Prevalence and Risk Factors of Clinically Significant Potential Drug–Drug Interactions in Turkish Pediatric Intensive Care Units: Results From a Nationwide Point Prevalence Study

Objective Polypharmacy is a major concern in pediatric intensive care units (PICUs), where critically ill children receive multiple medications, increasing the risk of clinically significant potential drug–drug interactions (pDDIs). However, data on pDDI prevalence in PICUs remain limited. This study investigates the prevalence, characteristics, and risk factors of pDDIs in PICU patients. Methods A nationwide, cross‐sectional point prevalence study was conducted in 50 Turkish PICUs, including hospitalized patients (1 month–18 years) receiving ≥ 2 medications. Demographic, comorbidity, medication use, mortality scores, ventilation status, and infection data were collected. pDDIs were identified by Lexicomp interactions and classified as A (no interaction), B (mild), C (moderate), D (severe), and X (contraindicated), with only D and X interactions analyzed. Results Among 517 patients (median age: 18.0 months [IQR: 7.0–60.0], 59.8% male), 51.2% (95% confidence interval [CI]: 46.8–55.6) had a clinically significant pDDI (D or X category). The most common X category interactions were chloral hydrate–furosemide (1.8%) and fluconazole–domperidone (1.2%), while D category interactions included fentanyl–midazolam (13.6%) and fentanyl–levetiracetam (6.0%). Risk factors for pDDIs included higher PRISM score (OR = 1.0; 95% CI: 1.0–1.0; and p < 0.001), increased number of medications (OR = 1.5; 95% CI: 1.4–1.6; and p < 0.001), polypharmacy (OR = 13.6; 95% CI: 6.1–30.3; and p < 0.001), mechanical ventilation (OR = 3.7; 95% CI: 2.5–5.6; and p < 0.001), and presence of infection (OR = 22.2; 95% CI:1.5–3.2; and p < 0.001). Conclusions This study confirms a high prevalence of clinically significant pDDIs in Turkish PICUs, mainly due to polypharmacy, organ dysfunction, and comorbidities. The high prevalence of fentanyl–midazolam interactions highlights the need to differentiate between harmful interactions and therapeutic synergies. Integrating clinical pharmacists and developing pediatric‐specific pDDI software are crucial to enhancing medication safety.