FDA Changes Opioid Pain Medication Labeling Requirements

FDA announced on July 31, 2025, that it is requiring changes to the safety labeling of all opioid pain medications so that the risks associated with the long-term use of these types of drugs are emphasized and explained. This change comes after FDA reviewed data showing the serious risk of misuse, addiction, and overdose.

Data from two large FDA-required observational studies, postmarketing requirements (PMR) 3033-1 and 3033-2, provided new data on how long-term opioid use can lead to serious side effects. These data combined with public comments, medical research, and a lack of studies on the long-term effectiveness of opioids led the agency to require the safety labeling changes so that health care professionals and patients can make more informed treatment decisions.

Required labeling changes

Among the required changes are:

• Clearer risk information, including a summary of study results showing the estimated risks for addiction, misuse, and overdose during long-term use
• Stronger warnings that higher doses come with greater risks that remain over time
• The removal of language that may be misinterpreted to support using opioid pain drugs indefinitely
• Guidance reinforcing that long-acting or extended-release opioids should only be considered when other treatments, including shorter-acting opioids, are inadequate
• A reminder that opioids should not be stopped suddenly in patients who may be physically dependent, to avoid serious harm
• Additional information on drugs that can reverse an opioid overdose
• Enhanced warning about combining opioids with other drugs that slow down the nervous system
• New information about a serious brain condition that may occur after an overdose (toxic leukoencephalopathy)
• Updates about opioid-related impacts on the esophagus.

Relevant drug manufacturers have 30 days to submit their labeling updates to FDA for review.The agency is also requiring an additional prospective, randomized, controlled clinical trial to examine the benefits and risks of long-term opioid use.

“The death of almost one million Americans during the opioid epidemic has been one of the cardinal failures of the public health establishment,” said FDA Commissioner Marty Makary, MD, MPH, in a press release (1). “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.”

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

Possible change in class for 7-OH drugs

In other opioid-related news, FDA recommended on July 29, 2025 that 7-hydroxymitragynine (7-OH) products be classified under the Controlled Substance Act (2). A concentrated byproduct of the kratom plant, according to FDA, binds to opioid receptors and, therefore, has the potential for abuse. While there are no 7-OH drugs approved by FDA, the agency has stated that approximately 1.7 million Americans aged 12 and older have used products to self-treat pain, coughing, diarrhea, anxiety, and depression that are prepared from the leaves of Mitragyna speciosa, a tropical tree native to Southeast Asia (3).

Biopharma developers exploring kratom-based therapeutics are being urged to be cautious. Enhanced 7-OH products may raise concern over abuse liability and may face future regulatory scheduling, which could impact clinical research and investigational drug approval. The Drug Enforcement Administration, which has final scheduling authority, is reviewing FDA’s recommendation on 7-OH.

References

1. FDA. FDA Requires Major Changes to Opioid Pain Medication Labeling to Emphasize Risks. Press Release. July 31, 2025. https://www.fda.gov/news-events/press-announcements/fda-requires-major-changes-opioid-pain-medication-labeling-emphasize-risks
2. FDA. FDA Takes Steps to Restrict 7-OH Opioid Products Threatening American Consumers. Press Release. July 29, 2025. https://www.fda.gov/news-events/press-announcements/fda-takes-steps-restrict-7-oh-opioid-products-threatening-american-consumers
3. FDA. FDA and Kratom. FDA.gov, last updated July 29, 2025 (accessed July 30, 2025).