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Off-Label Prescribing Common in Pediatric Ambulatory Care

September 17, 2019

By Anne Harding

NEW YORK (Reuters Health) - Nearly one in five pediatric ambulatory visits includes an order for at least one off-label systemic drug, according to new findings.

Three-quarters of off-label drugs were prescribed for unapproved conditions, Dr. Daniel B. Horton of Rutgers University in New Brunswick, New Jersey, and colleagues report in Pediatrics, online September 16.

"While some off-label use of medicines in children is clinically appropriate and supported by evidence or many years of clinical experience, that is not true for other off-label use," Dr. Horton told Reuters Health by email.

"When considering a treatment for a child that is off-label and off-evidence, doctors should engage the patient and family in shared decision-making, discussing what is and is not known and making sure that the potential benefits outweigh the potential risks for that child," he said.

The dearth of evidence from pediatric clinical trials means that many drugs are not indicated for children, Dr. Horton and his team note. While U.S. and European laws passed in the early 2000s have required or incentivized pediatric clinical trials, they add, "legislative efforts to stimulate clinical trials for both new and off-patent drugs may not yet have realized their potential."

Past studies of off-label drug prescribing in children have focused on inpatient settings and particular classes of drugs, or have been done outside the U.S.

To investigate trends in off-label drug use in the outpatient setting, where the vast majority of children receive care, the authors reviewed 2006-2015 data from the National Ambulatory Medical Care Survey (NAMCS) on 141 commonly used systemic drugs.

Of an estimated 1.74 billion ambulatory visits, 41.5% included an order for at least one of the drugs studied. And in 18.5% of visits at least one of the drugs was prescribed off-label, for a total of 41.2 million off label orders per year.

Orders were most often considered off-label because they were prescribed for an unapproved indication (74.6% of visits), while 17.6% were off label by age, 0.6% by weight and 4.7% by age, indication and weight when applicable.

Adolescents were the most likely to receive an off-label prescription, in absolute terms (321.5 orders per 1,000 visits), while neonates were the least likely (52.0 orders per 1,000 visits).

However, the youngest patients had the highest relative risk of being prescribed off-label drugs; about 83% of neonatal visits and 49% of infant visits included off-label prescribing, compared to 39%-44% for older patients.

The absolute rate of off-label orders was highest for nervous system drugs prescribed to adolescents (123 orders per 1,000).

Off-label ordering also increased over time in both absolute and relative terms, representing 47.2% of orders in 2012-2015 versus 41.9% in 2006-2008.

Off-label orders were relatively higher for girls, children with chronic illness or multiple drug orders, for subspecialists, and in the South.

Antihistamines were the drug class most commonly prescribed off-label, particularly for respiratory infections and illness, followed by several types of antibiotics, especially for viral infections, and antidepressants, particularly for ADHD.

In a study published earlier this year in JAMA Pediatrics, Dr. Horton and his colleagues found that antihistamine orders for acute respiratory illness increased at the same time as orders for cough and cold medications declined.

"We need more research on the factors driving the trends for antidepressants and many other medicines given to children, and the health consequences of these trends," the researcher said.

In an editorial accompanying the study, Dr. Katelyn Yackey of the University of Kentucky in Lexington and Dr. Rachel Stanley of Nationwide Children's Hospital in Columbus, Ohio, write, "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."


Pediatrics 2019.

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