New Brunswick, NJ—Increasing use of off-label prescriptions for children is raising concerns, according to a new study.

The report, published in the journal Pediatrics, analyzed data collected from 2006 to 2015 in the CDC’s National Ambulatory Medical Care Surveys, which provide information on physician office visits in the United States.

The study, touted as the first in a decade to look at how U.S. doctors outside of hospitals order a broad range of medicines off-label to children, focused on systemic drugs prescribed for pediatric conditions not approved by the FDA. The Rutgers Robert Wood Johnson Medical School–led researchers documented increases, despite recent efforts to bolster evidence and drug approvals for children.

“Off-label drug use in children is common and potentially harmful,” the authors write, adding, “In most previous off-label use research, authors studied hospitalized children, specific drug classes, or non-U.S. settings.”

In response, the study team characterized frequencies, trends, and reasons for off-label systemic drug orders for children in ambulatory U.S. settings. Looking at labeling for age, weight, and indication, researchers determined the top classes and diagnoses with off-label orders and analyzed factors and trends leading to them.

Results indicate that physicians ordered one or more off-label systemic drug at 18.5% (95% CI, 17.7%-19.3%) of visits, usually (74.6%) because of unapproved conditions.

The study found off-label ordering most common proportionally in neonates (83%). At the same time, off-label prescribing for adolescents occurred in 322 orders out of 1,000 visits.

Researchers documented that off-label ordering tended to be associated with female sex, subspecialists, polypharmacy, and chronic conditions, although rates and reasons for off-label orders varied considerably by age.

The study also points out that relative and absolute rates of off-label orders rose over time. “Among common classes, off-label orders for antihistamines and several psychotropics increased over time, whereas off-label orders for several classes of antibiotics were stable or declined,” researchers report.

“US office-based physicians have ordered systemic drugs off label for children at increasing rates, most often for unapproved conditions, despite recent efforts to increase evidence and drug approvals for children,” study authors conclude. “These findings can help inform education, research, and policies around effective, safe use of medications in children.”

“Off-label medications—meaning medications used in a manner not specified in the FDA’s approved packaging label—are legal. We found that they are common and increasing in children rather than decreasing,” explained senior author Daniel Horton, MD, assistant professor of pediatrics and a pediatric rheumatologist at Rutgers Robert Wood Johnson Medical School. "However, we don’t always understand how off-label medications will affect children, who don’t always respond to medications as adults do. They may not respond as desired to these drugs and could experience harmful effects.”

The study notes that in about 19% of the estimated 2 billion office visits for children in the study, one or more off-label systemic drugs were prescribed, often for common conditions such as respiratory infections, asthma, or mental-health disorders.

In visits with at least one drug order, physicians ordered drugs off-label in about 83% of newborn visits, 49% of infant visits, and about 40% of visits for other ages, according to the study, which also found that rates of ordering off-label increased from 42% in 2006 to 47% in 2015.

Most frequently ordered off-label were antihistamines for respiratory infections, several classes of antibiotics for respiratory infections, and antidepressants for attention-deficit/hyperactivity disorder. “Use of some off-label drugs is supported by high-quality evidence,” Dr. Horton points out. “For example, drugs approved to prevent vomiting caused by chemotherapy also work quite well in treating more common causes of vomiting in children, such as from viruses. We need this kind of evidence to determine the appropriateness of use of many other drugs currently used off-label to treat a wide range of conditions in children.”

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