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FDA updates opioid pain medication labeling requirements

The FDA will soon require opioid makers to update safety labels to highlight the risks of addiction, misuse, overdose, high doses and long-term use.

Alivia Kaylor, MSc
By
Published: 04 Aug 2025

Late last week, the FDA announced required changes to safety labeling for all opioid pain medications. Following the results of two post-marketing studies and an advisory committee review conducted earlier this year, the agency's updated label requirements call more attention to the potential risks associated with long-term use.

Data from the FDA-mandated studies (PMR 3033-1 and PMR 3033-2) demonstrated that continued use of opioid pain medications is associated with increased risks of addiction, misuse, overdose and other serious adverse effects. The observational findings, presented to the agency's Anesthetic and Analgesic Drug Products Advisory Committee in May, suggest that currently existing label information does not adequately depict the severity of the risks related to prolonged opioid use.

"This long-overdue labeling change is only part of what needs to be done," FDA Commissioner Marty Makary, M.D., M.P.H., said in a press release, adding that drug approval and post-market monitoring processes also need to be updated to prevent another epidemic.

Required labeling updates

The FDA's opioid safety labeling order includes quantifying clearer risk information, such as summarized study results that estimate addiction, misuse, and overdose risks associated with long-term use. The update also requires stronger warning labels disclosing that higher risks come with higher doses, with these risks remaining over time.

The update also mandates the following additional changes:

  • Clarified use limits. Vague labeling language that could imply continued use of opioids is acceptable must be removed.
  • Prescribing guidance. Labels will specify that extended-release opioids should only be used when short-acting formulations or other treatments aren't effective.
  • Discontinuation safety. Abruptly stopping opioids in physically dependent patients will be discouraged to prevent serious withdrawal-related harm.
  • Overdose reversal medications. More information on agents that can reverse an opioid overdose will be provided, including nalmefene (branded as OPVEE), which now joins naloxone (Narcan) as a recommended harm-reduction treatment.
  • Drug–drug interactions. Labels must contain stronger warnings about combining opioids with central nervous system depressants like gabapentinoids.
  • Additional overdose risk. New information will be added about toxic leukoencephalopathy, a rare but serious brain condition that can occur following an overdose.
  • Digestive effects. Opioid labels will be updated to encompass esophageal complications associated with use.

Industry impact

The FDA says it has sent letters to the manufacturers affected by these changes, giving them 30 days to submit updated labeling for review. To comply with the required changes, these companies must quickly update prescribing information and rethink relabeling logistics for all opioid products.

Alivia Kaylor is a scientist and the senior site editor of Pharma Life Sciences.

Editor's Note: Overdose reversal agents were updated on Aug. 5, 2025, to include OPVEE (nalmefene), in addition to naloxone (Narcan).

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