(2002; 19 pages)
Further to our earlier report (WHO Pharmaceuticals Newsletter No 3, 2002) on Spain’s decision to temporarily suspend the product and, in response to the recent interest in the drug we present below some background information on nimesulide.
Nimesulide is a non-steroidal anti-inflammatory analgesic and antipyretic drug (NSAID). It is a selective cyclooxygenase - 2 (COX -2) enzyme inhibitor and is effective in the treatment of a wide range of inflammatory and painful conditions including osteoarthritis, extra-curricular disorders such as tendonitis and bursitis, post-operative pain and primary dysmenorrhoea.
Nimesulide was first marketed in Italy in 1985 and since then has been launched in about 50 countries around the world. The drug is off-patent and is marketed by a variety of firms. Several adverse reactions were reported with nimesulide during the latter half of 1998 and the early months of the year 19991-3.
In Portugal, in 1999, following a risk-benefit assessment, a core SPC (Summary of Product Characteristics) was approved for nimesulide. Therapeutic indications were restricted to osteoarthritis, extra-articular rheumatic conditions, postoperative and/or post-traumatic pain and inflammation, oral/ dental inflammatory conditions and dysmenorrhoea. The core SPC also stated that
• Nimesulide should not be used for periods longer than 7 days in the treatment of acute pain
• Use in patients with hepatic failure is contraindicated
• Liver function should be monitored in patients with previous history of hepatic injury
• Precaution is needed when nimesulide is used with other drugs that may cause hepatic injury
The Portuguese marketing authorizations for paediatric nimesulide formulations were suspended in March 19991,2.
The Register of Adverse Reactions of the Finnish National Agency for Medicines (NAM) for the year 2000 shows that the majority of adverse drug reactions (ADRs) among non-steroidal anti-inflammatory drugs were associated with nimesulide; over half of the reports were associated with liver reactions4. According to NAM’s research director Dr Erkki Palva, so far 109 reports of adverse events (66 of which related to liver toxicity) and one fatality have been reported since the drug received marketing authorization in Finland in 19975. Finland has temporarily suspended the sale, supply and distribution of nimesulide products while NAM and the concerned firm continue to investigate6. The European Medical Products Evaluation Agency (EMEA) has also initiated a safety procedure to establish causality with nimesulide. In May 2002 the Spanish Regulatory Authority temporarily withdrew nimesulide products from the Spanish market pending conclusions from the EMEA evaluation7.
Nimesulide was authorised in Ireland in 1995. The potential for hepatic effects with nimesulide has been an on-going concern to the Irish Medicines Board (IMB) which reviewed the drug’s safety in 1999 and updated the prescribing information at that time to reflect concerns of hepatotoxicity. Following the IMB’s review in 1999 the concerned company in Ireland was requested to perform post-marketing authorization studies to address the safety issues with nimesulide. The interim data provided by the company on 1,212 patients indicate that, at this stage there is no apparent difference in the safety profiles of nimesulide, diclofenac and ibuprofen8.
Nimesulide has never been marketed in some countries such as the USA and Australia. In South East Asia the drug enjoys variable regulatory status. For example, in Thailand, only the tablet form of the drug is available; the suspension form was voluntarily withdrawn. In India, both tablet and gel forms have been available for almost 10 years. Although some hepatic adverse reactions have been reported with nimesulide to the Indian National Pharmaco-vigilance Centre, exact causality assessment is difficult since the patients were also using other analgesics at the time.
The Drug Controller General of India (DCGI) has asked manufacturers of nimesulide to submit the complete reports of Adverse Drug Reaction within a month9,10.
Nimesulide is marketed in Brazil as a prescription drug. The drug is available as tablets, paediatric suspensions, suppositories and paediatric drops.
1. Nimesulide ADR controversy in Portugal. Scrip 1999, No.2406:8.
2. Portugal suspends paediatric nimesulide. Scrip 1990, No.2431:20.
3. Israel nimesulide suspension inquiry. Scrip 1999, No.2434:23.
4. ADR News of National Agency for Medicines (TABU 2.2001), p.46. Available from URL: http://www.nam.fi/uploads/english/tabu_eng_2001
5. As reported by Reuters Health, London, 20 March 2002. Available from URL: http://dispatch.mail-list.com/archives/hbv_research
6. Press Release from Finnish National Agency for Medicines, 15 March 2002. Available from http://www.namfi/english/news
7. WHO Pharmaceuticals Newsletter No.3, 2002.
8. Irish Medicines Board Drug Safety Newsletter, Issue 15, July 2002.
9. National Pharmacovigilance Centre (India) Newsletter, vol.1, No.1, Dec 1999.
10. News Item in Daily Excelsior, New Delhi, 30 Oct 2002. Available from URL: http://www.dailyexcelsior.com/02oct31