Nimesulide: Difference between revisions

(346 intermediate revisions by more than 100 users not shown)

Line 1:

{{Drugbox| verifiedrevid = 408770143

{{Drugbox

|IUPAC_name = ''N''-(4-Nitro-2-phenoxyphenyl)methanesulfonamide

| Verifiedfields = changed

| image=nimesulide.png

| verifiedrevid = 413700508

| width=200px

| IUPAC_name = ''N''-(4-Nitro-2-phenoxyphenyl)methanesulfonamide

| CASNo_Ref = {{cascite|correct|CAS}}

| image = nimesulide.svg

| width = 200

| tradename =

| Drugs.com = {{drugs.com|international|nimesulide}}

| legal_AU = S4

| legal_status = prescription only

| routes_of_administration = [[By mouth]], [[Rectal administration|rectal]], [[Topical administration|topical]]

| protein_bound = >97.5%

| metabolism = Hepatic

| elimination_half-life = 1.8–4.7h

| excretion = Renal (50%), fecal (29%)

| IUPHAR_ligand = 7401

| CAS_number_Ref = {{cascite|correct|CAS}}

| 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}}

| 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

| KEGG = D01049

| InChIKey = HYWYRSMBCFDLJT-UHFFFAOYAR

| ChEBI_Ref = {{ebicite|changed|EBI}}

| smiles = [O-][N+](=O)c2cc(Oc1ccccc1)c(cc2)NS(=O)(=O)C

| ChEBI = 44445

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 56367

| C=13 | H=12 | N=2 | O=5 | S=1

| smiles = [O-][N+](=O)c2cc(Oc1ccccc1)c(cc2)NS(=O)(=O)C

| 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

| CAS_number=51803-78-2

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 4339

| ATC_prefix=M01

| ATC_suffix=AX17

| ATC_supplemental={{ATC|M02|AA26}}

| PubChem=4495

| DrugBank=

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D01049

| C=13 | H=12 | N=2 | O=5 | S=1

| molecular_weight =308.311 g/mol

| protein_bound = >97.5%

| metabolism = Hepatic

| elimination_half-life = 1.8–4.7h

| excretion = Renal (50%), fecal (29%)

| legal_status = Usually prescription only

| routes_of_administration= Oral, rectal, topical

}}

'''Nimesulide''' is a [[nonsteroidal anti-inflammatory drug]] (NSAID) with [[analgesic|pain medication]] and [[antipyretic|fever reducing]] properties. Its approved indications are the [[Pharmacotherapy|treatment]] of acute pain, the symptomatic treatment of [[osteoarthritis]], and primary [[dysmenorrhoea]] in [[Adolescence|adolescents]] and adults above 12 years old.

'''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. Due to concerns about the risk of [[hepatotoxicity]], nimesulide has been withdrawn from market in many countries.<ref>http://www.medindia.net/news/Unsafe-Drugs-Banned-79989-1.htm</ref>

Side effects may include [[liver problems]].<ref name=Liv2017>{{cite journal|title=Nimesulide|url=https://livertox.nih.gov/Nimesulide.htm|website=livertox.nih.gov|pmid=31643176 |access-date=22 December 2017|url-status=live|archive-url=https://web.archive.org/web/20171223043951/https://livertox.nih.gov/Nimesulide.htm|archive-date=23 December 2017}}</ref> It has a multifactorial mode of action and is characterized by a fast onset of action. It works by blocking the production of prostaglandins (a chemical associated with pain), thereby relieving pain and inflammation.

