Rampant Off-label Use Leads to NovoSeven Blood Clot Risks: Studies

Researchers say the widespread off-label use of the hemophilia drug NovoSeven by U.S. hospitals may be putting patients at an unnecessary risk of blood clots, as there are no signs that the drug actually saves lives. 

NovoSeven was approved in 1999 for the treatment of hemophilia, but since then it has been used almost exclusively off-label to stop bleeding during surgery, according to a study published this week by The Annals of Internal Medicine. Another study in the same issue finds that the off-label use has not resulted in more lives saved, and may increase the risk of thromboembolism events in patients.

NovoSeven was used about 18,311 times in U.S. hospitals in 2008, according to researchers. In only 3% of those uses was the drug actually prescribed to do what it was designed for; to stop bleeding in hemophiliacs. The other 97% of the times doctors used the drug for cardiovascular surgery, trauma surgery and to treat brain hemorrhages; none of which are uses approved by the FDA or tested by Novo Nordisk, which manufactures the drug.

Other research has found that the drug does not appear to actually save the lives of surgery patients. Reviewers looked at 16 randomized controlled trials, 26 comparative observational studies, and 22 noncomparative observational studies and found that trauma and surgery patients given the drug had the same mortality rate as those given a placebo. Additionally, medium and high doses of NovoSeven led to increased risks for blood clots in patients with brain hemorrhages and who underwent cardiovascular surgery.

Off-label uses are those uses that are not approved by the FDA. Drug companies are prohibited from advertising or promoting their drugs for off-label uses, but doctors are allowed to prescribe drugs as they see fit; even for uses that were not intended by the manufacturers.

The prescribing information (pdf) on NovoSeven labels carries a black box warning of “serious thrombotic adverse events” if the drug is used off-label, but that has not stopped its use among doctors from growing more than 140-fold from 2000 to 2008.