FDA: No Prescription Codeine, Tramadol for Kids Under 12

Warnings Also Issued for Adolescents With Medical Conditions, Breastfeeding Mothers

April 21, 2017 03:53 pm Chris Crawford

On April 20, the FDA issued a safety announcement(www.fda.gov) restricting the use of codeine and tramadol in children and requiring changes to labeling of prescription medications containing these ingredients.

[APAP/Codeine warning lable on bottle]

"We are requiring these changes because we know that some children who received codeine or tramadol have experienced life-threatening respiratory depression and death because they metabolize these medicines much faster than usual (called ultra-rapid metabolism), causing dangerously high levels of active drug in their bodies," said Douglas Throckmorton, M.D., deputy center director for regulatory programs in the agency's Center for Drug Evaluation and Research, in a statement.(www.fda.gov)

Throckmorton said this risk is especially concerning in children younger than 12 and in adolescents who are obese or who have conditions that may increase the risk of breathing problems, such as obstructive sleep apnea (OSA) or lung disease.

"Respiratory depression can also occur in nursing babies, when mothers who are ultra-rapid metabolizers take these types of medicines and pass it along to their children through their breastmilk," he said.

Story highlights
  • On April 20, the FDA issued a safety announcement restricting the use of codeine and tramadol in children and requiring changes to labeling of prescription medications containing these ingredients.
  • Specifically, the FDA is adding a contraindication to the drug labels of codeine and tramadol products stating that codeine should not be used to treat pain or cough in children younger than age 12 and tramadol should not be used to treat pain in these patients.
  • Label warnings also will be added to recommend against use of these products in adolescents ages 12-18 who are obese or who have conditions such as obstructive sleep apnea or severe lung disease, because these drugs may increase the risk of serious breathing problems.

The new labeling requirements expand on the FDA's 2013 announcement(www.fda.gov) that codeine use was contraindicated in children younger than 18 to treat pain after tonsillectomy or adenoidectomy.

The specific updates are as follows:

  • The FDA is adding a contraindication to the drug labels of codeine and tramadol products stating that codeine should not be used to treat pain or cough in children younger than 12 and tramadol should not be used to treat pain in these patients.
  • A contraindication will be added to tramadol product labels warning against its use in children younger than 18 to treat pain after tonsillectomy or adenoidectomy.
  • A warning will be added to the drug labels of codeine and tramadol to recommend against their use in adolescents ages 12-18 who are obese or who have conditions such as OSA or severe lung disease.
  • A strengthened warning will be added to advise nursing mothers that breastfeeding is not recommended when taking codeine or tramadol medications because of the risk of serious adverse reactions in breastfed infants. These can include excessive sleepiness, difficulty breastfeeding or serious breathing problems that could result in death.

FDA Safety Review

In addition to its 2013 codeine label boxed warning, the FDA issued Drug Safety Communications in July 2015(www.fda.gov) and September 2015(www.fda.gov) warning about the risk of serious breathing problems with use of codeine and tramadol, respectively, in some children with ultra-rapid metabolism, which can cause potentially dangerous levels of the drug to accumulate in their bodies too quickly. As part of a safety review conducted at that time, the codeine-related safety issues were discussed at a joint FDA advisory committee meeting(www.fda.gov) in December 2015.

A review of several decades of adverse event reports submitted to the FDA from January 1969 to May 2015 identified 64 cases of serious breathing problems, including 24 deaths, attributed to codeine-containing medicines in children younger than 18. This included only reports submitted to the FDA, so there may be additional cases.

The FDA also identified nine cases of serious breathing problems, including three deaths, with the use of tramadol in children younger than age 18 from January 1969 to March 2016. The majority of serious side effects with both codeine and tramadol occurred in children younger than age 12, and some cases occurred after a single dose of the medicine.

In its review of medical literature for data on codeine use during breastfeeding, the agency found numerous cases of excessive sleepiness and serious breathing problems in breastfed infants, including one death.

Although a literature review for data on tramadol use during breastfeeding found no reports of adverse events, tramadol and its active form are also present in breastmilk, and tramadol has the same risks associated with ultra-rapid metabolism as codeine.

The FDA said it plans to continue to monitor this safety issue and is considering additional regulatory action for OTC codeine products that are available in some states, including those available in combination with other medicines for cough and cold symptoms.

Finally, the agency said it's considering convening an FDA advisory committee meeting to discuss the role of prescription opioid cough-and-cold medicines, including codeine, to treat cough in children.

Advice for Health Care Professionals

The FDA reminded health care professionals that tramadol and single-ingredient codeine medicines are only FDA-approved for use in adults.

The agency suggested other OTC or FDA-approved prescription medications as alternatives for cough and pain management in children younger than 12 and in adolescents younger than 18, especially those with certain genetic factors, obesity and/or OSA or other breathing problems.

Note, too, said the FDA announcement, that because cough is often secondary to infection and usually resolves on its own, treatment may not be necessary.

AAFP Commission on Health of the Public and Science member Kenneth Lin, M.D., M.P.H., of Washington, D.C., told AAFP News there are two compelling reasons this FDA announcement is long overdue:

  1. There's no evidence that medications containing codeine or tramadol provide cold or pain relief for children under 12.
  2. There's good evidence that they can cause harms, of which respiratory sedation is the most concerning since it can be life-threatening.

"The same applies for older children with OSA or other respiratory conditions, and to breastfeeding mothers who may pass the drugs on to their babies in breast milk," Lin said.

"Data show that substantial numbers of children are being prescribed these medications, so hopefully, the warning will alert physicians and parents to the dangers and encourage a discussion of less harmful alternatives, including OTC acetaminophen or ibuprofen."

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List of Prescription Codeine and Tramadol Pain and Cough Medicines: Triacin-C (cough)  
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List of Prescription Codeine and Tramadol Pain and Cough Medicines: Generic products containing codeine  
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