FDA lets drugmakers advise doctors on unapproved uses

[AlaskaDenise]

WOW - is this a can or worms or not????
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WASHINGTON (Reuters) - U.S. health officials finalized guidelines that make it easier for pharmaceutical companies to tell doctors about unapproved uses of medicines, a practice opposed by critics of industry marketing.

The Food and Drug Administration (FDA) guidelines explain when manufacturers such as Pfizer Inc and Merck & Co may distribute copies of medical journal articles that describe unapproved uses. The action could help companies expand the markets for medicines and medical devices.

The move, announced a week before Republican President George W. Bush leaves office, puts in place a policy that drew objections from congressional Democrats and drug-industry critics when it was proposed last year. Opponents say it will allow promotion of uses without adequate testing.

"In the final hours of this administration, political appointees at FDA have given drug companies a long-coveted parting gift," said Rep. Henry Waxman, chairman of the House of Representatives Energy and Commerce Committee.

"This fundamentally undermines the requirement that companies prove to FDA that each new use is safe and effective. I hope this policy will be carefully re-examined by the new administration," added Waxman, a California Democrat.

By law, manufacturers are prohibited from marketing their medicines for uses not approved by the FDA. But doctors can prescribe drugs for any use they see fit, a practice known as "off-label" use.

Distribution of medical literature suggesting a drug may have merit for an unapproved use is a marketing area that has been in dispute for years.

The FDA in its guidelines said "public health can be served when health-care professionals receive truthful and non-misleading scientific and medical information on unapproved uses."

Industry critics say distribution of the journal articles promotes untested uses of drugs and may be dangerous. It also may deter manufacturers from doing more tests of the new uses and subjecting them to FDA scrutiny for possible approval.

Off-label use "means there isn't adequate evidence that the benefits outweigh the risks to have it approved by the FDA," said consumer advocate Sidney Wolfe, director of Public Citizen's Health Research Group. He called for the guidelines to be reversed once Democrat Barack Obama becomes president.

Unapproved use of medicines is common. A doctor may prescribe an antidepressant, for example, to treat insomnia, or a cancer drug for a type of cancer beyond what is approved.

About one of five prescriptions in the United States was written to treat a condition for which the drug was not approved, according to a 2006 study published in the Archives of Internal Medicine. The researchers said [/B]most off-label use occurs without scientific support[/B].

Handing out journal articles on off-label uses had been permitted under a legal provision that expired in 2006. The new guidelines "will clarify how and when manufacturers can provide unbiased, unembellished articles from peer-reviewed journals to health care professionals," said Alan Bennett, an attorney representing various drugmakers.

The FDA's guidance will help "assure that medical professionals receive timely and accurate medical information prior to the lengthy process" of securing FDA approval for wider use, said Ken Johnson, a spokesman for the Pharmaceutical Research and Manufacturers of America.

Off-label use "can save lives, especially in practice areas where there are few effective treatments," he added.

The FDA said articles circulated by companies should come from peer-reviewed journals that require disclosure of conflicts of interest for researchers. It also encouraged companies to seek FDA approval for unapproved uses.

The guidelines also apply to medical device makers.

The FDA proposed the guidelines in February 2008 and took public comments before finalizing them.

http://www.reuters.com/article/domesticNews/idUSTRE50C0QK20090113

[sharon sanders]

Re: FDA lets drugmakers advise doctors on unapproved uses

"Off-label use "can save lives, especially in practice areas where there are few effective treatments," he added.'


This may be required in a mass medical emergency, such as a pandemic, where a lessor standard of care will be the protocol.

[AlaskaDenise]

Re: FDA lets drugmakers advise doctors on unapproved uses

I would expect that during a pandemic, there will be a lot of "experimentation" and results will be publicized and used immediately - all "off label." there will probably be relaxing of many regulations.

However, during non-pandemic times, is the "off label use" best promoted by drug companies, or another entity without the profit motive? Doctors can already access the reported studies themselves - just as we do here at FT - so what is gained to have drug companies "pushing" off label use - profits????

.

[AlaskaDenise]

Re: FDA lets drugmakers advise doctors on unapproved uses

Eli Lilly Pleads Guilty, to Pay $1.42 Billion for Illegally Marketing Anti-Psychotic Drug for Off-Label Uses

Eli Lilly & Co. said Thursday it pleaded guilty to a charge that it illegally marketed anti-psychotic drug Zyprexa for off-label use, and will pay a combined $1.42 billion to settle civil suits and end the criminal investigation.

The Indianapolis-based company said it will pay $800 million to settle civil suits, including $438 million to the federal government and $362 million to states. It will pay $615 million to resolve the criminal probe, and plead guilty to a misdemeanor violation of the Food, Drug and Cosmetic Act for promoting Zyprexa as a dementia treatment.

