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acetaminophen/codeine FDA Alerts

The FDA Alert(s) below may be specifically about acetaminophen/codeine or relate to a group or class of drugs which include acetaminophen/codeine.

MedWatch Safety Alerts are distributed by the FDA and published by Drugs.com. Following is a list of possible medication recalls, market withdrawals, alerts and warnings. For the latest FDA MedWatch alerts, go here.

Recent FDA Alert(s) for acetaminophen/codeine

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

Apr 20, 2017

Audience: Pediatrics, OB/GYN, Internal Medicine

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:

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

Codeine Cough-and-Cold Medicines in Children: Drug Safety Communication - FDA Evaluating Potential Risk of Serious Side Effects

Jul 1, 2015

Audience: Family Practice, Pediatrics, Surgery, Patient

ISSUE: FDA is investigating the safety of using codeine-containing medicines to treat coughs and colds in children under 18 years because of the potential for serious side effects, including slowed or difficult breathing.

Children, especially those who already have breathing problems, may be more susceptible to these serious side effects. In 2013, FDA warned against using codeine in children who recently had surgery to remove their tonsils and/or adenoids.

In April 2015, the European Medicines Agency (EMA) announced that codeine must not be used to treat cough and cold in children under 12 years, and that codeine is not recommended in children and adolescents between 12 and 18 years who have breathing problems, including those with asthma and other chronic breathing problems.

FDA will continue to evaluate this safety issue and will consider the EMA recommendations. Final conclusions and recommendations will be communicated when the FDA review is complete.

BACKGROUND: Codeine is a specific type of narcotic medicine called an opioid that is used to treat mild to moderate pain and also to reduce coughing. It is usually combined with other medications in prescription and over-the-counter (OTC) cough-and-cold medicines.

RECOMMENDATION: Parents and caregivers who notice any signs of slow or shallow breathing, difficult or noisy breathing, confusion, or unusual sleepiness in their child should stop giving their child codeine and seek medical attention immediately by taking their child to the emergency room or calling 911. Parents and caregivers should always read the product label to find out if a medicine contains codeine and talk with their child’s health care professional or a pharmacist if they have any questions or concerns. Health care professionals should continue to follow the recommendations in the drug labels and use caution when prescribing or recommending codeine-containing cough-and-cold medicines to children.

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:


[07/01/2015 - Drug Safety Communication - FDA]
[07/01/2015 - Codeine Information - FDA]

Acetaminophen Prescription Combination Drug Products with more than 325 mg: FDA Statement - Recommendation to Discontinue Prescribing and Dispensing

Jan 14, 2014

Audience: Consumer, Dentistry, Emergency Medicine, Internal Medicine, Pharmacy, Pain Management, Surgery

ISSUE: FDA is recommending health care professionals discontinue prescribing and dispensing prescription combination drug products that contain more than 325 milligrams (mg) of acetaminophen per tablet, capsule or other dosage unit. There are no available data to show that taking more than 325 mg of acetaminophen per dosage unit provides additional benefit that outweighs the added risks for liver injury. Further, limiting the amount of acetaminophen per dosage unit will reduce the risk of severe liver injury from inadvertent acetaminophen overdose, which can lead to liver failure, liver transplant, and death.
 
Cases of severe liver injury with acetaminophen have occurred in patients who:

• took more than the prescribed dose of an acetaminophen-containing product in a 24-hour period;
• took more than one acetaminophen-containing product at the same time; or
• drank alcohol while taking acetaminophen products.

BACKGROUND: In January 2011 FDA asked manufacturers of prescription combination drug products containing acetaminophen to limit the amount of acetaminophen to no more than 325 mg in each tablet or capsule by January 14, 2014. FDA requested this action to protect consumers from the risk of severe liver damage which can result from taking too much acetaminophen. This category of prescription drugs combines acetaminophen with another ingredient intended to treat pain (most often an opioid), and these products are commonly prescribed to consumers for pain, such as pain from acute injuries, post-operative pain, or pain following dental procedures.

