Nimesulide

Last updated
Nimesulide
Nimesulide.svg
Clinical data
AHFS/Drugs.com International Drug Names
Routes of
administration 		By mouth, rectal, topical
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Protein binding >97.5%
Metabolism Hepatic
Elimination half-life 1.8–4.7h
Excretion Renal (50%), fecal (29%)
Identifiers
  • N-(4-Nitro-2-phenoxyphenyl)methanesulfonamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.052.194 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C13H12N2O5S
Molar mass 308.31 g·mol−1
3D model (JSmol)
  • [O-][N+](=O)c2cc(Oc1ccccc1)c(cc2)NS(=O)(=O)C
  • 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 Yes check.svgY
  • Key:HYWYRSMBCFDLJT-UHFFFAOYSA-N Yes check.svgY
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) with pain medication and fever reducing 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.

Contents

Side effects may include liver problems. [1] 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.

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. [2] 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. [3]

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. [4]

Pregnancy and lactation

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. [5]

Available forms

100mg Nimesulide pills Nimesulida100mg.jpg
100mg Nimesulide pills

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

Contraindications

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

Side effects

Due to concerns about the risk of liver toxicity, nimesulide has been withdrawn from market in several countries (Mexico, [6] Spain, Finland, Belgium, and Ireland). [7] Liver problems have resulted in both deaths and the need for transplantation. [1] This may occur in as little as three days after starting the medication. [1]

Continuous use of nimesulide (more than 15 days) may cause the following side effects:[ medical citation needed ]

Pharmacology

Pharmacodynamics

Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID), acting specifically as a relatively selective cyclooxygenase-2 inhibitor. [3] [8] However, the pharmacological profile of nimesulide is peculiar, and additional, unknown/yet-to-be-identified mechanisms appear to also be involved. [3] [8] One pathway that has been implicated in its actions is the ecto-5'-nucleotidase (e-5′NT/CD73)/adenosine A2A receptor pathway. [3]

Pharmacokinetics

Nimesulide is absorbed rapidly following oral administration. [9]

Nimesulide undergoes extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active). [9]

Food, sex, and advanced age have negligible effects on nimesulide pharmacokinetics. [9]

Moderate chronic kidney disease does not necessitate dosage adjustment, while in patients with severe chronic kidney disease or liver disease, nimesulide is contraindicated. [10]

Nimesulide has a relatively rapid onset of action, with meaningful reductions in pain and inflammation observed within 15 minutes from drug intake. [11] [12]

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

History

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

Society and culture

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)

India

Several reports have been made of adverse drug reactions in India. [15] [16] [17] [18] 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. [19] From 10 March 2011 onward Nimesulide formulations are not indicated for human use in children below 12 years of age. [20]

On September 13, 2011 Madras High Court revoked a suspension on manufacture and sale of paediatric drugs nimesulide and phenylpropanolamine (PPA). [21]

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. [22]

Irish Medicines Board

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. [23]

Bribes

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. [24] [25] 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, [26] a number of other companies started production and marketing of Nimesulide.

Related Research Articles

<span class="mw-page-title-main">Analgesic</span> Any member of the group of drugs used to achieve analgesia, relief from pain

An analgesic drug, also called simply an analgesic, pain reliever, or painkiller, is any member of the group of drugs used to achieve relief from pain. Analgesics are conceptually distinct from anesthetics, which temporarily reduce, and in some instances eliminate, sensation, although analgesia and anesthesia are neurophysiologically overlapping and thus various drugs have both analgesic and anesthetic effects.

<span class="mw-page-title-main">Ketoprofen</span> NSAID analgesic medication

Ketoprofen is one of the propionic acid class of nonsteroidal anti-inflammatory drugs (NSAID) with analgesic and antipyretic effects. It acts by inhibiting the body's production of prostaglandin.

