FDA orders more stringent labeling for opioid drugs

Responding to calls to stem a growing epidemic of prescription drug addiction and overdose deaths, federal officials are urging doctors to reserve the most powerful pain drugs for patients who need long-term, around-the-clock treatment that can’t be managed by other means.

Leaders of the Food and Drug Administration said they hoped new drug labeling guidelines unveiled Tuesday would prompt doctors to be more cautious in prescribing long-acting and extended-release forms of oxycodone, morphine and other narcotic painkillers, known as opioids.


Such drugs — sold as OxyContin, Opana and other brand names — account for less than 10% of all opioid prescriptions written in the U.S. More widely prescribed, fast-acting opioids, including hydrocodone, were not affected by the FDA action.

As a class, opioid painkillers have fueled a surge in prescription drug overdoses, which in 2009 surpassed traffic accidents as a leading cause of preventable deaths in the U.S. They are abused by more than 12 million people each day and contributed to 16,651 overdose deaths in 2010, according to the Centers for Disease Control and Prevention.


A Times analysis of nearly 4,000 prescription drug deaths in Southern California over a six-year period found that opioids and other drugs prescribed to victims played a role in nearly half the cases. Hydrocodone and oxycodone were among the drugs most frequently cited in these deaths.

The FDA will now require the manufacturers of 20 long-acting opioid products to rewrite the drugs’ labels to reflect that they should be used more sparingly. Those labels should be revised by December.

Drug manufacturers will also have to conduct new research aimed at identifying what doses and modes of use are most likely to harm patients, said FDA Commissioner Margaret A. Hamburg.

Public health and addiction experts who have been pressing the FDA to help scale back the use of all forms of opioid painkillers said the agency didn’t go nearly far enough. Andrew Kolodny, president of Physicians for Responsible Opioid Prescribing, said the group was considering taking the FDA to court to force it to impose tougher prescribing limits.


“This is just more hot air,” said Kolodny, an addiction specialist in New York. “This makes it look like they are doing something. But they are continuing to allow opioid manufacturers to promote their products for conditions where the risks are likely to outweigh the benefits.”

Lynn Webster, president of the American Academy of Pain Medicine, said those moves were a step in the right direction, particularly its call for drug makers to undertake safety and efficacy studies. But Webster said the action failed to address how well patients followed doctors’ orders, a factor he views as a key driver of overdose deaths.

“People who are in severe pain often take more than is prescribed to them, so limiting the label indication is not going to prevent that from happening,” said Webster, a pain medicine specialist and researcher in Salt Lake City. “To reduce the harm from opioids is going to take a lot more than a label change.”

Sales of opioids have quadrupled over the last decade, buoyed by robust marketing and a movement to relieve pain. Overdose deaths involving painkillers also skyrocketed over the same period.


When opioids reach the brain, they bind to particular receptors that dampen the perception of pain. They can also induce a feeling of euphoria that can become addictive. When taken in large enough doses, the drugs have a sedative effect that can cause people to stop breathing, leading to death.

Currently, the labels on long-acting and extended-release opioid narcotics say they should be used for “moderate-to-severe” pain. The revisions will remove “moderate pain” from the agency’s list of approved uses for the drugs, replacing it with “pain severe enough to require daily, around-the-clock, long-term opioid treatment” for which alternative treatments have failed.

Through labels, the FDA controls how drug makers may promote and market medications to physicians. Insurers use labels to help determine whether they will pay for a prescription. Those decisions, along with manufacturer marketing, influence doctors’ prescribing decisions.

In requiring drug makers to rewrite labels, the FDA aims to change the current practice of prescribing these powerful analgesics for use by patients on an “as needed” basis. Although the guidelines won’t place formal restrictions on prescribing by physicians who treat patients for pain, FDA leaders made clear they wanted to discourage physicians from prescribing the medications for anything other than ongoing, intractable pain.

Agency officials said they wanted to encourage patients and their physicians to focus not just on subjective levels of pain — such as “moderate” and “severe” — but on how long pain persists and on other treatment options.

“The goal here was to make every patient taking extended-release and long-acting opioids to have a conversation about whether these products are helping them as individuals,” said Dr. Douglas Throckmorton, deputy director for regulatory programs at the FDA’s Center for Drug Evaluation and Research. “I hope this encourages physicians and patients to be more thoughtful and more careful as they use these medications.”

Doctors will still have broad latitude to prescribe the drugs “off-label” where they judge their use to be medically warranted.

Purdue Pharma, the manufacturer of OxyContin, and Endo Pharmaceuticals, which makes Opana, said they were studying the details of the FDA announcement to determine how to respond. Blaine Davis, a spokesman for Endo, said it was too early to know how the guidelines would affect marketing or prescribing.

The decision does not change the labels or prescribing guidelines of fast-acting opioid pain relievers, which are often prescribed to patients following surgery, an injury or dental work. FDA officials said they focused first on the long-acting and extended-release formulations because they posed a higher risk of abuse, addiction and overdose.

Officials also said they had seen a sharp increase in the number of babies who had been exposed to opioid painkillers in utero — a condition that can result in painful and potentially life-threatening withdrawal symptoms in the early days of life. The label changes ordered Tuesday also encourage physicians to discuss with women of childbearing age the potential dangers of opioid medications to an unborn child.

Girion reported from Los Angeles and Healy from Bethesda, Md.

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