Nimesulide
From Wikipedia, the free encyclopedia
 |
This article or section is in need of attention from an expert on the subject. WikiProject Chemistry or the Chemistry Portal may be able to help recruit one. |
 |
|
|
Nimesulide
|
|
| Systematic (IUPAC) name | |
| N-(4-Nitro-2-phenoxyphenyl)methanesulfonamide | |
| Identifiers | |
| CAS number | |
| ATC code | M01 |
| PubChem | |
| Chemical data | |
| Formula | C13H12N2O5S |
| Mol. mass | 308.311 |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Protein binding | >97.5% |
| Metabolism | hepatic |
| Half life | 1.8-4.7h |
| Excretion | renal(50%), fecal(29%) |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status |
usually prescription only |
| Routes | oral, rectal, topical |
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. Due to concerns about the risk of hepatotoxicity, nimesulide has been withdrawn from market in many countries.
[edit] History
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 FDA evaluation in the United States, where it is not marketed.
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. 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. [1]
[edit] EMEA reports favourable benefit/risk ratio
On August 1, 2003 the Committee for Proprietary Medicinal Products (CPMP) of the 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. [2]
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.[3]
[edit] 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.[4]
[edit] Singapore Health Science Authority suspends Nimesulide containing drugs
Pending review of the drug's safety by the EMEA, nimesulide has been suspended with immediate effect (June 15, 2007)[5] [6]
[edit] EMEA confirms the positive benefit/risk ratio
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. [7]
[edit] RTE's Prime Time Investigates
On December 3rd, 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[citation needed].
[edit] Italian corruption probe involving vetting of Nimesulide
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 [8] [9]. 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. Nimesulide is sometimes sold over the counter at Italian chemist shops, even though it should legally only be made available to patients carrying a prescription from a physician.
[edit] Availability
It is available in a variety of forms: tablets, powder for dissolution in water, suppositories and topical gel.
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).
[edit] Trade names
Nimesulide is available through the world as original product with the following trademarks: Aulin, Ainex, Drexel, Donulide, Edrigyl, Eskaflam, Heugan, Mesulid, Minapon, Nexen, Nidolon, Nimed, Nimedex, Nimesil, Nimulid, Nimutab, Nise, 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, Sorini, Ventor, Willgo among others).
[edit] Pharmacokinetics
Nimesulide is rapidly absorbed following oral administration[10].
Nimesulide undergoes extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).[10].
Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics[10].
Moderate renal impairment does not necessitate dosage adjustment while patients with severe renal impairment or hepatic impairment are contraindicated[11]
Nimesulide has a relatively rapid onset of action, with meaningful reductions in pain and inflammation observed within 15 minutes from drug intake[12][13]. As many as almost 498 million patients have been treated with nimesulide from its launch until today[citation needed]. 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[12]. Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability[14].
As all anti-inflammatory drugs, it should be taken in compliance with the recommendations included in the patient leaflet.
[edit] 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.
[edit] References
- ^ No differences between nimesulide and other NSAIDs liver toxicity
- ^ European Commission CPMP favourable opinion on nimesulide
- ^ The end begins
- ^ IMB Announces Immediate Suspension of the Marketing of Medicines Containing Nimesulide
- ^ Channelnewsasia.com
- ^ [http://www.hsa.gov.sg/docs/HSAPressRelease_HSASuspendsSalesOfProductsContainingNimesulide_15Jun07.pdf
- ^ EMEA press release on nimesulide September 2007
- ^ «Mazzette per evitare i controlli sull'Aulin». Mario Pappagallo, Corriere della Sera, 23 May 2008
- ^ Italian medicines agency officials arrested in corruption probe. Manufacturing Chemist
- ^ a b c Bernareggi A. Clinical pharmacokinetics of nimesulide. Clin.Pharmacokinet. 1998; 35: 247-274
- ^ Microsoft Word - opnh.P.Nimesulide .EMEA-CPMP-3086-03-en-Final.doc
- ^ a b 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
- ^ 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
- ^ Laporte JR et al. Upper Gastrointestinal Bleeding Associated with the Use of NSAIDs. Drug Safety, 2004; 27 (6): 411-420
[edit] External links
|
||||||||
