Fw: FDA Safety Scientists Warn About Deaths - 4 Asthma Drugs

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FDA Safety Scientists Warn About Deaths - 4 Asthma Drugs

http://ahrp.blogspot.com/2008/12/fda-safety-scientists-warn-about-deaths.html

 

The New York Times reports (below) " Two federal drug officials have concluded

that asthma sufferers risk death if they continue to use four hugely popular

asthma drugs - Advair, Symbicort, Serevent and Foradil.... " Sudden deaths among

asthmatics still clutching their inhalers have fed the debate. "

 

No sooner was Serevent approved in 1994, than the agency began receiving reports

of deaths. A letter to the New England Journal of Medicine described two elderly

patients who died holding Serevent inhalers. Glaxo warned patients that the

medicine, unlike albuterol, does not work instantly and should not be used

during an attack.

 

In 1996, Glaxo began a study of Serevent's safety, but the company refused for

years to report the results until 2003 when Glaxo reported that patients given

the medicine were more likely to die than those given placebo inhalers. What led

FDA officials to remain silent about the lethal risk for 7 years!!! Glaxo said

problems with the trial made its results impossible to interpret.

 

So, what scientific evidence leads agency officials and others to disagree about

the drug's safety hazard? Could the high financial stakes involved have greater

persuasive power than the evidence???

 

Last year, Advair sales were $6.9 billion and may approach $8 billion this year,

making the medication GlaxoSmithKline's biggest seller and one of the

biggest-selling drugs in the world. Dr. Katharine Knobil, global clinical vice

president for Glaxo, dismissed the conclusions of FDA's drug-safety division as

" not supported by their own data. "

 

 

Whose drug safety assessment do you trust? [Link]

THE NEW YORK TIMES

December 6, 2008

Warning Given on Use of 4 Popular Asthma Drugs, but Debate Remains

By GARDINER HARRIS

 

WASHINGTON - Two federal drug officials have concluded that asthma sufferers

risk death if they continue to use four hugely popular asthma drugs -Advair,

Symbicort, Serevent and Foradil. But the officials' views are not universally

shared within the government.

 

The two officials, who work in the safety division of the Food and Drug

Administration, wrote in an assessment on the agency's Web site on Friday that

asthma sufferers of all ages should no longer take the medicines. A third

drug-safety official concluded that Advair and Symbicort could be used by adults

but that all four drugs should no longer be used by people age 17 and under.

 

Dr. Badrul A. Chowdhury, director of the division of pulmonary and allergy

products at the agency, cautioned in his own assessment that the risk of death

associated with the drugs was small and that banning their use " would be an

extreme approach " that could lead asthmatics to rely on other risky medications.

 

Once unheard of, public disagreements among agency experts have occurred on

occasion in recent years. The agency is convening a committee of experts on

Wednesday and Thursday to sort out the disagreement, which has divided not only

the F.D.A. but also clinicians and experts for more than a decade.

 

Sudden deaths among asthmatics still clutching their inhalers have fed the

debate. But trying to determine whether the deaths were caused by patients'

breathing problems or the inhalers has proved difficult.

 

The stakes for drug makers are high. Advair sales last year were $6.9 billion

and may approach $8 billion this year, making the medication GlaxoSmithKline's

biggest seller and one of the biggest-selling drugs in the world. Glaxo also

sells Serevent, which had $538 million in sales last year. Symbicort is made by

AstraZeneca and Foradil by Novartis.

 

Whatever the committee's decision, the drugs will almost certainly remain on the

market because even the agency's drug-safety officials concluded that they were

useful in patients suffering from chronic obstructive pulmonary disease, nearly

all of whom are elderly.

 

Dr. Katharine Knobil, global clinical vice president for Glaxo, dismissed the

conclusions of the agency's drug-safety division as " not supported by their own

data. " Dr. Knobil said that Advair was safe and that Serevent was safe when used

with a steroid.

 

Michele Meeker, a spokeswoman for AstraZeneca, said that the F.D.A.'s safety

division improperly excluded most studies of Symbicort in its analysis, and that

a review of all of the information shows that the drug does not increase the

risks of death or hospitalization.

 

Dr. Daniel Frattarelli, a Detroit pediatrician and member of the American

Academy of Pediatrics's committee on drugs, said that he was treating children

with Advair and that his committee had recently discussed the safety of the

medicines.

 

" Most of us felt these were pretty good drugs, " Dr. Frattarelli said. " I'm

really looking forward to hearing what the F.D.A. committee decides. "

 

About 9 percent of Advair's prescriptions go to those age 17 and under,

according to Glaxo. Ms. Meeker could not provide similar figures for Symbicort.

 

In 1994, Serevent was approved for sale, and the F.D.A. began receiving reports

of deaths. A letter to the New England Journal of Medicine described two elderly

patients who died holding Serevent inhalers. Glaxo warned patients that the

medicine, unlike albuterol, does not work instantly and should not be used

during an attack.

 

In 1996, Glaxo began a study of Serevent's safety, but the company refused for

years to report the results publicly. In 2001, the company introduced Advair,

whose sales quickly cannibalized those of Serevent and then far surpassed them.

 

Finally in 2003, Glaxo reported the results of its Serevent study, which showed

that those given the medicine were more likely to die than those given placebo

inhalers. Glaxo said problems with the trial made its results impossible to

interpret.

 

Asthma is caused when airways within the lungs spasm and swell, restricting the

supply of oxygen. The two primary treatments are steroids, which reduce

swelling, and beta agonists, which treat spasms. Rescue inhalers usually contain

albuterol, which is a beta agonist with limited duration. Serevent and Foradil

are both beta agonists but have a longer duration than albuterol and were

intended to be taken daily to prevent attacks.

 

Advair contains Serevent and a steroid. Symbicort, introduced last year,

contains Foradil and a steroid. In the first nine months of this year, Symbicort

had $209 million in sales.

 

The problem with albuterol is that it seems to make patients' lungs more

vulnerable to severe attacks, which is why asthmatics are advised to use their

rescue inhalers only when needed. The long-acting beta agonists may have the

same risks.

 

But drug makers say this risk disappears when long-acting beta agonists are

paired with steroids. The labels that accompany Serevent and Foradil instruct

doctors to pair the medicines with an inhaled steroid.