The company did not acknowledge any wrongdoing in the civil cases.

The plea resolves charges related to Lilly's marketing of Zyprexa between September 1999 and March 2001. The company plead guilty to marketing the drug as a treatment for dementia.

The case began in 2004 and was lead by the United States Attorney for the Eastern District of Pennsylvania and the Office of Consumer Litigation of the Department of Justice.

Patricia Hartman, a spokeswoman for the U.S. Attorney's Office, declined to comment on the case Thursday morning.

Lilly also said it agreed to resolve civil investigations brought by the Medicaid Fraud Control Units of the states involved in the settlement. The states were looking into rebate agreements between Lilly and pharmacy benefits managers related to Zyprexa and other drugs.

The company will enter a corporate integrity agreement with the government.

Zyprexa is approved to treat schizophrenia and bipolar disorder. Doctors are allowed to prescribe it for other uses, but Lilly is not allowed to market the drug for any other illnesses because it lacks Food and Drug Administration approval.

The drug was approved in 1996 and has been Lilly's top seller for years. It brought in $3.5 billion in revenue through the first three quarters of 2008, or roughly $1.5 billion more than the company's second-best seller, the antidepressant Cymbalta.

But the company has taken more than $1.6 billion in charges to settle allegations it improperly marketed the drug.

Lilly in October said it expected to pay $1.42 billion to end the investigations. It set aside that amount, or $1.29 per share, in the third quarter, which resulted in the company's first quarterly loss in three years.

Earlier the same month, Lilly agreed to pay $62 million to 32 states and the District of Columbia to resolve accusations it marketed Zyprexa for pediatric care, for use in high doses and for dementia.

The company has resolved more than 31,300 claims related to Zyprexa product liability, but other lawsuits and class actions are still pending. A group of insurance companies, unions and others are suing Lilly for billions, saying it broke marketing laws and overcharged for the drug.

http://www.foxnews.com/story/0,2933,480018,00.html

[AlaskaDenise]

Re: FDA lets drugmakers advise doctors on unapproved uses

The FDA is taking criminal action againt Lily for doing what the FDA just passed a regulation to allow??????

Wassup???

.

[tropical]

Re: FDA lets drugmakers advise doctors on unapproved uses

The FDA is taking criminal action againt Lily for doing what the FDA just passed a regulation to allow??????

Wassup???
.

A breaf look to the end of the text #14 words:
"A group of insurance companies, unions and others are suing Lilly for billions, saying it broke marketing laws and overcharged for the drug."

An new law on the matter obviously can't be applyed retroactively for the same matter when other regulations were in charge.

Other thing is if the new regulation is ok, or not.
But that scraphead is now legaly over if it passed ...

When an legal problem insurge, resolve it at the root - change the law ...

[AlaskaDenise]

Re: FDA lets drugmakers advise doctors on unapproved uses

oops....I read it too fast.
Another example of the issues about off-label use...
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Antipsychotic Drugs Linked to Sudden Cardiac Death

Susan Craig's brother Roger died of a pulmonary embolism in 2007, at age 38. Diagnosed with bipolar disorder in high school, he had been on antipsychotic drugs for years. At the time of his death, he was carrying 280 pounds on his 6-foot-4-inch frame.

Craig, a public relations specialist who works at Columbia University in New York City, knew that Roger's medications could cause weight gain. But she had never been told that the drugs he was taking might be harming his heart.

"We were never counseled by his psychiatrist or his primary care provider to watch for symptoms of heart disease or any risk of sudden death at all," Craig says. There's no evidence that Roger's medications caused his death, but his family might have been able to get him help sooner if they had known about the risks, Craig explains.

New research published Wednesday in the New England Journal of Medicine shows that antipsychotic drugs are not risk free, and the study's authors are urging much more caution in their use. The drugs are associated with a risk of sudden cardiac death, particularly at higher doses.

Craig's brother was taking haloperidol, which belongs to an older class of drugs called typical antipsychotics, which have long been known to increase the risk of sudden death due to cardiac causes. He was also on risperidone, a member of a newer class of drugs called atypical antipsychotics, which had been considered safer.

Doctors prescribe these newer medications, originally developed to treat schizophrenia, for a wide variety of problems -- from conduct disorder in kids to aggressive behavior in Alzheimer's patients. In fact, they've become so popular that three of them -- olanzapine, risperidone, and quetiapine -- are among the 10 top-selling drugs worldwide, with $14.5 billion in sales in 2007.

The new study suggests that among patients taking high doses of atypical antipsychotics, there are about 3.3 cases of sudden cardiac death per 1,000 patients per year, which an editorial characterizes as a risk that's "between 'moderate' and 'low,' but not 'rare.'"

