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{{Drugbox|
__NOTOC__
|IUPAC_name = N-(4-Nitro-2-phenoxyphenyl)methanesulfonamide
{{CMG}}
| image=nimesulide.png
{{Drugbox
| width=200px
| Verifiedfields = changed
| CAS_number=51803-78-2
| verifiedrevid = 413700508
| ATC_prefix=M01
| IUPAC_name = ''N''-(4-Nitro-2-phenoxyphenyl)methanesulfonamide
| ATC_suffix=AX17
| image = Nimesulide structure.png
| ATC_supplemental=
| width = 200px
| PubChem=4495
 
| DrugBank=
<!--Clinical data-->
| C=13 | H=12 | N=2 | O=5 | S=1
| tradename =
| molecular_weight =308.311
| Drugs.com = {{drugs.com|international|nimesulide}}
| legal_AU = S4
| legal_status = Usually prescription only
| routes_of_administration = Oral, rectal, topical
 
<!--Pharmacokinetic data-->
| protein_bound = >97.5%
| protein_bound = >97.5%
| metabolism = Hepatic
| metabolism = Hepatic
| elimination_half-life = 1.8-4.7h
| elimination_half-life = 1.8–4.7h
| excretion = Renal(50%) Fecal(29%)
| excretion = Renal (50%), fecal (29%)
| legal_status =Prescription only Drug
 
| routes_of_administration= oral, rectal, topical
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 51803-78-2
| ATC_prefix = M01
| ATC_suffix = AX17
| ATC_supplemental = {{ATC|M02|AA26}}
| PubChem = 4495
| DrugBank_Ref = {{drugbankcite|changed|drugbank}}
| DrugBank = DB04743
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4339
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = V4TKW1454M
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D01049
| ChEBI_Ref = {{ebicite|changed|EBI}}
| ChEBI = 44445
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 56367
 
<!--Chemical data-->
| C=13 | H=12 | N=2 | O=5 | S=1
| molecular_weight = 308.311 g/mol
| smiles = [O-][N+](=O)c2cc(Oc1ccccc1)c(cc2)NS(=O)(=O)C
| InChI = 1/C13H12N2O5S/c1-21(18,19)14-12-8-7-10(15(16)17)9-13(12)20-11-5-3-2-4-6-11/h2-9,14H,1H3
| InChIKey = HYWYRSMBCFDLJT-UHFFFAOYAR
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C13H12N2O5S/c1-21(18,19)14-12-8-7-10(15(16)17)9-13(12)20-11-5-3-2-4-6-11/h2-9,14H,1H3
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = HYWYRSMBCFDLJT-UHFFFAOYSA-N
}}
}}
==Overview==
'''Nimesulide''' is a relatively [[COX-2 inhibitor|COX-2 selective]], [[non-steroidal anti-inflammatory drug]] (NSAID) with [[analgesic]] and [[antipyretic]] properties. Its approved indications are the [[Pharmacotherapy|treatment]] of acute pain, the [[symptom]]atic treatment of [[osteoarthritis]] and primary [[dysmenorrhoea]] in [[adolescent]]s and adults above 12 years old. It has a multifactorial mode of action and is characterized by a fast onset of action.
==History==
It was launched in [[Italy]] for the first time as Aulin and Mesulid in 1985 and is available in more than 50 countries worldwide, including among others [[France]], [[Portugal]], [[Greece]], [[Switzerland]], [[Belgium]], [[Russia]] [[Thailand]] and [[Brazil]]. Nimesulide has never been filed for [[Food and Drug Administration (United States)|Food and Drug Administration]] (FDA) evaluation in the [[United States]], where it is not marketed.<ref>{{cite journal |author=Traversa G, Bianchi C, Da Cas R, Abraha I, Menniti-Ippolito F, Venegoni M |title=Cohort study of hepatotoxicity associated with nimesulide and other non-steroidal anti-inflammatory drugs |journal=BMJ |volume=327 |issue=7405 |pages=18–22 |date=July 2003 |pmid=12842950 |pmc=164233 |doi=10.1136/bmj.327.7405.18 |url=http://www.bmj.com/content/327/7405/18.full}}</ref><!--The linked abstract does not include any info on where it is used.-->
Due to concerns about the risk of [[hepatotoxicity]], nimesulide has been withdrawn from market in many countries.{{which|date=June 2014}}
==Advantages==
* Nimesulide has similar gastrointestinal safety as compared to other NSAIDs. {{citation needed|date=December 2012}}
* Its multifactorial mode of action gives it a unique and broad action on inflammatory processes. {{citation needed|date=December 2012}}
* It may be taken through prescription in the treatment of Acute (short term) pain, and Primary dysmenorrhea (Period Pains). It should never be taken in Painful osteoarthritis (Swelling in the joints) .<ref>{{cite web|title=Current status: European Commission final decision|url=http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/referrals/Nimesulide/human_referral_000275.jsp&mid=WC0b01ac0580024e9a|accessdate=12 November 2014}}</ref>
==Availability==
It is available in a variety of forms: tablets, powder for dissolution in water, suppositories, mouth dissolving tablets and topical gel.
A recent evaluation from the [[European Medicines Agency]] (EMA) concluded that the overall benefit/risk profile of nimesulide is favourable and in line with that of the other NSAIDs such as [[diclofenac]], [[ibuprofen]], and [[naproxen]].
==Trade names==
Nimesulide is available through the world as original product with the following trademarks: Sulide, Nimalox, Mesulid (Novartis, Brazil, Boehringer Ingelheim, Greece), Coxtal (Sanofi, China, Czech, Bulgaria),Sintalgin (Abbott, Brazil), Eskaflam (GSK, Brazil, Mexico), Octaprin,  Nimside (Teva,Pakistan), Nise (Dr. Reddy’s Laboratories, India, Russia, Venezuela, Vietnam, Ukraine), Nilsid (Egypt); Aulin, Ainex, Drexel, Donulide, Edrigyl, Enetra, Heugan, Mesulid, Minapon, NeRelid, Nexen, Nidolon, Nilden (Mexico); Nimed, Nimedex, Nimesil, Nimulid, Nimutab, Nimdase, Nimopen-MP (India), Nisulid, Nodard Plus, Nicip, Nimcap, Nic-P, Nic-Spas (India); Novolid, Relmex (Ecuador); Remisid (Ukraine); Scaflam, Scaflan, Sulidin (Turkey), Xilox (Hungary); Modact-IR (Pakistan);<ref>[http://www.druginfosys.com/Brand.aspx?Code=10576]</ref> Sulidene and Zolan for veterinary use. Many generic and copy-products also exist (Lusemin, Medicox, Nidol, Nimalox, Nimesil, Nimotas, Nimulid, Nizer, Sorini, Ventor, Vionim, Neolide, Willgo among others), new-aid (S.A.R.), Nims (Nepal).
==Pharmacokinetics==


