The fast-acting narcotic lollipop Actiq is FDA-approved for treating cancer pain, and cancer pain only. Patients are warned not to ingest more than 120 doses per month. Ed McAteer, however, does not have cancer, and in an average month he may suck on as many as 300 of the potent raspberry-flavored pops, a dosage so high and constant that its sugar content has corroded away all his teeth. "Actiq is the best thing I've ever tried," he says. Anyone who didn't know him might assume he was abusing the drug, and that his only prescription should be for rehab.
But McAteer, a soft-spoken 43-year-old, doesn't take the drug to get high. It simply makes him "able to survive as a human being," he says, dulling migraines so severe that even the odor of fresh-cut grass can set them off. His doctor, who regularly prescribes the drug to patients who don't fit the FDA's indications, is one of the nation's top authorities on pain, Russ Portenoy of Beth Israel Medical Center in New York. Portenoy's "off-label" prescribing is legal, and the drug is "safe and effective" for many patients, he says, whether they have cancer or not. So why is Actiq's widespread off-label use at the heart of a major controversy?
When the FDA approved Actiq in 1998, it did so based on the only available studies, all done on cancer patients. Since then, the drug's popularity has surged among both docs who don't specialize in cancer and patients who don't have it. As many as 80 percent of the 400,000 prescriptions written each year for Actiq and its generic versions (licensed by Actiq's maker, Cephalon) go to sufferers of chronic, noncancer pain. There are no large, completely objective studies of Actiq's effectiveness in these patients, but the drug's active ingredient, fentanyl, has been used widely for more than 40 years. Docs of all stripes learn about fentanyl in medical school, and so, says John Osborn, Cephalon general counsel, they are comfortable with it.
But Cephalon, many critics charge, has itself grown too comfortable with the idea of docs' prescribing its drug to noncancer patients—and according to an ongoing lawsuit and government probes, the company may have encouraged them to do so. Unlike off-label prescribing, off-label marketing is illegal. But it is not uncommon; nearly every major drug company in the United States has been investigated for the practice in the past few years.
A lawsuit filed by a former Cephalon employee raises questions about the company's methods. David Brennan was working as an auditor for Cephalon in 2003 when he found that 80 percent of docs prescribing Actiq were not cancer specialists. "If the percentage of off-label prescriptions was higher than 15 percent, Cephalon was supposed to write letters to doctors and offending groups—in other words, marketing in reverse," Brennan says, citing FDA rules. "But they didn't do that." Brennan alleges that his bosses first refused to publish his report, then stalled and eventually fired him.
Cephalon spokeswoman Stacey Beckhardt says the company has written at least 2,000 letters to doctors since Actiq's launch. She also says Brennan's firing was unrelated to his Actiq audit and disputes his interpretation of the 15 percent rule. "We feel his lawsuit has no merit," she says.
The charges, however, don't end there. California Democrat Henry Waxman, chair of the House Oversight and Government Reform Committee, is looking into marketing at Cephalon and other companies. Cephalon is also under scrutiny by several state attorneys general. Connecticut A.G. Richard Blumenthal says he's found evidence that Cephalon paid doctors to promote off-label use and targeted even those who admitted they did not "have the potential to treat cancer pain."
Blumenthal launched his query after learning of a fatal Actiq overdose at a party. The "perc-o-pop" can be deadly and addictive if it's not prescribed in a controlled environment. Susan Kathryn Smith, 24, is clean today, but she describes Actiq's euphoria as "like going back to the womb." Her father, an anesthesiologist, found her passed out in his office after she stole his samples. Still, Portenoy and others note that the drug is not nearly as rife on the street as painkillers such as OxyContin and Vicodin. "If you're talking about denying it to people with chronic pain who really need it, out of concern that a very small proportion of people will abuse it," says Portenoy, "that's a terrible public-health decision."
Cephalon stopped promoting Actiq last September, when its patent expired, though it could still be subject to fines and other sanctions if it is found to have violated the law. In the meantime, the company has shifted its focus to Fentora, a new painkilling tablet that, like Actiq, is approved only for cancer pain. Later this year, though, the company plans to petition the FDA for broader Fentora approval. That's one way to avoid off-label marketing—make a bigger label.