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Aim: To identify and evaluate the potential drug–drug interactions (PDDI) in hospitalized patients in a pediatric intensive care unit (PICU). Materials and Methods: In this cross-sectional observational study, we analyzed prescriptions of children aged 1 month–15 years admitted to PICU for PDDIs, and categorized them based on the severity (mild, moderate, and severe), underlying mechanisms, number of concomitant drugs used and potential outcomes of these PDDIs, using a drug interaction checking software. Results: Of the 122 prescriptions, we found 175 PDDIs in 77 prescriptions, of which 75.43% were of moderate, 17.71% minor, 6.86% major severity, and none was contraindicated.. The number of PDDIs increased with the number of medications per prescription. The average number of PDDIs per prescription was the highest in those that had >10 drugs (4.29). Pharmacodynamic interactions constituted the majority (73.71%) compared to pharmacokinetic interactions (23.43%). Common PDDIs encountered were between salbutamol and phenylephrine (11.43%), between anti-epileptic drugs (10.86%) and 3rd generation cephalosporins and aminoglycosides (10.29%). The most common potential outcome of these DDIs was hypokalemia (13.71%). Conclusion: There is a high prevalence of PDDIs in PICUs, mostly of moderate severity, with a significant relationship with the number of concomitant medications prescribed. Precaution is required while implementing polypharmacy in children. [ABSTRACT FROM AUTHOR]