Comparative Effectiveness and Safety of Combined Acetaminophen and Ibuprofen Versus Monotherapy in Acute Pain Management Among Pediatric Patients

Abstract

Background: Acute pain is a common presenting complaint in pediatric healthcare settings, yet optimal analgesic management remains challenging. Acetaminophen and ibuprofen are widely used first-line analgesics with distinct mechanisms of action, suggesting potential synergistic benefits when combined. However, comparative evidence regarding the effectiveness and safety of combination therapy versus monotherapy in pediatric acute pain management is limited.
Methods: This prospective, randomized, double-blind, controlled clinical trial enrolled 180 pediatric patients aged 6 months to 12 years with mild to moderate acute pain. Participants were randomly allocated in a 1:1:1 ratio to receive either combined acetaminophen and ibuprofen, acetaminophen monotherapy, or ibuprofen monotherapy at standard weight-based doses. The primary outcome was pain reduction assessed using validated age-appropriate pain scales at baseline, 30, 60, and 120 minutes. Secondary outcomes included time to analgesia onset, duration of pain relief, rescue analgesia requirements, caregiver satisfaction, and adverse events.
Results: Baseline characteristics were comparable across all groups. Combination therapy demonstrated significantly greater pain reduction at all time points compared with either monotherapy (P<0.001). At 120 minutes, mean pain scores were 1.21±0.70 in the combination group versus 2.62±0.91 and 2.08±0.83 in the acetaminophen and ibuprofen groups, respectively. Combination therapy produced faster analgesia onset (18.4 vs. 28.9 vs. 23.8 minutes), longer duration of relief (6.5 vs. 4.4 vs. 5.3 hours), and lower rescue analgesia requirements (13.3% vs. 33.3% vs. 23.3%). Caregiver satisfaction was significantly higher with combination therapy (95% satisfied/very satisfied vs. 80% for both monotherapies). Adverse event rates were low and comparable across groups (16.7%, 15.0%, and 23.3%, respectively; P=0.451), with no serious complications reported.
Conclusion: Combined acetaminophen and ibuprofen therapy demonstrated superior analgesic efficacy compared with either monotherapy in pediatric acute pain management, with faster onset, prolonged duration, reduced rescue analgesia requirements, and higher caregiver satisfaction, without increasing adverse events. These findings support combination therapy as an effective and safe first-line approach for managing mild to moderate acute pain in children.