Safety of oral use of nimesulide in children: systematic review of randomized controlled trials.

BACKGROUND Nimesulide has been widely used to treat fever in children. Due to reports of adverse drug reactions, discontinuation or modification of its use has been suggested. OBJECTIVE To evaluate the safety of oral use of nimesulide in children. DESIGN Systematic review of published randomized controlled trials. SEARCH STRATEGY Electronic searches of databases (PubMed, Cochrane, Toxnet) for relevant trials upto January 2003 using specified key words. The studies were also identified by searching the references of available meta-analyses and review articles, and bibliography of pertinent references. INCLUSION CRITERIA Randomized controlled trials in children (less than or equal to 18 years of age) comparing the use of oral nimesulide with placebo or other antipyretic, anti-inflammatory or analgesic agents. OUTCOME The primary outcome variable included the commonly encountered adverse effects of nimesulide therapy, i.e., hypothermia, abdominal symptoms, gastrointestinal bleeding, and elevated liver enzymes. DATA COLLECTION AND ANALYSIS One of the authors developed a questionnaire and independently extracted data on methods, type of participants, interventions and outcomes. The meta-analysis was conducted using pooled relative risk with 95% confidence intervals, with random effects model assumption. RESULTS We identified 16 trials that fulfilled the inclusion criteria. These included 1254 subjects, with mean age between 22 -140 months. Nimesulide was primarily used for its antipyretic (10 trials) or anti-inflammatory and analgesic activity (4 trials). One study each evaluated the symptomatic improvement in ARI and bronchial asthma. The control group included administration of placebo (3 studies), paracetamol (9 studies), and ketoprofen, naproxen, mefanemic acid and aspirin in one study each. The pooled effect sizes of various adverse events as compared between nimesulide and different control groups were: hypothermia (RR: 1.055; 95% CI: 0.184 - 6.047; P = 0.952), abdominal symptoms (RR: 0.464; 95% CI: 0.264 - 0.816; P = 0.008), gastrointestinal bleeding (RR: 0.914; 95% CI: 0.236 - 3.543; P = 0.896), and asymptomatic liver enzyme elevation (RR: 2.678; 95% CI, 0.558-12.853; P = 0.218). Cutaneous and renal adverse effects were not seen in any of the included studies. CONCLUSION Oral nimesulide is as safe or unsafe as other analgesics-antipyretics for short-term use (less than or equal to 10 d) in children. The drug is best avoided in known or suspected liver disease; caution is warranted while prescribing nimesulide concomitantly with other hepatotoxic drugs. There is limited data for drawing concrete inferences below the age of six months.