Nimesulide

Nimesulide
Names
IUPAC name
  • N-(4-Nitro-2-phenoxyphenyl)methanesulfonamide
Clinical data
Drug classNSAIDs
Main usesAcute pain, painful periods[1]
Side effectsLiver problems[2]
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Routes of
use		By mouth, rectal, topical
External links
AHFS/Drugs.comInternational Drug Names
Legal
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetics
Protein binding>97.5%
MetabolismLiver
Elimination half-life1.8–4.7h
ExcretionKidney (50%), fecal (29%)
Chemical and physical data
FormulaC13H12N2O5S
Molar mass308.31 g·mol−1
3D model (JSmol)
SMILES
  • [O-][N+](=O)c2cc(Oc1ccccc1)c(cc2)NS(=O)(=O)C
InChI
  • InChI=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 checkY
  • Key:HYWYRSMBCFDLJT-UHFFFAOYSA-N checkY

Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) used for acute pain and painful periods.[1][3] Use is recommended for less than 15 days.[1] There is no evidence of benefit over other NSAIDs and due to side effects it is considered a second line treatment.[2][1]

Side effects may include liver problems including those that result in the need for a liver transplant or death.[2][1][4] Other side effects may include stomach problems.[1] This issue occurs at a higher rate than other NSAIDs.[2] It works primarily by blocking the enzyme COX-2 that makes prostaglandins.[5]

Nimesulide has been approved for medical use in parts of Europe since 1985.[1] It has never been approved in the United States, United Kingdom, Canada, Australia, New Zealand, or Japan due to safety concerns.[2] Approval has been withdrawn in a number of countries including Spain, Ireland, and Finland.[2]

Medical uses

Nimesulide is not available in the United States, however is approved in some countries for acute pain.[6] 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.[7]

Side effects

Due to concerns about the risk of liver toxicity, nimesulide has been withdrawn from market in several countries (Spain, Finland, Belgium, Ireland, and United States).[8] Liver problems have resulted in both deaths and the need for transplantation.[6] This may occur in as little as three days after starting the medication.[6]

Nimesulide may cause the following side effects:

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

It should be avoided by children under 12 and people with liver problems or flu-like symptoms.

Children

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.[9]

Pregnancy and breastfeeding

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.[10]

Pharmacokinetics

Nimesulide is absorbed rapidly following oral administration.[11]

Nimesulide undergoes extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).[11]

Food, gender, and advanced age have negligible effects on nimesulide pharmacokinetics.[11]

Moderate chronic kidney disease does not necessitate dosage adjustment, while in patients with severe chronic kidney disease or liver disease, Nimesulide is contraindicated.[12]

Nimesulide has a relatively rapid onset of action, with meaningful reductions in pain and inflammation observed within 15 minutes from drug intake.[13][14]

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.[13] Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability.[15]

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.[16] Nimesulide has never been filed for Food and Drug Administration (FDA) evaluation in the United States, where it is not marketed.

Society and culture

Availability

100mg nimesulide pills

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 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, Czechia, Italy), Ainex, Drexel, Donulide, Edrigyl, Enetra, Heugan, Mesulid, Minapon, NeRelid, Nexen, Nidolon, Nilden (Mexico); Emsulide, Nimed, Nimedex, Nimesil (Czechia, Moldova, Latvia), Nimulid (Trinidad & Tobago), Nimutab, Nimdase, Nimopen-MP Nise, Nimuwin, Nisulid, Nodard Plus, Nicip, Nimcap, Nic-P, Nic-Spas (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 (Syria), Nims, Nice, Nimulide (Nepal)

India

Several reports have been made of adverse drug reactions in India.[17][18][19][20] 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.[21] From 10 March 2011 onward Nimesulide formulations are not indicated for human use in children below 12 years of age.[22]

On September 13, 2011 Madras High Court revoked a suspension on manufacture and sale of paediatric drugs nimesulide and phenylpropanolamine (PPA).[23]

Europe

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.[24]

Ireland

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.[25]

Bribes

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.[26][27] 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[28], a number of other companies started production and marketing of nimesulide.

