The FDA announced that all opioid pain medications must update their safety labeling information to better emphasize the risks associated with long-term use. These changes are intended to help health care professionals and patients better understand the benefit-risk profile of opioid pain medicines and make more informed decisions.
The FDA noted that this decision follows a review of new findings presented in May 2025, when the FDA convened a joint meeting of the Drug Safety and Risk Management Advisory Committee and the Anesthetic and Analgesic Drug Products Advisory Committee. The meeting discussed two recently completed observational studies examining the risks of misuse, abuse, addiction, and fatal and non-fatal overdose in patients on long-term opioid analgesic therapy.
The studies (postmarketing requirements [PMR] 3033-1 and 3033-2) provided new, quantitative data on risks of serious adverse outcomes in patients prescribed opioid pain medicines long term. After reviewing those results, public comments, medical research and recognizing the absence of adequate and well-controlled studies on long-term opioid effectiveness, the FDA decided to require safety labeling changes to help health care professionals and patients make treatment decisions rooted in the latest evidence.
The labeling changes will include the following updates:
- Clearer Risk Information: A summary of study results showing the estimated risks of addiction, misuse, and overdose during long-term use
- Dosing Warnings: Stronger warnings that higher doses come with greater risks, and that those risks remain over time
- Clarified Use Limits: Removing language which could be misinterpreted to support using opioid pain medications over indefinitely long duration
- Treatment Guidance: Labels will reinforce that long-acting or extended-release opioids should only be considered when other treatments, including shorter-acting opioids, are inadequate
- Safe Discontinuation: A reminder not to stop opioids suddenly in patients who may be physically dependent, as it can cause serious harm
- Overdose Reversal Agents: Additional information on medicines that can reverse an opioid overdose
- Drug Interactions: Enhanced warning about combining opioids with other drugs that slow down the nervous system—now including gabapentinoids
- More Risks with Overdose: New information about toxic leukoencephalopathy – a serious brain condition that may occur after an overdose
- Digestive Health: Updates about opioid-related problems with the esophagus
The FDA has sent letters to drug manufacturers and has given them 30 days to submit their labeling updates to the FDA for review.
In addition to required label change, a separate prospective, randomized, controlled clinical trial will address a different PMR to examine the risks relative to the efficacy of long-term opioid use.
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