<span class="mw-page-title-main">Nonsteroidal anti-inflammatory drug</span> Class of therapeutic drug for relieving pain and inflammation

Non-steroidal anti-inflammatory drugs (NSAID) are members of a therapeutic drug class which reduces pain, decreases inflammation, decreases fever, and prevents blood clots. Side effects depend on the specific drug, its dose and duration of use, but largely include an increased risk of gastrointestinal ulcers and bleeds, heart attack, and kidney disease.

<span class="mw-page-title-main">Ibuprofen</span> Medication used for treating pain, fever, and inflammation

Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) that is used to relieve pain, fever, and inflammation. This includes painful menstrual periods, migraines, and rheumatoid arthritis. It may also be used to close a patent ductus arteriosus in a premature baby. It can be used orally or intravenously. It typically begins working within an hour.

<span class="mw-page-title-main">Diclofenac</span> Nonsteroidal anti-inflammatory drug

Diclofenac, sold under the brand name Voltaren, among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain and inflammatory diseases such as gout. It is taken by mouth or rectally in a suppository, used by injection, or applied to the skin. Improvements in pain last for as much as eight hours. It is also available in combination with misoprostol in an effort to decrease stomach problems.

<span class="mw-page-title-main">Naproxen</span> Nonsteroidal anti-inflammatory drug (NSAID) used to treat pain

Naproxen, sold under the brand name Aleve among others, is a nonsteroidal anti-inflammatory drug (NSAID) used to treat pain, menstrual cramps, inflammatory diseases such as rheumatoid arthritis, gout and fever. It is taken orally. It is available in immediate and delayed release formulations. Onset of effects is within an hour and lasts for up to twelve hours.

<span class="mw-page-title-main">Prednisolone</span> Chemical compound (steroid medication)

Prednisolone is a corticosteroid, a steroid hormone used to treat certain types of allergies, inflammatory conditions, autoimmune disorders, and cancers. Some of these conditions include adrenocortical insufficiency, high blood calcium, rheumatoid arthritis, dermatitis, eye inflammation, asthma, and multiple sclerosis. It can be taken by mouth, injected into a vein, used topically as a skin cream, or as eye drops. It differs from the similarly named prednisone in having a hydroxyl at the 11th carbon instead of a ketone.

COX-2 inhibitors (coxibs) are a type of nonsteroidal anti-inflammatory drug (NSAID) that directly target cyclooxygenase-2, COX-2, an enzyme responsible for inflammation and pain. Targeting selectivity for COX-2 reduces the risk of peptic ulceration and is the main feature of celecoxib, rofecoxib, and other members of this drug class.

<span class="mw-page-title-main">Mefenamic acid</span> Chemical compound

Mefenamic acid is a member of the anthranilic acid derivatives class of nonsteroidal anti-inflammatory drugs (NSAIDs), and is used to treat mild to moderate pain.

<span class="mw-page-title-main">Oxaprozin</span> Chemical compound

Oxaprozin, also known as oxaprozinum, is a nonsteroidal anti-inflammatory drug (NSAID), used to relieve the inflammation, swelling, stiffness, and joint pain associated with osteoarthritis and rheumatoid arthritis. Chemically, it is a propionic acid derivative. Safety and efficacy has been established in children over 6 years with juvenile rheumatoid arthritis only, and there is an increased risk of adverse reactions in the elderly population.

<span class="mw-page-title-main">Meloxicam</span> Nonsteroidal anti-inflammatory drug (NSAID)

Meloxicam, sold under the brand name Mobic among others, is a nonsteroidal anti-inflammatory medication (NSAID) used to treat pain and inflammation in rheumatic diseases and osteoarthritis. It is used by mouth or by injection into a vein. It is recommended that it be used for as short a period as possible and at a low dose.

<span class="mw-page-title-main">Carprofen</span> Non-steroidal anti-inflammatory drug

Carprofen is a nonsteroidal anti-inflammatory drug (NSAID) of the carbazole and propionic acid class that was previously for use in humans and animals but is now only available to veterinarians for prescribing as a supportive treatment for various conditions in animals. Carprofen reduces inflammation by inhibition of COX-1 and COX-2; its specificity for COX-2 varies from species to species. Marketed under many brand names worldwide, carprofen is used as a treatment for inflammation and pain, including joint pain and postoperative pain.

