FDA panel says risk of opioid use in kids’ cough medicines outweighs benefits

ROCKVILLE, Md. — A federal advisory committee sent a strong message to the Food and Drug Administration on Monday, declaring nearly unanimously that the risks of using certain opioids in children’s cough medications outweighs the benefits.

“We have a disease with a very low risk profile, yet we’re looking at a drug that has a risk of death,” said Dr. Christy Turer, an assistant professor of pediatrics, clinical sciences, and medicine at the University of Texas Southwestern. “That, to me, seems very disproportionate.”

The recommendation by the FDA advisory committee was part of the agency’s ongoing effort to consider whether and how opiates and opioids should be used in medicine for children, an issue that has been the subject of hearings and warnings for a decade. The panel on Monday was convened to consider whether the benefits of children using cough medications containing codeine or hydrocodone outweigh the risks, focusing specifically on children in two age groups: those 6 to 12, for whom the FDA already recommends against using codeine for cough, and those 12 to 18.

With increased public attention on prescription opioid abuse, the meeting was also cast as an attempt to think about the question of cough medicine in a new way, taking into account the broad public health implications of a world with more opioids.

But a Harvard professor who gave a presentation at the meeting questioned whether focusing on age limits was the most effective way to stop abuse.

“It’s not clear to me that changing the age will have the largest impact on this, because most of the misuse that we’re seeing in adolescents is actually due to diversion, and not necessarily that kids are misusing the medications that are prescribed to them,” said Dr. Sharon Levy, assistant professor of pediatrics at Harvard Medical School and the director of the adolescent substance abuse program at Boston Children’s Hospital.

Doctors on the committee mainly expressed concern not that kids will get addicted to codeine or hydrocodone in cough medicine prescribed to them — rather, that there’s little evidence the drugs work to treat cough in children, and there’s lots of evidence that they can have serious side effects. The body turns codeine into morphine, but at unpredictable rates, so the safe dose for one child could be deadly for another.

“I haven’t … ever been taught that morphine is an appropriate anti-cough medicine,” said Dr. Kelly Wade, a neonatologist at the Children’s Hospital of Philadelphia. She added, “This is really historic and antiquated cough medicine.”

Indeed, one committee member compared the question of the day to “Mrs. Winslow’s Soothing Syrup,” a 19th-century cough medicine, ridiculed as a “baby killer” in a 1911 American Medical Association publication, “Nostrums and Quackery.” The active ingredient in the syrup was morphine.

The FDA already warned in August that cough syrup containing codeine should not be given to children younger than 12. If the agency acts in line with this advisory committee, it might consider expanding the warning for children up to age 18.

The August warning came after a different FDA advisory committee meeting in December 2015. After the committee discussed the safety of codeine in children, a majority voted to recommend that codeine not be used to treat cough in children under 18.

But the agency decided not to follow the committee’s advice, limiting its warning to cover only children under the age of 12. A couple of attendees at Monday’s meeting asked why.

“It was a difficult decision,” said Dr. Sally Seymour, the deputy director for safety in the division of pulmonary, allergy, and rheumatology products at the Center for Drug Evaluation and Research at the FDA, who participated in the 2015 meeting. “In the end, we came to the decision primarily on the data and where the cases were for respiratory depression and death, and they were primarily in children less than 12 years of age.”

Those data come from the FDA Adverse Event Reporting System. Between January 1969 and May 2015, there were 64 reported cases of respiratory depression, which is incredibly slow breathing that leads to a buildup of carbon dioxide in the lungs. Twenty-four of those cases resulted in death in individuals younger than 18, according to the agency.  Twenty-one of those children who died were younger than 12.

Seymour also noted that the FDA wanted to make sure that cough medicines containing codeine were available for older children who needed them, while keeping them away from children who might be more at risk of being harmed.

Some committee members also brought up over-the-counter medications that contain codeine, and wondered whether they would be dealt with in a similar way to prescription medications.

“We do think that, ultimately, whatever decision you make today with respect to what you would recommend for the prescription products will be — we will try to apply those consistent determinations to what is done with the OTC products,” said John Alexander, the FDA’s deputy director for the division of pediatric and maternal health in the Office of Drug Evaluation in the Center for Drug Evaluation and Research.