FDA Mandates Major Opioid Label Revisions to Highlight Long-Term Risks

The FDA has announced changes to the labeling of all opioid pain medications, including immediate-release and extended-release, to better communicate long-term risks like abuse, addiction, overdose, and drug interactions, according to a news release from the agency.¹

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The newly mandated labeling will remove language suggesting long-term opioid use is supported by evidence, provide short summaries of study findings showing risks of addiction, misuse, and overdose, and emphasize that higher doses carry higher risk over time. Extended-release opioids may now be labeled only when non-opioid therapies and immediate-release formulations prove lacking, and labels must caution against abrupt discontinuation in physically dependent patients due to potential withdrawal, uncontrolled pain, or suicidal thoughts.¹

Labels will also expand warnings about central nervous system (CNS) depressant interactions, including benzodiazepines and gabapentinoids, and incorporate new alerts for rare but serious outcomes like opioid-induced esophageal dysfunction and toxic leukoencephalopathy in overdose situations.²

These labeling changes are aligned with the CDC's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain, which applies to outpatient adults with acute, subacute, or chronic pain, excluding cancer-related, sickle cell, palliative, or end-of-life contexts.³ The guideline presents 12 voluntary, evidence-based suggestions for opioid management.

Suggestions for providers featured in the guidelines include determining if opioids should take place, selecting appropriate dosages, determining prescription length and follow-up, and assessing and reducing risks of misuse, overdose, and opioid use disorder.⁴ It encourages increased use of nonopioid pharmacologic and nonpharmacologic therapies, initiation of immediate-release opioids only when necessary at the lowest effective dose, and frequent reevaluation of therapy goals, function, and risk.^3,4

For pharmacists, these guideline and rule changes solidify a critical clinical role. Educating patients on new risk summaries and study estimates now required on labels, properly instructing the use of naloxone and nalmefene, and explaining interaction concerns are all valuable counseling activities. Pharmacists need to verify the indication for prescriptions of extended-release opioids, review co-prescribing of CNS depressants, and begin taper planning with prescribers as needed to avoid withdrawal and other harms.⁴

By integrating FDA's new labeling requirements and CDC's framework into daily practice, pharmacists can significantly lessen opioid risk. These changes allow pharmacists to effectively support safer pain management through communication, medication review, and interdisciplinary collaboration, with the final result being better outcomes and reduced opioid-related harm.

REFERENCES

1. FDA Requires Major Changes to Opioid Pain Medication Labeling to Emphasize Risks. U.S. Food and Drug Administration. Published 2025. Accessed August 1, 2025. https://www.fda.gov/news-events/press-announcements/fda-requires-major-changes-opioid-pain-medication-labeling-emphasize-risks

2. Johnson V. FDA Emphasizes Opioid Risks in New Labeling Requirement. HCP Live. Published July 31, 2025. Accessed August 1, 2025. https://www.hcplive.com/view/fda-emphasizes-opioid-risks-in-new-labeling-requirement

3. Dowell D, Ragan K, Jones C, Baldwin G, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain. MMWR Recommendations and Reports. 2022;71(3):1-95. doi:10.15585/mmwr.rr7103a1

4. CDC. Guideline Recommendations and Guiding Principles. Overdose Prevention. Published May 6, 2024. https://www.cdc.gov/overdose-prevention/hcp/clinical-guidance/recommendations-and-principles.html