Comparison of the Analgesic Efficacy of Concurrent Ibuprofen and Paracetamol With Ibuprofen or Paracetamol Alone in the Management of Moderate to Severe Acute Postoperative Dental Pain in Adolescents and Adults: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Single-Dose, Two-Center, Modified Factorial Study

Background: Combination analgesics may offer improved analgesic efficacy, particularly for moderate to severe pain. Objective: This study evaluated the analgesic benefits of concurrent ibuprofen and paracetamol compared with each drug used alone in the management of acute postoperative dental pain. Methods: Healthy patients aged 16 to 40 years undergoing surgical removal of 3 to 4 impacted molars (total impaction score >= 9) were enrolled in this randomized, double-blind, placebo-controlled, parallel-group, single-dose, 2-center, modified factorial US study. Patients were randomly assigned in a ratio of 2:1:2:1:1 to ibuprofen 400 mg/paracetamol 1000 mg, ibuprofen 200 mg/paracetamol 500 mg, ibuprofen 400 mg, paracetamol 1000 mg, or placebo when postoperative pain reached moderate to severe intensity. The primary efficacy end point was the sum of pain relief and pain intensity differences from 0 to 8 hours (SPRID8). Several secondary end points were also measured, including total pain relief (TOTPAR), sum of pain intensity differences (SPID), and SPID on the visual analog scale (SPID VAS) at various time points. Other analgesic efficacy measures included peak effect, onset and duration of effect, and patients' overall assessment of treatment. The tolerability of study medications was assessed in terms of the frequency and nature of adverse events, which were assessed with standard questions, as well as changes from baseline in vital signs. Results: A total of 234 patients were randomly assigned to treatment and included in the intent-to-treat population. The patients were predominantly female (74.4% [174/234]) and white (76.5% [179/234]); mean (SD) age was 20.8 (3.1) years and weight was 69.1 (16.5) kg. For SPRID8, the group treated with ibuprofen 400 mg/paracetamol 1000 mg had significantly better mean scores compared with ibuprofen alone (P < 0.001), paracetamol alone (P < 0.001), and ibuprofen 200 mg/paracetamol 500 mg (P = 0.02). The group taking ibuprofen 200 mg/paracetamol 500 mg achieved significantly better mean SPRID8 scores than paracetamol alone (P = 0.03), but not ibuprofen alone (P = NS). Ibuprofen 400 mg/paracetamol 1000 mg was associated with significantly better scores than was single-agent therapy for TOTPAR, SPID, and SPID VAS at all time intervals and for SPRID from 4 to 6 hours (all, P < 0.001). Pairwise comparisons found statistically significant differences in favor of all active treatments versus placebo for virtually all efficacy end points, thereby supporting assay sensitivity. Adverse events were similar across treatments; the most frequent were nausea (26.1% [61/234]), vomiting (18.8% [44/234]), headache (10.3% [24/234]), and dizziness (8.1% [19/234]). Conclusion: Concurrent ibuprofen and paracetamol appeared to provide significantly better analgesic efficacy compared with ibuprofen or paracetamol alone for acute postoperative dental pain in these adolescents and adults. (Clin Ther. 2010;32:882-895) (C) 2010 Excerpta Medica Inc.