FDA WANTS MORE INFORMATION ON PRESCRIPTION LABELS

Side Effects Can Be Deadly, Experts Warn

The computer printout that Pat and Ben Christen picked up along with
their son's medicine contained a litany of warnings: Dry mouth.
Constipation. Blurred vision. Drowsiness. Dizziness. These were just a
few of the side effects of the drug imipramine, which a psychiatrist
had prescribed for their 7-year-old son, Cory, who suffered from
attention deficit disorder.

Cory Christen had been taking the drug for several months when his
second-grade teacher noticed that his hands were trembling. His
parents checked the warning sheet for guidance, but ``there was
nothing in it,'' Pat Christen said. Soon after, while he was leaning
over a school water fountain, Cory collapsed and died. ``His heart
just gave out,'' his mother said.

An autopsy concluded that Cory had overdosed; lawyers for the
Christens and the doctor, who settled a lawsuit with the parents
without acknowledging wrongdoing, disagree on who was responsible. But
experts say Cory's tremors may have been a sign he was getting too
much of the drug: cardiac arrhythmia, a heart-rhythm disturbance, is a
well-known side effect.

Cory's death in his tiny hometown of Weimar, Texas, on September 19,
1996, highlights what drug safety experts describe as a dangerous flaw
in the way consumers are informed of the risks of prescription
medicines. While officials at the Food and Drug Administration will
soon begin requiring standard, easy-to-read labels for all
over-the-counter drugs and dietary supplements, the government does
not control the information that patients receive with prescription
medicines, which are typically much more dangerous.

That is not for lack of trying. Four years ago, the FDA announced a
plan to require drug manufacturers to publish ``med guides,''
government-approved patient brochures for prescription drugs fashioned
after the popular ``nutrition facts'' labels on food. But the plan
drew intense opposition from the drug industry and pharmacists, and
Congress rejected it in 1997, deciding that private companies could do
the job better.

As a flood of new prescription medications fills the nation's pharmacy
shelves, however, drug safety experts and FDA officials are growing
increasingly concerned about deaths and injuries from the drugs that
the agency approves. And so last month, the FDA put into effect a rule
allowing it to require med guides for a handful of especially risky
prescription medications, no more than 10 each year. The specific
drugs will be announced later.

``Congress specifically said that we could not implement a
comprehensive program, but we felt that there was sufficient support
for us to ensure that people taking these special drugs were warned,''
said Dr. Nancy Ostrove, the agency official in charge of the med
guides plan. She said the guides ``will become a signal to consumers
that this is a product that you really need to be careful about.''

But experts in prescription drug safety say the new rule does not go
nearly far enough.

``On boxes of cereal, we have a very standard label that tells the
content, and it is the same on every one of them,'' complained Dr.
Lucian L. Leape, a health policy analyst at the Harvard School of
Public Health. ``I don't know why cereal is more important than
medicines.''

Scientists estimate that more than 100,000 hospital patients each year
die of reactions to their medication, and 2.2 million are injured. At
least some of those deaths, Leape and others say, could be prevented
if patients had clear, concise information about how to use their medication.

In the absence of government-approved guides, consumers are left to
rely primarily on computer printouts of the sort the Christens
received. But few people realize that these printouts, called
``patient information leaflets,'' are manufactured by private
companies and are not required by any government agency.

Drug stores distribute the leaflets voluntarily, but not all do so.
And authorities on drug safety complain that the leaflets are
inconsistent; they say the pamphlets vary from pharmacy to pharmacy
and omit information or contain errors that contribute to deaths.

The voluntary system is the result of more than two decades of debate
among regulators, the pharmaceutical industry and consumer advocates
about how to provide patients with accurate, complete information
about the risks of prescription drugs. At the crux of the discussion
is a delicate risk-versus-benefit analysis: Experts want consumers to
be well-informed about the risks that drugs carry, but they do not
want to scare patients away from taking medicine that might save their
lives.

