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recombinant coagulation factor VIIa (Novo-Seven, rFVIIa, Niastase, Novo, Nordisk)

Indications: 1) treatment of bleeding episodes in patients with hemophilia who have inhibitors to factor XIII or factor IX 2) rapid reversal of excessive anticoagulation with warfarin (not recommended) [7] 3) reversal of anticoagulation for urgent/emergency surgery NOT associated with bleeding 4) used off-label in patients with central nervous system bleeding* & in patients with severe hemorrhage related to trauma, surgery, or liver disease [2,4] * earlier report of improved 90 day outcome in patients with intracranial hemorrhage [2] has not been observed in other studies [4] Contraindications: - of no benefit for intracranial hemorrhage [6] Dosage: - single 3-5 minute intravenous infusion (40-160 ug/kg) Storage: room temperature Phamacokinetics 1) reduces INR immediately, followed by slow increase but < original value 2) immediate resolution of active bleeding Adverse effects: - serious adverse arterial thromboembolic events (5%) [2,3] including myocardial ischemia, myocardial infarction, cerebral ischemia &/or infarction - off-label use associated with high risk for arterial thromboembolism [4] Notes: - cost $204/ug (2005) 160 ug/kg for a 70 kg man would cost $20,000 - off label use high despite lack of evidence for reduction in mortality [5]

General

coagulation factor VIIa recombinant protein; chimer

References

  1. Journal Watch 23(4):31-32, 2003
  2. Deveras RAE & Kessler CM Reversal of warfarin-induced excessive anticoagulation with recombinant human factor VIIa concentrate. Ann Intern Med 137:884, 2002 PMID: 12458988
  3. FDA Mewatch http://www.fda.gov/medwatch/safety/2005/safety05.htm#NovoSeven
  4. Levi M et al. Safety of recombinant activated factor VII in randomized clinical trials. N Engl J Med 2010 Nov 4; 363:1791 PMID: 21047223 - Aledort LM. Off-label use of recombinant activated factor VII - Safe or not safe? N Engl J Med 2010 Nov 4; 363:1853. PMID: 21047230
  5. Logan AC et al. Off-label use of recombinant factor VIIa in U.S. hospitals: Analysis of hospital records. Ann Intern Med 2011 Apr 19; 154:516. PMID: 21502649 - Yank V et al. Systematic review: Benefits and harms of in-hospital use of recombinant factor VIIa for off-label indications. Ann Intern Med 2011 Apr 19; 154:529. PMID: 21502651
  6. The NNT: Recombinant Activated Factor VII for Acute Spontaneous Intracerebral Hemorrhage. http://www.thennt.com/nnt/factor-vii-for-intracerebral-hemorrhage/ - Al-Shahi Salman R Haemostatic drug therapies for acute spontaneous intracerebral haemorrhage. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD005951 PMID: 19821350 - Diringer MN, Skolnick BE, Mayer SA et al Thromboembolic events with recombinant activated factor VII in spontaneous intracerebral hemorrhage: results from the Factor Seven for Acute Hemorrhagic Stroke (FAST) trial. Stroke. 2010 Jan;41(1):48-53. PMID: 19959538
  7. Medical Knowledge Self Assessment Program (MKSAP) 18, American College of Physicians, Philadelphia 2018