Published April 19, 2011
A drug approved only to treat the rare bleeding disorder hemophilia is being used much more often in other patients, such as those having cardiac surgery or a liver transplant, according to new research.
While such "off-label" prescribing is allowed by the U.S. Food and Drug Administration, the researchers found there is little evidence that the drug, called NovoSeven and marketed by the company Novo Nordisk, actually helps prevent death in people who have conditions other than hemophilia.
Dr. Veronica Yank, a member of the research team from Stanford University, said that she and her colleagues were "surprised by the amount of off-label use that we saw."
Based on the findings, doctors "need to temper their enthusiasm and be more cautious" with the use of this drug, Yank told Reuters Health.
In people with hemophilia, blood takes a long time to clot. NovoSeven is used in these patients to promote clotting and reduce the chance that they will have dangerous bleeding.
But the drug is being prescribed more and more to control bleeding in other patients, despite a lack of definitive evidence that it's beneficial in those cases.
In two articles published today in the Annals of Internal Medicine, Yank and her colleagues analyzed data on how NovoSeven is used in U.S. hospitals -- and the benefits and harms to patients who are given the drug.
In the first study, the researchers collected information on close to 13,000 patients who were treated with NovoSeven during a hospital stay between 2000 and 2008.
While use of the drug more than tripled between the beginning and end of the study period in patients with hemophilia, prescriptions of NovoSeven grew much faster in patients with brain trauma or bleeding in the skull, for example.
By 2008, 97 percent of the time NovoSeven was used, it was for something besides hemophilia.
The authors calculated that about 18,000 patients were treated with NovoSeven for conditions other than hemophilia in 2008.
And it may not be helping those patients survive. In the second article, the Stanford researchers consulted 64 past studies and found that in patients being treated for bleeding in the skull, brain and body trauma, or those undergoing cardiac or prostate surgery or a liver transplant did not have a better chance of surviving if they were given NovoSeven.
In some of those patients, NovoSeven increased the chance of getting a dangerous clot in a blood vessel.
Yank and her colleagues also note that NovoSeven doesn't come cheap - one dose can cost about $10,000 for the average adult patient.
A representative from Novo Nordisk expressed concern that the articles do not reflect evidence that the majority of NovoSeven use happens in an outpatient setting and not in hospitals, suggesting that many hemophilia patients using the drug are not represented in the study's statistics.
"It's important to note that Novo Nordisk does not promote the off-label use of NovoSeven(r) RT, and proactively worked with the FDA to update our label to address safety concerns when used outside of approved indications," the representative told Reuters Health in an e-mail.
Dr. Jerrold Levy, who has studied NovoSeven at the Emory University School of Medicine in Atlanta, said that it isn't surprising that many patients treated with the drug still die - but that doesn't mean it can't be useful, for example in preventing the need for a blood transfusion.
"A lot of times when this is used it's used after everything else fails," Levy told Reuters Health. "You're already in a bad situation."
Other drugs and procedures used in patients with dangerous bleeds are associated with bad outcomes too, Levy said, but "if you don't plug up holes, you'll bleed out and you'll die."
In an editorial that accompanies the findings titled, "A Hemorrhage of Off-Label Use," Dr. Jerry Avorn and Dr. Aaron Kesselheim of Harvard Medical School in Boston point out that doctors like to make their own decisions about what drugs to prescribe, and many using NovoSeven are hoping to protect patients from bleeding too much.
However, noting the drug's high price and the apparent increased risk to patients, they write, "Allowing physician autonomy to choose medications is appealing, but not when it results in unhelpful, dangerous, and costly decisions."