In the late 1970s, the FDA tried to require drug companies to provide
written information for consumers, but the plan was quashed by the
Reagan administration. In 1995, Dr. David Kessler, then the
commissioner of Food and Drugs, resurrected the idea with the med
guides plan.

``I went to pick up a prescription for my daughter the other day,''
Kessler said in a recent interview. ``There were all these little
stickers on it and they were covering each other and I had to peel
them off. That's no way to provide information.''

But pharmacists complained about the FDA's plan to restrict the
content of the guides to information about government-approved uses of
the drugs. Doctors can prescribe medications ``off-label'' for any
condition; the drug thalidomide, for instance, is commonly used to
treat AIDS but was initially approved only for leprosy. The FDA's med
guides, pharmacists argued, would leave many patients
ill-informed.

Drug manufacturers also objected, fearing that they would be sued if
they provided patients with a condensed, simpler version of the risk
information they were already required to give doctors.

And, said Marjorie Powell, a lawyer for a drug industry trade group,
Pharmaceutical Research and Manufacturers of America, the
manufacturers feared that if the FDA had to approve information given
patients, it would take longer to get new drugs approved. ``We didn't
need to convert a commercial program into a government-run program,''
she said. Congress was sympathetic and rejected Kessler's plan.

The result was a compromise adopted by the Department of Health and Human
Services: By next year, 75 percent of all prescriptions must be accompanied
by leaflets that contain ``useful'' information; by 2006, the figure must
rise to 95 percent. If those standards have not been met, the FDA will be
free to propose the med guides plan again.

The agency is now trying to determine how close the voluntary system
is to meeting the goal. Dr. Ostrove said the agency was evaluating the
leaflets in more than 350 pharmacies in about 10 states, and planned
to conduct a larger study next year.

Dr. Raymond Woosley, chairman of the pharmacology department at the
Georgetown University Medical Center in Washington, said a study he
conducted several years ago found that ``a third of the time, people
get nothing, and what they do get is often inadequate or
misleading.''

In 1997, Public Citizen published an analysis of the patient
information leaflets for 18 different pain relievers in the class
known as nonsteroidal anti-inflammatory drugs. It found that only
one-fourth of the leaflets warned patients to stop the drug if they
experienced abdominal pain, a symptom that can signal serious, and
potentially life-threatening, internal bleeding.

The leaflet that Cory Christen's parents were given, for example,
contained no information on serious, lasting side effects of imipramine.

Thomas J. Moore, a drug safety expert at the George Washington
University Medical Center, said that was not surprising; he said the
leaflets typically leave out information about the most dire side effects.

Historically, it has been left to doctors and pharmacists to educate
their patients about the dangers of prescription drugs. But with the
rise of managed health care, doctors have less time to talk to their
patients. In a 1997 survey of 1,000 patients, the FDA found that only
one-third had received information from their doctors about the
dangerous side effects of drugs they were taking. Pharmacists, too,
say they are often too busy filling prescriptions to counsel patients.

Dr. Sidney M. Wolfe, director of Public Citizen's Health Research
Group, an advocacy organization based in Washington, says this is all
the more reason to have government-approved med guides for all drugs.

``You need to have some backup,'' he said. ``And the backup is a
mandatory patient information leaflet.''

The printout that accompanied Cory Christen's prescription was
produced by Medi-Span Inc. of Indianapolis, one of a number of
commercial vendors that supply computer software to pharmacies. Citing
the lawsuit, the company declined to comment. But Jim Breen, an
official at Medi-Span's parent company, First Databank, said the
guides were ``merely a supplement for the pharmacist,'' and were not
intended to replace the advice of a doctor.

Even so, Susan Winckler, director of policy and legislation for the
American Pharmaceutical Association, which represents 52,000
pharmacists, acknowledged that her profession could do better.

``We are trying to remind our members that we fought the mandate but
they have to do it voluntarily.'' she said.

As to the quality of the leaflets, she said, ``A lot of them are
good.'' But she added, ``They all should be improving.''