FDA Mandates New Opioid Labeling to Address Long-Term Use Risks

The U.S. Food and Drug Administration (FDA) has mandated significant changes to the safety labeling of all opioid pain medications to better emphasize the risks associated with their long-term use. This directive, announced on July 31, 2025, follows a comprehensive review of data indicating serious risks such as misuse, addiction, and both fatal and non-fatal overdoses linked to prolonged opioid therapy.

The decision stems from findings presented during a May 2025 advisory committee meeting, which evaluated data from two extensive observational studies—postmarketing requirements (PMR) 3033-1 and 3033-2. These studies highlighted the significant dangers associated with extended opioid use, prompting the FDA to implement more stringent labeling requirements to inform healthcare professionals and patients.

The updated labeling requirements include:

• Clearer Risk Information: Summarizing study results to show estimated risks of addiction, misuse, and overdose during long-term use.

• Dosing Warnings: Emphasizing that higher doses carry greater risks, which persist over time.

• Clarified Use Limits: Removing language that could be misinterpreted to support indefinite opioid use.

• Treatment Guidance: Reinforcing that long-acting or extended-release opioids should only be considered when other treatments, including shorter-acting opioids, are inadequate.

• Safe Discontinuation: Advising against abrupt cessation in physically dependent patients to prevent serious harm.

• Overdose Reversal Agents: Providing additional information on medications that can reverse an opioid overdose.

• Drug Interactions: Enhancing warnings about combining opioids with other central nervous system depressants, including gabapentinoids.

• Overdose Risks: Introducing information about toxic leukoencephalopathy, a serious brain condition that may occur after an overdose.

• Digestive Health: Updating information on opioid-related esophageal problems.

Manufacturers have 30 days to submit their labeling updates to the FDA for review. Additionally, the FDA is requiring a prospective, randomized, controlled clinical trial to further examine the benefits and risks of long-term opioid use.

FDA Commissioner Marty Makary, M.D., M.P.H., emphasized the gravity of the opioid epidemic, stating, "The death of almost one million Americans during the opioid epidemic has been one of the cardinal failures of the public health establishment. This long-overdue labeling change is only part of what needs to be done—we also need to modernize our approval processes and post-market monitoring so that nothing like this ever happens again."

Health and Human Services Secretary Robert F. Kennedy, Jr. added, "I know firsthand how devastating addiction is—not just for individuals, but for entire families and communities. Today’s FDA action is a long-overdue step toward restoring honesty, accountability, and transparency to a system that betrayed the American people."

The opioid crisis has had a profound impact on American society, with nearly one million deaths attributed to opioid overdoses. The FDA's new labeling requirements aim to provide clearer guidance to healthcare professionals and patients, potentially reducing the risks associated with long-term opioid therapy. This initiative reflects a broader effort to address the opioid crisis through improved education, regulation, and monitoring.

This is not the first time the FDA has mandated changes to opioid labeling. In December 2023, the FDA approved safety labeling changes for opioid pain medicines, including warnings about opioid-induced hyperalgesia and recommendations for appropriate patient populations and dosages. The current changes build upon these previous efforts by incorporating new data and addressing additional risks associated with long-term opioid use.

The FDA's mandate for comprehensive labeling changes represents a significant step in addressing the opioid crisis. By providing clearer risk information and guidance, the agency aims to mitigate the dangers associated with long-term opioid use, ultimately striving to prevent further loss of life and promote public health.