Acetaminophen is also widely used as an over-the-counter (OTC) pain and fever medication, and is often combined with other ingredients, such as cough and cold ingredients. FDA will address OTC acetaminophen products in another regulatory action. Many consumers are often unaware that many products (both prescription and OTC) contain acetaminophen, making it easy to accidentally take too much.

More than half of manufacturers have voluntarily complied with the FDA request. However, some prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit remain available. In the near future FDA intends to institute proceedings to withdraw approval of prescription combination drug products containing more than 325 mg of acetaminophen per dosage unit that remain on the market.

RECOMMENDATION: FDA recommends that health care providers consider prescribing combination drug products that contain 325 mg or less of acetaminophen. FDA also recommends that when a pharmacist receives a prescription for a combination product with more than 325 mg of acetaminophen per dosage unit that they contact the prescriber to discuss a product with a lower dose of acetaminophen. A two tablet or two capsule dose may still be prescribed, if appropriate. In that case, the total dose of acetaminophen would be 650 mg (the amount in two 325 mg dosage units). When making individual dosing determinations, health care providers should always consider the amounts of both the acetaminophen and the opioid components in the prescription combination drug product.

Health care providers and pharmacists who have further questions are encouraged to contact the Division of Drug Information at 888.INFO.FDA (888-463-6332) or druginfo@fda.hhs.gov.

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:

[01/14/2014 -  FDA Statement - FDA]
[Acetaminophen Information - FDA]

Acetaminophen: Drug Safety Communication - Association with Risk of Serious Skin Reactions

Aug 1, 2013

Audience: Dermatology, Primary Care, Pharmacy

ISSUE: FDA notified healthcare professionals and patients that acetaminophen has been associated with a risk of rare but serious skin reactions. Acetaminophen is a common active ingredient to treat pain and reduce fever; it is included in many prescription and over-the-counter (OTC) products.  These skin reactions, known as Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), can be fatal. These reactions can occur with first-time use of acetaminophen or at any time while it is being taken.  Other drugs used to treat fever and pain/body aches (e.g., non-steroidal anti-inflammatory drugs, or NSAIDS, such as ibuprofen and naproxen) also carry the risk of causing serious skin reactions, which is already described in the warnings section of their drug labels.

BACKGROUND: This new information resulted from the Agency’s review of the FDA Adverse Event Reporting System (FAERS) database and the medical literature to evaluate cases of serious skin reactions associated with acetaminophen (see Data Summary at link below).  It is difficult to determine how frequently serious skin reactions occur with acetaminophen, due to the widespread use of the drug, differences in usage among individuals (e.g., occasional vs. long-term use), and the long period of time that the drug has been on the market; however it is likely that these events (i.e., SJS, TEN, and AGEP) occur rarely.

RECOMMENDATIONS: Health care professionals should be aware of this rare risk and consider acetaminophen, along with other drugs already known to have such an association, when assessing patients with potentially drug-induced skin reactions. Any patient who develops a skin rash or reaction while using acetaminophen or any other pain reliever/fever reducer should stop the drug and seek medical attention right away.  Anyone who has experienced a serious skin reaction with acetaminophen should not take the drug again and should contact their health care professional to discuss alternative pain relievers/fever reducers.

FDA will require that a warning be added to the labels of prescription drug products containing acetaminophen to address the risk of serious skin reactions. FDA will also request that manufacturers add a warning about serious skin reactions to the product labels of OTC acetaminophen drug products marketed under a new drug application and will encourage manufacturers of drug products marketed under the OTC monograph do the same.