{{CMG}}
Nimesulide is rapidly absorbed following oral administration.<ref name="clinpharmacokinet">{{cite journal |author=Bernareggi A |title=Clinical pharmacokinetics of nimesulide |journal=Clin Pharmacokinet |volume=35 |issue=4 |pages=247–74 |date=October 1998 |pmid=9812177 |url=http://content.wkhealth.com/linkback/openurl?issn=0312-5963&volume=35&issue=4&spage=247 |doi=10.2165/00003088-199835040-00001}}</ref>


{{EH}}
Nimesulide undergoes extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).<ref name="clinpharmacokinet"/>


'''Nimesulide''' is a prescription non-[[steroidal]] [[anti-inflammatory]] [[drug]] (NSAID) with [[analgesic]] and [[antipyretic]] properties and its approved indications are the [[Pharmacotherapy|treatment]] of acute pain, the [[symptom]]atic treatment of [[osteoarthrosis]] and primary [[dysmenorrhoea]] in [[adolescent]]s and [[adult]]s above 12 years old.
Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics.<ref name="clinpharmacokinet"/>
Nimesulide is among the top 5 non-steroidal anti-inflammatory drugs worldwide.  


==History==
Moderate renal impairment does not necessitate dosage adjustment while patients with severe renal impairment or hepatic impairment are contraindicated.<ref>[http://www.emea.europa.eu/pdfs/human/referral/nimesulide/308603en.pdf Microsoft Word - opnh.P.Nimesulide .EMEA-CPMP-3086-03-en-Final.doc<!-- Bot generated title -->]</ref>


It was launched in [[Italy]] for the first time as Aulin and Mesulid in 1985 and is presently available in more than 50 countries worldwide, among others [[France]], [[Portugal]], [[Greece]], [[Switzerland]], [[Belgium]], [[Mexico]], [[Brazil]]. Nimesulide has never been filed for [[FDA]] evaluation in the [[United States]], where it is not marketed.
Nimesulide has a relatively rapid onset of action, with meaningful reductions in pain and inflammation observed within 15 minutes from drug intake.<ref name="currmedresopin">{{cite journal |author=Rainsford KD |title=Nimesulide – a multifactorial approach to inflammation and pain: scientific and clinical consensus |journal=Curr Med Res Opin |volume=22 |issue=6 |pages=1161–70 |date=June 2006 |pmid=16846549 |doi=10.1185/030079906X104849 |url=http://informahealthcare.com/doi/abs/10.1185/030079906X104849}}</ref><ref>{{cite journal |author=Bianchi M, Broggini M |title=A randomised, double-blind, clinical trial comparing the efficacy of nimesulide, celecoxib and rofecoxib in osteoarthritis of the knee |journal=Drugs |volume=63 |issue=Suppl 1|pages=37–46 |year=2003 |pmid=14506910 |url=http://content.wkhealth.com/linkback/openurl?issn=0012-6667&volume=63&issue=&spage=37 |doi=10.2165/00003495-200363001-00006}}</ref>


