What’s New in the Patient Safety World

May 2017

FDA Finally Restricts Codeine in Kids; Tramadol, Too



After almost 5 years of warnings about the safety of codeine in children (and more recent warnings about the safety of tramadol) the FDA (FDA 2017) is finally issuing its strongest warning, a Contraindication, alerting that codeine and tramadol should not be used to treat pain in children younger than 12 years, and codeine should not be used to relieve cough in these children. And it added a new Contraindication to the tramadol label to restrict its use in children younger than 18 years to treat pain after a tonsillectomy and/or adenoidectomy.


The FDA also issued 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 compromised respiratory function that may increase the risk of serious breathing problems. And it strengthened the Warning to patients that breastfeeding is not recommended during treatment with codeine or tramadol due to the potential for serious adverse reactions in a breastfed infant, such as excess sedation, respiratory depression, and death.


It also cautions healthcare professionals who determine that a codeine-or tramadol-containing product is appropriate for an adolescent patient to counsel parents and caregivers on how to recognize the signs of opioid toxicity, and advise them to stop giving the adolescent codeine or tramadol and seek medical attention immediately if their adolescent is exhibiting these signs.


The FDA safety announcement also has a list of prescription codeine and tramadol pain and cough medicines.


Our previous 6 columns on the dangers of codeine in children discussed the multiple prior safety alerts from the FDA (FDA 2012, FDA 2013, FDA 2015). These columns described cases of death and serious adverse effects in children treated with codeine following adenotonsillectomy for obstructive sleep apnea. The problem originally noted for codeine was that there are genetic variations that cause some people to be “ultra-rapid metabolizers” of codeine, which leads to higher concentrations of morphine in the blood earlier.


In our January 2016 What's New in the Patient Safety World column “FDA Gets Even Tougher on Codeine in Kids” we noted that an advisory committee to the FDA recommended that codeine be contraindicated for pain and cough management in children and adolescents (Firth 2015). They also recommended restricting codeine's over-the-counter availability for this group. Of 29 voting members, 20 voted to contraindicate use of the drug for pain and cough in children younger than 18 years old. Most of the others voted to restrict its use only in younger children. However, the FDA did not take formal action on those recommendations until now.


While the initial warnings focused on avoiding codeine in children who were undergoing adenotonsillectomy for obstructive sleep apnea (OSA), the dangers apply more globally to children. Perhaps influencing the FDA was the American Academy of Pediatrics in a statement “Codeine: Time to Say ‘No’ ” (Tobias 2016) that we discussed in our October 2016 What's New in the Patient Safety World column “Another Codeine Warning for Children. That paper reiterated the evidence of adverse effects of codeine in children and their mechanisms. It noted that codeine is still available in over-the-counter cough formulas in 28 states and the District of Columbia without a prescription. The Tobias paper also discussed the pros and cons of alternatives to codeine in the pediatric population, noting that almost all of them also have some potential downsides.


Our May 2014 What's New in the Patient Safety World column “Pediatric Codeine Prescriptions in the ER” noted the continued frequent prescription of codeine-containing products in children despite the previous warnings about adverse reactions. In our November 2015 What's New in the Patient Safety World column “FDA Safety Communication on Tramadol in Children” we noted that education does not seem to have reduced prescription of codeine-containing products. We therefore advocated incorporating “hard stops” (alerts requiring acknowledgement of the warnings about codeine or other opioid in children) into CPOE and e-prescribing systems.


We are pleased that the FDA has finally taken this action to restrict the use of codeine and tramadol in the pediatric population.




Some of our previous columns on opioid safety issues in children:







FDA (US Food & Drug Administration). FDA Drug Safety Communication: FDA restricts use of prescription codeine pain and cough medicines and tramadol pain medicines in children; recommends against use in breastfeeding women. FDA Safety Announcement 2017; April 20, 2017




FDA. FDA Drug Safety Communication: Codeine use in certain children after tonsillectomy and/or adenoidectomy may lead to rare, but life-threatening adverse events or death. 8/15/12




FDA. FDA Drug Safety Communication: Safety review update of codeine use in children; new Boxed Warning and Contraindication on use after tonsillectomy and/or adenoidectomy. Update February 20, 2013




FDA (Food and Drug Administration) Briefing Document: The safety of codeine in children 18 years of age and younger. Joint Pulmonary-Allergy Drugs Advisory Committee and Drug Safety and Risk Management Advisory Committee Meeting . December 10, 2015




Firth S. FDA Panel Urges Stronger Regulation of Codeine. An FDA advisory committee voted 28-0 to remove the drug from its OTC monograph for cough and cold. MedPage Today 2015; December 11, 2015




Tobias JD, Green TP, Coté CJ, Section on Anesthesiology and Pain Medicine, Committee on Drugs. Codeine: Time to Say “No”. Pediatrics 2016; Originally published online September 19, 2016






Print “PDF version













Tip of the Week Archive


What’s New in the Patient Safety World Archive