FEDERAL AGENCIES SEEK TO CURB ABUSE OF POTENT PAINKILLERS

Federal regulators are preparing plans to deal with the rising problems of
abuse and addiction tied to powerful prescription painkillers.

The plans, from the Food and Drug Administration and the Drug Enforcement
Administration, include pushing companies that seek to market the most
potent new drugs to develop programs to reduce the risk of abuse.

The agencies' focus is particularly on products with time-release
mechanisms that are supposed to help a patient absorb a large dose of
medicine gradually over a long time period. One such painkiller, OxyContin,
has been widely abused partly because users are able to defeat the
time-release mechanism to get all of the drug's effect at once.

The issue is becoming more important as drug makers roll out a growing
number of new formulations of opioid drugs -- narcotics with effects
similar to those of opium-derived products. Sales of narcotic painkillers,
OxyContin among them, were $4.67 billion last year, up 18% from the year
before, and 136% from 1998, according to market researcher IMS Health.
Purdue Pharma LP, the maker of OxyContin, is currently seeking FDA approval
for Palladone, a new extended-release opioid that is even more potent.

Before these new drugs will be allowed on the market, the FDA is expected
to make abuse-management programs a part of the approval process, people
briefed on the effort say. The agency is expected to stop short of saying
it will explicitly require such programs, which generally include elements
such as physician education, because officials believe it may not have the
legal authority to do so. But drug companies are almost certain to comply
with the FDA's approach. The FDA is expected to revamp the labeling on some
existing medicines to include more detailed information on appropriate
prescribing, these people say. The agency will also likely urge doctors to
screen patients to pinpoint those who may be at higher risk of addiction.

For its part, the DEA is planning to work with state medical boards to add
training in opioid use to their continuing-education requirements for
physicians. The agency has struck agreements with pain-specialty groups to
develop educational initiatives.

These efforts stop short of some of the more stringent proposals discussed
in a recent meeting of an FDA advisory panel, which included seeking to
limit the distribution of potent and easily abused drugs to certain
pharmacies or physicians. The FDA has never limited any opioid to certain
pharmacies, and agency officials say they don't have the authority to block
certain physicians from prescribing a drug . The DEA isn't expected to
immediately move toward a federal doctor-education requirement for opioids,
which like other prescription drugs with addictive potential are overseen
by both agencies.

The two agencies are trying to strike a difficult balance. Many researchers
and pain doctors argue that patients with severe pain often don't get the
drugs they need. One major 1998 study of 13,625 nursing-home cancer
patients found that more than a quarter of those who suffered daily pain
got no analgesic at all.

Sharp restrictions on prescribing opioids risk "greatly decreasing the
availability of these drugs to people who need them," says Russell
Portenoy, chairman of the Beth Israel Medical Center department of pain
medicine and palliative care. Allowing only pain specialists to prescribe
the drugs "would be a disaster in terms of access," he says. Dr. Portenoy,
who served on the FDA panel that examined opioids, has consulting
arrangements with several drug makers that make painkillers.

At the same time, the agencies need to keep the drugs out of the hands of
potential abusers. Last year, a federal survey estimated that 29.6 million
people had at some point used painkillers without a medical need. An
estimated 4.4 million had used one in the past month. About 1.9 million
people had at some point used OxyContin without a medical need.

DEA officials, and some members of Congress, urged the FDA advisory panel
to support tougher restrictions on the distribution or dispensing of
powerful opioids. The DEA also wanted to narrow the number of situations in
which the powerful painkillers are recommended. "By having the indications
so broad, you enable [doctors] to prescribe these substances for back pain
or neck pain or any other pain, and as an initial treatment that is not
appropriate," says Terrance Woodworth, departing deputy director of the
DEA's office of diversion.

The FDA advisory committee voted against the more severe limits,
disagreeing with the DEA, and the FDA is expected to generally follow the
panel's lead. The committee also generally supported the risk-management
plan proposed by Purdue for Palladone but recommended an extension of a
planned four-month limited rollout to evaluate risks.

Committee members expressed concerns about Palladone's risks. The drug is
"going to be more sought-after and more appealing to addicts than
OxyContin," says Gregory Skipper, an FDA panel member who is a professor at
the University of Alabama. In the committee meeting, an FDA official said
Palladone's active ingredient, hydromorphone, may be more appealing to
addicts than OxyContin's oxycodone, though a committee member challenged
that conclusion.

J. David Haddox, Purdue's vice president for health policy, says the "jury
is out" on which opioids are most appealing to addicts, and "desirability
of a drug to abusers is a complex function and includes a number of
factors," including the drug's formulation. Purdue says it plans to meet
with FDA to discuss its risk-management plan for Palladone.

Palladone is one of a spate of expected new opioids. Aradigm Corp.,
Hayward, Calif., is developing asthma-style inhalers to administer morphine
and fentanyl, a synthetic opioid. The company says it plans special safety
measures to ensure that only patients can use the products. Endo
Pharmaceuticals Holdings Inc., Chadds Ford, Pa., is seeking to market both
immediate and extended-release versions of oxymorphone, another opioid drug
. Johnson & Johnson, which makes the Duragesic fentanyl patch, is also
hoping to sell other painkilling patches.

The FDA has already begun requiring precautions for some opioids. OxyContin
was approved in 1995, but it wasn't until 2001 that the FDA reviewed a
risk-management program for it. The program's measures include tracking of
diversion and special prescription pads for doctors. In 1998, the agency
approved Cephalon Inc.'s Actiq, which offers the opioid fentanyl in a
sweet-flavored lozenge, with several childproofing measures.

The majority of opioid drugs , some of which were approved decades ago,
still have no formal FDA-reviewed safety plans tied to their distribution
or use, the agency says. Even some of the powerful extended-release opioids
have no risk-management program, the FDA says.

"We are very attuned to keeping an eye out for situations where we might
need to initiate formal risk-management plans," says Robert Meyer, director
of the FDA's Office of Drug Evaluation II. He declines to comment on the
agency's planned new moves.

A coming study from the congressional General Accounting Office is expected
to focus on problems associated with OxyContin. Purdue's Dr. Haddox says
the company is "committed to being a leader for risk management" for
opioids, and Purdue officials believe their safety measures for OxyContin
are beginning to have some effects.