Adderall Deaths - Canada Suspends ADHD Drug, FDA Disagrees

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Adderall Deaths - Canada Suspends ADHD Drug, FDA Disagrees

Pharma

Linked to 20 deaths, Shire Pharmaceuticals' Attention Deficit and Hyperactivity

Disorder drug Adderall was suspended by Health Canada, resulting in a ten per

cent drop in the UK company's shares, according to a Bloomberg report.

The US FDA instead, citing their evaluation of Adderall before approval of the

drug, says it has no plans to change the status of the drug in the United

States.

This uncovers a fault in the regulation of pharmaceutical drugs: the absence of

ongoing monitoring of the " performance " and especially the safety of drugs. Once

approved, it appears that the FDA relies on voluntary reporting by the drug

companies to tell it about side effects - a bit like having the fox guard the

hen house.

According to Senator Grassley of Iowa, the US agency has even asked its Canadian

counterpart not to suspend the drug. Grassley is quoted in the article,

published in the New York Times, as saying that the Food and Drug Administration

had made the request of Canadian health officials because the F.D.A. could not

handle another " drug safety crisis. "

Why is there such a difference in the treatment of the drug's safety problems by

Canadian and US authorities? One reason may be a difference in the laws of the

two countries, where Canadian legislation allows suspension of a drug while

security concerns are investigated, while US law apparently does not support

such a course of action.

Another reason is that there seems to be a much closer relation of the

pharmaceutical industry and the FDA than there is to corresponding agencies in

other countries. After all, the FDA is looked upon as a " lead agency " in drug

approvals and drug safety. Expanding sale of drugs to other countries is much

easier after FDA approval has been obtained.

That would presume that the FDA is upholding the highest standards on drug

safety, which however does not seem to be the case. Perhaps the agency should

take a cue from National Institutes of Health chairman Dr. Elias Zerhouni, who,

according to the LA Times, says that consulting payments from drug companies are

" a systemic problem " and asks for an ethics summit, a forum for wider discussion

on conflicts of interest in medical research.

Shire Shares Fall After Canada Pulls Adderall XR Drug

(original here)

Feb. 10 (Bloomberg) -- Shares of Shire Pharmaceuticals Group Plc, the U.K.'s

third-biggest drugmaker, fell the most in two years after Canada ordered the

withdrawal of its best-selling product, Adderall XR, after it was linked to at

least 20 deaths.

Adderall XR, used to treat attention deficit hyperactivity disorder, had

third-quarter sales of $140 million, more than 40 percent of Shire's revenue for

the period. Shire, whose shares fell 10 percent, maintains the drug is safe and

" strongly disagrees with the conclusions drawn by Health Canada,'' the

Basingstoke, England-based company said today in a statement on Regulatory News

Service.

Health Canada told Shire yesterday to take Adderall XR off the Canadian market,

where it had sales of $10 million last year, based on information the company

supplied about the deaths of 14 children and six adults. The drug remains

available in the U.S., its biggest market, where regulators advised parents to

consult their doctors before changing their children's medication.

" We do expect this to have a negative influence on U.S. sales,'' said

Latorre, a fund manager at Deutscher Investment Trust in furt, which has

about 56 billion euros under management. " What we do find astonishing is that

two regulators have come to different conclusions on the basis of the same

data.''

Shares of Shire fell 64.5 pence to 577.5 pence at the close of trading in

London. The 10 percent drop was the steepest percentage decline for the shares

since January 2003.

Drug Safety Concerns

The U.S. Food and Drug Administration has allowed the drug, sold as Adderall in

the U.S., to remain on the market with a revised label warning against its use

in patients with heart conditions.

" I think for kids who are stable on these medications and who don't have cardiac

problems, there's no reason to make an immediate change,'' said Fassler,

48, a professor at the University of Vermont College of Medicine in Burlington

and a child and adolescent psychiatrist. " However I expect there will be parents

who have questions and concerns.''

Some doctors may " alter their prescribing patterns until they have more

information,'' he said.

Drug safety is getting increased attention since Merck & Co.'s Vioxx painkiller

was withdrawn last September because of a link to heart attacks, prompting U.S.

and European regulators to assess the risks of all painkillers in the same

class.

