The Food and Drug Administration (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 also recommends against the use of codeine and tramadol medicines in breastfeeding mothers due to possible harm to their infants.

As a result, FDA requires several changes to the labels of all prescription medicines containing these drugs. 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.

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.

In early 2013, FDA added a Boxed Warning to the codeine drug label cautioning against prescribing codeine to children of any age to treat pain after surgery to remove tonsils or adenoids. FDA also issued Drug Safety Communications in July 2015 and September 2015 warning about the risk of serious breathing problems in some children who metabolized codeine and tramadol much faster to their active form than usual (called ultra–rapid metabolism), causing potentially dangerously high levels in their bodies too quickly.

Our review of several decades of adverse event reports submitted to FDA from January 1969 to May 2015 identified 64 cases of serious breathing problems, including 24 deaths, with codeine–containing medicines in children younger than 18 years. FDA also identified nine cases of serious breathing problems, including three deaths, with the use of tramadol in children younger than 18 years from January 1969 to March 2016 (see Data Summary). The majority of serious side effects with both codeine and tramadol occurred in children younger than 12 years, and some cases occurred after a single dose of the medicine.

In our review of the medical literature for data regarding codeine use during breastfeeding, FDA found numerous cases of excess sleepiness and serious breathing problems in breastfed infants, including one death. A review of the available medical literature for data regarding tramadol use during breastfeeding did not reveal any cases of adverse events. However, tramadol and its active form are also present in breast milk, and tramadol has the same risks associated with ultra–rapid metabolism as codeine.