1. NIMESULIDE DR.B.B.SAHNI SR.SPECIALIST TATA CENTRAL HOSPITAL DHANBAD

2. CONTROVERSY NIMESULIDE IS NOT A SAFE DRUG FOR CHILDREN MEDIA REPORTS ACTION GROUPS

3. SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS IN 2003 BY DR.H.PS.SACHDEV PAST PRESIDENT IAP Inclusion Criteria FOR 16 STUDIES FROM GERMANY,INDIA,SWITZERLAND,ITALY,BE LGIUM Studies with following pre-determined criteria were included: (i) randomized trials with oral nimesulide and a control group, receiving any other analgesic, anti-inflammatory, antipyretic agent or placebo; studies employing a rectal route were not eligible; (ii) trials restricted to children £ 18 years of age; and (iii) must have evaluated one or more adverse effects as an outcome measure.

4. SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS IN 2003 BY DR.H.PS.SACHDEV PAST PRESIDENT IAP key message — For short-term use (£10 days) in children, nimesulide is as ‘unsafe’ or as ‘safe’ as other analgesics-antipyretics.

5. Forest plot for relative risk of elevation of liver enzymes. There is no significant difference (P = 0.218) between nimesulide and the control groups.

6. Forest plot for relative risk of epigastric pain, vomiting, and diarrhea. These symptoms were significantly (P = 0.008) lower in the nimesulide group roughly half) in comparison to the control groups. However, this difference was not significant (P = 0.276) if the control group of only paracetamol or placebo (was considered (plot not shown).

7. Forest plot for relative risk of hypothermia. There is no significant difference (P = 0.952) in the risk of hypothermia between nimesulide and the control groups

8. Forest plot for relative risk of gastrointestinal bleeding. There is no significant difference (P = 0.896) in the risk of gastrointestinal bleeding between nimesulide and the control groups.

9. IAP COMMITTEE FOR PROTECTION OF CHILD CONSUMER CHAIRPERSON-DR.S.C.ARYA PAST PRESIDENT-IAP The following sources and methods were utilized by the Committee to formulate this Consensus Statement: (i) Non-funded meta-analysis of 16 randomized controlled trials including 1254 children, which was conducted to specifically resolve this controversy(1); (ii) Review of other published literature on the subject; (iii) Opinions of the speakers, faculty and delegates during a specific session on this issue in the Indo-UK Symposium on "Hot Topics in Pediatrics" on February 1, 2003; (iv) Discussions with some of the doctors who had expressed reservations about usage of Nimesulide in the local press; (v) Circulation of the draft recommendations to members of the Committee unable to participate in the Symposium

10. IAP COMMITTEE OF PROTECTION FOR CHILD CONSUMER REPORT For short-term (<10 days) use in children, Nimesulide is as "safe" or "unsafe" as other analgesic-antipyretics. There is no significant increase(1) in the risk of hypothermia, gastrointestinal bleeding, epigastric pain, vomiting, diarrhea and transient asymptomatic hepatic enzyme elevation with Nimesulide as compared to the control groups (Paracetamol, Placebo, or other non-steroidal anti-inflammatory drugs like Ibuprofen, Mefenamic Acid, Salicylates).

11. IAPCPCC REPORT- HEPATIC ADVERSE REACTION The estimated incidence (all ages) of 1 per 1 million treated patients (lower than or comparable to other non-steroidal anti- inflammatory drugs) suggests that rare cases of such liver injury may be caused by a metabolic idiosyncrasy. Further, the published "Case Reports" of serious hepato-toxicity are mostly restricted to prolonged usage (reported mean 2 months) and adults (reported mean age 62 years) Administration of Nimesulide, like other NSAIDs should be avoided in known or suspected liver disease or with the use of other hepato-toxic drugs.

12. DELHI HIGH COURT JUDGEMENT MARCH 2003 JUDGEMENT BASED ON REPORTS OF DRUG TECHNICAL ADVISORY BOARD (DTAB)OF DRUG CONTROLLER OF INDIA IMA AND IAP REPORTS AIIMS REPORTS ADR CENTRES OF DELHI,LUKNOW AND BANGALORE STANDARD TEXT GUIDELINES OF DELHI SOCIETY FOR PROMOTION OF RATIONAL DRUGS

13. DELHI HIGHCOURT OBSERVATIONS evidences available so far does not indicate any causal relationship of the drug with the alleged adverse reactions 'Standard Treatment Guideline 2002' (STG)of DELHI SOCIETY FOR RATIONAL DRUGS recommended the use of Nimesulide alongwith other drugs like ibuprofen and paracetamol for controlling fever in adults as well as children.

14. RECOMMENDATIONS OF DTAB The rationality of the formulations containing Nimesulide with Paracetamol or Muscle Relaxants was reviewed by the Sub Committee in its meeting held on 30th January, 2002, and the committee felt that as such, fixed dose combinations of NSAIDs like paracetamol, Diclofenec, ibuprofen and with Nimesulide have been in use for considerable period and well accepted. There are no reports of any adverse effects for these formulations which are mostly used on short term basis for relief from pain and inflammation. These formulations may be permitted to be continued. This opinion in respect of Nimesulide has already been provided to the Hon'ble Court.

15. IMA RECOMMENDATION Use of Nimesulide was suspended only in 3 countries, though it is in use in about 50 countries. Israel has again permitted its use, after evaluating its overall safety data. According to him the survey conducted by Indian Medical Association was extensive one and revealed that the drug is very useful and well accepted by medical community.

16. DEHI HIGH COURT JUDGEMENT It may be stated at this juncture that this Court took cognizance of the matter because of the alleged adverse effect of the drug on children. That issue has been cleared by the report of the DTAB

17. DTAB REPORT After detailed deliberations, members opined that having considered the issues raised by the petitioner and the overall data on this drug, there is no ground for banning of drug Nimesulide for adult or pediatric use. The drug is considered to be as safe or unsafe as any other commonly used NSAID.

18. DTAB REPORT (CONTD.) The drug has dose convenience, as it is to be taken only twice a day and have lesser Gastro-intestinal irritation.