TCS Daily


By Sally Satel - February 3, 2003 12:00 AM

OxyContin, the potent prescription painkiller, is in the spotlight - again. Two summers ago it was news because drug addicts in New England and Appalachia were injecting it to get a heroin-like high. Pharmacies were robbed, drug-rings sprang up, unscrupulous doctors ran pill mills.

Incredibly, the drug's maker, Purdue Pharma, was directly blamed for the intentional abuse of its product. Almost 200 lawsuits were filed by plaintiffs charging the company with over-marketing OxyContin -allegedly leading to its over-prescription by doctors and thus greater chances of getting into the wrong hands. To date, judges have dismissed all cases before them - mainly because the plaintiffs turned out to be already-established
abusers of heroin, cocaine or illegally obtained pain pills - but now, thanks to the FDA, trail lawyers are again circling.

In late December, the FDA's Division of Drug Marketing, Advertising and Communications issued a seven-page warning letter to Purdue. "Your journal advertisements omit and minimize the serious safety risks associated with OxyContin and promote it for uses beyond which have been proven safe and effective" charged federal regulators in a letter described by the Wall Street Journal as "unusually harsh" and "blistering" by the Boston Globe.

Before reviewing the FDA's specific anxieties, some background. OxyContin is an opioid drug in the same category as morphine. It is not intended for toothaches and transient postoperative pain; it is for people with searing and prolonged agony due to diseases like cancer, neurological illness, degenerative discs, and deforming rheumatoid arthritis. The name is a contraction of oxycodone (the active ingredient in Percocet) and the word continuous, referring to its slow release feature. For comparison: the strongest dose of a single Percocet pill contains 10 mg. of oxycodone while OxyContin is available in strengths of up to 80 mg.

Available since 1995, the medication is now the most prescribed narcotic, in large part because it is taken only twice a day; other narcotic painkillers are taken every three to six hours. The 12-hour controlled delivery keeps blood levels steady, an important feature when pain is constant and severe. Also, the fewer daily peaks in blood level and the slower the rate of increase in blood level - both afforded by regular administration of a time release drug - the lower its addictive potential. The medication is widely praised by patients and physicians for severe, uncompromising pain.

Now the FDA is charging Purdue with "false and misleading messages" based on two advertisements that appeared this fall in the Journal of the American Medical Association. The body of the first ad depicts a man fishing with a young boy in a bucolic stream. "There can be life with relief" reads the large print message. The text says, in part: "For moderate to severe pain when a continuous, around-the-clock analgesic is needed for an extended period of time.... The most serious risk with opioids, including OxyContin, is respiratory depression." Finally, the ad instructs the reader to consult the package insert text and the "boxed warning," both on the reverse side of the ad.

The second ad carries the same indication and risk information but instead of the fishing man, the ad shows just dispensing cups, comparing the number needed for other painkillers (up to six dosings a day) with only two for OxyContin. (The full text of the warning letter and displays of the ads are available here).

Here are the key objections of the FDA:

1. Failure to mention risks: Fatal risks (of complete respiratory depression, bowel paralysis, and potential for abuse) are not mentioned on the illustrated body of the ads. Thus, according to the warning letter, the ad "reinforces the impression that the most serious risks have been disclosed when the fact is they have not." The letter also admonishes Purdue for not warning in the ad's body against breaking, crushing or chewing tablets.

2. Misleading illustration: The regulators claim that the fishing man depicted in the ad is "seemingly healthy, unimpaired ...and taking care of a child" and so not the "typical person" taking OxyContin. This suggests to doctors reading the ad, FDA insists, that the drug is meant for a "broader range" of patients than is actually appropriate. The dispensing cup visuals are also a problem, regulators say, as they are likely to be interpreted by doctors as indicating that OxyContin is to be used for acute post-operative
pain, which it is not.

3. Misleading headline: The FDA says "it is particularly disturbing that your [fishing ad] would tout 'Life with Relief,' yet fail to warn that patients can die from taking OxyContin".

These gripes are plainly absurd.

First, every bit of information that the FDA says is missing from the body of the ad can be found in the fine print section of the ad on the reverse side of the page. The FDA's drug advertising regulation, 21 C.F.R. section 202.1, requires "fair balance" between risks and effectiveness, though does not say precisely what has to be in the body of the ad in every specific. Taken as prescribed by a competent physician, OxyContin actually poses minimal risks (e.g., constipation, nausea, itching) and great potential benefit. Chopped up and snorted or injected - the way it is consumed by addicts, not legitimate pain patients - the medication can indeed lead to overdose and death. But the ads are for doctors, not patients and certainly not drug abusers.

Second, does the FDA think doctors are stupid? We know that opioids have enormous abuse potential and at high doses can lead to respiratory collapse. We learn this by the third year of medical school. In addition, detailed information outlining the menu of possible risks appear on the reverse page. These ads are not direct-to-consumer; they are for doctors. Doctors know that if you crush a time release pill and swallow it, a potentially fatal dose is released. Doctors know that "boxed warnings" need to be taken very seriously.

Third, and more generally, this episode raises the question: what is the standard here? Many of the assumptions made by regulators - that doctors will interpret the fishing man as meaning OxyContin is to be used for mild pain; that dispensing cups signify acute post-op use; that doctors will not read an entire ad or that they have minimal implicit knowledge of opioids- are unfounded and arbitrary. Companies are keen to comply with FDA guidelines but such subjective, almost capricious, interpretations by the marketing division can make the task nearly impossible.

I have no idea what's behind the FDA censure. Surely, the agency could have simply asked Purdue to rearrange the ad text but a warning letter - especially one condemning ads as "egregious and alarming" - exposes the company to liability anew. ''This [letter] will go a long way in the courts,'' said Troy N. Giatras, a Charleston, W. Va. lawyer who heads the Association of Trial Lawyers of America's OxyContin litigation group. ''Coming from the FDA, it will have great weight with judges and juries," he told the Boston Globe in late January.

Recently, Mark McLellan, a physician and well-regarded policymaker, was appointed FDA commissioner. Among his many stated goals - ironically, perhaps, in light of Purdue's circumstances - is a crack-down on misleading pharmaceutical advertising. Fine, but Dr. McLellan needs to make sure that his people know a misleading ad when they see one. Moreover, the Bush administration has made clear its commitment to tort reform. Issuing a groundless and inflammatory warning has consequences that can only undermine the progress the FDA, under new leadership, hopes to make.

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