MAKER CHOSE NOT TO ACT TO REDUCE ABUSE OF OXYCONTIN

The maker of the widely abused narcotic painkiller OxyContin knew that
other companies had used a chemical safeguard to reduce misuse of
their products but decided not to take similar steps before marketing
the drug, company officials said yesterday. Officials of the
manufacturer, Purdue Pharma, said in statements over the weekend that
they had not expected abusers to crush the powerful drug and then
inject or snort it so they had not initially considered adding a
compound that blocks the drug's narcotic effect when it is taken those
ways. Over the last two years, OxyContin has been cited as a factor in
more than 100 overdose deaths nationwide, and people desperate for the
drug have been involved in pharmacy robberies and other crimes. Last
week, Purdue Pharma said that it was working to develop a painkiller
like OxyContin that would also contain a compound to combat abuse.

These narcotic antagonists do not affect a drug if it is taken
normally.

But if an abuser crushes a drug tablet and injects or snorts the
powder an antagonist will block its opiate effect and reduce its
appeal. The company, based in Stamford, Conn., said it would probably
take three to five years to develop and test the new drug. Antagonists
work by blocking receptors in the brain that are also used by opiates.
"This is very time-consuming research for which there is no road map,"
Purdue officials stated in response to a series of written questions
from The New York Times. But in interviews last week, some drug-abuse
experts were critical of Purdue, saying that the company could have
initiated such action earlier and that its projected timetable would
do little to immediately address OxyContin abuse. "This should have
dawned on them before," said Terry Woodworth, the deputy director of
the division of diversion control at the federal Drug Enforcement
Administration. Purdue officials said they had hoped to avert
OxyContin misuse by encapsulating its active narcotic, a compound
called oxycodone, in a time-released formula.

The company said it believed that by doing so it would make the drug
less appealing to abusers who wanted a quick high. But even before
OxyContin was first sold in 1995, some companies found that some of
their products had become popular with drug abusers, and a few
manufacturers moved promptly to reformulate those products with
antagonists. In 1983, for instance, Winthrop Laboratories, which was
then a subsidiary of Sterling Drugs, added naloxone, an antagonist, to
Talwin, one of its pain relievers. Some people were abusing Talwin by
crushing the drug, adding an antihistamine and injecting the mixture.
"This seemed to help," said Dr. Sharon Jacobs, the senior medical
director at Sanofi-Synthelabo, which acquired Sterling. "It decreased
the abuse." Another manufacturer, Reckitt Benckiser Pharmaceuticals,
which makes buprenorphine, another painkiller, also added naloxone
when the drug became abused in New Zealand in the 1980's, said Charles
O'Keeffe, the president of the company.

As with Talwin, abuse of the compound quickly dropped. A German
manufacturer also took similar steps when one of its products was
abused, Mr. O'Keeffe said. Experts said it took about a year or less
to reformulate both Talwin and buprenorphine. Mr. Woodworth, the
D.E.A. official, said he was troubled by Purdue's timetable. "The
reformulation is a good initiative," said Mr. Woodworth. "But
completing it four years out is not helpful in addressing the
immediate diversion problems which are rapidly increasing." Purdue
officials said they knew about naloxone's use in drugs like Talwin
before the company began selling OxyContin in 1995, but they did not
anticipate the ways in which the drug would be abused. The company
officials said naloxone was not a suitable antagonist for oxycodone,
the active narcotic in OxyContin, for a variety of technical and
medical reasons.

It could, for example, produce withdrawal symptoms in patients
receiving high levels of oxycodone, the officials said. As a result,
they said, Purdue has decided to use a different but related substance
called naltrexone in a new drug they hope to develop. They called
their timetable "aggressive," given the lack of previous work in
combining naltrexone and a narcotic in the same tablet. "We have been
working in an area of basic research for which there is little
scientific literature or prior experience," the company said. "We will
have to enroll approximately 2,000 pain patients in a series of
clinical trials, which will take years to complete." Naltrexone has a
history of use. Over the last two decades it has been used with
varying success in different countries as a substitute for methadone
in the treatment of drug addicts. Dr. Joseph R. Volpicelli, the
director of the treatment program at the University of Pennsylvania
Medical Center in Philadelphia, said the effort failed in this country
because heroin addicts preferred methadone to naltrexone. It has had
far more success in the treatment of alcohol dependence, Dr.
Volpicelli said. He said that the principal difference between
naloxone and naltrexone was that naltrexone was a longer-acting drug.
That would appear to make it a better choice for OxyContin, which is a
slow-acting, time-released medication. Some addiction experts said
they believed that all narcotics manufacturers should consider adding
antagonists to their products, given the drug industry's experiences
with Talwin and OxyContin. "You have drug makers complaining all the
time about overregulation," said Dr. Theodore V. Parran Jr., an
associate professor at Case Western University School of Medicine.
"But gosh, there are some really simple things they can do to decrease
diversion." Dr. Parran, who specializes in training doctors in how to
properly dispense narcotics, said corporate profits might be at the
root of any resistance to such change. "People would have lower sales
because addicts won't want the drug," he said. "But the sales they
would be left with would be real." Purdue officials said they planned
to submit any new painkiller that includes naltrexone to the Food and
Drug Administration for approval.

The agency has an expedited process of six to ten months under which a
manufacturer can seek permission for changes to approved drugs without
extensive clinical trials.