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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.
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.
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."
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 hours -- even 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 that -- at least in those days -- did not
carry the negative associations of morphine.
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.
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.
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.
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.
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.
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.
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.
OxyContin abuse cases -- admittedly rising in number -- are 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 patients -- those with
moderate to severe chronic pain from nonmalignant causes, not just
cancer patients. This idea still encounters resistance from some
doctors and public officials.
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.
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.
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.
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.
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."
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 tables 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.
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.
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.
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.
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.
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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