Oxydose FDA Alerts

FDA Requires Major Changes to Opioid Pain Medication Labeling to Emphasize Risks

July 31, 2025 -- The U.S. Food and Drug Administration is requiring safety labeling changes to all opioid pain medications to better emphasize and explain the risks associated with their long-term use. These changes follow a public advisory committee meeting in May that reviewed data showing serious risks—such as misuse, addiction, and both fatal and non-fatal overdoses—for patients who use opioids over long periods. 

“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, M.D., M.P.H. “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.” 

Tragically, the new drug application for OxyContin was initially approved without study data supporting its long term use to treat pain in many patient populations for which it has been prescribed. The updated labeling change reflects robust data from two large FDA-required observational studies, called postmarketing requirements (PMR) 3033-1 and 3033-2, which recently provided new data on how long-term opioid use can lead to serious side effects. 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.  

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

FDA has required an additional prospective, randomized, controlled clinical trial to directly examine the benefits and risks of long-term opioid use. The Agency will be closely monitoring the progress of this clinical trial to ensure its timely completion.

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 sent letters to the relevant applicants outlining the required changes. The companies will have 30 days to submit their labeling updates to the FDA for review.

More information is available in the FDA’s Drug Safety Communication.

Drug Safety Communication: All Opioid Pain Medicines - FDA Updates Prescribing Information to Provide Additional Guidance for Safe Use

ISSUE: The FDA is requiring several updates to the prescribing information for both immediate-release (IR) and extended release/long acting (ER/LA) opioid pain medicines. This includes stating for all opioid pain that the risk of overdose increases as the dose increases.

• The updates to IR opioids state these products should not be used for an extended period unless the pain remains severe enough to require them and alternative treatments continue to be inadequate, and that many acute pain conditions treated in the outpatient setting require no more than a few days of an opioid pain medicine. This may include pain occurring with a number of surgical conditions or musculoskeletal injuries.
• The FDA is also updating the approved use for ER/LA opioid pain medicines to recommend they be reserved for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate.
• The FDA is also adding a new warning about opioid-induced hyperalgesia (OIH) for both IR and ER/LA opioid pain medicines. This includes information describing the symptoms that differentiate OIH from opioid tolerance and withdrawal.
• Information in the Boxed Warning, FDA’s most prominent warning, for all IR and ER/LA opioid pain medicines will be updated and reordered to elevate the importance of warnings concerning life-threatening respiratory depression, and risks associated with using opioid pain medicines in conjunction with benzodiazepines or other medicines that depress the central nervous system (CNS).
• Other changes are also being required to several sections of the prescribing information, including to the Indications and Usage, Dosage and Administration, and Warnings and Precautions sections. The FDA is also requiring updates to the existing patient Medication Guides to help educate patients and caregivers about these risks.

BACKGROUND: Opioid pain medicines are a class of powerful pain medicines prescribed to treat pain that does not respond well to other treatments or non-opioid pain medicines. They activate an area of nerve cells in the brain and body that block pain signals. These medicines have benefits when used appropriately, but they also have serious risks, including misuse and abuse, addiction, overdose, and death. Examples of common opioid pain medicines include codeine, hydrocodone, hydromorphone, morphine, oxycodone, oxymorphone, fentanyl, buprenorphine, and tramadol.

RECOMMENDATIONS:

Patients/Parents/Caregivers

• Always take your opioid medicines exactly as prescribed. Do not take more of the medicine or take it more often than prescribed without first talking to your health care professional. Talk with them if your pain increases, you feel more sensitive to pain, or if you have new pain, especially from touch or other things that are not usually painful such as combing your hair.
• Store your opioid pain medicines securely, out of sight and reach of children, and in a location not accessible by others, including visitors to the home. Do not share these medicines with anyone else, and immediately dispose of unused or expired opioids or take them to a drug take-back site, location, or program. If provided, use the prepaid mail-back envelopes included with the prescription.
• Seek emergency medical help or call 911 immediately if you or someone you are caring for experiences symptoms of respiratory problems, which can be life-threatening. Signs and symptoms include serious slowed, shallow, or difficult breathing, severe sleepiness, or not being able to respond or wake up.
• Talk to your health care professionals about the benefits of naloxone, which can reverse an opioid overdose, and how to obtain it. Your health care professional can give you a prescription for naloxone. Additionally, in most states and the District of Columbia you can obtain naloxone from a pharmacy under a standing order that takes the place of an individual prescription. Some states also allow you to obtain naloxone without a prescription from a community-based program or pharmacy. Check with your state Health Department for more information. In March 2023, FDA approved an inhaled nasal spray version of naloxone to be sold over-the-counter without a prescription while multiple forms of naloxone remain available as prescription only.

