- Last year, about 16,000 Americans died from treating
their arthritis with FDA-approved drugs such as Advil and Aleve so-called
non-steroidal anti-inflammatory drugs. That's what happens if millions
of people, to treat their chronic pain, take a kind of drug that can increase
the risk of bleeding ulcers and other complications when used over long
periods. During the same time, around 200 people died from the purposeful
abuse of oxycodone, the active ingredient of OxyContin and other powerful
analgesics.
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- With terrible shortsightedness, federal bureaucrats have
now decided that the second number is the problem. Earlier this month,
the Drug Enforcement Administration (DEA) announced a high-profile campaign
against doctors and pharmacists "responsible" for the abuse.
Purdue Pharma, which makes OxyContin, subsequently announced it was suspending
shipment of "large dose tablets" of the drug. The inevitable
consequence of this campaign will be less pain relief for those who need
it, and possibly a higher death toll from overuse of substitute painkillers.
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- OxyContin was introduced in the United States in 1995
by Purdue Pharma, a privately held pharmaceutical company based in Stamford,
Connecticut. Its active ingredient, oxycodone, had been in use for over
60 years. But the innovative delivery system of this ingredient was the
key to the new drug's clinical success. For several decades, pain specialists
have recognized that opioids (the class of drugs that used to be called
narcotics) are safe and effective in relieving the severe pain of cancer
and other chronic conditions. The key to their successful use is having
a steady amount in the bloodstream. It seems obvious now, but it was an
insight then: If pain is present all the time, pain medication should also
be present in the bloodstream constantly. The drug should not be taken
just "as needed."
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- The problem that Purdue overcame is that morphine, oxycodone,
and other opioids relieve pain for only a few hours. A patient would have
to take his medication every four hoursóeven setting a clock to
get up at night for a dose. Purdue developed systems by which a medication
tablet would deliver its contents continuously (hence the name) over 12
hours. The company's first such analgesic was MS-Contin. Although clinically
effective, the drug did not reach its full commercial potential in large
part because of the stigma associated with its active ingredient, morphine.
OxyContin, Purdue's second continuous-release opioid, contained oxycodone,
a drug whose pharmacologic effect is very similar to that of morphine,
but one thatóat least in those daysódid not carry the negative
associations of morphine.
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- OxyContin proved to be a billion dollar home run for
Purdue. Its success was due to the confluence of several factors. First,
the drug was indeed just as the FDA recognized it to be: safe and effective
for the management of moderate to severe chronic pain. It was introduced
at a time when doctors were becoming more aware of the scandalous undertreatment
of chronic pain, and learning that when properly used, opioids carried
little risk of addiction. And Purdue marketed the drug brilliantly.
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- Early in the promotion of the product, Purdue recognized
that both patient success in getting pain relief and Purdue's success in
the marketplace would be limited by the same factor: physician ignorance.
My own experience in medical training was typical: I learned virtually
nothing in medical school about pain, and most of what I was taught as
an intern and resident was wrong. Purdue concluded that it could do well
by doing good, and beefed up its existing program of physician education.
Their goal was to get doctors up to date, not just about opioids, but about
all aspects of pain management. (Full disclosure: I have given many lectures
about pain management sponsored by Purdue; I have done the same for Purdue's
competitors.) Doctors began to take the pain complaints of their patients
seriously, and to treat them effectively.
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- With success, however, have come predictable problems.
As OxyContin has achieved a larger share of the analgesic marketplace,
its share in the drug-abuse marketplace has risen, too. Junkies learned
that by grinding OxyContin tablets and snorting or injecting them, they
could overcome the slow delivery system that Purdue scientists had worked
so hard to create. And since OxyContin is a drug of known quality and purity,
it has become popular among addicts. Lurid stories in Time, Newsweek, and
the New York Times have only served to increase the interest of customers
in the illegal market.
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- Purdue is thus in a difficult position. Its major profit
center is a drug whose distribution is strictly controlled by federal law.
So while it is arguable whether the DEA has the authority to disrupt the
marketing of a legal drug, Purdue is hardly in a position to criticize
a wrongheaded law-enforcement offensive.
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- Indeed, Purdue is probably more eager than the DEA to
curtail abuse and diversion of its number one product. For the company,
the misuse of OxyContin is not a source of profit but a nightmare of the
first order. The abuse cases are relatively rare but have a huge and disproportionate
impact in deterring doctors from prescribing the medication for patients
who could truly benefit from it. Purdue has thus rolled out its own 10-point
plan to reduce prescription drug abuse. Among other things, the company
has modified its educational programs to include more training for doctors
and pharmacists in distinguishing genuine pain patients from scam artists.
At the same time, in a meeting it sought with the DEA, Purdue and the agency
agreed that OxyContin should only be prescribed according to the FDA-approved
indication and should only be prescribed by physicians knowledgeable in
the use of opioids to treat pain.
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- On a formal level, this agreement is not unlike an agreement
between two countries in conflict that merely serves to paper over the
stark differences between them. And the differences are substantial. Indeed,
a spokesperson for the DEA says the agency is not satisfied with this agreement
and has "suggested" that Purdue market the drug only to pain
specialists, and that it be distributed only by a limited number of pharmacies.
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- Anyone who cares about the relief of suffering should
hope that the company resists that suggestion. The DEA stance is misconceived
in several ways. First, the problem of OxyContin abuse has been hyped by
both the media and press-savvy law enforcement spokesmen. To put the question
in perspective, an American is twice as likely to be struck by lightning
as he is to die from abusing OxyContin. The government's most recent Drug
Abuse Warning Network data show that purposeful misuse of acetaminophen
(Tylenol) is over three times as likely to result in an emergency room
visit as is purposeful misuse of oxycodone. Among medical examiner (coroner)
cases, codeine is five times as likely to be mentioned as contributing
to death as oxycodone.
