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

Abstract

BACKGROUND: Off-label drug use in children is common and potentially harmful. In most previous off-label use research, authors studied hospitalized children, specific drug classes, or non-US settings. We characterized frequencies, trends, and reasons for off-label systemic drug orders for children in ambulatory US settings.METHODS: Using nationally representative surveys of office-based physicians (National Ambulatory Medical Care Surveys, 2006, we studied off-label orders of systemic drugs for children age ,18 based on US Food and Drug Administration-approved labeling for age, weight, and indication. We characterized the top classes and diagnoses with off-label orders and analyzed factors and trends of off-label orders using logistic regression.RESULTS: Physicians ordered $1 off-label systemic drug at 18.5% (95% confidence interval: 17.7%-19.3%) of visits, usually (74.6%) because of unapproved conditions. Off-label ordering was most common proportionally in neonates (83%) and in absolute terms among adolescents (322 orders out of 1000 visits). Off-label ordering was associated with female sex, subspecialists, polypharmacy, and chronic conditions. Rates and reasons for off-label orders varied considerably by age. 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.CONCLUSIONS: 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. These findings can help inform education, research, and policies around effective, safe use of medications in children.WHAT'S KNOWN ON THIS SUBJECT: In past studies, pediatric off-label use was shown to be common and potentially harmful, but researchers have focused predominantly on acute care settings, specific classes of drugs, outpatient prescribing outside the United States, or older data sources. WHAT THIS STUDY ADDS:In 2006-2015, US office-based physicians ordered systemic drugs off label for children at rising rates, particularly for unapproved conditions. Updated data on common off-label drugs, classes, and unapproved conditions treated in children will help inform education, research, and policies.

Pharmacotherapy for the Treatment of Overweight and Obesity in Children, Adolescents, and Young Adults in a Large Health System in the US

“…A recent study demonstrates that pediatricians are least likely to become certified by the ABOM to treat patients with obesity despite the consistent rise of obesity among the pediatric population (19,46). Still, off-label systemic medication prescribing for unapproved conditions in pediatrics has increased in recent years (47). As seen in this study, most of the medications on market and in use for separate indications are FDA-approved for adults for obesity and are often used off-label to treat obesity in the pediatric population.…”

Valproic Acid Induced Pancreatitis Presenting With Decreased Level of Consciousness in a Child With Tuberous Sclerosis Complex

“…3,4 Children with chronic neurologic conditions are particularly at risk of ADRs because of underlying conditions and the high frequency of polypharmacy. 2,5 The highest rate of fatalities due to antiepileptic drugs (AEDs) have been reported to occur in children. 6 One such widely used AED, valproic acid (VPA), has regularly been incriminated in significant ADR and even fatalities.…”

Comparing Two Methods of Tablet Manipulation to Adjust the Warfarin Dose in Paediatric Care

“…For this reason, drugs are used off-label-i.e., outside what is approved by governing bodies [3,4]. Despite several efforts made to improve the situation, e.g., through the European Pediatric Regulation of 2007 [5], the practice is still considered an important public health issue [6]-and seems to be increasing, if anything [7]. One type of off-label handling is manipulation of drug form (e.g., splitting and crushing of tablets, opening of capsules, and dispersion of the resulting powders) [8].…”

“…SmPC; 2 Mean (g) ± sd (n = 10);3 Diameter × height (Mean, n = 3; sd% < 0.7%); 4 pH of the suspension of one tablet suspended in 10 mL purified water;5 Percent lost upon friability testing (Ph.Eur.9.2) (n = 54);6 Average time (seconds) to disintegrate (n = 6, low-high);7 Calculated from breaking strength (N), diameter (mm) and height (mm). Average values are given (n = 10, low-high).…”