Natrecor: Safety Concerns And Off-Label Investigation Plague Scios And J&J

Medical Journal Articles About Natrecor And Renal Failure May Have Been Cause Of Reduced Natrecor Use In Late 2005

Steve Johnson provides some insights about the so-called "off-label" use of prescription drugs with his October 22, 2006 article "Off-label drug marketing: Missing the mark", in the San Jose Mercury News.

This article uses the heart-failure drug Natrecor (nesiritide) -- made by Scios, Inc. and marketed by Johnson & Johnson (J&J) -- as the vehicle for exploring several aspects of the problem, such as: what is the practice of off-label prescribing; how off-label use can be dangerous to patients; and, why a drug company encouraging doctors to write off-label prescriptions can be the subject of a federal criminal investigation.

The FDA approved Natrecor in 2001 for treating congestive heart failure patients who were having trouble breathing, even while doing minimal activity or resting, such that they had to be hospitalized.  In this situation, the administration of Natrecor would typically be done in the hospital, i.e., in-patient setting.

As regards Natrecor and its off-label use, we learn this from Steve Johnson's October 22, 2006 article:

Besides its use in hospitalized patients, many clinics began giving [Natrecor] to walk-in patients in weekly sessions dubbed "tuneups." Some people -- including prominent heart specialist Dr. Eric Topol -- say Scios encouraged this with a hotline and brochure explaining how to bill Medicare for the sessions.

There was only one problem: Some medical experts contend Natrecor was never approved for such tuneups. Some also say it may not be as safe as initially thought.

Scios says studies show the drug is safe. And it has launched a campaign to clarify to doctors that the drug is not recommended for repeated use in patients in a clinic setting.

Nevertheless, the drug's sales have sagged and the company is under investigation by the U.S. attorney in San Francisco for allegedly engaging in "off-label" marketing, promoting drugs for uses not approved by the government.

Since this case came to light, critics in two major medical journals have cited Natrecor as an example of how easy it is for drug companies to peddle their medicines for unapproved purposes. Although doctors are allowed to prescribe drugs for off-label treatments, companies are forbidden from promoting their drugs for such uses....

As regards the drug-safety issue, Dr. Jonathan Sackner-Bernstein, a prominent heart doctor, published two reports in 2005 warning that Natrecor use was possibly linked to significantly increased rates of kidney problems and death.  Scios and J&J announced in June 2006 that they are planning a large study concerning Natrecor -- which many critics claim is long overdue.  The results from that study, however, will not be known for at least two or three years according to these drug companies.

We return to the October 2006 Mercury News article by Steve Johnson for the criminal ramifications of drug companies promoting the off-label use of their drugs.

FDA and Justice Department officials said they don't track how many companies have been prosecuted for off-label marketing. But Ioana Petrou, chief of major crimes for the U.S. attorney in San Francisco, said federal authorities have been paying increasing attention to such practice, given the grave danger it can pose to the public.

"In the vast majority of the cases prosecuted, there are misleading statements being made to the medical community by the pharmaceutical companies," she said. "So the patients can't rely on their doctors to tell them what is safe and effective."

Meanwhile, "Use of Nesiritide Before and After Publications Suggesting Drug-Related Risks in Patients With Acute Decompensated Heart Failure" -- published in the October 18, 2006 edition of The Journal of the American Medical Association (JAMA) -- provides this perspective on the reduced use of Natrecor in the second half of 2005.

Objective To evaluate the use of [Natrecor] before and after March and April 2005 publications in 2 high-impact journals that suggested an increased risk of renal failure and mortality with intravenous nesiritide for acute decompensated heart failure.

Results  [Natrecor] use decreased from a peak of 16.6% (2351 of 14,167 admissions) in March 2005 to 5.6% (611 of 10,822 admissions) in December 2005....

Conclusions  Rapid de-adoption of [Natrecor] occurred following 2 publications suggesting risk with the drug. Further analyses are required to evaluate the consequences of these changes on patient outcomes and to anticipate how publications of adverse findings can influence practice.

This Natrecor story is far from done and one we will continue to watch.

(Posted by: Tom Lamb)