The American Academy of Pediatrics recommended against any use of codeine in children, citing genetic variants that affect the drug's metabolism and potentially make it lethal for certain patients.

For a small but non-negligible number of children, codeine treatment may cause respiratory depression or even death because they "overmetabolize" codeine into morphine, according to Joseph Tobias, MD, and colleagues in AAP's Section on Anesthesiology and Pain Medicine and its Committee on Drugs.

Writing in Pediatrics, they cite the number of health organizations that have issued regulatory warnings about the use of codeine in children -- most recently the European Medicines Agency in 2015, who recommended against using the drug in patients ages 12 years and younger.

An FDA advisory committee has already recommended stronger restrictions on the use of codeine in the pediatric population, though final agency action on those recommendations is still pending at this time, the authors wrote.



"I think we would like the FDA to really ban the use of codeine – it's not better than some of the alternative methods we have to control pain and it's an older drug, has to be metabolized to work. Given these risks, we really need to stop its use throughout the country," Tobias told MedPage Today separately. "I'd love to see a nationwide removal of codeine – not only for its use to control pain, but also as a cough suppressant and any other of these ancillary uses of codeine." Tobias added that many hospitals, including his own, have taken codeine off the formulary.

Codeine is a prodrug that has to be metabolized into morphine in order to be effective, and the authors estimated that genetic anomalies in a certain portion of patients may lead to overmetabolization of the drug. Research estimates these anomalies occur in almost 30% of African/Ethiopian heritage, 20% of those from the Middle East and about 3%-5% of other African-American and white individuals.

"As you look at the literature, we're seeing more and more case reports of patients dying after getting codeine and originally, maybe it was related to patients with sleep-disordered breathing or obstructive sleep apnea, but I think it became even more apparent that it was related to the excessive metabolism of codeine," said Tobias. "I think you put those risks together with the fact that there is no inherent advantage to codeine and you come to the conclusion of why are we even using it anymore."

The authors noted that codeine can be prescribed in the context of outpatient surgery, such as a tonsillectomy, and in fact, otolaryngologists were the most frequent prescribers of codeine (19.6%), followed by dentists (13.3%) and pediatricians (12.7%).

Alternatives to the drug for pain relief may include oxycodone, hydrocodone and oral morphine elixir -- although the authors noted there is insufficient data to endorse their "widespread" use in children.

In the case where codeine is still available over-the-counter -- as an antitussive agent for coughs -- Tobias said that patients and parents need more education from clinicians and pharmacists. He noted that cough syrup with codeine is still sold in 28 states and the District of Columbia.

"We need to warn patients and parents, if you're using an over-the-counter medication, read the ingredients and if they have questions, call the pediatrician or talk to a pharmacist," said Tobias. "Both clinicians and parents need to be more well-informed."