Asthma Drugs Among Those Implicated in Major Drug-Drug Exposures in Children

One in 5 children enrolled in Medicaid are at risk of experiencing major drug-drug interactions (DDIs) from 2 or more prescribed medications annually, according to a new study published online today. Drugs that are frequently implicated in major DDI exposures include allergy and asthma drugs.

Close up of doctor hand holding blue asthma inhaler and writing medical prescription on rx form for treatment asthma

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“Our study thus fills a critical gap by quantifying and characterizing major DDI exposures in children of all ages who are prescribed medications in the general outpatient setting in the United States,” wrote the researchers of the study. “These findings have several implications for outpatient pediatric prescribers.”

This cross-sectional study, published in Pediatrics, aimed to determine the prevalence of major DDI exposure and the factors that may be associated with higher DDI exposure rates among children in an outpatient setting.

The study included children aged 0 to 18 years who had 2 or more dispensed outpatient prescriptions in 2019. Children who were not continuously enrolled in Medicaid for 11 or more months were excluded. This information was gathered using the 2019 Marketscan Medicaid database, which included detailed claims data from 11 geographically diverse states, including inpatient, outpatient, retail/mail order pharmacy claims, and patient and clinical characteristics.

Additionally, DDIs, which were defined as exposure to a major DDI for 1 or more day, and the adverse physiologic effects of each DDI were obtained using DrugBank’s interaction database.

The researchers’ primary outcomes were the prevalence and rate of major DDI exposure and the patient characteristics associated with DDI exposure.

A total of 781,019 children were identified with 2 or more medication exposures during the study period. Of these individuals, 21.4% experienced 1 or more DDI exposures. Children aged 12 to 18 years (50.6%) and males (58.6%) made up the larger portions of children with DDI exposure. Additionally, approximately 8% of infants and 17% of younger children experienced DDI exposure (8.3%).

Patient characteristics associated with increased odds of DDI exposure were age and medical and mental health complexity. Compared with children aged 0 to 1 years, adolescents experienced a 4 times higher rate of DDI exposure (adjusted rate ratio [aRR], 4.04; 95% CI, 4.02-4.07). Additionally, the major DDI exposure rate increased as the number of noncomplex chronic diseases increased. For example, children with more than 6 chronic diseases had an aRR of 3.03 (95% CI, 3.02-3.05). Similarly, children with more than 6 mental health conditions had an aRR of 4.15 (95% CI, 4.14-4.16). The most frequently implicated drugs among children were clonidine, psychiatric medications, and asthma medications.

The researchers acknowledged their study had some limitations, such as only including children insured by Medicaid and no over-the-counter drug data. Additionally, the researchers were unable to link DDI exposure to true adverse drug events (ADEs) due to the lack of patient-level clinical data and they did not analyze the duration of DDI exposure.

Despite these limitations, the researchers believe their study suggests that children of all ages are commonly exposed to major DDIs in the general outpatient setting in a Medicaid population.

“This analysis identified the most frequently implicated drug–drug pairs in major DDI exposures, as well,” wrote the researchers. “Although adverse physiologic effects were also analyzed, the probability of true ADEs resulting from DDI exposures remains uncertain; further surveillance and study of ADEs in children are imperative. In the meantime, prescribers should consider how and when to counsel patients about the risk of ADEs associated with DDIs, or when to simply monitor for ADEs in patients knowingly exposed to DDIs when the risk/benefit balance is favorable.”

Reference

Kyler KE, Hall M, Antoon JW, et al. Major drug-drug interaction exposure among Medicaid-insured children in the outpatient setting. Pediatrics. Published online January 4, 2024. doi:10.1542/peds.2023-063506