'Climate Is changing'

" I do think the climate is changing,'' Fassler said. " I think we are becoming

more aware that the FDA has had less resources to devote to post-marketing

surveillance. Most of the emphasis in recent years has been on the approval of

new medications. My sense is that there may be a re-evaluation of that balance

under way.''

Adderall, has about 24 percent of the market share for attention deficit

hyperactivity disorder treatments, which are most commonly prescribed for

children. Adderall is an amphetamine, which stimulates the central nervous

system and can increase the heart rate. The drug isn't sold in Europe.

" Health Canada's decision comes as a result of a thorough review of safety

information provided by the manufacturer, which indicated there were 20

international reports of sudden death'' in patients taking either Adderall or

Adderall XR, the agency said.

" Although we are complying with this request we strongly disagree with this

decision,'' Shire spokeswoman Mann said in an interview. " We have

confidence in the safety and efficacy of Adderall XR.''

None of the reported deaths occurred in Canada, Health Canada said. Adderall XR

has been sold in Canada for a year.

'Real Question'

" The real question is whether this suspension could spill over into the U.S.,''

Nomura International Plc analyst Frances Cloud wrote in a note to clients. " In

our view, the risk of this is low since the FDA has already seen this data and

only requested a labeling revision.''

Nomura raised its rating on Shire shares to " buy'' from " neutral'' today. Of 21

analysts who cover Shire, 16 have a " buy'' rating, two have " hold'' ratings and

three rate the shares a " sell.''

The FDA is consulting with Canadian authorities on their action and plans no

immediate changes to the drug's labeling or approved use, the agency said in a

statement on its web site.

" At this time, FDA cannot conclude that recommended doses of Adderall can cause

sudden unexplained death, but is continuing to carefully evaluate these data,''

the agency said on its web site.

The FDA said in a public health advisory that it had evaluated the risk of

sudden death with Adderall before approving the drug for use in adults last

year. The agency said it decided not to take action at this time because, " it

does not appear the number of deaths reported is greater than the number of

sudden deaths that would be expected to occur in this population without

treatment.''

The FDA drew that conclusion from the rate of sudden death based on 30 million

prescriptions written between 1999 and 2003.

To contact the reporter on this story: Zimm

To contact the editor responsible for this story. Mark Rohner

Last Updated: February 10, 2005 11:51 EST

- - - - -

New York Times:

Senator Says F.D.A. Asked Canada Not to Suspend Drug

By GARDINER HARRIS and BENEDICT CAREY

Published: February 11, 2005

(go to original)

WASHINGTON, Feb. 10 - A day after Canadian officials suspended the use of a

hyperactivity drug amid reports of deaths associated with its use, Senator

E. Grassley of Iowa contended that United States health officials had

asked the Canadian regulators not to do so.

Senator Grassley, a Republican, said on Thursday that the Food and Drug

Administration had made the request of Canadian health officials because the

F.D.A. could not handle another " drug safety crisis. " Mr. Grassley said he was

basing his contentions on reports from whistle-blowers within the agency.

Dr. , director general of the therapeutic products directorate at

Health Canada, said through a spokeswoman that reports that F.D.A. had asked

Health Canada to refrain from suspending the drug " are untrue. "

Brad Stone, a spokesman for the F.D.A., declined to respond directly to Mr.

Grassley's contention but said of Dr. 's rejection that, " We believe the

Canadian response is the correct one. " Canadian health officials, citing 20

deaths among patients taking the British-made drug Adderall XR, said on

Wednesday night that they were suspending sales of the hyperactivity drug

indefinitely. The F.D.A. is allowing the drug to continue to be sold in the

United States, saying there is little evidence that Adderall XR caused the

deaths.

Mr. Grassley, who has been investigating the Food and Drug Administration for

about a year, demanded in a letter written on Thursday that the agency answer

questions about any discussions its officials may have had with the Canadians

about the drug.

Dr. Temple, director of the F.D.A.'s office of medical affairs, said the

agency's decision to permit the continued sale of Adderall was not influenced by

the controversies swirling around the F.D.A.

" It's still our job to get as close as we can to the right answer and not panic

and do things for the wrong reasons, " Dr. Temple said.