In 2002 nimesulide benefit/risk profile was reviewed by the [[EMEA]] following decision to temporarily suspend the drug from the market in March 2002, in relation to the reporting of hepatic adverse effects in patients apparently treated with nimesulide.
The therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine.<ref name="currmedresopin"/>
It was later demonstrated that the occurrence of hepatic reactions with nimesulide is similar to that of any other [[NSAIDs]] as confirmed by a study published by the British Medical Journal in 2003. <ref>[http://www.bmj.com/cgi/content/abstract/327/7405/18?ck=nck No differences between nimesulide and other NSAIDs liver toxicity]</ref>
Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability.<ref>{{cite journal |author=Laporte JR, Ibáñez L, Vidal X, Vendrell L, Leone R |title=Upper gastrointestinal bleeding associated with the use of NSAIDs: newer versus older agents |journal=Drug Saf |volume=27 |issue=6 |pages=411–20 |year=2004 |pmid=15144234 |url=http://content.wkhealth.com/linkback/openurl?issn=0114-5916&volume=27&issue=6&spage=411 |doi=10.2165/00002018-200427060-00005}}</ref>


=== EMEA reports favourable benefit/risk ratio ===
== Nimesulide Events ==


On August 1, 2003 the Committee for Proprietary Medicinal Products ([[CPMP]]) of the [[European Medicines Agency|EMEA]] reported that the benefit/risk profile of nimesulide containing medicinal products (Aulin, Mesulide, Nimed and associated product names) for systemic and topical use is favourable and that Marketing Authorisations should be maintained/granted. The CPMP recommended to restrict the use of nimesulide to the indications of treatment of acute pain, symptomatic treatment of painful osteoarthritis and primary dysmenorrhoea for the systemic formulations and symptomatic relief of pain associated with sprains and acute [[tendinitis]] for the topical formulation. <ref>[http://www.emea.europa.eu/pdfs/human/press/pr/375403en.pdf European Commission CPMP favourable opinion on nimesulide]</ref>
=== Madras High Court revokes suspension on manufacture and sale of Nimesulide in India ===


[[Alembic]] Ltd. issued a circular asking wholesalers and retailers to withdraw all stocks of Nimegesic Drops (a pediatric dosage form of nimesulide) in 2003, consistent with the fact that nimesulide is, like most NSAIDs, not indicated in children.<ref>[http://www.pharmabiz.com/article/detnews1.asp?articleid=15959&sectionid=47 The end begins]</ref>
On September 13, 2011 Madras High Court revoked a suspension on manufacture and sale of paediatric drugs nimesulide and phenylpropanolamine (PPA).<ref>[http://www.scribd.com/doc/64907025/Madras-High-Court-Revokes-Ban-on-Manufacture-and-Sale-PPA Madras High Court Revokes Suspension on Manufacture and Sale PPA]</ref>


=== Irish Medicines Board (IMB) suspends Nimesulide containing drugs (15 May 2007) ===
=== EMEA re-confirms efficacy of Nimesulide ===


The Irish Medicines Board (IMB) has decided to suspend Nimesulide from the Irish market and refer it to the EU Committee for Human Medicinal Products (CHMP) for a review of its benefit/risk profile. The decision is due to the reporting of six (6) cases of potentially related liver failures to the IMB by the National Liver Transplant Unit, St Vincent Hospital. These cases occurred in the period from 1999 to 2006.<ref>[http://www.imb.ie/safety.asp?nav=70&action=view&safety_item_id=64 IMB Announces Immediate Suspension of the Marketing of Medicines Containing Nimesulide]</ref>
On 23 June 2011, the European Medicines Agency concluded the review of systemic nimesulide-containing medicine. They concluded that the benefits of systemic nimesulide continue to outweigh their risks in the treatment of patients with acute pain and primary dysmenorrhea.


