In May, the U.S. Food and Drug Administration (FDA) held an advisory committee meeting in which experts reviewed data showing serious risks such as misuse, addiction, and both fatal and non-fatal overdoses for patients who use opioids over extended periods. As a result, the FDA is requiring safety labeling changes to all opioid pain medications, including both immediate-release and extended-release formulations, to better emphasize and explain the risks associated with their long-term use, as per its July 31, 2025, Drug Safety Communication.
The new labeling requirements address longstanding gaps in opioid regulation. For example, a New Drug Application for OxyContin was initially approved without appropriate study data supporting its long-term use for many of the patient populations in which it has been prescribed. FDA Commissioner Marty Makary, M.D., M.P.H., emphasized that while this labeling change is long overdue, it is only part of what needs to be done, and that post-market monitoring is also necessary to prevent another opioid crisis from happening again. Two large FDA-required observational studies, known as Post-Marketing Requirements (PMR) 3033-1 and 3033-2, recently provided detailed data showing how long-term opioid use can lead to serious side effects. After reviewing these study results and recognizing the absence of adequate and well-controlled trials on the long-term effectiveness of opioids, the FDA determined that significant labeling changes were necessary to help health care professionals and patients make treatment decisions based on the latest evidence. The FDA has also required an additional prospective, randomized, controlled clinical trial to directly examine the benefits and risks of long-term opioid use, and the agency will be closely monitoring the progress of this trial to ensure its timely completion.
The labeling changes include a number of critical updates. Labels will now provide clearer risk information by summarizing study results that estimate the risks of addiction, misuse, and overdose during long-term use. Stronger dosing warnings will emphasize that higher doses carry greater risks and that these risks persist over time. Language that could be misinterpreted to support indefinite use of opioid pain medications will be removed. Treatment guidance will reinforce that long-acting or extended-release opioids should only be considered when other treatments, including shorter-acting opioids, are inadequate. Labels will also caution against abruptly stopping opioids in physically dependent patients, as sudden discontinuation can lead to withdrawal, uncontrolled pain, or suicidal thoughts. In addition, labels will provide more information on overdose reversal agents, such as Naloxone and Nalmefene, expand warnings about combining opioids with other central nervous system depressants, including Gabapentinoids, and add information on rare but serious conditions such as toxic leukoencephalopathy, which can occur after an overdose, and opioid-induced esophageal dysfunction.
These changes align with the CDC’s 2022 Clinical Practice Guideline for Prescribing Opioids for Pain, which applies to outpatient adults with acute, subacute, or chronic pain, to make informed, patient-centered decisions about pain care. The guideline recommends that prescribers carefully determine whether opioids are clinically appropriate, initiate immediate-release opioids at the lowest effective dose when necessary, limit prescription duration, and frequently reassess therapy goals, patient function, and the risks of misuse, overdose, and opioid use disorder. It also encourages greater use of nonopioid pharmacologic and nonpharmacologic pain treatments whenever possible.
Practical Implications for Clinicians
For pharmacists and prescribers, the FDA’s new opioid labeling requirements directly affect daily patient care, counseling, and documentation. These regulatory changes create both compliance obligations and opportunities to improve patient safety.
In practice, this means taking a closer look at how opioids are prescribed, dispensed, and monitored, and ensuring that both patients and providers are fully equipped to make informed decisions. Key areas of focus include:
Patient Counseling and Education
Updated labels must now be translated into clear, actionable conversations with patients. This includes:
- Explaining the risks of addiction, misuse, and overdose in plain language.
- Setting realistic expectations about the short-term role of opioids and emphasizing non-opioid alternatives where possible.
- Counseling patients and caregivers on overdose reversal agents, when to use them, and how to access them.
- Documenting counseling sessions to demonstrate both compliance and quality of care.
Prescribing and Dispensing Practices
Clinicians should adjust prescribing protocols to reflect the new labeling standards:
- Verify clinical justification for extended-release (ER) or long-acting opioids, ensuring other therapies have been tried and deemed inadequate.
- Initiate with the lowest effective dose and titrate cautiously.
- Monitor for dose escalation over time, documenting clinical rationale for any changes.
- Ensure prescribers and pharmacists collaborate on tapering or discontinuation strategies to prevent abrupt withdrawal.
Drug Interaction and Risk Management
The updated labels underscore risks of combining opioids with other CNS depressants, including benzodiazepines and gabapentinoids. Clinicians should:
- Conduct thorough medication reconciliation to catch potential interactions.
- Flag at-risk patients for closer monitoring.
- Educate patients about avoiding alcohol and sedatives while on opioid therapy.
Clinical Documentation and Liability Protection
From a compliance standpoint, meticulous documentation is essential:
- Record the clinical reasoning behind opioid initiation, dose adjustments, and continuation.
- Note counseling provided, including naloxone discussion and education on tapering plans.
- Maintain clear records of risk/benefit reassessments and functional outcome evaluations at regular intervals.
Multidisciplinary Collaboration
Managing long-term pain safely often requires collaboration:
- Prescribers and pharmacists should maintain open communication about patient progress, dose appropriateness, and refill requests.
- Behavioral health providers can support patients at risk for misuse or with co-occurring mental health conditions.
- Legal and compliance advisors can help practices align protocols with evolving federal and state regulations.
By proactively integrating the FDA’s updated labeling requirements into clinical workflows and aligning them with the CDC’s evidence-based prescribing guidelines, pharmacists and prescribers can meaningfully reduce opioid-related harm while protecting themselves against regulatory and legal exposure.
How Can Frier Levitt Help
As healthcare attorneys with deep experience representing pharmacists, prescribers, and health systems, we assist in navigating the legal and regulatory implications of FDA and CDC policy changes. This includes reviewing policies and procedures to ensure compliance with updated labeling requirements, advising on documentation and patient counseling practices that reduce liability exposure, and guiding providers through complex federal and state-controlled substance regulations. Ultimately, this will help protect your practice, support patient safety, and ensure you remain compliant in an increasingly complex regulatory environment. Contact us today to speak with an attorney.
