Abstract: Nimesulide shows preferential inhibition for the cyclooxygenase-2 enzyme, that blocks the formation of prostaglandins critical in pain and inflammatory pathways. Few studies in the past have reported rare and unpredictable hepatic effects with nimesulide.

Objective: The study aimed to evaluate the safety and efficacy of nimesulide/paracetamol (100 mg + 325 mg) fixed-dose combination twice a day for 2 weeks in the management of acute pain due to trauma and dental pain, dental procedure/surgery in Indian population.

Materials and Methods: The study was performed on 500 patients with acute pain conditions, by 25 experienced physicians across India. The primary outcome assessed clinical safety at 2 weeks for mild/serious adverse effects, change in liver function tests (LFTs), serum bilirubin and alkaline phosphatase levels. The secondary outcomes assessed the clinical effectiveness in reduction of pain at rest and at movement measured by numerical rating scale (NRS) and Physician/Patient Global Assessment Scale (GAS).

Results: Analysis of LFT at 2 weeks showed a slight increase (mean change) in the (AST){˗0.73 [95% confidence interval (CI) ˗1.54, 0.09; p = 0.081]}, alanine transaminase (ALT) [˗1.73 (95% CI ˗2.82, ˗0.64; p = 0.002)], serum bilirubin [˗0.02 (95% CI ˗0.04, ˗0.001; p = 0.018)] and alkaline phosphatase levels [˗1.92 (95% CI ˗5.84, 2; p = 0.336) but not exceeding the normal range. Only 1/500 patients reported adverse effects. The NRS score for intensity of pain at rest and at movement at 2 weeks, ≤7 days and > 7 days was 68.38%, 68.64% and 68.4%; and 65.43%, 64.60% and 66.02%, respectively. An improvement of 96.6% was observed in patient GAS and 97.4% physician GAS.

Conclusion: Nimesulide/paracetamol combination was safe, effective and well-tolerated in acute pain conditions and did not lead to clinically significant change in liver parameters indicating hepatic safety.