==~~History~~==

==Medical uses==

It may be used for pain, including period pains. Nimesulide is not recommended long-term, as for chronic conditions such as arthritis. This is due to its association with an increased risk of liver toxicity, including liver failure.<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|access-date=12 November 2014|url-status=live|archive-url=https://web.archive.org/web/20141019113817/http://www.ema.europa.eu/ema/index.jsp?curl=pages%2Fmedicines%2Fhuman%2Freferrals%2FNimesulide%2Fhuman_referral_000275.jsp&mid=WC0b01ac0580024e9a|archive-date=19 October 2014}}</ref> Despite its risk of hepatotoxicity, a 2012 evaluation by 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]] provided that the duration of use is limited to 15 days and the dose does not exceed 200 mg/day.<ref name="pmid30689999" />

{{Unreferenced section|date=January 2010}}

===Children===

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]] and [[India]]. 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 |year=2003 |month=July |pmid=12842950 |pmc=164233 |doi=10.1136/bmj.327.7405.18 |url=http://www.bmj.com/content/327/7405/18.full}}</ref>

Less than 10 days of nimesulide does not appear to increase the risk of hypothermia, gastrointestinal bleeding, epigastric pain, vomiting, diarrhea, or transient, asymptomatic elevation of liver enzymes compared to [[ketoprofen]], [[paracetamol]], [[mefenamic acid]], [[aspirin]], or [[ibuprofen]] in children. However, data does not speak to populations less than 6 months old.<ref name="Gupta and Sachdev">{{cite journal | vauthors = Gupta P, Sachdev HP | title = Safety of oral use of nimesulide in children: systematic review of randomized controlled trials | journal = Indian Pediatrics | volume = 40 | issue = 6 | pages = 518–531 | date = June 2003 | pmid = 12824661 }}</ref>

===Pregnancy and lactation===

=== European Medicines Agency reports favourable benefit/risk ratio ===

Women should use the drug with caution during lactation and nimesulide is contraindicated during pregnancy, and research suggest that it is also contraindicated in lactating women.<ref>{{cite web|url=http://www.pharmaceutical-drug-manufacturers.com/pharmaceutical-drugs/nimesulide.html|title=Nimesulide, Nimesulide Tablets, Ainex Nimesulide, Nimesulide Manufacturers|website=www.pharmaceutical-drug-manufacturers.com|url-status=live|archive-url=https://web.archive.org/web/20160303202009/http://www.pharmaceutical-drug-manufacturers.com/pharmaceutical-drugs/nimesulide.html|archive-date=2016-03-03}}</ref>

===Available forms===

On August 1, 2003 the [[Committee for Proprietary Medicinal Products]] (CPMP) of the [[European Medicines Agency]] (EMA) 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>

[[File:Nimesulida100mg.jpg|left|thumb|100mg Nimesulide pills]]

Nimesulide is available in a variety of forms: tablets, powder for dissolution in water, suppositories, mouth dissolving tablets, and [[Topical gels|topical gel]].

[[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>

==Contraindications==

=== Central Drugs Standard Control Organization of India bans Nimesulide===

It should be avoided by children under 12 and people with liver problems.

==Side effects==

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, [http://www.expressindia.com/latest-news/Nimesulide-for-kids-to-be-banned-finally/749147/ Express India reported] that the Union Ministry of Health and Family Welfare had finally decided to ban the pediatric use of the analgesic, Nimesulide suspension. A notification to this effect was expected soon, following which the drug would be off the shelves

Due to concerns about the risk of [[hepatotoxicity|liver toxicity]], nimesulide has been withdrawn from market in several countries (Mexico,<ref>{{cite web |title=Aviso sobre los riesgos del consumo y uso de los medicamentos que contengan en su formulación Nimesulida |url=https://www.gob.mx/cofepris/articulos/aviso-sobre-los-riesgos-del-consumo-y-uso-de-los-medicamentos-que-contengan-en-su-formulacion-nimesulida?idiom=es |publisher=Cofepris |access-date=1 July 2023 |language=es |date=30 May 2019}}</ref> Spain, Finland, Belgium, and Ireland).<ref>{{cite journal | vauthors = McNaughton R, Huet G, Shakir S | title = An investigation into drug products withdrawn from the EU market between 2002 and 2011 for safety reasons and the evidence used to support the decision-making | journal = BMJ Open | volume = 4 | issue = 1 | pages = e004221 | date = January 2014 | pmid = 24435895 | pmc = 3902466 | doi = 10.1136/bmjopen-2013-004221 }} {{open access}}</ref> Liver problems have resulted in both deaths and the need for transplantation.<ref name=Liv2017/> Although the frequency of nimesulide-induced liver injury is estimated at around 1 in 50,000 patients and is less common when use is limited to 15 days, severe injury has occurred in as little as three days after starting the medication.<ref name=Liv2017/><ref>https://www.ncbi.nlm.nih.gov/books/NBK547948/</ref>

