Letters to the Editor

Indian Pediatrics 2002; 39:890-891

Post-Marketing Surveillance of Nimesulide Suspension

I read with interest the article(1) and have the following comments:

1. The product has been marketed aggressively for years now and why was the mandatory post-marketing surveil-lance not completed earlier?

2. The authors imply that Nimesulide has rarely been implicated in the adverse effect of being hepatotoxic and fails to illustrate the risk-benefit of using Nimesulide in children for fever which may not justify even the small risk of hepatotoxicity(2,7).

3. The study design is defective for there is no mention of the distribution of age groups. The fact that two children with hepatitis actually received Nimesulide as a part of the study suggests that there are suspicious inclusion and exclusion criteria if any. This leads to research ethical questions with regards the lack of informed consent and risks being discussed with the parents involved in the study. This study ignores that there was an unjustifiable risk to the child receiving the medication. There are no details of the actual dose, frequency and duration of the medication utilized for the "study". It is also unclear the criteria for an unbiased choice of 600 national Pediatricians and reasons why 28.3% dropped out and failed to report. Was there a conflict of interest involved? Would their reports have made a difference to the results of the study? Is this drop out rate acceptable especially since it is these doctors who carried out the study with no objective criteria for reporting adverse effects? The attempt to make it a "real practice condition" as opposed to a "clinical trail condition" is unusual in this day and age of Evidence based Medicine! It is also unusual that a combination of antipyretics was permitted in the study.

4. The results reported are said to be similar to that of another study is misleading. The compared study reference given is not a standard, peer reviewed, Pub Med or National Library of Medicine indexed journal. Would this in anyway endanger the reputation of our own journal and the referees? Clinical jaundice, though noticed in 2 children, was not considered due to the drug by Pediatricians. What was the clinical basis for this rejection and what were the causes of the jaundice? Why were liver enzymes not monitored during the use of Nimesulide in all children to actually detect subtle hepatic damage? It is difficult to believe that all of the 4097 children given Nimesulide were followed up with no dropouts? The authors’ final statement on conscious reporting amending limitations in monitoring makes no sense. How does conscious reporting assist in the objective detection of liver toxicity when one is to clear a suspect drug for use in children?

5. The conclusion that there was no hepatotoxicity is wrong as there are too many defects in the conduct of the study in the absence of enzyme monitoring, lack of standardization of methodology, a biased population observing and studying, and, the lack of scientific objective data presented.

6. The presence of two letters to editors and one non-indexed journal article as reference for this study does not help the case.

7. There is unfortunately an obvious conflict of interest taking into consideration that this drug is not licensed in Canada, USA, UK, Scandinavia, Australia, Sri Lanka and New Zealand. These could be considered reference drug regulatory authorities. It has also been withdrawn in Portugal and Israel for the same resons(8).

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References

references

1. Srishyla MV, Sireesha K, Bhaduri J, Kumaresan S. A countrywide post-marketing surveillance of Nimesulide suspension. Indian Pediatr 2002; 39: 310-311.

2. McCormick PA, Kennedy F, Curry M, Traynor O. COX2 inhibitor and fulminant hepatic failure. Lancet 1999; 353; 40-41.

3. Lal A, Gomber S, Talukdar B. Antipyretic effects of nimesulide, paracetamol and ibuprofen-paracetamol. Indian J Pediatr 2000; 67: 865-870.

4. Malhotra S, Pandhi P. Analgesics for pediatric use. Indian J Pediatr 2000; 67: 589-590.

5. Weiss P, Mouallem M, Bruck R, Hassin D, Tanay A, Brickman Cm et al. Nimesulide-induced hepatitis and acute liver failure. Isr Med Assoc J 1999; 1: 89-91.

6. Van Steenbergen W, Peeters P, DeBondt J, Staessen D, Buscher H, Laporta T et al. Nimesulide-induced acute hepatitis: evidence from six cases. J Hepatol 1998; 29: 135-141.

7. Bernareggi A. Clinical pharmacokinetics of nimesulide. Clin Pharmacokinet 1998; 35: 247-274.

8. Weerasuriya K. Registration of new drugs in developing countries. Lancet 1999; 353: 2161-2162.