FDA: Revise Opioid Pain Medication Labeling to Emphasize Risks of Overdose and Addiction

In July 2025 the Food and Drug Administration (FDA) required safety labeling changes to all opioid pain medications to better explain the risks of overdose and addiction associated with the long-term use of these products.

Although the labeling changes improve upon the previous labeling, they fall short of the changes that the FDA should have required. Moreover, although they are already years overdue, the labeling changes have yet to be fully implemented.

Background

Opioids such as morphine (MS CONTIN and generics), codeine (generics only), oxycodone (OXYCONTIN, ROXICODONE, ROXYBOND, XTAMPZA ER and generics) and hydrocodone (HYSINGLA ER and generics) are oral or injectable drugs for acute analgesia, including the pain relief and sedation essential for surgical anesthesia.

Opioids are also highly addictive.[1] In 2024 approximately 4.5 million adults in the United States had opioid use disorder (OUD);[2] opioid overdoses led to about 55,000 deaths.[3] The Text Box below shows the standard diagnostic criteria for OUD.

In 2012, Physicians for Responsible Opioid Prescribing petitioned the FDA to revise opioid labels to indicate use for severe pain only, and to set maximum daily doses at 100-milligram morphine equivalents and maximum treatment duration at 90 days.[4] Public Citizen and other groups were co-petitioners.

In 2013 the FDA required opioid manufacturers to conduct postmarket studies that addressed misuse, addiction and overdose related to the clinical use of opioid products.[5] In 2016, language about addiction was added to the required FDA labeling for opioid pain medications. In 2019, language about serious harms that may result from abruptly halting opioid use (physiologic withdrawal and psychological distress) was added to the drug labels. In 2020 the drug labeling was revised to encourage clinicians to concomitantly prescribe naloxone (KLOXXADO, NARCAN, REXTOVY, RIVIVE and generics), a medication that can reverse an overdose by attaching to opioid receptors in the brain, thereby blocking the effects of other opioids. In 2023, language was added about the risks of high-dose and long-duration opioid treatment, including new warnings about hyperalgesia (hypersensitivity to pain).

Studies supporting the 2025 drug label revisions

The 2025 revisions to the labeling of opioid pain medications were based on a review of several prior studies and supported by the results of two studies that the FDA required more than a decade ago.[6] One FDA-mandated study focused on the risks of misuse and addiction, and the other on the risk of overdose. In May 2025 the FDA convened an advisory committee to discuss these long-anticipated study findings.[7]

The misuse and addiction study was a prospective observational review of approximately 2,200 adults (age 18 to 79 years) who filled opioid prescriptions and were followed between 2017 and 2021 from ten sites across eight U.S. states, including California, Florida, Michigan and Pennsylvania.[8]

Participants could not have a terminal illness and had to be enrolled in a health insurance plan or health care system with complete records for at least 12 months both before and after initiating opioids. Participants also had to have filled opioid prescriptions with at least a 28-day supply followed by a refillwithin seven days of long-acting orextended-release opioids or a 70-day supply of opioids filled over a 90-day period.

During the 12 months after beginning extended-duration opioid treatment, 3.4% to 5.8% of the patients were newly diagnosed with OUD. These percentages were markedly higher than the prevalence (background percentage) of approximately 1.8% of OUD in the general population.[9] By 12 months, about 23% of long-term opioid users newly developed “opioid misuse,” defined as taking opioids for a “therapeutic purpose inappropriately outside labeling directions or in a way other than prescribed …”.[10] Opioid misuse is concerning because it suggests latent or emerging OUD.

Criteria for Diagnosing Opioid Use Disorder

Opioid use disorder is diagnosed if at least two of the following 11 signs are evident in a 12-month period:[11]

1. Opioids are often taken more frequently or in larger amounts than intended.
2. Many unsuccessful attempts have been made to cut back.
3. Much time is spent obtaining opioids or recovering from opioid use.
4. Patient craves opioids.
5. Recurrent use leads to failure to fulfill responsibilities/roles at work, school or home.
6. Continued use despite interpersonal problems connected to that use
7. Important activities (occupational, social, recreation) disrupted because of opioid use.
8. Recurrent use in physically hazardous situations
9. Continued use despite knowledge of physical and psychological harms
10. Tolerance (needing a higher dose to achieve the same effect) increases.
11. Withdrawal symptoms (ill effects with opioid reduction) occur.

The overdose study was a retrospective review of opioid analgesic use from 2006 to 2016.[12] Participants were enrolled in commercial health care or Medicaid for at least nine months before entering the study. Opioid users were selected from this population if they had at least a six-month opioid-free period before starting long-term opioid use for chronic pain, and use of opioids for at least 70 days during a 90-day period. People with previous opioid overdoses were excluded.

Follow-up for up to five years of approximately 220,000 patients revealed new opioid overdoses in 1.5% to 4% of the population, with approximately 17% of these overdoses resulting in death. Overdoses were more likely in participants aged 18 to 24 years and as the cumulative amounts of opioids used increased. Because less than one-fifth of the population was followed for five years, the percentage of participants with opioid overdoses may have been underestimated.

The FDA’s required labeling changes

According to the FDA, the labeling changes include: (1) clearer risk information, such as a summary of study results on the estimated risks of addiction, misuse and overdose during long-term use; (2) stronger warnings that higher doses of opioids come with greater risks and that these risks persist over time; (3) the removal of language that could be misinterpreted to support using opioid pain medications indefinitely; (4) guidance that extended-release opioids should only be considered when shorter-acting opioids and other treatments are inadequate; (5) instructions on safe discontinuation; and (6) additional information on naloxone and medications that can reverse an opioid overdose. It is uncertain whether the changes will sufficiently emphasize the life-threatening risks of overdose and addiction or how many people will even read the fine print.