References

  1. 1 2 3 4 5 6 7 "Nimesulide". European Medicines Agency. 2012. Archived from the original on 22 October 2020. Retrieved 27 October 2020.
  2. 1 2 3 4 5 6 "Nimesulide must be withdrawn worldwide due to serious liver damage". www.ti.ubc.ca. Archived from the original on 8 November 2020. Retrieved 27 October 2020.
  3. ↑ "Nimesulide". Drugs.com. Archived from the original on 12 November 2020. Retrieved 27 October 2020.
  4. ↑ Kwon, J; Kim, S; Yoo, H; Lee, E (2019). "Nimesulide-induced hepatotoxicity: A systematic review and meta-analysis". PloS one. 14 (1): e0209264. doi:10.1371/journal.pone.0209264. PMID 30677025.
  5. ↑ Aronson, Jeffrey K. (2016). Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. Elsevier. p. 738. ISBN 978-0-444-53716-4. Archived from the original on 10 November 2021. Retrieved 27 October 2020.
  6. 1 2 3 "Nimesulide". livertox.nih.gov. Archived from the original on 23 December 2017. Retrieved 22 December 2017.
  7. ↑ "Current status: European Commission final decision". Archived from the original on 19 October 2014. Retrieved 12 November 2014.
  8. ↑ McNaughton, R.; Huet, G.; Shakir, S. (2014). "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". BMJ Open. 4 (1): e004221. doi:10.1136/bmjopen-2013-004221. PMC 3902466. PMID 24435895. open access
  9. ↑ Gupta, P; Sachdev, HP (June 2003). "Safety of oral use of nimesulide in children: systematic review of randomized controlled trials". Indian Pediatrics. 40 (6): 518–31. PMID 12824661.
  10. ↑ "Nimesulide, Nimesulide Tablets, Ainex Nimesulide, Nimesulide Manufacturers". www.pharmaceutical-drug-manufacturers.com. Archived from the original on 2016-03-03.
  11. 1 2 3 Bernareggi, Alberto (October 1998). "Clinical pharmacokinetics of nimesulide". Clinical Pharmacokinetics. 35 (4): 247–74. doi:10.2165/00003088-199835040-00001. PMID 9812177. S2CID 26895870.
  12. ↑ Microsoft Word - opnh.P.Nimesulide .EMEA-CPMP-3086-03-en-Final.doc Archived 2007-06-11 at the Wayback Machine
  13. 1 2 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. S2CID 23004446.
  14. ↑ 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. S2CID 19826636.
  15. ↑ 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. S2CID 1786767.
  16. ↑ K.D. Rainsford (red.) (2005). Nimesulide – Actions and Uses. Bazylea, Boston, Berlin: Birkhäuser Verlag. p. 7. ISBN 978-3-7643-7068-8.
  17. ↑ Safety of nimesulide. CD ROM, Appropriate Use of Antipyretics / Analgesics in Children, Health Informatics, New Delhi, 2004.
  18. ↑ Rahman SZ, Khan RA (2004). "Is nimesulide safe in a cardiovascular-Compromised patient?". Indian J Pharmacol. 36: 252–3.
  19. ↑ Khan RA, Rahman SZ (2004). "A Case Report on Nimesulide and its Relation with Angina". J Pharmacovigilance Drug Safety. 1: 19–21.
  20. ↑ Khan RA, Rahman SZ (2004). "Nimesulide Induced Coronary Artery Insufficiency – A Case Report". J Pharmacovigilance Drug Safety. 1: 11–3.
  21. ↑ Thacker, Teena (12 February 2011). "Nimesulide for kids to be banned, finally". The Indian Express. Archived from the original on 2018-05-20. Retrieved 2018-05-19.
  22. ↑ CDSCO website-wide gazette notification GSR 82(E) dated 10.03.2011.
  23. ↑ "Madras High Court Revokes Ban on Manufacture and Sale PPA - Adverse Effect - Medical Treatments". Scribd. Archived from the original on 2014-01-07.
  24. ↑ EMA press release on nimesulide September 2007 Archived 2009-07-18 at the Portuguese Web Archive
  25. ↑ "Error Page". www.imb.ie. Archived from the original on 2007-09-28. Retrieved 2007-05-15.
  26. ↑ «Mazzette per evitare i controlli sull'Aulin». Mario Pappagallo, Corriere della Sera, 23 May 2008 Archived May 25, 2008, at the Wayback Machine
  27. ↑ "Italian medicines agency officials arrested in corruption probe". Manufacturing Chemist. 22 May 2008. Archived from the original on 2018-05-20. Retrieved 2018-05-19.
  28. ↑ "Archive copy". Archived from the original on 2021-04-02. Retrieved 2020-06-03.{{cite web}}: CS1 maint: archived copy as title (link)
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