Table 1

Main Food and Drug Administration (FDA) drug safety communications restricting the use of codeine in children in the USA

DateSafety announcementMain evidence behind announcement*
20 February 2013Boxed warning and contraindication restricting the use of codeine in postoperative pain management in children (age<18 years) following tonsillectomy and/or adenoidectomy.13 cases of paediatric deaths associated with codeine between 1969 and 2012 in the FDA’s Adverse Event reporting System database. Most of the cases (11/13) were reported in the setting of adenotonsillectomy (n=8) or respiratory tract infection (n=3). In most of these cases, the children appeared to receive appropriate doses of codeine. Suspicion that cytochrome P450 2D6 (CYP2D6) metaboliser status was among the reasons behind the deaths, with some of these children being characterised as ultrarapid metabolisers (rapid conversion of codeine into morphine).
20 April 2017Contraindication for the use of codeine to treat pain or cough in children aged<12 years.
Boxed warning recommending against the use of codeine in adolescents (age 12–17 years) who are obese or have conditions such as obstructive sleep apnea or severe lung disease.
64 cases of respiratory depression, including 24 deaths, with codeine-containing medicines in children aged<18 years. Fifty of the 64 cases (78.1%) occurred in children aged<12 years.
Of the 24 cases reporting death, 21 (87.5%) occurred in children aged<12 years. The reasons for codeine-containing medicine use in these cases included post-tonsillectomy and/or adenoidectomy pain management, other postoperative pain, general pain, sore or strep throat pain and cough and cold. Although few cases mentioned the status of CYP2D6 genotype, ultrametabolisation remains a key suspected driver of these adverse events.
11 January 2018Safety labelling changes contraindicating the use of prescription opioid cough and cold medicines containing codeine in children aged<18 years.After FDA review of the data and discussion with a panel of outside experts, there was a conclusion that the risks of slowed or difficult breathing, misuse, abuse, addiction, overdose and death with these medicines outweigh their benefits in patients younger than 18 years.
  • *These are based on information provided in the drug safety communications published in the FDA’s website.