=== Singapore Health Science Authority suspends Nimesulide containing drugs ===
=== Central Drugs Standard Control Organization of India Restricts use of Nimesulide under 12 years of age.===
Pending review of the drug's safety by the EMEA, nimesulide has been suspended with immediate effect (June 15, 2007)<ref>[http://www.channelnewsasia.com/stories/singaporelocalnews/view/282397/1/.html]</ref>
<ref>[http://www.hsa.gov.sg/docs/HSAPressRelease_HSASuspendsSalesOfProductsContainingNimesulide_15Jun07.pdf</ref>


=== EMEA confirms the positive benefit/risk ratio ===
Several reports have been made of [[adverse drug reactions]] in India.<ref>Safety of nimesulide. CD ROM, Appropriate Use of Antipyretics / Analgesics in Children, Health Informatics, New Delhi, 2004.</ref><ref>{{cite journal |author=Rahman SZ, Khan RA |title=Is nimesulide safe in a cardiovascular-Compromised patient? |journal=Indian J Pharmacol |volume=36 |pages=252–3 |year=2004 }}</ref><ref>{{cite journal |author=Khan RA, Rahman SZ |title=A Case Report on Nimesulide and its Relation with Angina |journal=J Pharmacovigilance Drug Safety |volume=1 |issue= |pages=19–21 |year=2004 }}</ref><ref>{{cite journal |author=Khan RA, Rahman SZ |title=Nimesulide Induced Coronary Artery Insufficiency – A Case Report |journal=J Pharmacovigilance Drug Safety |volume=1 |issue= |pages=11–3 |year=2004 }}</ref> On Feb 12, 2011, [[Express India]] that the Union Ministry of Health and Family Welfare had finally decided to suspend the pediatric use of the analgesic, Nimesulide suspension.<ref>[http://www.expressindia.com/latest-news/Nimesulide-for-kids-to-be-banned-finally/749147/ Nimesulide for kids to be suspended finally]</ref> From 10 March 2011 onwards Nimesulide formulations not indicated for human use in children below 12 years of age.<ref>CDSCO website-wide gazette notification GSR 82(E) dated 10.03.2011.</ref>
On September 21, 2007 the EMEA released a press release on their review on the liver-related safety of nimesulide. The EMEA has concluded that the benefits of these medicines outweigh their risks, but that there is a need to limit the duration of use to ensure that the risk of patients developing liver problems is kept to a minimum. Therefore the EMEA has limited the use of systemic formulations (tablets, solutions, suppositories) of nimesulide to 15 days. <ref>[http://www.emea.europa.eu/pdfs/general/direct/pr/43260407en.pdf EMEA press release on nimesulide September 2007]</ref>


===[[Radio Telefís Éireann|RTE's]] [[Prime Time]] Investigates===
=== EMA confirms the positive benefit/risk ratio ===
On December 03rd, 2007 Ireland's RTÉ aired an investigative programme highlighting the deadly side affects of Nimesulide and how it has been linked to over 300 cases of liver disease throughout Europe. Despite several attempts to get it banned; it remains on the market due mainly to EU Bureaucratic red tape{{Fact|date=December 2007}}. It has been responsible for the deaths of many people both in Ireland and worldwide, it should be avoided especially when safer alternatives are available.
On September 21, 2007 the EMA released a press release on their review on the liver-related safety of nimesulide. The EMA has concluded that the benefits of these medicines outweigh their risks, but that there is a need to limit the duration of use to ensure that the risk of patients developing liver problems is kept to a minimum. Therefore the EMA has limited the use of systemic formulations (tablets, solutions, suppositories) of nimesulide to 15 days.<ref>[http://www.emea.europa.eu/pdfs/general/direct/pr/43260407en.pdf EMA press release on nimesulide September 2007]</ref>


==Availability==
=== Irish Medicines Board (IMB) suspends Nimesulide containing drugs (15 May 2007) ===


It is available in a variety of forms: tablets, powder for dissolution in water, suppositories and topical gel.
The Irish Medicines Board (IMB) has decided to suspend Nimesulide from the Irish market and refer it to the EU Committee for Human Medicinal Products (CHMP) for a review of its benefit/risk profile. The decision is due to the reporting of six (6) cases of potentially related liver failures to the IMB by the National Liver Transplant Unit, St Vincent Hospital. These cases occurred in the period from 1999 to 2006.<ref>[http://www.imb.ie/safety.asp?nav=70&action=view&safety_item_id=64 IMB Announces Immediate Suspension of the Marketing of Medicines Containing Nimesulide]</ref>
A recent evaluation from EMEA (the European Medicines Agency) concluded that the overall benefit/risk profile of nimesulide is favourable and in line with that of the other NSAIDs (such as for example, diclofenac, ibuprofen, naproxen).


