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.

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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.

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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.

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  • Thijs is ridiculous. Opiates have been in children’s medications since the late 19th century, and the generations who grew up between 1880 and 1914 (when the Harrison Act was passed) did not grow up to engage in the type of stereotypical antisocial that our government, media and Hollywood want us to believe to be the result of certain drugs leading to “addiction.”

  • So over 46 years, 64 kids died from using codeine cough syrup. How many kids died from croup or other respiratory conditions that are made worse by coughing? How many were prevented from going to the hospital (or dying) because they had effective codeine cough syrup? In my experience, properly administered (i.e. not too much) codeine-containing cough syrup is VERY effective for overnight coughing. (Not particularly effective in the day, as I think it’s primary means of efficacy is by allowing the patient to sleep.)

    • Excellent point.

      Autopsies are expensive, and if you divide the number of deaths by the amount America expends on death investigations, it runs at less than $3 per deceased. Most American decedents are not autopsied.

      Also, it’s important to realize “opiate death” is a bureaucratic category, a box on a form, not the result of a scientific investigation. Numbers of deaths attributed to opiates cannot possibly be accurate. Among the 2342 offices that have the authority to declare a cause of death on a birth certificate, 2/3 are run by elected coroners, most required to have no scientific or medical credentials, 2/3 have no in-house toxicology lab (sending samples out for drug testing is not cheap), 2/3 have no in-house histology lab, 1/3 have no in-house x-ray. Both jurisdictions with medical examiners and with coroners suffer chronic shortages of staff.

      Also note that someone who uses opiates (whether prescribed or illicit), can die of something other than opiates – say being hit by a bus, or having a health problem that caused the pain treated with the opiate

      Different death investigation offices test for different drugs, or the same office may test for different drugs in different years. Federal totals of opiate deaths were determined not just by the cause-of-death, but, “Relative increases in the death rates involving specific drugs and the rankings of these drugs may be affected by improvements in reporting, real increases in the numbers of death, or both.”
      https://www.cdc.gov/nchs/data/nvsr/nvsr65/nvsr65_10.pdf

      “ First, several factors related to death investigation might affect estimates of death rates involving specific drugs. At autopsy, toxicological laboratory tests might be performed to determine the type of drugs present; however, the substances tested for and circumstances under which the tests are performed vary by jurisdiction. Second, in 2013 and 2014, 22% and 19% of drug overdose deaths, respectively, did not include information on the death certificate about the specific types of drugs involved. The percent of overdose deaths with specific drugs identified on the death certificate varies widely by state. Some of these deaths might have involved opioids. This increase in the reporting of specific drugs in 2014 might have contributed to some of the observed increases in drug overdose death rates involving different types of opioids from 2013 to 2014.”

      —https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6450a3.htm

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