When drugs are used off-label (mentions Neurontin)

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When drugs are used off-label (mentions Neurontin) Los Angeles Times

June 7, 2004

Doctors often prescribe medicines for other than their intended use. The

benefits are well-proven, but the risks are often unknown.

By Costello, Special to The Times

After two months of sleepless nights, anxiety and constantly feeling

like she was " swimming in a thick fog all day long, " Caryl Westwood was

fed up. She suspected her pain medication, Neurontin, which her doctor

had recently prescribed for her lower back pain.

What Westwood didn't know — and she says her doctor didn't tell her —

was that Neurontin wasn't a pain medication at all. Instead, it was a

powerful epilepsy drug that doctors across the country were increasingly

prescribing for many conditions for which the drug had not been

approved: attention deficit disorder, migraines, drug and alcohol

addiction, and pain. Surprisingly, there was little clear proof

Neurontin worked for any of these conditions.

Although doctors are allowed to prescribe an FDA-approved drug for any

reason they see fit, companies are barred from marketing or promoting

drugs for any use beyond what's listed on its label. Last month, Pfizer

Inc. agreed to plead guilty and pay a $430-million fine to settle

federal criminal charges that the pharmaceutical giant promoted

Neurontin for uses for which it had no scientific support.

According to the government's complaint, the promotion amounted to an

" illegal and fraudulent promotion scheme " that put patients " at risk. "

It is estimated that 90% of Neurontin's $2.7 billion in sales last year

were for off-label uses.

" I'm angry, " says Westwood, a 52-year-old food service worker from Santa

Fe, N.M. " How could a doctor not tell their patient about this? How can

the government let this happen? "

Off-label prescription drugs are immensely common — accounting for up to

40% of all prescriptions written each year. In the vast majority of

cases, the practice is safe. Moreover, off-label use has spawned many

medical innovations that doctors might otherwise not have discovered.

It's how medical science first learned that aspirin could reduce the

risk of heart disease; that antibiotics were the best way to treat

ulcers; and that an angina drug produced an unexpected side effect in

men, which would later lead to the development of the blockbuster drug

Viagra.

Moreover, stories about the importance of off-label usage to treat

life-threatening conditions such as AIDS and cancer are plentiful. Most

front-line drugs used to treat terminal illnesses are approved for one

purpose, but then quickly prescribed as a second or third option for

patients with other illnesses who don't respond to traditional

treatments. A 1997 survey by the American Cancer Society found that 60%

of cancer doctors used drugs for unapproved reasons.

The American Medical Assn. says it strongly supports doctors' rights to

prescribe FDA-approved drugs for any reasons that physicians believe are

helpful. Such uses do not, as some critics charge, amount to turning

patients into human guinea pigs, says Dr. Nielsen, a Buffalo,

N.Y., internist and speaker of the AMA's House of Delegates. Doctors,

she says, " are making decisions based on the best science and what's in

the patient's best interest. "

Still, the Neurontin case and other ongoing federal investigations into

drug makers' promotions of off-label uses, indicate that the government

is growing increasingly worried about the issue. The concern is that

some drug companies are finding ways to abuse the system and promote

their products for unapproved use even when they have little good

science to back up their claims. Both Schering-Plough Corp. and Wyeth

are being investigated by the federal government for their off-label

prescription practices.

In some cases, taking a drug off- label may be a waste of money. As

highly effective as some new drugs can be, older and cheaper drugs often

are sometimes just as effective. In other cases, there's a risk to

taking medications for conditions for which the FDA never evaluated the

drug. It wasn't long ago, after all, that doctors were regularly

prescribing fen-phen, a combination of two FDA-approved drugs —

fenfluramine and phentermine — as an unapproved weight-loss treatment

that was later suspected of causing heart valve damage in up to 30% of

users.

Dr. Woosley, vice president of the Arizona Health Sciences

Center at the University of Arizona in Tucson, says that most patients

taking off-label drugs are getting the best treatment.

Even so, Woosley cautions that patients should be careful, especially

when taking a relatively new drug that is being prescribed for several

off-label uses, or when a drug is being used off-label for medical

conditions not well understood by doctors and for which there are no

" standard " treatments.

One example: drugs used to treat neurological conditions, such as

depression, attention deficit disorder or anxiety. The brain " is still a

vastly confusing area, " he says, " and that's something drug companies

can exploit. "

Working the system

One important way that companies can circumvent regulations is by

capitalizing on the different rules and accepted practices involving

scientific research. In some cases, well-respected research articles

demonstrating another use for an FDA-approved drug appear in major

medical journals years before the agency catches up and endorses it.

In those cases, it's perfectly acceptable for drug companies to talk

about those newly discovered benefits. The problem is, not all research

is created equal. In some cases, drug companies conduct their own

research and then hire ghostwriters to put their name on a paper before

it's submitted for publication. (That relationship isn't always

disclosed.)

As recently as the mid-'90s, the FDA tried to block companies from

sending questionable research material directly to doctors. The agency

was stymied by successful industry lawsuits claiming the practice was

protected under free speech. The FDA still insists that drug companies

can distribute research only after a physician has requested it.

There are ways around that too. Some doctors say that drug

representatives start a conversation by saying they can't talk about

off-label uses. But then, they will say that other doctors have used the

drug for different reasons and they'd be happy to send along information

about some ideas.

The AMA's Nielsen acknowledges that she and other physicians remain

concerned about the increasing influence drug makers have over doctors'

decision-making.

nn Caprino, a Pfizer spokeswoman, says the illegal activity

highlighted in the Neurontin case happened before the company acquired

Warner-Lambert in 2000.

Officials of Schering-Plough acknowledged in an interview that the

company is under investigation by the U.S. Justice Department for

off-label marketing of a cancer medication, while Wyeth said the federal

Office of Personnel Management, the agency that oversees benefits for

federal employees, has subpoenaed company records involving Wyeth's

promotion of an antidepressant drug, Effexor.

Curbs in question

It's unclear just how effective the government's actions will be in

curbing off-label marketing. Two years ago, the pharmaceutical industry

instituted voluntary guidelines to ban most gifts and payments to

doctors, which were aimed at slowing aggressive marketing tactics around

both on-label and off-label promotions.

But some companies continue to underwrite seminars for doctors where

off-label uses are discussed while others pay doctors to sit in the room

with patients and discuss treatment advice, a financial agreement some

characterize as quid pro quo payments.

Doctors are not required to tell patients they are writing off-label

prescriptions, but many will discuss it if patients ask. Patients can

also seek information about a drug's authorized uses on the FDA's

website (www.fda.gov).

As part of its settlement agreement, Pfizer is required to spend a

portion of its fine — $38 million — on a public-awareness campaign for

doctors and patients.

After hearing about Pfizer's fine last month, Westwood says she decided

to file a complaint against her doctor with the state medical board for

not informing her Neurontin was not approved by the FDA as a pain

medication and certain other uses. She realizes that the board is

unlikely to act, but she remains resolute.

" I don't want anyone to have to go through this, " she says. " It's not

right. "