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- OxyContin abuse casesóadmittedly rising in numberóare
clearly less of a social problem than those associated with several other
drugs. Why, then, the inordinate attention to this particular drug? Part
of the answer lies in the fact that OxyContin is so prominent in the legitimate
pain market. More important, I think, is the fact that Purdue has used
OxyContin to legitimize the very concept of ongoing opioid therapy for
a larger class of patientsóthose with moderate to severe chronic
pain from non-malignant causes, not just cancer patients. This idea still
encounters resistance from some doctors and public officials.
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- Keep in mind that virtually all of the oxycodone deaths
are due to purposeful abuse of the drug. Limiting patient access to OxyContin
because of these rare tragedies is like limiting access to rope because
some people hang themselves. Unfortunately, despite DEA protestations to
the contrary, sharply limited access to pain relief is the completely predictable
result of the agency's plan.
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- There are an estimated 30-50 million Americans who live
in chronic pain. Only one in four of them is now receiving proper treatment.
For many people in pain, opioids are the safest and most effective (or
only effective) form of relief. There are only about 3,000 pain specialists
in the country, and many parts of the country have none at all. These few
specialists could no more take care of all the pain patients who need opioids
than a few thousand endocrinologists could take care of all the diabetics
who need insulin.
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- While they may rely on occasional specialist consultation,
primary care physicians must treat pain patients or they simply will not
be treated. Similarly, reducing the number of pharmacies that stock OxyContin
will do little more than inconvenience patients whose ability to travel
is already restricted by their illness.
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- Even in the absence of DEA action, the OxyContin frisson
has already resulted in a diminished quality of life for pain patients.
Consider Purdue's May 11 decision to "temporarily suspend" shipment
of the 160 mg tablets. This is the strongest dose form of the drug, and
accounts for less than 1 percent of total sales. Many of the people taking
this high dose of opioid are end-stage cancer patients. Now their final
months will be burdened by having to swallow twice as many pills (the 80
mg tablets are still available). For many dying patients, the very act
of swallowing medication is painfully difficult. Purdue acknowledges that
there have been few reports of diversion of the 160 mg tablets, and the
DEA has no idea which dose form is most likely to be abused. It is hard
to see the benefit of such a policy. And for some patients, the problem
will be worse than inconvenience. In many states, Medicaid rules limit
the filling of opioid prescriptions to a certain number of pills, not a
certain total dose. So cancer pain patients who can't afford to pay out
of pocket for the expensive drugs will find that they'll simply have to
get by on a lower dose. In other words, they'll just have to suffer.
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- Terrence Woodworth, deputy director of the DEA's office
of Diversion Control, was quoted in a New York Times report as saying that
the agency believes the drug has "been frequently prescribed by doctors
who could have recommended less powerful drugs before turning to OxyContin."
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- As a pain specialist, I wonder what drugs he has in mind.
Could he mean the non-steroidal anti-inflammatory drugs, which are of limited
benefit in treating chronic pain, but add a significant risk of stomach
bleeding and kidney damage? Or perhaps he means tablets such as Vicodin,
which combine the opioid hydrocodone with acetaminophen. These are less
potent in relieving pain than most strengths of OxyContin, and their acetaminophen
ingredient carries a risk of serious liver damage.
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- Even if the DEA sat in on every office visit of every
patient receiving a prescription for OxyContin, it would still not be able
to say what percentage of the prescriptions are medically necessary. The
DEA, fundamentally not a medical but a police agency, has no such expertise.
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- But power it does have. Even if it cannot usurp the FDA
in controlling how Purdue markets and distributes the drug, it can certainly
affect the prescribing of it. A few well-publicized intimidating visits
to doctors who prescribe OxyContin will have a profound chilling effect
on the willingness of most doctors to prescribe the drug. Indeed, the media
circus surrounding the drug, and the statements of the DEA, have already
had that effect.
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- The full adverse impact will not be limited to OxyContin
and the patients who use it. Intimidating doctors from prescribing one
opioid will limit their willingness to prescribe any. Moreover, there are
several new sustained-release opioids already or soon to be submitted for
FDA approval. There has never been, and likely never will be, any opioid
analgesic on the market that cannot be abused or diverted by a motivated
drug addict. Dr. Cynthia McCormick, head of the FDA branch that approves
opioid analgesics, is reportedly embarrassed by the abuse now attributed
to a drug her agency approved. The bureaucratically safe solution to her
problem is to just say no, or to set the standard of approval unrealistically
high. The losers, as always, will be people in pain.
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- In light of this, many in the pain management field find
it ominous that Dr. McCormick recently scheduled a rare meeting of the
Anesthetic and Life Support Drugs Advisory Committee, only to abruptly
cancel it after many concerned clinicians got wind of it. The committee's
agenda was to include "concerns regarding the abuse potential, diversion,
and increasing incidence of addiction to opiate analgesics, especially
to the modified-release opiate analgesics." Nor is it very comforting
to realize that the members of the advisory committee are selected by the
FDA itself. Keen readers of the Federal Register will also note that within
a week of announcing the committee meeting, the FDA announced that it is
prepared to appoint five more committee members immediately, and four more
within the next year.
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- While abuse and diversion of OxyContin is clearly a problem
that should not be neglected, the response of the Drug Enforcement Administration
is both disproportionate and counterproductive. Similar action by the FDA
to limit legitimate use of this or other opioids puts at risk the long-overdue
progress that has recently been made in the management of chronic pain.
Perhaps we cannot avoid death and taxes, but must we live in pain?
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- By Eric Chevlen
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