In the wake of the European Medicines Agency’s (EMA) recently announced warning against giving codeine to children under 12 years old, the FDA announced its own safety investigation of the drug for use in children. The FDA’s renewed interest in pediatric codeine use comes two years after the agency issued a black box warning, its strongest warning of potential harmful side effects, on codeine pain management for children following surgery to remove the tonsils and/or adenoids.

The black box warning stemmed from a series of incidents where children suffered serious injuries or died after surgery that was followed by a codeine pain management regimen. The FDA’s new investigation focuses on codeine in cough and cold medication administered to children, because of the risk of serious side effects, particularly for children with pre-existing breathing problems. This investigation targets both prescription and over-the-counter cold and cough medication with codeine.

Administering codeine to children is potentially problematic because of how it is metabolized. Codeine relieves pain as the liver converts it into morphine. Unfortunately, children who are “ultra-rapid metabolizers” turn too much codeine into morphine, up to 30 times more than an average metabolizer. These children can develop potentially life-threatening breathing problems from toxic levels of morphine. While codeine causes severe reactions in some children, others suffer from a lack of reaction. Up to one-third of children cannot fully metabolize codeine, leaving them without proper pain relief.

The American Academy of Pediatrics (AAP) first warned of codeine’s potential for harm in 1997. The AAP’s 1997 report found that cough medications with codeine were no more effective than the placebo in repressing a child’s cough. According to a 2014 study tracing the prescribing patterns for codeine nationwide, “[b]ecause of the unreliable effect of the drug and its associated risk for death, national and international guidelines have recommended against codeine use in children for both of its common indications, analgesia and cough suppression.”

The FDA’s announcement stated it will consider the EMA’s recommendations. The EMA recommended that codeine not be administered to any child under 12, and that children between 12 and 18 with a history of breathing problems likewise should not be given codeine.

The FDA also will hold a public advisory committee meeting to discuss the issue and consider the EMA’s recommendations. Once the meeting is scheduled, the FDA will post the announcement in the Federal Register and on the Advisory Committee’s web page.

The FDA urges healthcare providers, parents, and caregivers to report side effects involving codeine to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

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