A Comparative Analysis of the Efficacy and Safety of Nimesulide/Paracetamol Fixed-Dose Combination With Other NSAIDs in Acute Pain Management: A Randomized, Prospective, Multicenter, Active-Controlled Study (the SAFE-2 Study).

Objective In this study, we aimed to compare the efficacy and safety of the fixed-dose combination (FDC) of nimesulide (100 mg) + paracetamol (325 mg) [NP], ketorolac (10 mg) [Kt] alone, diclofenac (50 mg) + paracetamol (325 mg) [DP], and aceclofenac (100 mg) + paracetamol (325 mg) [AP] in patients with acute painful conditions. Methods This was a randomized, prospective, open-label, multicentre, active-controlled study involving patients aged ≥18 years, with acute painful conditions like low back pain, acute musculoskeletal disorders, and trauma such as tendinitis, tenosynovitis, bursitis, sprains and strains, migraine, dental pain, painful dental procedures, and post-surgical pain. Reduction in pain intensity and liver, renal, gastrointestinal, and cardiovascular safety were assessed on days seven and 14. Results A total of 600 patients were randomized into NP, Kt, DP, and AP groups in a 1:1:1:1 ratio. NP, DP, and AP were administered twice a day while Kt was given three times a day. The reduction of pain as measured by the numerical rating scale (NRS) scores at the end of day seven was 3.75 ± 1.58 in the NP group, 2.96 ± 1.18 in the Kt group, 3.42 ± 1.42 in the DP group, and 3.47 ± 1.30 in the AP group. The pain reduction in the NP group was significantly greater (p<0.001) as compared to the Kt group and non-inferior to the DP and AP groups on days seven and 14. Non-inferiority was concluded between the NP, DP, and AP groups as the lower limit of 95% CI of the difference in the change of pain intensity on both days seven and 14 was above the predefined margin of -1.0. All the drugs were well tolerated, but a significantly greater number of adverse events were reported in the DP group (32) as compared to the NP group (14) (p<0.05). The most common adverse events reported during the study were nausea, gastritis, and abdominal pain in all four groups. There was no significant alteration in liver and renal function tests except a rise in serum creatinine in the DP group. Conclusions The FDC of nimesulide with paracetamol is superior to ketorolac and non-inferior to the FDC of diclofenac with paracetamol and aceclofenac with paracetamol in the management of pain in patients with acute painful conditions. The tolerability profile of the FDC of nimesulide with paracetamol is similar to that of ketorolac but better than diclofenac with paracetamol and aceclofenac with paracetamol combinations.

An Open-label, Prospective, Multicentric, Cohort Study of Nimesulide/Paracetamol Fixed Drug Combination for Acute Pain Management: Sub-group Analysis.

OBJECTIVE: Nimesulide has been evaluated in numerous clinical studies in the management of a variety of acute painful conditions. However, there is limited Indian data available on the nimesulide/paracetamol fixed drug combination (FDC). Hence, an open-label prospective multicentric study was conducted to evaluate the safety and efficacy of this FDC in the management of acute painful conditions in real-world settings. MATERIALS AND METHODS: A prospective, open-label, and multicenter study conducted at 24 centers across Indian patients with acute painful conditions due to trauma, tendinitis, myalgia, low backache, sprains, pulled muscle, soft tissue injury, dental pain, and dental procedure/surgery. Nimesulide/paracetamol FDC was prescribed by clinicians as a part of routine practice. The effectiveness was evaluated on the numerical rating scale (NRS), that is, pain intensity at rest and movement, and the physician/patient global assessment scale (GAS) among the subgroups of acute painful conditions like myalgia, dental pain, low backache, etc. Hepatic safety was also evaluated among the subgroups at the end of treatment. RESULT: A total of 464 patients were included in the study. The reduction in NRS score at rest and movement during treatment duration across different types of pain was statistically significant (p < 0.001). Pain reduction was evident as per patient and physician GAS at the end of treatment in all indications. No clinically significant difference was found in liver parameters at the end of the study. Nimesulide/paracetamol (FDC) was well tolerated across all the subgroups. CONCLUSION: Nimesulide/paracetamol FDC was found to be well-tolerated and effective in pain management across all acute painful conditions in a real-world setting without any hepatic safety concerns.

An In Vitro Susceptibility Study of Cefotaxime-Sulbactam on Clinical Bacterial Isolates From Various Regions in India: A Comparison With Ceftriaxone-Sulbactam.

Background and objective Combining sulbactam with cefotaxime/ceftriaxone augments its antimicrobial activity against ß-lactamase-producing bacteria. They are widely used as empirical treatment for many clinical infections. However, there is a scarcity of data on the susceptibility of various organisms to these antibiotics in the Indian region. In light of this, the present in vitro study evaluated the susceptibility of bacterial isolates to cefotaxime-sulbactam and compared it with ceftriaxone-sulbactam. Methodology Clinical samples with positive bacterial cultures from various laboratories in India were subjected to antibiotic sensitivity testing using in vitro E-test strips and disk diffusion methods to determine the minimum inhibitory concentration (MIC) and zone of inhibition (ZOI), respectively. MIC50 and MIC90 values were determined along with the measurement of the ZOI for the effectiveness of antibiotics. Interpretations of MIC and ZOI values were made as per the criteria set by the Clinical and Laboratory Standards Institute (CLSI) guidelines to estimate the proportion of sensitive organisms. Results Among 400 clinical isolates evaluated, Escherichia coli (E. coli) (47.75%) was the most common organism isolated followed by Klebsiella (26%), Salmonella (7.75%), Proteus (3.8%), and Acinetobacter (2.8%). The mean ZOI was found significantly higher for E. coli, Klebsiella, and Salmonella in the cefotaxime-sulbactam group than in the ceftriaxone-sulbactam group. MIC50 values for E. coli and Klebsiella were 0.25 and 0.19 µg/ml, respectively in the cefotaxime-sulbactam group as compared to 0.38 and 0.25 µg/ml, respectively for ceftriaxone-sulbactam. The proportion of sensitive isolates was also higher in the cefotaxime-sulbactam group for E. coli, Klebsiella, and Salmonella. Conclusions The in vitro effect of cefotaxime-sulbactam on organisms is similar to that of ceftriaxone-sulbactam in terms of MIC, ZOI, and proportion of sensitivity based on our study involving clinical isolates from various parts of India. Cefotaxime-sulbactam may be preferred in the empirical management of various clinical infections.