===Trade names===
=== Delhi High Court verdict ===


Nimesulide is available through the world as original product with the following trademarks: Aulin, Ainex, Drexel, Donulide, Edrigyl, Eskaflam, Heugan, Mesulid, Minapon, Nexen, Nimed, Nimedex,Nimutab, Nisulid, Scaflam, Scaflan. Sulidene and Zolan for veterinary use. Many generic and copy-products also exist (Coxtral, Lusemin, Medicox, Nidol, Nimalox, Nimesil, Nimotas, Nimulid, Nise, Ventor, Willgo among others).
In response to a petition against Nimesulide filed in May 2004,  the Delhi High Court passed a verdict that Nimesulide will continue to be marketed in India since the concerns over its side effect profile are unsubstantiated. The High court sought the help of leading pediatricians and medical agencies from India to arrive at the conclusion that Nimesulide is a safe NSAID with a side effect profile that is comparable to the other NSAIDs.


==Pharmacokinetics==
===Bribes allegedly paid in Italy to spare few drugs from official scrutiny===
In May 2008, Italy's leading daily paper ''[[Corriere della Sera]]'' and other media outlets{{citation needed|date=June 2014}} reported that a top-ranking official at Italy's medicines agency AIFA had been filmed by police while accepting bribes from employees of pharmaceutical companies.<ref>[http://www.corriere.it/cronache/08_maggio_23/aulin_mazzette_controlli_torino_2eed67d6-288a-11dd-97ea-00144f02aabc.shtml «Mazzette per evitare i controlli sull'Aulin». Mario Pappagallo, ''Corriere della Sera'', 23 May 2008] {{dead link|date=June 2014}}</ref><ref>[http://www.manufacturingchemist.com/story.asp?sectioncode=109&storycode=53665&c=1 Italian medicines agency officials arrested in corruption probe. ''Manufacturing Chemist'']</ref>  The money was allegedly being paid to ensure that certain drugs would be spared scrutiny from the drugs watchdog. The investigation had started in 2005 following suspicions that some AIFA drug tests had been faked. Eight arrests were made. Nimesulide can be bought carrying a prescription from a physician that is kept as a receipt at the chemist shop, nominally allowing strong control over selling.


Nimesulide is rapidly absorbed following oral administration<ref name="clinpharmacokinet">Bernareggi A. Clinical pharmacokinetics of nimesulide. Clin.Pharmacokinet. 1998; 35: 247-274</ref>.
The original manufacturer of Nimesulide is Helsinn Healthcare SA, Switzerland, which acquired the rights for the drug in 1976. After the patent protection had terminated, a number of other companies have started production and marketing of Nimesulide.


Nimesulide undergoes extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).<ref name="clinpharmacokinet"/>.
=== European Medicines Agency reports increased risk of liver toxicity ===


Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics<ref name="clinpharmacokinet"/>.
The Committee noted that the studies looking into the effectiveness of nimesulide in acute pain relief have shown that it is as effective as other NSAID pain killers such as diclofenac, ibuprofen and naproxen.


Moderate renal impairment does not necessitate dosage adjustment while patients with severe renal impairment or hepatic impairment are contraindicated<ref>http://www.emea.europa.eu/pdfs/human/referral/nimesulide/308603en.pdf</ref>
In terms of safety, the Committee noted that nimesulide has the same risk of causing stomach and gut problems as other NSAIDs. To limit the risk of side effects affecting the liver, several restrictions have already been introduced in the past, including restriction to second line treatment, the use of lowest effective doses for the shortest possible duration, and a maximum duration of treatment for acute pain.


Nimesulide has a relatively rapid onset of action, with meaningful reductions in pain and inflammation observed within 15 minutes from drug intake<ref name="currmedresopin">KD Rainsford and Members of the Consensus Report Group on Nimesulide. Nimesulide – a multifactorial approach to inflammation and pain: scientific and clinical consensus. Curr. Med. Res. Opin 2006; 22 (6): 1161-1170</ref><ref>Bianchi M and Broggini M. A Randomized, Double-Blind, Clinical Trial Comparing the Efficacy of Nimesulide, Celecoxib and Rofecoxib in osteoarthritis of the Knee. Drugs, 2003; 63, Suppl. 1: 37-46</ref>.
The CHMP concluded that nimesulide was associated with an increased risk of liver toxicity compared with other anti-inflammatory treatments. The CHMP is now recommending, as a further restriction, that systemic nimesulide should no longer be used for treating painful osteoarthritis. The Committee considered that the use of systemic nimesulide for the treatment of painful osteoarthritis, which is a chronic condition, will increase the risk of the medicines being used for long-term treatment with a consequent increase in the risk of liver injury.
As many as almost 498 million patients have been treated with nimesulide from its launch until today{{Fact|date=June 2007}}.
The therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine<ref name="currmedresopin"/>.
Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability<ref>Laporte JR et al. Upper Gastrointestinal Bleeding Associated with the Use of NSAIDs. Drug Safety, 2004; 27 (6): 411-420</ref>.


