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In ambulatory care, 75% of pediatric off-label drugs used for unapproved conditions
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During a recent 10-year period, physicians in the United States ordered at least one off-label systemic drug in nearly 19% of pediatric ambulatory care visits, and around 75% of the orders were for unapproved conditions, according to findings published in Pediatrics. This trend contradicts recent efforts to increase evidence and drug approvals for children, researchers noted.
“Children often take drugs off label, outside of an approved age, indication, weight, dose, formulation, or route of administration,” Divya Hoon, from the Rutgers Robert Wood Johnson Medical School, and colleagues wrote. “Off-label prescribing has been associated with higher rates of adverse effects in children.”
Although the practice can be potentially harmful for children, off-label prescribing is legal and “can represent best practice on the basis of extensive clinical experience and supporting evidence of efficacy and safety,” the researchers wrote. This is particularly common when no labeled alternatives exist, they added.
To characterize frequencies, trends and reasons for off-label systemic drug orders for children in U.S. ambulatory settings, Hoon and colleagues analyzed data from the National Ambulatory Medical Care Surveys, which were distributed to office-based physicians between 2006 and 2015. They specifically studied off-label orders of systemic drugs for children aged younger than 18 years, based on FDA-approved labeling for age, indication and weight. Using logistic regression, they characterized the top classes and diagnoses with off-label orders and analyzed trends and factors of these orders.
They found that physicians ordered one or more off-label systemic drugs at 18.5% (95% CI, 17.7%-19.3%) of visits. Of these, 74.6% were because of unapproved conditions, they reported. The practice was most common proportionally in neonates (83%) and in absolute terms among adolescents, with 322 orders out of 1,000 visits, they wrote. It was also associated with several factors, including female sex, subspecialists, polypharmacy and chronic conditions. Age played a significant role in rates and reasons for off-label orders — a notable example included absolute rates of off-label orders being higher in nervous system drugs for adolescents, with 123 orders per 1,000 visits, according to the researchers.
Over time, relative and absolute rates of off-label orders increased. They observed this increase among common classes, which included antihistamines and several psychotropics. However, off-label orders for several classes of antibiotics declined or remained stable, they said.
“The rates and reasons for off-label orders vary by age, with more off-label orders for [gastrointestinal] conditions in the youngest age groups, psychiatric conditions in older age groups, and infections and respiratory across age groups,” they wrote. “These results can help inform ongoing education, research, and policies around efficacious, effective, and safe use of medications in children.”
In a related editorial, Katelyn Yackey, MD, assistant professor of emergency medicine at the University of Kentucky, and Rachel Stanley, MD, MHSA, chief of the division of emergency medicine at Nationwide Children's Hospital, noted the tension between efficacy and risk for physicians to recommend off-label drugs.
“[O]ff label is not synonymous with off evidence,” they wrote. “Although drugs are often used off label, there may be sufficient preliminary research about a medical condition and particular drugs to support their use. This highlights the continued need for comprehensive drug development studies evaluating safety, efficacy, pharmacokinetics, and optimal dosing in pediatric patients.” – by Joe Gramigna
Disclosures: The authors report no relevant financial disclosures.
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