FDA Restricts Long-term Opioid Use to Combat Abuse

September 10, 2013

Extended-release and long-acting (ER/LA) opioid pain relievers are no longer indicated for merely moderate pain, the US Food and Drug Administration (FDA) announced today as part of a sweeping move to stem the deadly misuse and abuse of the drugs.

Previously, the labels for ER/LA opioid analgesics stated that they were indicated for "moderate to severe pain in patients requiring continuous, around-the-clock opioid treatment for an extended period of time." The labels now will state that the drugs are indicated "for the management of pain severe enough to require daily, around-the-clock opioid treatment and for which alternative treatments are inadequate." The new labeling emphasizes first considering potentially less addictive measures.

The new wording is designed to make a clinician go beyond a pain-intensity scale to consider what an individual patient needs to "live and function better," said Douglas Throckmorton, MD, deputy director of regulatory programs in the FDA's Center for Drug Evaluation and Research, in a press conference today.

"What could be moderate to me could be severe to you, or mild," Dr. Throckmorton said.

In addition, the labels will include a boxed warning stating that long-term maternal use of ER/LA opioid pain relievers can result in potentially fatal neonatal opioid withdrawal syndrome.

The FDA will require manufacturers of these drugs to perform more studies and clinical trials to "further assess the known risks" of misuse, abuse, hyperalgesia, addiction, overdose, and death.

"The FDA is invoking its authority to require safety label changes and postmarket studies to combat the crisis of misuse, abuse, addiction, overdose, and death from these potent drugs that have harmed too many patients and devastated too many families and communities," said FDA Commissioner Margaret Hamburg, MD, in a news release.

Physician Coalition Sought Tighter Indication

The FDA announcement comes roughly a year after a coalition of 37 physicians, including pain management and addiction experts, asked the agency to tighten label restrictions for opioid analgesics — and remove the indication for moderate noncancer pain — to combat the epidemic of addiction and fatal overdoses associated with these drugs.

The coalition, called Physicians for Responsible Opioid Prescribing (PROP), also asked the FDA to establish the equivalent of 100 mg of morphine as the maximum daily dose and make 90 days the maximum duration for continuous daily use. The FDA declined to adopt those thresholds because it lacks the data to do so, said Dr. Throckmorton at today's press conference. However, the FDA hopes that the additional studies required of manufacturers will shed enough light on the issues of dose and duration to inform future label changes, he said.

Andrew Kolodny, MD, the president of PROP, told Medscape Medical News that the FDA's inaction on dose and duration limits "left the door wide open" for drug manufacturers to continue promoting high-dose, long-term opioid treatment for common chronic conditions such as fibromyalgia, "where the risks are likely to outweigh the benefits."

Dr. Kolodny, the chief medical officer of a substance-abuse treatment and prevention organization called Phoenix House, said he is pleased that the FDA partially responded to his group's petition by striking "moderate to severe pain" from the indication for ER/LA opioid analgesics. However, he is not completely satisfied with the "pain severe enough" replacement. "It's hard to understand what they mean," said Dr. Kolodny.

He also expressed disappointment that the FDA excluded immediate-release opioid analgesics from the label changes announced today. "Our petition was for all opioids," he said.

Fears of Denials by Third-Party Payers

One pain-management expert who opposed the PROP petition to the FDA said that removing "moderate pain" from the indication for ER/LA opioid analgesics could give some third-party payers an excuse to deny coverage for patients with moderate to severe pain who have been stabilized thanks to the pain-killers. However, wording the indication as "pain severe enough" to warrant daily, around-the-clock treatment should give clinicians enough flexibility to prescribe, said Lynn Webster, MD, president of the American Academy of Pain Medicine.

"There's a huge distinction between 'severe' and 'severe enough,' " Dr. Webster told Medscape Medical News.

Dr. Webster said he applauds the FDA's push for more postmarket studies by opioid manufacturers to fine-tune prescribing.

"They're long overdue," said Dr. Webster, "We need that kind of information so we can do a better job selecting patients who are appropriate [for opioid therapy] and will not be harmed."

More information about today's announcement is available on the FDA Web site.


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