A formal review of the safety of nimesulide at European level will start next week, writes Dr Muiris Houston, Medical Correspondent.
With over 30,000 prescriptions issued every month for the drug, the decision by the Irish Medicines Board (IMB) to suspend nimesulide from the market will have a significant impact on patients.
But the inconvenience for those taking the non-steroidal anti-inflammatory drug (NSAID) is minor compared with the trauma suffered by the nine patients who have developed liver failure while taking nimesulide, which is marketed under the trade names Aulin, Mesulid and Mesine.
Six cases of liver failure were recently reported to the IMB by the National Liver Transplant Unit in St Vincent's Hospital, Dublin. Some three patients have died from liver failure, an indication of the severe effect the drug can have on one of the body's essential organs. Those affected have varied from a man in his 20s to a woman in her 60s . They had been taking the drug for periods from one week to four months.
While nimesulide and other NSAIDs are known to cause mild elevation of liver function tests, these are usually reversible following withdrawal of the drug. Liver failure is the result of a rare idiosyncratic reaction to nimesulide. Called fulminant hepatitis, the reaction causes widespread destruction of liver cells (necrosis). This process is irreversible, with liver transplantation the only possible treatment.
Liver disorders associated with nimesulide are "very rare", occurring in fewer than one in 10,000 patients taking the drug, according to manufacturers. The IMB has been notified of 53 adverse reactions to nimesulide since it was introduced here in 1995.
The IMB has been concerned about potential liver side-effects of nimesulide since 1999, when it first advised health professionals that care was needed in prescribing the drug. Warnings were repeated in 2002, 2003 and 2004. The manufacturer was asked by the IMB to issue a "Dear Doctor" letter in 2004, warning physicians about potential side-effects. It is understood that a post-marketing survey requested by the IMB in 1999 found no cause for alarm.
In 2002, both Spain and Finland suspended nimesulide from their markets, and requested a formal review of the drug's safety by the European Medicines Agency. This review concluded that the benefits of nimesulide outweighed its risks. However, a Spanish review of NSAIDs indicated that nimesulide had a higher risk of liver toxicity than comparable drugs and that nimesulide reactions were more severe. Although never marketed in the UK or the US, nimesulide has been taken by some 450 million patients in 50 countries.
Now that the Republic has declared nimesulide "no longer safe under normal conditions of use", the European Medicines Agency is obliged to start a formal review of the drug's safety. This will commence next week and it is expected that the results of the review will be known in about 12 months' time.
What symptoms might a patient experience should nimesulide cause liver problems? They will range from no symptoms in mild cases to nausea, vomiting, abdominal pain, fatigue, and dark urine in cases with more moderate damage. However, patients who develop fulminant hepatitis will progress rapidly to jaundice, liver failure and will quickly become seriously ill.
Other, more common side-effects of the drug (affecting up to one person in 100) include diarrhoea, dizziness, increased blood pressure, constipation, stomach inflammation, sweating and skin rash.
If you are currently taking nimesulide. you should stop taking the drug immediately.
If you have taken the drug in the past and feel well and have no symptoms, there is no need to seek medical advice.