Continuous use of nimesulide (more than 15 days) may cause the following side effects:{{Medcn|date=June 2014}}

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

* Diarrhea

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>

* Vomiting

* Skin rash

* Itchiness

* Dizziness

* Bitterness in mouth

==Pharmacology==

=== Singapore Health Science Authority suspends Nimesulide containing drugs ===

Pending review of the drug's safety by the EMA, nimesulide has been suspended with immediate effect (June 15, 2007)<ref>[http://www.channelnewsasia.com/stories/singaporelocalnews/view/282397/1/.html Channelnewsasia.com]</ref><ref>http://www.hsa.gov.sg/docs/HSAPressRelease_HSASuspendsSalesOfProductsContainingNimesulide_15Jun07.pdf</ref>

===Pharmacodynamics===

=== EMA confirms the positive benefit/risk ratio ===

Nimesulide is a [[nonsteroidal anti-inflammatory drug]] (NSAID), acting specifically as a relatively [[binding selectivity|selective]] [[COX-2 inhibitor|cyclooxygenase-2 inhibitor]].<ref name="pmid30689999">{{cite journal | vauthors = Caiazzo E, Ialenti A, Cicala C | title = The relatively selective cyclooxygenase-2 inhibitor nimesulide: What's going on? | journal = European Journal of Pharmacology | volume = 848 | issue = | pages = 105–111 | date = April 2019 | pmid = 30689999 | doi = 10.1016/j.ejphar.2019.01.044 | s2cid = 59339842 }}</ref><ref name="pmid18333314">{{cite journal | vauthors = Suleyman H, Cadirci E, Albayrak A, Halici Z | title = Nimesulide is a selective COX-2 inhibitory, atypical non-steroidal anti-inflammatory drug | journal = Current Medicinal Chemistry | volume = 15 | issue = 3 | pages = 278–283 | date = 2008 | pmid = 18333314 | doi = 10.2174/092986708783497247 }}</ref> However, the pharmacological profile of nimesulide is peculiar, and additional, unknown/yet-to-be-identified mechanisms appear to also be involved.<ref name="pmid30689999" /><ref name="pmid18333314" /> One pathway that has been implicated in its actions is the [[ecto-5'-nucleotidase]] (e-5′NT/CD73)/[[adenosine A2A receptor|adenosine A2A receptor]] pathway.<ref name="pmid30689999" />

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>

===Pharmacokinetics===

===RTÉ's Prime Time Investigates===

Nimesulide is absorbed rapidly following oral administration.<ref name="clinpharmacokinet">{{cite journal | vauthors = Bernareggi A | title = Clinical pharmacokinetics of nimesulide | journal = Clinical Pharmacokinetics | volume = 35 | issue = 4 | pages = 247–274 | date = October 1998 | pmid = 9812177 | doi = 10.2165/00003088-199835040-00001 | s2cid = 26895870 }}</ref>

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

On December 3, 2007 Ireland's RTÉ aired an investigative programme highlighting the deadly side effects of Nimesulide and how it has been linked to over 300 cases of liver disease throughout Europe.

