwatch/safety/2009/safety09.htm#Xigris
  8. Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
  9. FDA MedWatch: 10/25/2011 Xigris [drotrecogin alfa (activated)]: Market Withdrawal - Failure to Show Survival Benefit - Marti-Carvajal A, Salanti G, Cardona AF. Human recombinant activated protein C for severe sepsis. Cochrane Database Syst Rev. 2008 Jan 23;(1):CD004388 PMID: 18254048 - Ranieri VM et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med 2012 May 31; 366:2055. PMID: 22616830