As all anti-inflammatory drugs, it should be taken in compliance with the recommendations included in the patient leaflet.


==Side effects==
==Side effects==
 
The use of nimesulide in children under the age of 12 is contraindicated. Continuous use of nimesulide (more than 15 days) can cause the following side effects:
Like most drugs in NSAID category, nimesulide is known to be [[hepatotoxic]] (damaging to the liver) in rare but unpredictable cases and should be taken with care. The patient information leaflet informs that the use of nimesulide in children under the age of 12 is contraindicated.
* Diarrhea
* Vomiting
* Skin rash
* Pruritis
* Dizziness
* Bitterness in mouth
Women should use the drug with caution during lactation and it is contraindicated during pregnancy.<ref>http://www.pharmaceutical-drug-manufacturers.com/pharmaceutical-drugs/nimesulide.html</ref>


==References==
==References==
{{reflist|2}}
20. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Nimesulide_31/WC500107957.pdf


<references/>
==External links==


*[http://www.nimesulide.net Official page]
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15144234&query_hl=12&itool=pubmed_docsum PubMed document]
*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16846549&query_hl=7&itool=pubmed_docsum NCBI document]


{{NSAIDs}}
{{Anti-inflammatory and antirheumatic products}}
{{Anti-inflammatory and antirheumatic products}}
[[pt:Nimesulida]]
[[ro:Nimesulid]]
[[sr:Нимезулид]]


[[Category:Non-steroidal anti-inflammatory drugs]]
[[Category:Non-steroidal anti-inflammatory drugs]]
[[Category:Antipyretics]]
[[Category:Antipyretics]]
[[Category:Analgesics]]
[[Category:Analgesics]]
[[Category:Drugs]]
[[Category:Phenol ethers]]
 
[[tr:Nimesulid]]
 
{{jb1}}
{{WH}}
{{WikiDoc Sources}}

Latest revision as of 20:08, 9 January 2015

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]

Nimesulide
Clinical data
AHFS/Drugs.comInternational Drug Names
Routes of
administration		Oral, rectal, topical
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • Usually prescription only
Pharmacokinetic data
Protein binding>97.5%
MetabolismHepatic
Elimination half-life1.8–4.7h
ExcretionRenal (50%), fecal (29%)
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC13H12N2O5S
Molar mass308.311 g/mol
3D model (JSmol)
 ☒N☑Y (what is this?)  (verify)

Overview

Nimesulide is a relatively COX-2 selective, non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties. Its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthritis and primary dysmenorrhoea in adolescents and adults above 12 years old. It has a multifactorial mode of action and is characterized by a fast onset of action.

History

It was launched in Italy for the first time as Aulin and Mesulid in 1985 and is available in more than 50 countries worldwide, including among others France, Portugal, Greece, Switzerland, Belgium, Russia Thailand and Brazil. Nimesulide has never been filed for Food and Drug Administration (FDA) evaluation in the United States, where it is not marketed.[1] Due to concerns about the risk of hepatotoxicity, nimesulide has been withdrawn from market in many countries.Template:Which

Advantages

  • Nimesulide has similar gastrointestinal safety as compared to other NSAIDs. [citation needed]
  • Its multifactorial mode of action gives it a unique and broad action on inflammatory processes. [citation needed]
  • It may be taken through prescription in the treatment of Acute (short term) pain, and Primary dysmenorrhea (Period Pains). It should never be taken in Painful osteoarthritis (Swelling in the joints) .[2]

Availability

It is available in a variety of forms: tablets, powder for dissolution in water, suppositories, mouth dissolving tablets and topical gel.

A recent evaluation from the European Medicines Agency (EMA) concluded that the overall benefit/risk profile of nimesulide is favourable and in line with that of the other NSAIDs such as diclofenac, ibuprofen, and naproxen.