About 325,000 people in the United States each year die of sudden cardiac death, which has an incidence of 0.1 to 0.2 percent per year in adults.

"[The drugs] have potentially very serious side effects," says Wayne A. Ray, Ph.D., the director of the division of pharmacoepidemiology at Vanderbilt University School of Medicine, in Nashville. "So whenever a decision is made to use one, consideration of potential side effects needs to be made." Ray and his colleagues found that atypical antipsychotics doubled the risk of sudden death from heart-related causes, most likely by causing disturbances in heart rhythms.

First introduced in the mid-nineties, atypical antipsychotics were praised for having none of the troublesome side effects of their predecessors, including frequent, involuntary movements of the face and mouth that were in some cases irreversible.

But the new study shows that the increased risk of sudden cardiac death seen with the older drugs is nearly identical to that of the newer medications. There had been suspicions that the drugs were risky, especially when used in older patients, but the current study is the first to systematically investigate their association with sudden cardiac death.

Ray and his colleagues reviewed data on Tennessee Medicaid patients, comparing 44,218 people using older typical antipsychotics and 46,089 taking the newer atypical antipsychotics to 186,600 people who had never used the drugs. People with schizophrenia may have a higher rate of cardiac problems, due to smoking and other factors. To account for this, researchers also compared antipsychotic drug users without schizophrenia to non-drug users who had characteristics (in most cases, mood disorders) that made them likely candidates for the drugs.

Overall, people taking typical antipsychotics were at 1.99-times greater risk of sudden cardiac death, while the risk for those on atypical antipsychotics was increased 2.26 times. The increased risk was greater for people on higher doses of the drugs. People who had used the drugs in the past but stopped weren't at greater risk of sudden cardiac death.

"The drugs are still very effective for conditions that there's proven evidence for," says Jeffrey A. Lieberman, M.D., a professor and chair of psychiatry at Columbia University, in New York City, and the director of the New York State Psychiatric Institute, who was not involved with Ray's research. "They clearly need to still be able to be used. I think this [study] really underscores the need to be very judicious about how these medications are used and whom they're given to."

While atypical antipsychotics have been used to ease aggressive behavior for patients with Alzheimer's disease, for example, they are not approved for this purpose by the U.S. Food and Drug Administration; in fact, in 2005, the FDA issued a warning that these drugs increased the risk of death among elderly people, extending the warning to all antipsychotic drugs last year, notes Sebastian Schneeweiss, M.D., Sc.D., an associate professor of medicine at Harvard Medical School, in Boston, who coauthored an editorial accompanying the current study.

Given the lack of better alternatives, these drugs are still widely used in patients with dementia despite the warnings, he adds. But while there's anecdotal evidence that they will "cool these patients down" and reduce their aggressive behaviors, there's no scientific evidence that they really help patients or their caregivers, Dr. Schneeweiss says.

In his editorial, Dr. Schneeweiss and coauthor Jerry Avorn, M.D., also of Harvard, call for patients to undergo an electrocardiogram before and shortly after being placed on atypical antipsychotics, to determine if the drugs are causing any heart rhythm disturbances.

For people who must be on these medications, Ray says, it's essential for their doctors to treat any other conditions, such as high blood pressure, that can harm the heart. "Sudden cardiac death usually occurs when multiple risk factors are present," he explains. "When you add one, it's kind of like the straw that broke the camel's back."

"Absolutely the lowest dose that works should be used, because we found a strong dose response," Ray says.

Jamaison Schuler, a spokesperson for Eli Lilly and Company, the maker of Zyprexa, says, "Although the study appears to have important limitations, it provides additional information for practicing physicians to consider as they decide how to treat very complex diseases such as schizophrenia and bipolar disorder."

The FDA has approved atypical antipsychotics for treating bipolar disorder, Ray adds. But the researcher recommends that physicians first try safer alternatives, such as the mood stabilizer lithium. "That's a very serious illness, and it has important consequences for patients' quality of life and relationships," Ray notes. "If the mood stabilizer doesn't work, I think it's very reasonable to consider an antipsychotic, but...other drugs should be considered first."

Finally, he says, a patient should never stop taking any drug without consulting his or her physician. Nevertheless, anyone taking an atypical antipsychotic for a non-FDA-approved use should consult his physician. "I think off-label use should be undertaken very cautiously, and its frequency should be much less than it is currently," Ray says.

For Susan Craig, the new research makes it clear that treating serious mental illness must go far beyond just prescribing pills. "We need to be supporting these people in a better, more systematic way," she says. "There's no magic pill. It's treating the whole person."

http://www.cnn.com/2009/HEALTH/01/15/healthmag.antipsychotic.sudden.death/