FDA warns of codeine, breast milk

Breast- feeding mothers who take medications containing codeine should watch their infants for possible signs of morphine overdose, such as becoming overly sleepy, Food and Drug Administration officials warned Friday.

A new agency advisory says that a small percentage of mothers metabolize codeine at rapid rates, turning it into morphine and putting their babies at risk for overdose.

The agency became aware of the issue after the death of a 13-day-old Toronto infant last year was attributed to his mother’s being an “ultra-rapid metabolizer.”

“When codeine enters the body and metabolizes, it changes to morphine,” said Dr. Sandra L. Kweder, the FDA’s deputy director of the Office of New Drugs. “That can be transported in the blood and through breast milk.”

Kweder said some people have a biological variation in a liver enzyme that renders them capable of changing codeine to morphine more quickly and completely than others do.

Codeine is often taken by women who have recently given birth -- after caesarean sections and episiotomies, for instance. Codeine is common in low-grade painkillers such as some forms of Tylenol and even in some nonprescription cough syrups.

The FDA has asked makers of codeine-containing drugs to include a warning on labels about the danger of passing morphine through breast milk.

However, officials said they did not want to discourage breast-feeding. “Our best advice to physicians prescribing codeine-containing products to nursing mothers is to prescribe the lowest dose needed for the shortest amount of time,” said Kweder.

The advisory also advised mothers to be vigilant about monitoring the side effects they might experience, and especially to watch for any effects the drugs might have on their infants.

Common symptoms of morphine problems in infants include sleeping for long stretches, having problems breast-feeding, being constipated, having breathing problems and showing limpness in the arms and legs.

For a first-time parent or someone who has not taken a codeine-containing medicine before, knowing when to become concerned can be difficult, acknowledged Marcia L. Buck, a clinical associate professor at the University of Virginia medical center.

Such parents should maintain “a very low threshold” for deciding when to seek help, she said. “Don’t hesitate to call in to the doctor’s office.”

In the Toronto case, a woman took her son to the pediatrician four days after he became lethargic and started to refuse to breast-feed. Two days after that visit, the baby died. He had more than six times the safe limit of morphine in his body.

New genetics technology that makes it possible to classify how well a person metabolizes certain drugs is moving medicine forward. But Buck said it is also making the FDA’s job more difficult.

“I understand their dilemma about wanting to be transparent and get information out, and at the same time not alarm the public,” she said. “To be clear, this is something that is rare.”

According to Kweder, FDA studies have found that 1% to 10% of whites and about 3% of Asian Americans and African Americans have the liver enzyme combination that causes them to be rapid metabolizers.

North Africans, Saudis and native Africans are at higher risk of having the combination: Up to 28% of those populations are rapid metabolizers, according to some studies.

The FDA recently approved a test for liver enzymes that can diagnose someone as an ultra-rapid metabolizer, but it is a costly and uncommon procedure.

“We wouldn’t even make it a recommendation for the average breast-feeding woman,” said Buck.

“It costs between $100 and $500, and the average third-party payer [health insurance] doesn’t cover it.”

claudia.lauer@latimes.com