Trade names

Nimesulide is available through the world as original product with the following trademarks: Sulide, Nimalox, Mesulid (Novartis, Brazil, Boehringer Ingelheim, Greece), Coxtal (Sanofi, China, Czech, Bulgaria),Sintalgin (Abbott, Brazil), Eskaflam (GSK, Brazil, Mexico), Octaprin, Nimside (Teva,Pakistan), Nise (Dr. Reddy’s Laboratories, India, Russia, Venezuela, Vietnam, Ukraine), Nilsid (Egypt); Aulin, Ainex, Drexel, Donulide, Edrigyl, Enetra, Heugan, Mesulid, Minapon, NeRelid, Nexen, Nidolon, Nilden (Mexico); Nimed, Nimedex, Nimesil, Nimulid, Nimutab, Nimdase, Nimopen-MP (India), Nisulid, Nodard Plus, Nicip, Nimcap, Nic-P, Nic-Spas (India); Novolid, Relmex (Ecuador); Remisid (Ukraine); Scaflam, Scaflan, Sulidin (Turkey), Xilox (Hungary); Modact-IR (Pakistan);[3] Sulidene and Zolan for veterinary use. Many generic and copy-products also exist (Lusemin, Medicox, Nidol, Nimalox, Nimesil, Nimotas, Nimulid, Nizer, Sorini, Ventor, Vionim, Neolide, Willgo among others), new-aid (S.A.R.), Nims (Nepal).

Pharmacokinetics

Nimesulide is rapidly absorbed following oral administration.[4]

Nimesulide undergoes extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).[4]

Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics.[4]

Moderate renal impairment does not necessitate dosage adjustment while patients with severe renal impairment or hepatic impairment are contraindicated.[5]

Nimesulide has a relatively rapid onset of action, with meaningful reductions in pain and inflammation observed within 15 minutes from drug intake.[6][7]

The therapeutic effects of Nimesulide are the result of its complete mode of action which targets a number of key mediators of the inflammatory process such as: COX-2 mediated prostaglandins, free radicals, proteolytic enzymes and histamine.[6] Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability.[8]

Nimesulide Events

Madras High Court revokes suspension on manufacture and sale of Nimesulide in India

On September 13, 2011 Madras High Court revoked a suspension on manufacture and sale of paediatric drugs nimesulide and phenylpropanolamine (PPA).[9]

EMEA re-confirms efficacy of Nimesulide

On 23 June 2011, the European Medicines Agency concluded the review of systemic nimesulide-containing medicine. They concluded that the benefits of systemic nimesulide continue to outweigh their risks in the treatment of patients with acute pain and primary dysmenorrhea.

Central Drugs Standard Control Organization of India Restricts use of Nimesulide under 12 years of age.

Several reports have been made of adverse drug reactions in India.[10][11][12][13] On Feb 12, 2011, Express India that the Union Ministry of Health and Family Welfare had finally decided to suspend the pediatric use of the analgesic, Nimesulide suspension.[14] From 10 March 2011 onwards Nimesulide formulations not indicated for human use in children below 12 years of age.[15]

EMA confirms the positive benefit/risk ratio

On September 21, 2007 the EMA released a press release on their review on the liver-related safety of nimesulide. The EMA has concluded that the benefits of these medicines outweigh their risks, but that there is a need to limit the duration of use to ensure that the risk of patients developing liver problems is kept to a minimum. Therefore the EMA has limited the use of systemic formulations (tablets, solutions, suppositories) of nimesulide to 15 days.[16]

Irish Medicines Board (IMB) suspends Nimesulide containing drugs (15 May 2007)

The Irish Medicines Board (IMB) has decided to suspend Nimesulide from the Irish market and refer it to the EU Committee for Human Medicinal Products (CHMP) for a review of its benefit/risk profile. The decision is due to the reporting of six (6) cases of potentially related liver failures to the IMB by the National Liver Transplant Unit, St Vincent Hospital. These cases occurred in the period from 1999 to 2006.[17]

Delhi High Court verdict

In response to a petition against Nimesulide filed in May 2004, the Delhi High Court passed a verdict that Nimesulide will continue to be marketed in India since the concerns over its side effect profile are unsubstantiated. The High court sought the help of leading pediatricians and medical agencies from India to arrive at the conclusion that Nimesulide is a safe NSAID with a side effect profile that is comparable to the other NSAIDs.

Bribes allegedly paid in Italy to spare few drugs from official scrutiny

In May 2008, Italy's leading daily paper Corriere della Sera and other media outlets[citation needed] reported that a top-ranking official at Italy's medicines agency AIFA had been filmed by police while accepting bribes from employees of pharmaceutical companies.[18][19] The money was allegedly being paid to ensure that certain drugs would be spared scrutiny from the drugs watchdog. The investigation had started in 2005 following suspicions that some AIFA drug tests had been faked. Eight arrests were made. Nimesulide can be bought carrying a prescription from a physician that is kept as a receipt at the chemist shop, nominally allowing strong control over selling.

The original manufacturer of Nimesulide is Helsinn Healthcare SA, Switzerland, which acquired the rights for the drug in 1976. After the patent protection had terminated, a number of other companies have started production and marketing of Nimesulide.

