Off-Label Prescribing: Part 1
Off-labeling a powerful pain med: Actiq
Off-label: The prescription of a drug to treat a condition other than that for which it is approved. The results of this prohibited practice can be devastating, causing severe side effects and even death.
Pharmaceutical companies are prohibited from marketing drugs “off-label”
Although doctors are allowed to prescribe drugs for any use that they choose, pharmaceutical companies are strictly prohibited from marketing drugs for off-label uses. The prohibition hasn’t stopped them—in fact, most of the large drug companies have paid enormous fines in recent years for their off-label marketing schemes. The fines, however, are much less than the profit that was made by selling the drug for off label use. For this reason, this practice continues with drug companies, and they view the fines as a mere cost of doing business. And while some off-label uses for drugs have been studied and do make sense, many more have been found to be dangerous to patients as well as ineffective.
Should doctors be encouraged to prescribe a powerful, addictive opiate for migraines?
Actiq (fentanyl) is an extremely powerful opiate—so powerful that the FDA approved it only for opioid-tolerant cancer patients with breakthrough cancer pain, to be prescribed by an oncologist or pain specialist familiar with opioids.1 It is delivered to patients in the form of a lollipop.
The reasons behind the FDA’s limited approval were obvious. Actiq is 100 times more potent than morphine. It is extremely addictive, and the serious complications that can result from its use include potentially fatal health risks, such as respiratory depression, sedation and cardiac arrest.2
The safety risks are even greater when the drug is prescribed for patients who have not developed a tolerance for such opioid drugs.
But when Cephalon acquired Actiq from Anesta in October of 2000, it did so with a plan to market the drug on a much larger – and off-label – scale.
Rather than market just to physicians who treated cancer pain, Cephalon initiated a marketing plan that targeted all physicians who might treat chronic pain sufferers, including family practice physicians, internists, neurologists, psychiatrists, and even general practitioners.
Using the mantra “pain is pain,” Cephalon instructed the Actiq sales representatives to focus on physicians other than oncologists, including general practitioners, and to promote this drug for many uses other than breakthrough cancer pain, including migraine headaches, sickle-cell pain crises, and in anticipation of radiation therapy or changing wound dressings.3
According to charges brought by the United States Attorney General, from 2000 to 2004, Cephalon provided more than $80 million to fund continuing medical education programs intended to promote Actiq and 2 other drugs for off-label use.4
In addition to medical education funding, Cephalon also used bribery to promote the off-label use of Actiq, regularly sending doctors to lavish resorts for supposed “consultant” meetings to hear discussions about off-label uses of Actiq. The doctors “invited to these resorts were those that the Cephalon sales reps believed had the greatest potential to write off-label prescriptions."5
Speakers at the resorts included doctors like Michael Brennan of Fairfield, Connecticut. In 2011, Dr. Brennan wrote 105 prescriptions for Actiq, more than twice the number written by any other Connecticut physician. He was also a consultant for Cephalon, paid over $31,000 in “consulting” fees.6 Dr. Brennan is not an oncologist—his training is in physical rehabilitation medicine, with a “special interest” in “pain management.”7
The promotion worked. Actiq sales went from $15 million in 2000 to $570 million in 2006.
Casualties from off-label marketing of Actiq
With the additional sales, however, came casualties:
- Deaths: More than 120 deaths have been reported from the misuse or abuse of Actiq.8
- Children: Two of the deaths reported were of children who mistook the lollipops for candy.9
- Criminal charges: In South Carolina, Patricia Ann Taylor, 56, was charged with murder charges after investigators linked her prescription Actiq to the death of 27-year-old Jason Ramsdell, a Fort Ripley man who allegedly purchased the medication from Taylor.10
- From street use: In 2004 alone, illegal use of fentanyl accounted for 8,000 U.S. emergency room visits, a third more than codeine and two and a half times more than amphetamines.11
According to Laurie Magid, acting U.S. Attorney for the Eastern District of Pennsylvania, “These are potentially harmful drugs that were being peddled as if they were, in the case of Actiq, actual lollipops instead of a potent pain medication intended for a specific class of patients.
"This company subverted the very process put in place to protect the public from harm, and put patients’ health at risk for nothing more than boosting its bottom line.
“People have an absolute right to their doctors’ best medical judgment. They need to know the recommendations a doctor makes are not influenced by sales tactics designed to convince the doctor, but rather that the drug being prescribed is safe for uses beyond what the FDA has approved.”12
Cephalon settled the Federal charges, agreeing to pay $425 million in fines for its off-label promotion of Actiq and 2 other dangerous medications.13 Given the rate of sales that Cephalon experienced from its marketing campaigns, it may be that – as is often the case – the fine was viewed by Cephalon and its shareholders as simply a “cost of doing business.”
- Information, United States v. Cephalon, Inc., para. 6
- Ibid. para. 21
- Ibid. para. 13
- Ibid. para. 17
- Ibid. para. 18
- “40% Of High-Prescribing Docs Get Pharma Perks,” New Haven Independent,
- “Cephalon Drug Is Tied to Several Deaths: Off-Label Marketing Of Cancer Painkiller Is Focus of Three Probes,” Online Wall Street Journal, Sept. 14, 2007
- “South Carolina Woman’s Murder Trial Could Have Lasting Affect on Future Actiq Fentanyl Lawsuits,”
- “A Killer Painkiller,” O Magazine, April, 2007
- “Biopharmaceutical Company, Cephalon, to Pay $425 Million & Enter Plea to Resolve Allegations of Off-Label Marketing, “ DOJ press release, September, 2008