Warning: 4 Popular Asthma Drugs: Advair, Symbicort, Serevent, Foradil: but Debate Remains

[Guest guest]

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

By GARDINER HARRIS

http://www.nytimes.com/2008/12/06/health/policy/06allergy.html

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

GlaxoKline'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. 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.

..

[Guest guest]

My son was on Advair and Singulair for his asthma for awhile. During

that time, we had more ER visits than without. We also had extreme

behavior problems that nearly resulted in his expulsion from first

grade. The teachers could not believe the difference (ie improvement)

in behavior when we got him off those drugs!

C

Houston

>

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

>

> By GARDINER HARRIS

> http://www.nytimes.com/2008/12/06/health/policy/06allergy.html

>

>

> 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

> GlaxoKline'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. 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.

>

>

>

> .

>

>

>

>

>