Food, sex, and advanced age have negligible effects on nimesulide pharmacokinetics.<ref name="clinpharmacokinet"/>

===Bribes allegedly paid in Italy to spare nimesulide from official scrutiny===

In May 2008, Italy's leading daily paper ''[[Corriere della Sera]]'' and other media outlets 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]</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 (nimesulide-containing Aulin being the most prominent) 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. Following this, concerns about nimesulide hepatotoxicity became more widely reported by the Italian media. A government minister ordered an inquiry. Presently{{When|date=April 2010}}, 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.

Moderate [[chronic kidney disease]] does not necessitate dosage adjustment, while in patients with severe chronic kidney disease or liver disease, nimesulide is contraindicated.<ref>{{cite web | url = http://www.emea.europa.eu/pdfs/human/referral/nimesulide/308603en.pdf | title = Nimesulide Tablets: Summary of Product Characteristics | work = Europeans Medicines Agency | date = 2004 | archive-url = https://web.archive.org/web/20070611052514/http://www.emea.europa.eu/pdfs/human/referral/nimesulide/308603en.pdf | archive-date = 11 June 2007 }}</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 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 | vauthors = Rainsford KD | title = Nimesulide -- a multifactorial approach to inflammation and pain: scientific and clinical consensus | journal = Current Medical Research and Opinion | volume = 22 | issue = 6 | pages = 1161–1170 | date = June 2006 | pmid = 16846549 | doi = 10.1185/030079906X104849 | s2cid = 23004446 }}</ref><ref>{{cite journal | vauthors = 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 | date = 2003 | pmid = 14506910 | doi = 10.2165/00003495-200363001-00006 | s2cid = 19826636 }}</ref>

===Prohibition in several European countries===

The therapeutic effects of nimesulide are the result of its complex 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"/>

Like in Ireland, Nimesulide has been prohibited in several other European countries{{Specify|date=January 2010}}, based on the serious hepatotoxicity that has been suspected of causing several hundred deaths.

Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability.<ref>{{cite journal | vauthors = 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 Safety | volume = 27 | issue = 6 | pages = 411–420 | year = 2004 | pmid = 15144234 | doi = 10.2165/00002018-200427060-00005 | s2cid = 1786767 }}</ref>

==History==

===Illicit marketing as "food supplement" in Scandinavia and the UK===

Nimesulide 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]].<ref>{{cite book | vauthors = Rainsford KD |title= Nimesulide – Actions and Uses|location= Bazylea, Boston, Berlin|publisher= Birkhäuser Verlag|page= 7|date=2005|isbn= 978-3-7643-7068-8}}</ref> 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.

==Society and culture==

After serious medical problems including deaths from the food supplement "Fortodol", analysis demonstrated that in several instances this "food supplement from natural products", declared to contain [[turmeric]] and [[phenyl alanine]], contained therapeutic doses of Nimesulide. This was thus probably the reason for the serious side effects of this preparation.<ref>http://www.lakemedelsverket.se/Tpl/NewsPage____8325.aspx (Swedish)</ref> Identical or similar preparations containing turmeric tainted with nimesulide have been marketed in Denmark, Finland and in the UK under the brand name "Miradin".<ref>http://www.food.gov.uk/enforcement/alerts/2009/mar/miradinfortodol</ref>

