Numorphan FDA Alerts

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

Endo Pharmaceuticals Opiate Products by Novartis Consumer Health: Public Health Advisory - Potential Safety Risk

Including the following products:

• Opana ER (oxymorphone hydrochloride) Extended-Release Tablets CII
• Opana (oxymorphone hydrochloride) CII
• Oxymorphone hydrochloride Tablets CII
• PERCOCET (oxycodone hydrochloride and acetaminophen USP) Tablets CII
• PERCODAN (oxycodone hydrochloride and aspirin, USP) Tablets CII
• ENDOCET (oxycodone hydrochloride and acetaminophen USP) Tablets CII
• ENDODAN (oxycodone hydrochloride and aspirin, USP) Tablets CII
• MORPHINE SULFATE Extended-Release Tablets CII
• ZYDONE (hydrocodone bitartrate/acetaminophen tablets, USP) CIII

[Posted 01/09/2012]

ISSUE: FDA is advising healthcare professionals and patients of a potential problem with opiate products manufactured and packaged for Endo Pharmaceuticals by Novartis Consumer Health at its Lincoln, Nebraska manufacturing site. Due to problems that occurred when these products were packaged and labeled at the site, tablets from one product type may have carried over into packaging of another product. This could result in a stray pill of one medicine ending up in the bottle of another product. 

BACKGROUND: Opiates are potent medications used to alleviate pain and are available only by prescription. Endo Pharmaceuticals reports that they are aware of only three product mix-ups with respect to these products since 2009; all three were detected by pharmacists. Endo is not aware of any patient having experienced a confirmed product mix-up, nor any adverse events attributable to a product mix-up.

RECOMMENDATION: FDA advises patients and healthcare professionals to examine opiate medicines made by Endo in their possession and ensure that all tablets are the same.

Healthcare 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: www.accessdata.fda.gov/scripts/medwatch/index.cfm
• Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

[01/09/20121 - Public Health Advisory - FDA]