Health Care Professionals 

• In assessing the severity of pain, discuss with the patient the impact of the pain on their ability to function and their quality of life. Assessment of pain should consider both the cause of pain and individual patient factors.
• If the patient’s pain is severe enough to require an opioid pain medicine and alternative treatment options are insufficient, prescribe the lowest effective dose of an IR opioid for the shortest duration of time to reduce the risks associated with these products.
• Reserve ER/LA opioid pain medicines only for severe and persistent pain that requires an extended treatment period with a daily opioid pain medicine and for which alternative treatment options are inadequate.
• For all patients prescribed opioid pain medicines, discuss the availability of naloxone, and consider prescribing it to those at increased risk of overdose.
• Be aware that the symptoms of OIH, a condition where opioids cause an increase in pain (called hyperalgesia) or an increased sensitivity to pain (called allodynia), are distinct from opioid tolerance and withdrawal and can be difficult to recognize.
• If a patient is suspected to be experiencing OIH, carefully consider an appropriate decrease in dose of the current opioid pain medicine or safely switching them to a different opioid product, if tolerated. Advise patients about the risk of OIH and tell them to never increase the opioid dosage without first consulting a health care professional, because this could worsen the pain and increase the risk of respiratory depression.

Health care professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report online.

• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on form, or submit by fax to 1-800-FDA-0178.

[04/13/2023 - Drug Safety Communication - FDA] 
[04/13/2023 - CDER Statement - FDA] 

Source: FDA

Opioid Pain Relievers or Medicines to Treat Opioid Use Disorder - FDA Recommends Health Care Professionals Discuss Naloxone with All Patients when Prescribing

ISSUE: FDA is requiring drug manufacturers for all opioid pain relievers and medicines to treat opioid use disorder (OUD) to add new recommendations about naloxone to the prescribing information.  This will help ensure that health care professionals discuss the availability of naloxone and assess each patient’s need for a naloxone prescription when opioid pain relievers or medicines to treat OUD are being prescribed or renewed.  The patient Medication Guides will also be updated.

BACKGROUND: Opioid pain relievers are medicines that can help manage pain when other treatments and medicines are not able to provide enough pain relief.  Certain opioids are also used to treat OUD.  Opioids have serious risks, including misuse and abuse, addiction, overdose, and death.  Naloxone can help reverse opioid overdose to prevent death.

The misuse and abuse of illicit and prescription opioids and the risks of addiction, overdose, and death are a public health crisis in the United States.  As a result, FDA is committed to encouraging health care professionals to raise awareness of the availability of naloxone when they are prescribing and dispensing opioid pain relievers or medicines to treat OUD.  FDA held discussions about naloxone availability with the Anesthetic and Analgesic Drug Products and the Drug Safety and Risk Management Advisory Committees, which recommended that all patients being prescribed opioids for use in the outpatient setting would benefit from a conversation with their health care professional about the availability of naloxone. 

RECOMMENDATION:
Patients: 

• Talk to your health care professionals about the benefits of naloxone and how to obtain it.  
• Recognize the signs and symptoms of a possible opioid overdose.  These include slowed, shallow, or difficult breathing, severe sleepiness, or not being able to respond or wake up.  If you know or think someone is overdosing, give the person naloxone if you have access to it, and always call 911 or go to an emergency room right away.  Naloxone is a temporary treatment, so repeat doses may be required.  Even if you give naloxone, you still need to get emergency medical help right away.
• If you have naloxone, make sure to tell your caregivers, household members, and other close contacts that you have it, where it is stored, and how to properly use it in the event of an overdose.  When using opioid medicines away from home, carry naloxone with you and let those you are with know you have it, where it is, and how to use it.  Read the Patient Information leaflet or other educational material and Instructions for Use that comes with your naloxone because it explains important information, including how to use the medicine.  

Health Care Professionals: 

• Discuss the availability of naloxone with all patients when prescribing or renewing an opioid analgesic or medicine to treat OUD.  
• Consider prescribing naloxone to patients prescribed medicines to treat OUD and patients prescribed opioid analgesics who are at increased risk of opioid overdose.  
• Consider prescribing naloxone when a patient has household members, including children, or other close contacts at risk for accidental ingestion or opioid overdose.
• Additionally, even if the patients are not receiving a prescription for an opioid analgesic or medicine to treat OUD, consider prescribing naloxone to them if they are at increased risk of opioid overdose. 
• Educate patients and caregivers on how to recognize respiratory depression and how to administer naloxone.  Inform them about their options for obtaining naloxone as permitted by their individual state dispensing and prescribing requirements or guidelines for naloxone. Emphasize the importance of calling 911 or getting emergency medical help right away, even if naloxone is administered. 

Patients and health care professionals are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Complete and submit the report online.
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the form, or submit by fax to 1-800-FDA-0178

[07/23/2020 - Drug Safety Communication - FDA] 

Source: FDA

OxyContin, Illegal Promotion by Manufacturer

[Posted 05/10/2007] FDA informed healthcare professionals of criminal charges and civil liabilities brought against Purdue Frederick in connection with several illegal schemes to promote, market and sell OxyContin, a powerful prescription pain reliever that the company produces. The manufacturer's sales force was trained to make false claims about the product to healthcare professionals, thereby, misbranding OxyContin by illegally promoting the drug as being less addictive, less subject to abuse, and less likely to cause tolerance and withdrawal than other pain medications. These practices falsely promote the product and may cause health risks for consumers.