<span class="mw-page-title-main">Norfloxacin</span> Chemical compound, antibiotic

Norfloxacin, sold under the brand name Noroxin among others, is an antibiotic that belongs to the class of fluoroquinolone antibiotics. It is used to treat urinary tract infections, gynecological infections, inflammation of the prostate gland, gonorrhea and bladder infection. Eye drops were approved for use in children older than one year of age.

<span class="mw-page-title-main">Diflunisal</span> NSAID analgesic and anti-inflammatory drug

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It was developed by Merck Sharp & Dohme in 1971, as MK647, after showing promise in a research project studying more potent chemical analogs of aspirin. It was first sold under the brand name Dolobid, marketed by Merck & Co., but generic versions are now widely available. It is classed as a nonsteroidal anti-inflammatory drug (NSAID) and is available in 250 mg and 500 mg tablets.

<span class="mw-page-title-main">Nabumetone</span> NSAID analgesic and anti-inflammatory drug

Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID). Nabumetone was developed by Beecham and first received regulatory approval in 1991. It is available under numerous brand names, such as Relafen, Relifex, and Gambaran.

<span class="mw-page-title-main">Deracoxib</span> NSAID analgesic veterinary drug

Deracoxib is a nonsteroidal anti-inflammatory drug (NSAID) of the coxib class, used in dogs to treat pain associated with osteoarthritis, or to prevent pain following orthopedic or dental surgery. It is available as beef-flavored tablets.

<span class="mw-page-title-main">Tolmetin</span> NSAID analgesic medication

Tolmetin is a nonsteroidal anti-inflammatory drug (NSAID) of the heterocyclic acetic acid derivative class.

<span class="mw-page-title-main">Lornoxicam</span> NSAID analgesic medication

Lornoxicam, also known as chlortenoxicam, is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with analgesic, anti-inflammatory and antipyretic properties. It is available in oral and parenteral formulations.

<span class="mw-page-title-main">Tenoxicam</span> Non-steroidal anti-inflammatory drug

Tenoxicam, sold under the brand name Mobiflex among others, is a nonsteroidal anti-inflammatory drug (NSAID). It is used to relieve inflammation, swelling, stiffness, and pain associated with rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, tendinitis, bursitis, and periarthritis of the shoulders or hips.

Prostaglandin inhibitors are drugs that inhibit the synthesis of prostaglandin in human body. There are various types of prostaglandins responsible for different physiological reactions such as maintaining the blood flow in stomach and kidney, regulating the contraction of involuntary muscles and blood vessels, and act as a mediator of inflammation and pain. Cyclooxygenase (COX) and Phospholipase A2 are the major enzymes involved in prostaglandin production, and they are the drug targets for prostaglandin inhibitors. There are mainly 2 classes of prostaglandin inhibitors, namely non- steroidal anti- inflammatory drugs (NSAIDs) and glucocorticoids. In the following sections, the medical uses, side effects, contraindications, toxicity and the pharmacology of these prostaglandin inhibitors will be discussed.