Cabrey, a spokesman for the maker of Adderall, Shire Pharmaceuticals

Group of Britain, said Adderall was safe and effective. " We are very surprised

at the actions of Health Canada, and we disagree with their interpretations of

the data around these extremely rare cases of sudden death, " Mr. Cabrey said.

The controversy - and the sudden appearance of Mr. Grassley, the chairman of the

Senate Finance Committee, in it - promises to engulf the F.D.A. in more

questions about its oversight of the pharmaceutical industry.

Critics have accused agency officials of being too cozy with drug makers and of

being slower than their counterparts in other nations to acknowledge drug-safety

problems.

The controversy is also bound to fuel a long-running battle over whether drugs

like Adderall and Ritalin are overprescribed to children, and whether the drugs'

longterm risks have been adequately explored.

More than 700,000 Americans use Adderall and its extended release counterpart,

Adderall XR. Shire sold $759 million of Adderall products in the United States

last year and $10 million in Canada.

In the letter Thursday to the F.D.A., Mr. Grassley wrote that reports given to

his staff suggested that the agency was not acting with scientific integrity.

" Unfortunately, such allegations raise additional concerns about the culture at

the F.D.A., " he wrote.

Dr. of Health Canada described discussions between the two regulatory

bodies as " collegial. "

Differing health regulations govern the differing responses of the two agencies

to the Adderall reports, Dr. said. Canadian law lets regulators suspend

a drug's sales while safety questions are investigated; United States law does

not. Health Canada approved Shire's application to sell Adderall XR in January

2004. In September, the company reported to Canadian authorities that 20 people,

12 of them children, had died suddenly in the United States while taking the

drug.

Shire asked the Canadian regulators for permission to change the drug's label to

reflect the possible dangers, as had been done in the United States that month.

Some of the deaths, which had not been previously reported to Canadian

authorities, occurred well before Health Canada approved Adderall XR for sale,

Dr. said.

Canada and the United States both require pharmaceutical companies to report all

adverse outcomes from drugs promptly.

" We were surprised to find these cases, " Dr. said in an interview on

Thursday.

Dr. said that an early analysis of the data suggested that Adderall XR

might be linked to two to three times as many sudden deaths as Ritalin and its

cousin, Concerta, which are prescribed for similar disorders.

Further, Dr. said that Canadian authorities were uncertain about how to

warn patients about the risks of sudden death.

" It's very difficult to generate a benefit-to-risk balance when the risk is

sudden and unexpected death, " Dr. said.

Mr. Cabrey of Shire Pharmaceuticals said that the company had forwarded reports

of the deaths to Canadian authorities promptly.

Dr. Temple of the F.D.A. said that 7 children taking Ritalin and Concerta died

during the same period that 12 children taking Adderall died, suggesting

equivalent risks. Many had structural problems with their hearts and several

were engaged in vigorous exercise, he said.

There is little evidence that the drugs caused any of the deaths, he said. " There

is a tendency to believe that sudden death doesn't occur in children. That is

wrong, " Dr. Temple said. He added: " Psychiatrists say that these drugs are

needed. To get rid of them for something that may well be a background rate of

death is not responsible. " Doctors have known since the 1930's that stimulant

medications like these can calm hyperactive, or aggressive, children. But no one

knows precisely how the drugs induce this effect, and there have always been

concerns about the drugs' long-term effect on development.

Prescriptions for these drugs to be used by children with attention-deficit

disorder more than doubled in the 1990's, experts say, heightening the concerns

of some doctors.

The drugs are far more popular in the United States than in Europe. Last year,

doctors in the United States wrote more than 23 million prescriptions for the

four most popular drugs used to treat attention deficit disorder.

- - - - -

LA Times:

NIH Chief Calls for Ethics Summit

Dr. Elias Zerhouni, who banned drug company payments to agency scientists, wants

a wider discussion on conflicts in medical research.

BETHESDA, Md. - The director of the National Institutes of Health - describing

consulting payments from drug companies as a " systemic problem " that threatened

the integrity of his agency - has called for a summit of government and academic

leaders to address conflicts of interest throughout American medical research.