Rare Side-Effect of Codeine in Nursing Mothers
FDA Patient Safety News: Show #69, November 2007
FDA is alerting healthcare professionals about a very rare but serious side effect that can affect the babies of nursing mothers who are taking drugs that contain codeine. The problem affects mothers who are "ultra-rapid metabolizers" of codeine. Ultra-rapid metabolizers have a specific genotype that causes them to convert codeine to its active metabolite, morphine, more rapidly and completely than other people. This can result in the mother having unusually high morphine levels in her serum and breast milk, and this can put her nursing infant at risk of morphine overdose.
A recent report in the literature described a healthy, 13-day-old breast-feeding baby who died of a morphine overdose. His mother was taking codeine at less than the usual analgesic dose.
The prevalence of the ultra-rapid metabolizers of codeine varies for different populations. Among Caucasians, the figure is about 1 to 10 percent. Among African-Americans, about 3 percent are ultra-rapid metabolizers of codeine, and among Asians and Hispanics, about 1 percent. The highest prevalence is among some groups of North Africans, Ethiopians and Saudis, where it can be as high as 28 percent.
It is important to note that nursing mothers have used codeine safely for many years. Many women are sent home after having a baby with analgesics such as acetaminophen with codeine to relieve episiotomy pain or abdominal cramping and many of these women are also breast feeding. Despite this widespread use, FDA was able to find only the one case where the baby clearly died as a result of morphine overdose from breast milk. This means that many breast fed babies born to mothers who are ultra-rapid metabolizers and who are taking codeine will not have a problem, but some babies may.
FDA has cleared a genetic test that can determine whether someone is a rapid metabolizer of a number of drugs, but there's only limited information on using it for codeine. Which means at this point, the test result alone may not correctly predict whether the mother is an ultra-rapid metabolizer of codeine. In other words, the test is not a substitute for a doctor's judgment.
FDA recommends that clinicians who prescribe codeine for a nursing mother do so in the lowest dose for the shortest period of time in order to relieve pain. Clinicians should also educate nursing mothers who may be taking codeine about the signs of morphine overdose in themselves or their infants.
Mothers should understand that they don't need to go without pain relief if they're breast feeding, but they should know what to look for if there's a morphine overdose. For the mother herself, the signs include extreme sleepiness and constipation. The mother should also watch for increased sleepiness in her baby, keeping in mind that breastfed babies usually nurse every two to three hours and shouldn't sleep more than four hours at a time. She should also watch for trouble breast feeding, breathing difficulties and limpness. Mothers should also be aware that morphine may remain in the infant's body for up to several days after the last codeine dose.
Finally, in order to help the FDA understand and quantify this problem, it's important to report possible cases of morphine overdose in mothers and infants. To report an adverse event to the FDA please see the below link.
Additional Information:
FDA MedWatch Safety Alert. Codeine Products Used By Nursing Mothers. August 17, 2007.
http://www.fda.gov/medwatch/safety/2007/safety07.htm#Codeine
FDA MedWatch. Reporting Adverse Events to FDA. April 19, 2007.
http://www.fda.gov/medwatch/how.htm