Ultram ER FDA Alerts

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

Codeine and Tramadol Medicines: Drug Safety Communication - Restricting Use in Children, Recommending Against Use in Breastfeeding Women

ISSUE: FDA is restricting the use of codeine and tramadol medicines in children. These medicines carry serious risks, including slowed or difficult breathing and death, which appear to be a greater risk in children younger than 12 years, and should not be used in these children. These medicines should also be limited in some older children. Single-ingredient codeine and all tramadol-containing products are FDA-approved only for use in adults. FDA is also recommending against the use of codeine and tramadol medicines in breastfeeding mothers due to possible harm to their infants.

As a result, FDA is requiring several changes to the labels of all prescription medicines containing these drugs. These new actions further limit the use of these medicines beyond the 2013 FDA restriction of codeine use in children younger than 18 years to treat pain after surgery to remove the tonsils and/or adenoids. FDA is now adding:

• FDA’s strongest warning, called a Contraindication, to the drug labels of codeine and tramadol alerting that codeine should not be used to treat pain or cough and tramadol should not be used to treat pain in children younger than 12 years.
• A new Contraindication to the tramadol label warning against its use in children younger than 18 years to treat pain after surgery to remove the tonsils and/or adenoids.
• A new Warning to the drug labels of codeine and tramadol to recommend against their use in adolescents between 12 and 18 years who are obese or have conditions such as obstructive sleep apnea or severe lung disease, which may increase the risk of serious breathing problems.
• A strengthened Warning to mothers that breastfeeding is not recommended when taking codeine or tramadol medicines due to the risk of serious adverse reactions in breastfed infants. These can include excess sleepiness, difficulty breastfeeding, or serious breathing problems that could result in death.

See the FDA Drug Safety Communication for a data summary, a list of approved drugs containing codeine and tramadol, and additional information.

BACKGROUND: Codeine is approved to treat pain and cough, and tramadol is approved to treat pain.

RECOMMENDATION: Health care professionals should be aware that tramadol and single-ingredient codeine medicines are FDA-approved only for use in adults. Consider recommending over-the-counter (OTC) or other FDA-approved prescription medicines for cough and pain management in children younger than 12 years and in adolescents younger than 18 years, especially those with certain genetic factors, obesity, or obstructive sleep apnea and other breathing problems. Cough is often secondary to infection, not serious, and usually will get better on its own so treatment may not be necessary.

Caregivers and patients should always read the label on prescription bottles to find out if a medicine contains codeine or tramadol. You can also ask your child’s health care provider or a pharmacist. Watch closely for signs of breathing problems in a child of any age who is taking these medicines or in infants exposed to codeine or tramadol through breastmilk. These signs include slow or shallow breathing, difficulty or noisy breathing, confusion, more than usual sleepiness, trouble breastfeeding, or limpness. If you notice any of these signs, stop giving the medicine and seek medical attention immediately by going to an emergency room or calling 911.

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

[04/20/2017 - Drug Safety Communication - FDA]

Tramadol: Drug Safety Communication - FDA Evaluating Risks of Using in Children Aged 17 and Younger

ISSUE:  FDA is investigating the use of the pain medicine tramadol in children aged 17 years and younger, because of the rare but serious risk of slowed or difficult breathing. This risk may be increased in children treated with tramadol for pain after surgery to remove their tonsils and/or adenoids. FDA is evaluating all available information and will communicate final conclusions and recommendations to the public when the review is complete.

Tramadol is not FDA-approved for use in children; however, data show it is being used “off-label” in the pediatric population. Health care professionals should be aware of this and consider prescribing alternative FDA-approved pain medicines for children.

BACKGROUND: In the body, tramadol is converted in the liver to the active form of the opioid, called O-desmethyltramadol. Some people have genetic variations that cause tramadol to be converted to the active form of the opioid faster and more completely than usual. These people, called ultra-rapid metabolizers, are more likely to have higher-than-normal amounts of the active form of the opioid in their blood after taking tramadol, which can result in breathing difficulty that may lead to death. Recently, a 5-year-old child in France experienced severely slowed and difficult breathing requiring emergency intervention and hospitalization after taking a single prescribed dose of tramadol oral solution for pain relief following surgery to remove his tonsils and adenoids. The child was later found to be an ultra-rapid metabolizer and had high levels of O-desmethyltramadol in his body.

RECOMMENDATION: Parents and caregivers of children taking tramadol who notice any signs of slow or shallow breathing, difficult or noisy breathing, confusion, or unusual sleepiness should stop tramadol and seek medical attention immediately by taking their child to the emergency room or calling 911. Parents and caregivers should talk with their child’s health care professional if they have any questions or concerns about tramadol or other pain medicines their child is taking.

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

[09/21/2015 - Drug Safety Communication - FDA]

Ultram (tramadol hydrochloride), Ultracet (tramadol hydrochloride/acetaminophen): Label Change

[Posted 05/25/2010] Ortho-McNeil-Janssen and FDA notified healthcare professionals of changes to the Warnings section of the prescribing information for tramadol, a centrally acting synthetic opioid analgesic indicated for the management of moderate to moderately severe chronic pain. The strengthened Warnings information emphasizes the risk of suicide for patients who are addiction-prone, taking tranquilizers or antidepressant drugs and also warns of the risk of overdosage. Tramadol-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation or attempts, as well as histories of misuse of tranquilizers, alcohol, and other CNS-active drugs. Tramadol may be expected to have additive effects when used in conjunction with alcohol, other opioids or illicit drugs that cause central nervous system depression. Serious potential consequences of overdosage with tramadol are central nervous system depression, respiratory depression and death. Tramadol has mu-opioid agonist activity, can be abused and may be subject to criminal diversion.

[April 2010 - Dear Healthcare Professional Letter: Ultram - Ortho-McNeil-Janssen]
[April 2010 - Dear Healthcare Professional Letter: Ultracet - Ortho-McNeil-Janssen]