Despite a lack of data on efficacy and safety, off-label medications are often prescribed to children. Most studies assessing off-label use have focused on inpatient settings specific drugs or drug classes, or non-US settings. To characterize frequencies, trends, and reasons for off-label systemic drug use orders for US children in ambulatory settings, Daniel B. Horton, MD, MSCE, and colleagues conducted a study that was published in Pediatrics.

The researchers used data from the National Ambulatory Medical Care Survey to assess rates of off-label orders—based on FDA-approved labeling for age, weight, and indication—for more than 140 drugs and nearly 50 drug classes among children younger than 18 between 2006 and 2015. “We focused on systemic medicines, given their greater potential for causing side effects and toxicities,” explains Dr. Horton.

Physicians in this nationally representative sample ordered one or more off-label systemic drugs at nearly one-fifth of visits, most often because of unapproved conditions (75%). Whereas rates and reasons for off-label use varied by age group, the practice was most common proportionally in neonates (83%) and in absolute terms among adolescents (322 orders per 1,000 visits). Female sex, subspecialists, polypharmacy, and chronic conditions were associated with off-label ordering. “As we hypothesized, off-label drug use in children has been rising in the US, both in absolute rates and relative to all drugs ordered,” adds Dr. Horton. “In particular, physicians are increasingly ordering medicines to treat children with unapproved conditions, including antihistamines, antidepressants, corticosteroids, and acid suppressive drugs.”

Dr. Horton notes that pediatricians and others who treat children are well aware that some off-label medication use is clinically appropriate and supported by evidence or extensive clinical experience. But for cases in which off-label use is not well support by evidence, or “off-evidence,” he suggests that more research is needed to promote safe and effective use of such agents. In the meantime, he recommends that “when considering a treatment for a child that is off-label and off-evidence, doctors should ideally engage the patient and family in shared decision making, discussing what is and is not known about the drug, assessing the family’s priorities and risk tolerance, and making sure that the potential benefits outweigh the potential risks for that child.”


Trends in Off-Label Drug Use in Ambulatory Settings: 2006–2015