From the Journals

Buprenorphine endangers lives and health of children



Eleven children died from exposure to buprenorphine – a drug used to treat opioid exposure – from 2007 to 2016, mostly very young children who accidentally ingested the drug.

Four deaths, however, were teens who took buprenorphine recreationally or used it in a suicide attempt, according to a new database review by Sara Post, MS, of the Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, and her associates.

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“In 2016, the American Academy of Pediatrics issued a statement advocating for increased access to buprenorphine for opioid-addicted adolescents in primary care settings,” the authors noted. “This recommendation is warranted because of the high and increasing prevalence of opioid dependence among adolescents. However, caution should be used, because increased prescriptions among adolescents could lead to increased diversion and abuse and increased access to younger children in the home. Therefore, patient education for adolescents should include information about the dangers of misusing and/or abusing prescription drugs and the proper storage of medications.”

The deaths comprise a small fraction of the 11,275 children aged 19 years and younger whose buprenorphine ingestions were reported to a poison control center during that time, the investigators said. Nevertheless, almost half (45%) of the exposed children were admitted to a health care facility – with 22% needing treatment in a critical care unit.

The rate of exposures was highest during the years when only tablet formulations were available and fell after film was introduced, wrote Ms. Post, a medical student at the Northeast Ohio Medical University in Rootstown, and her colleagues. But after 2013, the rate held steady, at about 38 exposures per 1 million children per year.

Childproof packaging for all buprenorphine formulations could help protect younger children, and education could help protect older ones, she and her coinvestigators said. Manufacturers should use unit-dose packaging for all buprenorphine products to help prevent unintentional exposure among young children. Health care providers should inform caregivers of young children about the dangers of buprenorphine exposure and provide instructions on proper storage and disposal of medications. Adolescents should receive information regarding the risks of substance abuse and misuse.”

Ms. Post and her colleagues analyzed calls to poison control centers affiliated with the National Poison Data System from 2007 to 2016. During that time, the centers received 11,275 calls about buprenorphine exposure among children and adolescents 19 years and younger.

The mean age of exposure in children was about 4 years; children younger than 6 years comprised 86% of the exposures (9,709).

The investigators noted temporal trends in exposure rates in this group. From 2007 to 2013, the rate increased by 215%, peaking at 20 per 1 million in 2010. A decline followed, with exposure dropping to 12 per 1 million in 2013, before rising again to 13 in 2016.

The increase “was likely attributable to the increasing number of buprenorphine prescriptions dispensed since the Food and Drug Administration approved its use as a treatment of opioid dependence in 2002,” Ms. Post and her colleagues wrote.

The transient decrease may have been related to a shift in adult prescribing patterns, as the drug was prescribed less often to those in their 20s and gradually given more often to people aged 40-59 years.

The decrease also was probably related to the packaging shift from tablet to film. “In 2013, the leading brand-name tablets were voluntarily withdrawn from the U.S. market because of potential risk of unintentional pediatric exposures,” the team wrote. Unfortunately, the film packaging didn’t completely deter some children; from 2013 to 2016, there was a 30% increase in the frequency of exposures to buprenorphine film.

The bulk of exposures were unintentional (98%) and involved ingestion of a single buprenorphine product. However, the authors noted, even a single adult therapeutic dose can be extremely dangerous to a small child.

“Therapeutic doses of buprenorphine-naloxone for pediatric patients are 2 to 6 mcg/kg, so ingestion of a single 2-mg sublingual tablet in a 10-kg child can result in more than a 30-fold overdose. This is particularly dangerous, because children exposed to buprenorphine do not display the ‘ceiling effect’ reported in adults, in which escalating doses do not lead to additional increases in respiratory depression,” Ms. Post and her coauthors said.

This was reflected in the serious clinical effects experienced: respiratory depression, bradycardia, coma, cyanosis, respiratory arrest, seizure, and cardiac arrest. These youngest children experienced the most serious outcomes, with half requiring a hospital admittance and 21% experiencing a serious medical outcome. Seven died, six of whom were 2 years or younger.

There were 315 (3%) exposures in children aged 6-12 years; most of these (83%) were either unintentional or therapeutic errors (18%). About 30% of the group required hospital admission and about 12% experienced a serious medical outcome. There were no fatalities among this group, the investigators noted.

Among adolescents aged 13-19 years, there were 1,251 (11%) exposures and four deaths. The bulk of these (77%) was intentional, with suspected suicide accounting for 12%, and 30% involving more than one substance. The exposure rate followed the same general trends, rising to a peak of about 6 per 1 million in 2010 and the falling and leveling off at about 3 per 1 million in 2016, they said.

About 22% of teen exposures required hospital admission, with 11% needing treatment in a critical care unit. The four deaths, one of which was a suicide, all involved multiple substances (benzodiazepines, alcohol, and marijuana).

Ms. Post received a research stipend from the National Student Injury Research Training Program while she worked on the study. The coauthors had no relevant financial disclosures.

SOURCE: Post et al. Pediatrics. 2018;142:e20173652 .

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