Study shows significant risk of major drug-drug interactions in outpatient children

Adverse drug events in the ambulatory setting are an important cause of morbidity and mortality in children, resulting in about 200,000 emergency department visits in the United States annually. They frequently cause hospitalizations and poor outcomes during hospitalization, including longer length of stay. About 20%-to-30% of adverse drug events are considered preventable, including those related to drug-drug interactions. However, little is known about drug-drug interactions in children in the outpatient setting. To learn more, a recent U.S. study investigated the prevalence of major drug-drug interactions and factors associated with higher drug-drug interaction exposure rates among children in an outpatient setting.The cross-sectional study included children aged zero-to-18 years with at least one ambulatory encounter, and two or more dispensed outpatient (retail pharmacy) prescriptions, based on the 2019 Marketscan Medicaid database. Drug-drug interaction exposures were defined as an exposure to a known major drug-drug interaction (as described in DrugBank) for one or more days. DrugBank is a publicly available online database also used by the National Institutes of Health and the National Library of Medicine. It categorizes drug-drug interactions as minor, moderate or major. Only major drug-drug interactions with moderate- or high-evidence levels were included in the analysis, to focus on the most serious and potential life-threatening drug-drug interaction exposures.Primary outcomes included the prevalence and rate of major drug-drug interaction exposures. Logistic regression was used to assess patient characteristics associated with drug–drug interaction exposure. The rates of drug-drug interaction exposures were identified per 100 children by adverse physiologic effects category, and organ-level effects (e.g., heart rate-corrected QT interval prolongation).Results showed the following:The study included 781,019 children with two or more medication exposures; 21.4% were exposed to at least one major drug-drug interaction during the study year. The highest major drug-drug interaction exposure was seen in adolescents (50.6%) and males (58.6%), but about 8% of infants and 17% of young children also experienced major drug-drug interaction exposure.The odds of major drug-drug interaction exposure increased with age and with multiple medical or mental health conditions. Adolescents experienced a four times higher rate of major drug-drug interaction exposure compared with children aged 0 to 1.Frequently implicated drugs included clonidine (most frequent), psychiatric medications (e.g., trazodone, risperidone), asthma medications (e.g., montelukast, cetirizine) and attention-deficit hyperactivity disorder drugs (e.g., amphetamine salt combinations). When examining the rate of major drug-drug interaction exposures per 100 drug-pair exposure days, the most frequently implicated drugs included dexamethasone (106.2), ziprasidone (102.0), clonidine, trazodone (84.0), loperamide (76.7), and mirtazapine (75.3).The most common categories of adverse physiologic effects caused by major drug-drug interactions were pharmacologic alterations (36.6%), neurologic effects (22.5%, particularly central nervous system depression) and cardiovascular effects (22.5%, particularly QT interval prolongation). The investigators conclude that based on this study, one in five US Medicaid-insured children are exposed to major drug-drug interactions annually, with higher exposures in adolescents and those with medical or mental health complexity. Drug-drug interaction exposure places children at risk for negative health outcomes and adverse drug events; this is particularly concerning in the harder-to-monitor outpatient setting.The authors encourage healthcare providers in the community to become aware of which medications are most frequently associated with major drug-drug interactions. Many of the commonly implicated drugs are very frequently prescribed, including clonidine, cetirizine, montelukast, dexamethasone and mental health medications. The authors advocate for additional retrospective and prospective research to improve our understanding of drug-drug interactions in children and to clarify the true risks posed by drug-drug interaction exposures.Reference1. Kyler KE, Hall M, Antoon JW, et al. Major drug-drug interaction exposure among Medicaid-insured children in the outpatient setting. Pediatrics 2024;153(2):e2023063506. (accessed February 8, 2024).

Study shows significant risk of major drug-drug interactions in outpatient children

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