The drug agency's misguided campaign against a painkiller.
June 4, 2001
Vol 6, Number 36
By Eric Chevlen
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 non-malignant 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 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.
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?
By Eric Chevlen