==~~Availability~~==

===Brand names===

Nimesulide is available throughout the world as original product with the following trademarks: Sulide, Nimalox, Mesulid (Novartis, Brazil, Boehringer Ingelheim, Greece, Italy), Coxtal (Sanofi, China, Bulgaria), Sintalgin (Abbott, Brazil), Eskaflam (GSK, Brazil, Mexico), Octaprin, Nimside (Teva, Pakistan), Nise (Russia, Venezuela, Vietnam, Ukraine), Nilsid (Egypt); Aulin (Bulgaria, Czech Republic, Italy, Romania, Poland), Ainex, Drexel, Donulide, Edrigyl, Enetra, Heugan, Mesulid, Minapon, NeRelid, Nexen, Nidolon, Nilden (Mexico); Emsulide, Nimed, Nimedex, Nimesil (Czech Republic, Moldova, Latvia, Lithuania, Kazhakhstan, Georgia, Poland), Nimulid (Trinidad & Tobago), Nimutab, Nimdase, Nimopen-MP Nise, Nimuwin, Nisulid, Nodard Plus, Nicip, Nimcap, Nic-P, Nic-Spas, Nimupain (India); Mesulid, Novolid, Relmex (Ecuador); Remisid (Ukraine); Coxulid, Emulid, Frenag, Fuzo, Motival, Nimeksil, Nimelid, Nîmes, Nimesdin, Romasulid, Sulidin, Suljel, Thermo Sulidin (Turkey), Xilox (Hungary); Modact-IR (Pakistan); and ad 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, Nexulide (Syria), Nims, Nice, Nimulide (Nepal)

[[File:Nimesulida100mg.jpg|left|thumb|100mg Nimesulide pills]]

It is available in a variety of forms: tablets, powder for dissolution in water, suppositories and topical gel '''(Sulidin® Gel)'''.

===India===

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]]).

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 |vauthors=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 |vauthors=Khan RA, Rahman SZ |title=A Case Report on Nimesulide and its Relation with Angina |journal=J Pharmacovigilance Drug Safety |volume=1 |pages=19–21 |year=2004 }}</ref><ref>{{cite journal |vauthors=Khan RA, Rahman SZ |title=Nimesulide Induced Coronary Artery Insufficiency – A Case Report |journal=J Pharmacovigilance Drug Safety |volume=1 |pages=11–3 |year=2004 }}</ref> On February 12, 2011, [[Indian Express]] reported that the Union Ministry of Health and Family Welfare finally had decided to suspend the pediatric use of the analgesic, Nimesulide suspension.<ref>{{cite news|last1=Thacker|first1=Teena|title=Nimesulide for kids to be banned, finally|url=http://indianexpress.com/article/news-archive/web/nimesulide-for-kids-to-be-banned-finally/|access-date=2018-05-19|work=The Indian Express|date=12 February 2011}}</ref> From 10 March 2011 onward Nimesulide formulations are 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 13, 2011 Madras High Court revoked a suspension on manufacture and sale of paediatric drugs nimesulide and phenylpropanolamine (PPA).<ref>{{cite web|url=https://www.scribd.com/doc/64907025/Madras-High-Court-Revokes-Ban-on-Manufacture-and-Sale-PPA|title=Madras High Court Revokes Ban on Manufacture and Sale PPA - Adverse Effect - Medical Treatments|website=Scribd|url-status=live|archive-url=https://web.archive.org/web/20140107193045/http://www.scribd.com/doc/64907025/Madras-High-Court-Revokes-Ban-on-Manufacture-and-Sale-PPA|archive-date=2014-01-07}}</ref>

===Trade names===

===EMA confirms the positive benefit/risk ratio===

Nimesulide is available through the world as original product with the following trademarks: sulide, nimalox, mesulid, nilsid (Egypt), Aulin, Ainex, Drexel, Donulide, Edrigyl, Enetra, Eskaflam, Heugan, Mesulid, Minapon, NeRelid, Nexen, Nidolon, Nilden (Mexico), Nimed, Nimedex, Nimesil, Nimulid, Nimutab, Nise, Nisulid, Nodard Plus, Nicip (India), Novolid, Pain Lock(VIP Pharma India

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>{{cite web | url = http://www.emea.europa.eu/pdfs/general/direct/pr/43260407en.pdf | title = EMA press release on nimesulide | date = September 2007 | archive-url = http://arquivo.pt/wayback/20090718094456/http://www.emea.europa.eu/pdfs/general/direct/pr/43260407en.pdf | archive-date=2009-07-18| work = European Medicines Agency }}</ref>

),Relmex (Ecuador), Scaflam, Scaflan, Sulidin® (Turkey), Modact-IR (Pakistan)[http://www.druginfosys.com/Brand.aspx?Code=10576]. Sulidene and Zolan for veterinary use. Many generic and copy-products also exist (Coxtral, Lusemin, Medicox, Nidol, Nimalox, Nimesil, Nimotas, Nimulid, Nise, Nizer, Sorini, Ventor, Vionim, Neolide, Willgo among others).