European Medicines Agency reports increased risk of liver toxicity

The Committee noted that the studies looking into the effectiveness of nimesulide in acute pain relief have shown that it is as effective as other NSAID pain killers such as diclofenac, ibuprofen and naproxen.

In terms of safety, the Committee noted that nimesulide has the same risk of causing stomach and gut problems as other NSAIDs. To limit the risk of side effects affecting the liver, several restrictions have already been introduced in the past, including restriction to second line treatment, the use of lowest effective doses for the shortest possible duration, and a maximum duration of treatment for acute pain.

The CHMP concluded that nimesulide was associated with an increased risk of liver toxicity compared with other anti-inflammatory treatments. The CHMP is now recommending, as a further restriction, that systemic nimesulide should no longer be used for treating painful osteoarthritis. The Committee considered that the use of systemic nimesulide for the treatment of painful osteoarthritis, which is a chronic condition, will increase the risk of the medicines being used for long-term treatment with a consequent increase in the risk of liver injury.


Side effects

The use of nimesulide in children under the age of 12 is contraindicated. Continuous use of nimesulide (more than 15 days) can cause the following side effects:

  • Diarrhea
  • Vomiting
  • Skin rash
  • Pruritis
  • Dizziness
  • Bitterness in mouth

Women should use the drug with caution during lactation and it is contraindicated during pregnancy.[20]

References

  1. ↑ Traversa G, Bianchi C, Da Cas R, Abraha I, Menniti-Ippolito F, Venegoni M (July 2003). "Cohort study of hepatotoxicity associated with nimesulide and other non-steroidal anti-inflammatory drugs". BMJ. 327 (7405): 18–22. doi:10.1136/bmj.327.7405.18. PMC 164233. PMID 12842950.
  2. ↑ "Current status: European Commission final decision". Retrieved 12 November 2014.
  3. ↑ [1]
  4. ↑ 4.0 4.1 4.2 Bernareggi A (October 1998). "Clinical pharmacokinetics of nimesulide". Clin Pharmacokinet. 35 (4): 247–74. doi:10.2165/00003088-199835040-00001. PMID 9812177.
  5. ↑ Microsoft Word - opnh.P.Nimesulide .EMEA-CPMP-3086-03-en-Final.doc
  6. ↑ 6.0 6.1 Rainsford KD (June 2006). "Nimesulide – a multifactorial approach to inflammation and pain: scientific and clinical consensus". Curr Med Res Opin. 22 (6): 1161–70. doi:10.1185/030079906X104849. PMID 16846549.
  7. ↑ Bianchi M, Broggini M (2003). "A randomised, double-blind, clinical trial comparing the efficacy of nimesulide, celecoxib and rofecoxib in osteoarthritis of the knee". Drugs. 63 (Suppl 1): 37–46. doi:10.2165/00003495-200363001-00006. PMID 14506910.
  8. ↑ Laporte JR, Ibáñez L, Vidal X, Vendrell L, Leone R (2004). "Upper gastrointestinal bleeding associated with the use of NSAIDs: newer versus older agents". Drug Saf. 27 (6): 411–20. doi:10.2165/00002018-200427060-00005. PMID 15144234.
  9. ↑ Madras High Court Revokes Suspension on Manufacture and Sale PPA
  10. ↑ Safety of nimesulide. CD ROM, Appropriate Use of Antipyretics / Analgesics in Children, Health Informatics, New Delhi, 2004.
  11. ↑ Rahman SZ, Khan RA (2004). "Is nimesulide safe in a cardiovascular-Compromised patient?". Indian J Pharmacol. 36: 252–3.
  12. ↑ Khan RA, Rahman SZ (2004). "A Case Report on Nimesulide and its Relation with Angina". J Pharmacovigilance Drug Safety. 1: 19–21.
  13. ↑ Khan RA, Rahman SZ (2004). "Nimesulide Induced Coronary Artery Insufficiency – A Case Report". J Pharmacovigilance Drug Safety. 1: 11–3.
  14. ↑ Nimesulide for kids to be suspended finally
  15. ↑ CDSCO website-wide gazette notification GSR 82(E) dated 10.03.2011.
  16. ↑ EMA press release on nimesulide September 2007
  17. ↑ IMB Announces Immediate Suspension of the Marketing of Medicines Containing Nimesulide
  18. ↑ «Mazzette per evitare i controlli sull'Aulin». Mario Pappagallo, Corriere della Sera, 23 May 2008 [dead link]
  19. ↑ Italian medicines agency officials arrested in corruption probe. Manufacturing Chemist
  20. ↑ http://www.pharmaceutical-drug-manufacturers.com/pharmaceutical-drugs/nimesulide.html

20. http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Nimesulide_31/WC500107957.pdf


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