Intended for healthcare professionals


Evidence and desperation in off-label prescribing: recombinant factor VIIa

BMJ 2012; 344 doi: (Published 16 January 2012) Cite this as: BMJ 2012;344:d7926
  1. Wendy Lipworth, postdoctoral fellow12,
  2. Ian Kerridge, director 2,
  3. Miles Little, emeritus professor2,
  4. Richard Day, professor of clinical pharmacology3
  1. 1Australian Institute of Health Innovation, University of New South Wales, Sydney, NSW 2052, Australia
  2. 2 Centre for Values, Ethics and the Law in Medicine, University of Sydney, Sydney
  3. 3University of New South Wales and St Vincent’s Hospital, Sydney
  1. Correspondence to: W Lipworth w.lipworth{at}
  • Accepted 2 November 2011

Wendy Lipworth and colleagues explore why clinicians prescribe recombinant factor VIIa off-label for major haemorrhage, despite a lack of supporting evidence—and why this matters

Off label prescribing—that is, prescribing a medicine for an indication not listed in the product information, or for a patient outside the approved age range—is common, but controversial. On the one hand, it can promote clinical innovation and provide options for patients for whom no other alternatives are available. On the other hand, it can be harmful, because safety data are often lacking; it impedes the generation of good quality evidence, and it comes at a considerable cost to patients, governments, and other payers.1 2

In this paper, we discuss the off-label use of recombinant factor VIIa (rFVIIa) for major haemorrhage, to provide insights into the forces driving off-label prescribing and to illustrate some of the inevitable limits to evidence based medicine.

Clinical disagreement

rFVIIa is a procoagulant approved for patients with haemophilia and antibody inhibitors against factor VIII or factor IX. Recent studies, however, have shown that up to 97% of rFVIIa prescribing is off-label, with the intent to stop bleeding in conditions such as intracranial haemorrhage, cardiac surgery, trauma, liver transplantation, and prostatectomy.3 It is estimated that rFVIIa was used in more than 70 000 hospital cases in the United States between 2000 and 2008. During this period its off-label use increased 140-fold, while use for haemophilia in hospitals increased less than fourfold.3 Although some evidence indicates that rFVIIa might reduce blood loss and transfusion requirements in patients without haemophilia, evidence has also been accumulating that it does not reduce mortality, might be associated with an increased rate of thromboembolic events including stroke and coronary occlusion,4 5 6 7 8 9 and costs approximately $10 000 (£6400, €7400) per patient.10

According to the …

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