Ledoren

===Irish Medicines Board===

==Pharmacokinetics==

The [[Irish Medicines Board]] 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 cases of potentially-related liver failures to the IMB by the National Liver Transplant Unit, [[St. Vincent's University Hospital]]. These cases occurred in the period from 1999 to 2006.<ref>{{cite web|url=https://www.irishtimes.com/news/irish-agency-rejects-european-ruling-on-safety-of-painkiller-1.964481|title=The Irish Times|website=www.irishtimes.com}}</ref>

===Bribes===

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 |year=1998 |month=October |pmid=9812177 |url=http://content.wkhealth.com/linkback/openurl?issn=0312-5963&volume=35&issue=4&spage=247}}</ref>

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>{{cite web | url = http://www.corriere.it/cronache/08_maggio_23/aulin_mazzette_controlli_torino_2eed67d6-288a-11dd-97ea-00144f02aabc.shtml | title = Mazzette per evitare i controlli sull'Aulin | vauthors = Pappagallo M | work = Corriere della Sera | date = 23 May 2008 | archive-url = https://web.archive.org/web/20080525221510/http://www.corriere.it/cronache/08_maggio_23/aulin_mazzette_controlli_torino_2eed67d6-288a-11dd-97ea-00144f02aabc.shtml | archive-date = 25 May 2008 }}</ref><ref>{{cite web|title=Italian medicines agency officials arrested in corruption probe|url=https://www.manufacturingchemist.com/news/article_page/Italian_medicines_agency_officials_arrested_in_corruption_probe/40712|publisher=Manufacturing Chemist|access-date=2018-05-19|date=22 May 2008}}</ref> The money allegedly was 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 terminated in 2015,<ref>{{Cite web|url=https://patents.google.com/patent/EP0782855B1/en|title=Nimesulide for external use}}</ref> a number of other companies started production and marketing of Nimesulide.

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

== References ==

Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics.<ref name="clinpharmacokinet"/>

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]</ref>

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 |year=2006 |month=June |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}}</ref>

As many as almost 498 million patients have been treated with nimesulide from its launch until today.{{Citation needed|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>{{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}}</ref>

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

==Dosage==

50–100 mg twice a day, after the meals.

==Side effects==

Like most drugs in NSAID category, nimesulide is known to be [[hepatotoxicity|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.

The drug has certain side effects, that can affect individuals in different ways. The following are some of the side effects, that are often associated with the drug:

* Diarrhoea

* Vomiting

* Skin rash

* Pruritis

* Dizziness

* Headache

* 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==

==External links==

*[http://www.nimesulide.net nimesulide.net], by pharmaceutical company [[Helsinn Healthcare]]

[[Category:Non-steroidal anti-inflammatory drugs]]

[[Category:Antipyretics]]

[[Category:~~Analgesics~~]]

[[Category:Drugs with unknown mechanisms of action]]

[[Category:Hepatotoxins]]

[[Category:Nitrobenzene derivatives]]

[[Category:Nonsteroidal anti-inflammatory drugs]]

[[Category:Phenol ethers]]

[[Category:~~Nitrobenzenes~~]]

[[Category:Withdrawn drugs]]

[[de:Nimesulid]]

[[es:Nimesulida]]

[[fr:Nimésulide]]

[[it:Nimesulide]]

[[nl:Nimesulide]]

[[pt:Nimesulida]]

[[ro:Nimesulid]]

[[ru:Нимесулид]]

[[sr:Нимесулид]]

[[tr:Nimesulid]]