A key limit is that the FDA is only requiring that the labeling changes be made deep within lengthy labels rather than in the prominent boxed warning.[13] At present, the boxed warning cautions about addiction and overdose as “risks” that “may occur,” not as the substantial risks confirmed by the mandated postmarketing studies.[14] Moreover, the labeling changes do not include daily-dose and treatment-duration limits, as Public Citizen’s Health Research Group and others have urged. Expert commentators have criticized the label changes as “smoke and mirrors” that fail to fully warn about the risks and further fail to address the lack of evidence supporting the long-term use of opioids for chronic pain.[15],[16]

What You Can Do

Do not use opioids to treat pain unless it is severe and unremitting. Consult with a qualified clinician about non-pharmacologic (for example, ice or physical therapy) and non-opioid (for example, anti-inflammatory medication) pain treatments. If non-pharmacologic and non-opioid drug treatments fail, consult with a clinician about limited-dose and limited-duration opioids and how to reduce the risks of addiction and overdose. Do not stop or change your opioid dose without professional, clinical help.

References

[1] Bonnet U, Scherbaum N. How addictive are gabapentin and pregabalin? A systematic review. Eur Neuropsychopharmacol. 2017;27(12):1185-1215.

[2] Substance Abuse and Mental Health Services Administration. (2025). Key substance use and mental health indicators in the United States: Results from the 2024 National Survey on Drug Use and Health (HHS Publication No. PEP25-07-007, NSDUH Series H-60). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/sites/default/files/reports/rpt56287/2024-nsduh-annual-national-report.pdf. Accessed November 17, 2025.

[3] Centers for Disease Control and Prevention. U.S. overdose deaths decrease almost 27% in 2024. May 14, 2025. https://www.cdc.gov/nchs/pressroom/releases/20250514.html. Accessed November 4, 2025.

[4] Physicians for Responsible Opioid Prescribing. Letter to the FDA regarding the regulation of opioid analgesics. July 25, 2012. https://www.citizen.org/news/doctors-researchers-and-health-officials-call-on-fda-to-change-labels-on-opioid-painkillers-to-deter-misprescribing/. Accessed November 17, 2025.

[5] FDA briefing document. Joint Meeting of the Drug Safety and Risk Management (DSaRM) Advisory Committee and Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC). May 5, 2025. https://www.fda.gov/media/186254/download. Accessed November 4, 2025.

[6] FDA Safety Communication. FDA is requiring opioid pain medicine manufacturers to update prescribing information regarding long-term use. July 31, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-opioid-pain-medicine-manufacturers-update-prescribing-information-regarding-long-term. Accessed November 4, 2025.

[7] Abrams MT. Testimony before the joint FDA Drug Safety and Analgesic Drug Products Advisory Committees regarding long-term opioid use. May 5, 2025. https://www.citizen.org/article/testimony-before-the-joint-fda-drug-safety-and-analgesic-drug-products-advisory-committees-regarding-the-long-term-opioid-use/. Accessed November 4, 2025.

[8] FDA briefing document. Joint Meeting of the Drug Safety and Risk Management (DSaRM) Advisory Committee and Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC). May 5, 2025. https://www.fda.gov/media/186254/download. Accessed November 4, 2025.

[9] Substance Abuse and Mental Health Services Administration. (2025). Key substance use and mental health indicators in the United States: Results from the 2024 National Survey on Drug Use and Health (HHS Publication No. PEP25-07-007, NSDUH Series H-60). Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration. https://www.samhsa.gov/data/sites/default/files/reports/rpt56287/2024-nsduh-annual-national-report.pdf. Accessed November 17, 2025.

[10] FDA briefing document. Joint Meeting of the Drug Safety and Risk Management (DSaRM) Advisory Committee and Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC). May 5, 2025. https://www.fda.gov/media/186254/download. Accessed October 31, 2025.

[11] Dowell D, Ragan KR, Jones CM, et al. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep. 2022;71(3):1-95.

[12] FDA briefing document. Joint Meeting of the Drug Safety and Risk Management (DSaRM) Advisory Committee and Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC). May 5, 2025. https://www.fda.gov/media/186254/download. Accessed November 4, 2025.

[13] FDA Safety Communication. FDA is requiring opioid pain medicine manufacturers to update prescribing information regarding long-term use. July 31, 2025. https://www.fda.gov/drugs/drug-safety-and-availability/fda-requiring-opioid-pain-medicine-manufacturers-update-prescribing-information-regarding-long-term. Accessed November 4, 2025.

[14] Purdue Pharma L.P. Label: oxycodone hydrochloride extended-release tablet (OXYCONTIN). December 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/022272s048lbl.pdf. Accessed August 12, 2025.

[15] Bicket MC, Bateman BT. Long-term opioid therapy for pain: What is known about harms-and still not known about benefits. JAMA. 2025 Sep 23;334(12):1057-1058.

[16] Marino, R. FDA’s opioid labeling initiative is smoke and mirrors—the administration has done little to nothing to meaningfully reduce overdoses. Medpage Today. August 25, 2025. https://www.medpagetoday.com/opinion/toxicology-report/117145. Accessed November 4, 2025.