The DCGI's decision to not to restrcit pediatric use of nimesulide based on the report of the Indian Academy of Pediatrics (IAP) is learnt to be inaccurate as the study was incomplete to prove the safety of the drug in children below 2 years of age.

Though the IAP had written to the DCGI in January that the meta analysis carried out by the academy had led to the finding that the drug is not unsafe like any other anti-pyretic drugs. A team of renowned pediatricians strongly object to the veracity of the study saying that they are unaware of any trial on nimesulide which has included children as young as 2 months and this despite there being literature on renal toxicity in neonates and young infants and lack of awareness of the pharmacokinetics of the drug in children below 2 years.

In an article published in the Indian Pediatrics, journal of the Indian Academy of Pediatrics, in its February 2003 edition, leading pediatricians; Dr Y.K. Amdekar and R.P. Khubchandani, Jaslok Hospital and Research Center, Mumbai, cautions that "since nimesulide is gaining rapid acceptance in our country as an antipyretic of first choice in children despite there being a paucity of worldwide literature for this indication and conflicting reviews from our country, it is now particularly relevant to to highlight flaws in the studies conducted on nimsulide."

Reviewing a recent paper titled "Comparison of antipyretic effect of nimesulide and paracetamol in children attending a secondary level hospital" the experts pointed out that while attempting to build on another study on the drug, the basic tenets seem flawed.

They also wondered that how is fever in an outpatient setting different in a primary vs secondary level hospital? If the objective of the study was to recruit patients who do not require hospitalization, it does not seem to have been met by the results which show that 50 per cent did require in-patient care and were not admitted purely for the purpose of the trial. Secondly, rational prescribing dictates as and when required rather than round the clock usage of antipyretics. Thus other studies that have evaluated antipyretics in field conditions have chosen to evaluate drug effect after single dose adminstration prior to instituting any specific therapy.

It may be mentioned that the IAP, while submitting the report to DCGI, had stated that as the data on the effect of the drug on children below six months are limited and hence no definite conclusions could be drawn on the effect of such use.

However, the pediatricians in their review of the above paper adds that since the age range chosen has been as wide as 2 months to 14 years some attempt should have been made to stratify the data age wise. The causes of fever in the patients enrolled were so varied that the patient population is very heterogenous and nowhere is there a mention of the time elapse between onset of fever and enrollment in the trial. A rational way would have been to enroll the patients within 24-48 hours of the onset of fever, probably studying children after booster dose DPT vaccine or children with fever who justify observation without instituting specific therapy.

The dose (10 mg/kg) and frequency (eight hourly) of paracetamol call for serious criticism, since the recommended dose is 10-15 mg/kg 4 hourly(8). While the authors have attempted to defend this by saying it would have come in the way of the blinding process several techniques could have been used to overcome this problem.

By monitoring fever hourly for the first eight hours and then four hourly thereafter how did the authors achieve two of their secondary outcome variables viz., "the time elapsed between dosing and the lowest temperature reached". Further, monitoring of side effects, we noted with anguish, was essentially clinical. This was despite the study being carried out in a secondary center where we are sure laboratory monitoring was easily feasible. In spite of this perfunctory monitoring of adverse effects the authors irrationally conclude "nimesulide appears to be as safe as paracetamol for use in children"(key message). In any case study of the safety profile/adverse effects was not part of their initially stated objectives.

It is also interesting to note that many of the references appeared on the paper are drawn from an industry sponsored symposium on nimesulide. Most of the studies on nimesulide during this period emanated from Italy after which a quiescent period descended on the drug. The latest flurry of data on this incompletely researched drug in pediatrics is from India over 2000-2002 while it continues to elude licensing in western countries such as the US and UK probably for want of enough data. It will be a sad commentary,therefore, such studies are used by the regulatory authorities after knowing that these are collected by the field forces of the industry to enhance the credibility of this drug, the experts say.