References

  1. 1 2 3 "Nimesulide". livertox.nih.gov. Archived from the original on 23 December 2017. Retrieved 22 December 2017.
  2. ↑ "Current status: European Commission final decision". Archived from the original on 19 October 2014. Retrieved 12 November 2014.
  3. 1 2 3 4 Caiazzo E, Ialenti A, Cicala C (April 2019). "The relatively selective cyclooxygenase-2 inhibitor nimesulide: What's going on?". European Journal of Pharmacology. 848: 105–111. doi:10.1016/j.ejphar.2019.01.044. PMID   30689999. S2CID   59339842.
  4. ↑ Gupta P, Sachdev HP (June 2003). "Safety of oral use of nimesulide in children: systematic review of randomized controlled trials". Indian Pediatrics. 40 (6): 518–531. PMID   12824661.
  5. ↑ "Nimesulide, Nimesulide Tablets, Ainex Nimesulide, Nimesulide Manufacturers". www.pharmaceutical-drug-manufacturers.com. Archived from the original on 2016-03-03.
  6. ↑ "Aviso sobre los riesgos del consumo y uso de los medicamentos que contengan en su formulación Nimesulida" (in Spanish). Cofepris. 30 May 2019. Retrieved 1 July 2023.
  7. ↑ McNaughton R, Huet G, Shakir S (January 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 logo PLoS transparent.svg
  8. 1 2 Suleyman H, Cadirci E, Albayrak A, Halici Z (2008). "Nimesulide is a selective COX-2 inhibitory, atypical non-steroidal anti-inflammatory drug". Current Medicinal Chemistry. 15 (3): 278–283. doi:10.2174/092986708783497247. PMID   18333314.
  9. 1 2 3 Bernareggi A (October 1998). "Clinical pharmacokinetics of nimesulide". Clinical Pharmacokinetics. 35 (4): 247–274. doi:10.2165/00003088-199835040-00001. PMID   9812177. S2CID   26895870.
  10. ↑ "Nimesulide Tablets: Summary of Product Characteristics" (PDF). Europeans Medicines Agency. 2004. Archived from the original (PDF) on 11 June 2007.
  11. 1 2 Rainsford KD (June 2006). "Nimesulide -- a multifactorial approach to inflammation and pain: scientific and clinical consensus". Current Medical Research and Opinion. 22 (6): 1161–1170. doi:10.1185/030079906X104849. PMID   16846549. S2CID   23004446.
  12. ↑ 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.
  13. ↑ 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 Safety. 27 (6): 411–420. doi:10.2165/00002018-200427060-00005. PMID   15144234. S2CID   1786767.
  14. ↑ Rainsford KD (2005). Nimesulide – Actions and Uses. Bazylea, Boston, Berlin: Birkhäuser Verlag. p. 7. ISBN   978-3-7643-7068-8.
  15. ↑ Safety of nimesulide. CD ROM, Appropriate Use of Antipyretics / Analgesics in Children, Health Informatics, New Delhi, 2004.
  16. ↑ Rahman SZ, Khan RA (2004). "Is nimesulide safe in a cardiovascular-Compromised patient?". Indian J Pharmacol. 36: 252–3.
  17. ↑ Khan RA, Rahman SZ (2004). "A Case Report on Nimesulide and its Relation with Angina". J Pharmacovigilance Drug Safety. 1: 19–21.
  18. ↑ Khan RA, Rahman SZ (2004). "Nimesulide Induced Coronary Artery Insufficiency – A Case Report". J Pharmacovigilance Drug Safety. 1: 11–3.
  19. ↑ Thacker, Teena (12 February 2011). "Nimesulide for kids to be banned, finally". The Indian Express. Retrieved 2018-05-19.
  20. ↑ CDSCO website-wide gazette notification GSR 82(E) dated 10.03.2011.
  21. ↑ "Madras High Court Revokes Ban on Manufacture and Sale PPA - Adverse Effect - Medical Treatments". Scribd. Archived from the original on 2014-01-07.
  22. ↑ "EMA press release on nimesulide" (PDF). European Medicines Agency. September 2007. Archived from the original (PDF) on 2009-07-18.
  23. ↑ "The Irish Times". www.irishtimes.com.
  24. ↑ Pappagallo M (23 May 2008). "Mazzette per evitare i controlli sull'Aulin". Corriere della Sera. Archived from the original on 25 May 2008.
  25. ↑ "Italian medicines agency officials arrested in corruption probe". Manufacturing Chemist. 22 May 2008. Retrieved 2018-05-19.
  26. ↑ "Nimesulide for external use".
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