Nimesulide

Nimesulide is a prescription non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic properties and its approved indications are the treatment of acute pain, the symptomatic treatment of osteoarthrosis and primary dysmenorrhoea in adolescents and adults above 12 years old. Nimesulide is among the top 5 non-steroidal anti-inflammatory drugs worldwide.

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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. 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]

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]

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]

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]}

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]

RTE's Prime Time Investigates

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^{[citation needed]}. 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.

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).

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, 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).

Pharmacokinetics

Nimesulide is rapidly absorbed following oral administration^[8].

Nimesulide undergoes extensive biotransformation, mainly to 4-hydroxynimesulide (which also appears to be biologically active).^[8].

Food, gender and advanced age have negligible effects on nimesulide pharmacokinetics^[8].

Moderate renal impairment does not necessitate dosage adjustment while patients with severe renal impairment or hepatic impairment are contraindicated^[9]

Nimesulide has a relatively rapid onset of action, with meaningful reductions in pain and inflammation observed within 15 minutes from drug intake^[10][11]. 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^[10]. Clinical evidence is available to support a particularly good profile in terms of gastrointestinal tolerability^[12].

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

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.

References

1. ^ No differences between nimesulide and other NSAIDs liver toxicity
2. ^ European Commission CPMP favourable opinion on nimesulide
3. ^ The end begins
4. ^ IMB Announces Immediate Suspension of the Marketing of Medicines Containing Nimesulide
5. ^ [1]
6. ^ [http://www.hsa.gov.sg/docs/HSAPressRelease_HSASuspendsSalesOfProductsContainingNimesulide_15Jun07.pdf
7. ^ EMEA press release on nimesulide September 2007
8. ^ ^{a b c} Bernareggi A. Clinical pharmacokinetics of nimesulide. Clin.Pharmacokinet. 1998; 35: 247-274
9. ^ http://www.emea.europa.eu/pdfs/human/referral/nimesulide/308603en.pdf
10. ^ ^{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
11. ^ 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
12. ^ Laporte JR et al. Upper Gastrointestinal Bleeding Associated with the Use of NSAIDs. Drug Safety, 2004; 27 (6): 411-420