[8/01/2013 - Consumer Update - FDA]

[8/01/2013 - Drug Safety Communication - FDA]

Codeine Use in Certain Children After Tonsillectomy and/or Adenoidectomy: Drug Safety Communication - Risk of Rare, But Life-Threatening Adverse Events or Death

Feb 20, 2013

Audience: Pediatricians, Surgery, Consumer

[UPDATED 02/20/2013] FDA notified the public about new actions being taken to address a known safety concern with codeine use in certain children after tonsillectomy and/or adenoidectomy (surgery to remove the tonsils and/or adenoids). A new BOXED WARNING, FDA’s strongest warning, will be added to the drug label of codeine-containing products about the risk of codeine in post-operative pain management in children following tonsillectomy and/or adenoidectomy. A Contraindication, which is a formal means for FDA to make a strong recommendation against use of a drug in certain patients, will be added to restrict codeine from being used in this setting. The Warnings/Precautions, Pediatric Use, and Patient Counseling Information sections of the drug label will also be updated.

Health care professionals should prescribe an alternate analgesic for post-operative pain control in children who are undergoing tonsillectomy and/or adenoidectomy. Codeine should not be used for pain in children following these procedures.

For management of other types of pain in children, codeine should only be used if the benefits are anticipated to outweigh the risks. 

 

[Posted 08/15/2012]

ISSUE: The FDA is reviewing reports of children who developed serious adverse effects or died after taking codeine for pain relief after tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome. Recently, three pediatric deaths and one non-fatal but life-threatening case of respiratory depression were documented in the medical literature.

These children (ages two to five) had evidence of an inherited (genetic) ability to convert codeine into life-threatening or fatal amounts of morphine in the body. All children had received doses of codeine that were within the typical dose range.

BACKGROUND: When codeine is ingested, it is converted to morphine in the liver by an enzyme called cytochrome P450 2D6 (CYP2D6). Some people have DNA variations that make this enzyme more active, causing codeine to be converted to morphine faster and more completely than in other people. These “ultra-rapid metabolizers” are more likely to have higher than normal amounts of morphine in their blood after taking codeine. High levels of morphine can result in breathing difficulty, which may be fatal. Taking codeine after tonsillectomy and/or adenoidectomy may increase the risk for breathing problems and death in children who are “ultra-rapid metabolizers.” See the FDA Drug Safety Communication for additional information, including a Data Summary.

RECOMMENDATION: Health care professionals should be aware of the risks of using codeine in children, particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome. If prescribing codeine-containing drugs, the lowest effective dose for the shortest period of time should be used on an as-needed basis (i.e., not scheduled around the clock).

Parents and caregivers who observe unusual sleepiness, confusion, or difficult or noisy breathing in their child should seek medical attention immediately, as these are signs of overdose.


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:

 

[02/20/2013 - Drug Safety Communication - FDA]
[08/15/2012 - Drug Safety Communication - FDA] 
[08/15/2012 - Consumer Update - FDA]
 

Codeine Use in Certain Children After Tonsillectomy and/or Adenoidectomy: Drug Safety Communication - Risk of Rare, But Life-Threatening Adverse Events or Death

Aug 15, 2012

Audience: Pediatricians, Surgery, Consumer

ISSUE: The FDA is reviewing reports of children who developed serious adverse effects or died after taking codeine for pain relief after tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome. Recently, three pediatric deaths and one non-fatal but life-threatening case of respiratory depression were documented in the medical literature.

These children (ages two to five) had evidence of an inherited (genetic) ability to convert codeine into life-threatening or fatal amounts of morphine in the body. All children had received doses of codeine that were within the typical dose range.

BACKGROUND: When codeine is ingested, it is converted to morphine in the liver by an enzyme called cytochrome P450 2D6 (CYP2D6). Some people have DNA variations that make this enzyme more active, causing codeine to be converted to morphine faster and more completely than in other people. These “ultra-rapid metabolizers” are more likely to have higher than normal amounts of morphine in their blood after taking codeine. High levels of morphine can result in breathing difficulty, which may be fatal. Taking codeine after tonsillectomy and/or adenoidectomy may increase the risk for breathing problems and death in children who are “ultra-rapid metabolizers.” See the FDA Drug Safety Communication for additional information, including a Data Summary.

RECOMMENDATION: Health care professionals should be aware of the risks of using codeine in children, particularly in those who have undergone tonsillectomy and/or adenoidectomy for obstructive sleep apnea syndrome. If prescribing codeine-containing drugs, the lowest effective dose for the shortest period of time should be used on an as-needed basis (i.e., not scheduled around the clock).

