Prevalence of Clinically Significant Drug-Drug Interactions Across US Children's Hospitals

Pediatrics. 2020 Nov;146(5):e20200858. doi: 10.1542/peds.2020-0858. Epub 2020 Oct 9.


Background: Little is known about the prescribing of medications with potential drug-drug interactions (DDIs) in the pediatric population. The objective of this study was to determine the prevalence and variation of prescribing medications with clinically significant DDIs across children's hospitals in the United States.

Methods: We performed a retrospective cohort study of patients <26 years of age who were discharged from 1 of 52 US children's hospitals between January 2016 and December 2018. Fifty-three drug pairings with clinically significant DDIs in children were evaluated. We identified patient-level risk factors associated with DDI using multivariable logistic regression. Adjusted hospital-level rates of DDI exposure were derived by using a generalized linear mixed-effects model, and DDI exposure variations were examined across individual hospitals.

Results: Across 52 children's hospitals, 47 414 (2.0%) hospitalizations included exposure to a DDI pairing (34.9 per 1000 patient-days) during the study period. One-quarter of pairings were considered contraindicated (risk grade X). After adjusting for hospital and clinical factors, there was wide variation in the percentage of DDI prescribing across hospitals, ranging from 1.05% to 4.92%. There was also substantial hospital-level variation of exposures to individual drug pairings. Increasing age, number of complex chronic conditions, length of stay, and surgical encounters were independently associated with an increased odds of DDI exposure.

Conclusions: Patients hospitalized at US children's hospitals are frequently exposed to medications with clinically significant DDIs. Exposure risk varied substantially across hospitals. Further study is needed to determine the rate of adverse events due to DDI exposures and factors amenable for interventions promoting safer medication use.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Interactions*
  • Drug Prescriptions / statistics & numerical data*
  • Drug-Related Side Effects and Adverse Reactions / epidemiology*
  • Female
  • Hospitals, Pediatric
  • Humans
  • Infant
  • Male
  • Retrospective Studies
  • Risk Assessment
  • United States / epidemiology
  • Young Adult