FDA Warns of Codeine Use in Nursing Mothers With Genetic Variation

Nursing infants may be at an increased risk of morphine overdose if their mothers take codeine and have a genetic variation that causes them to be “ultra-rapid metabolizers” of the drug, the FDA warned.

Once codeine is in the body, some of it is metabolized into morphine. However, ultra-rapid metabolizers convert the drug too quickly, leading to high levels of morphine in the blood and breast milk that can be transferred to a nursing infant, CDER’s Office of New Drugs Deputy Director Sandra Kweder said.

High levels of morphine can lead to severe and life-threatening side effects in infants if not addressed, Kweder added. The agency began investigating the topic after an article in The Lancet last year reported the death of a 13-day-old nursing infant who died from a morphine overdose. Although the mother was taking small doses of codeine, the morphine levels in her breast milk were abnormally high. A genetic test showed the mother was an ultra-rapid metabolizer of morphine, the agency said.

Some people have a variation in a liver enzyme that makes the change from codeine to morphine more rapid and more complete, Kweder said. While most people do not know if they have the variation, there is a widely available, FDA-approved genetic test to determine whether a patient has the variation, she added.

The FDA is requiring manufacturers of prescription products containing codeine to include the information about the risk for nursing infants in their drug labeling, Kweder said, adding that the use of codeine to manage pain after birth is common. In addition, manufacturers of OTC products containing codeine will put similar information on their labels, she said.