Parents and caregivers who observe unusual sleepiness, confusion, or difficult or noisy breathing in their child should seek medical attention immediately, as these are signs of overdose.


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:

 

[08/15/2012 - Drug Safety Communication - FDA] 
[08/15/2012 - Consumer Update - FDA]
 

Acetaminophen Prescription Products Limited to 325 mg Per Dosage Unit: Drug Safety Communication

Jan 13, 2011

Audience: Pharmacy, Pain Management

ISSUE: FDA notified healthcare professionals that it has asked drug manufacturers to limit the strength of acetaminophen in prescription drug products, predominantly combinations of acetaminophen and opioids, to 325 mg per tablet, capsule, or other dosage unit, making these products safer for patients. This action will help to reduce the risk of severe liver injury and allergic reactions associated with acetaminophen. A Boxed Warning highlighting the potential for severe liver injury and a Warning highlighting the potential for allergic reactions (swelling of the face, mouth, and throat, difficulty breathing, itching, or rash) will be added to the label of all prescription drug products that contain acetaminophen.

BACKGROUND: Acetaminophen, one of the most commonly used drugs in the United States, is widely and effectively used in both prescription and over-the-counter (OTC) products to reduce pain and fever. Examples of prescription products that contain acetaminophen include hydrocodone with acetaminophen (Vicodin, Lortab), and oxycodone with acetaminophen (Tylox, Percocet). OTC products containing acetaminophen (e.g., Tylenol) are not affected by this action. Information about the potential for liver injury is already required on the label for OTC products containing acetaminophen. FDA is continuing to evaluate ways to reduce the risk of acetaminophen related liver injury from OTC products. No drug shortages are expected, because the 3-year implementation period should permit adequate time for necessary reformulations.

RECOMMENDATION: Healthcare professionals were reminded to advise patients not to exceed the acetaminophen maximum total daily dose (4 grams/day), and not to drink alcohol while taking acetaminophen-containing medications.

Healthcare professionals were encouraged to inform patients that there is no immediate danger to patients who take these combination pain medications, and patients should continue to take them as directed by their health care provider. The Drug Safety Communication provides additional information for healthcare professionals, information for patients, a data summary and a list of all affected products.

[01/13/2011 - Drug Safety Communication - FDA]
[01/13/2011 - Q&As - FDA]
[01/13/2011 - News Release - FDA]
[01/13/2011 - Consumer Update - FDA]
[01/13/2011 - Prescription Acetaminophen/Opioid Combinations - FDA Video]

Codeine Products Used By Nursing Mothers

Aug 17, 2007

Audience: Obstetricians, pediatricians, other healthcare professionals, consumers

[Posted 08/17/2007] FDA issued a Public Health Advisory with important new information about a very rare, but serious, side effect in nursing infants whose mothers are taking codeine and are ultra-rapid metabolizers of codeine. When codeine enters the body and is metabolized, it changes to morphine, which relieves pain. Many factors affect codeine metabolism, including a person’s genetic make-up. Some people have a variation in a liver enzyme and may change codeine to morphine more rapidly and completely than other people. Nursing mothers taking codeine may also have higher morphine levels in their breast milk. These higher levels of morphine in breast milk may lead to life-threatening or fatal side effects in nursing babies. In most cases, it is unknown if someone is an ultra-rapid codeine metabolizer.

When prescribing codeine-containing drugs to nursing mothers, physicians should choose the lowest effective dose for the shortest period of time and should closely monitor mother-infant pairs. There is an FDA cleared test for determining a patient’s CYP2D6 genotype. The test is not routinely used in clinical practice but is available through a number of different laboratories. The results of this test predict that a person can convert codeine to morphine at a faster rate than average, resulting in higher morphine levels in the blood. When levels of morphine are too high, patients have an increased risk of adverse events.

[August 17, 2007]

More acetaminophen/codeine Resources