NIMESULIDE

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NIMESULIDE

• DR.B.B.SAHNI
• SR.SPECIALIST
• TATA CENTRAL HOSPITAL
• DHANBAD

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CONTROVERSY

• NIMESULIDE IS NOT A SAFE DRUG FOR CHILDREN
• MEDIA REPORTS
• ACTION GROUPS

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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,BELGIUM
• 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.

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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.

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Forest plot for relative risk of elevation of
liver enzymes. There is no significant
difference (P 0.218) between nimesulide and
the control groups.
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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).
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Forest plot for relative risk of hypothermia.
There is no significant difference (P 0.952)
inthe risk of hypothermia between nimesulide and
the control groups
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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.
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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

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IAP COMMITTEE OF PROTECTION FOR CHILD CONSUMER
REPORT

• For short-term (lt10 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).

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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.

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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

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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. 

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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.

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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. 

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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

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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. 

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DTAB REPORT (CONTD.)

• The drug has dose convenience, as it is to be
  taken only twice a day and have lesser
  Gastro-intestinal irritation. 

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thank you