Nimesulide Induced Hepatitis in a child of 5 years: A Case Report
K. C. Singhal* & S. Z. Rahman
Department of Pharmacology, J. N. Medical College, AMU, Aligarh-202002
*Honorary Consultant, WHO Collaborating Center for ADR Monitoring, Uppsala, Sweden
Introduction:
Nimesulide (4-nitro—2 phenoxymethane sulphonamide), which is a nonsteroidal anti-inflammatory drug, has been available in the Indian Market since 1997 for its antipyretic and anti-inflammatory activity. None of the reports in medical literature indicate its superior efficacy as antipyretic as compared to paracetamol and anti-inflammatory compared with other drugs of this class such as diclofenac and piroxicam. Numerous studies have established the life threatening adverse events with nimesulide such as hepatotoxicity, renal toxicity, severe skin reactions including fixed eruptions, gastrointestinal toxicity, potentiation of seizures, potentiation of colitis in passive cigarette smoking. A plethora of scientific data shows that nimesulide should not be used as the primary mode of treatment as an antipyretic or analgesic, especially in children, for whom much better and safer choices are available. No rationale exists for selecting nimesulide as the first drug of choice for fever or pain. Nimesulide is not used in the United States, Finland, Spain, Portugal and Israel. These countries have withdrawn the pediatric nimesulide formulation. The drug was never licensed for use in Canada, Britain and Australia.
The continuing use of nimesulide for Indian children is shocking. Published studies from India indicate rampant abuse of nimesulide. At least 12 paediatric preparations of nimesulide are available in India, which affirms the widespread use of the drug in children (1). Barring few, no dependable post-marketing surveillance for adverse drug reactions is undertaken in India. Moreover, unlike in the West, Indian doctors are not under any real supervision and therefore do not necessarily keep up with the rapidly changing information about adverse effects. Patients receiving nimesulide should be closely monitored for evolving hepatic failure. Indian patients may not follow necessary guidelines, for simple economic reasons.
Case Report:
Although there might be several cases of NSAIDs induced hepatic damage in Aligarh and elsewhere that are not being reported, but we could find one definite case of Nimesulide induced hepatitis in Aligarh.
The 5-year-old male child, wt 22 Kg came to see a private paediatric consultant with a complaint of fever for the last 8 days on 28.2.2003. The history of present illness was elicited from patient’s attendant who says that his child was apparently well before 8 days when he developed fever, which was unrecorded, continuous and low grade initially and not, associated with chills and rigors. The fever has increased in intensity for the last 8 days (It is very hot to touch the patient now). The fever was not associated with vomiting, cough or yellow discoloration of urine or clay colored stool. The patient was seen by pediatricians and started prophylactic treatment for Paratyphoid as Ofloxacin (Syrup Zenflox Forte) 1-1/4 spoonful twice daily for 10 days, Syrup Corcef 100 mg twice daily and Nimesulide (Syrup Nimica 50) 1-1/4 spoonful (5 ml). On second day, Enzymes (Syrup Gastrium) for 6 weeks and Multivitamins + Iron (Elixir Nigoadine) 1-1/4 spoonful thrice daily were added.
Haemogram and widal test were done. On the same day of visiting, the widal came out to positive. Other examination showed pulse rate as 110 /min; respiratory rate – 18/min; temperature 1040 F; pallor – mild; no icterus; tongue coated. On systemic examination, chest bilaterally was clear, on per abdominal examination, no tenderness, spleen was palpable but no hepatomegaly was there. No abnormality was detected during CVS and CNS examination. Patient had no history of jaundice in past or history of blood transfusion or antitubercular treatment or any other drug as such. Family history showed no history of contact with jaundiced patient in family. Immunization status showed no history of receiving Hepatitis B Vaccines.
After 15 days of the above treatment i.e. on 15.3.2003, the patient felt weakness and on 18.3.2003, the patient was diagnosed as a case of jaundice on the basis of the following signs and symptoms. On general examination, icterus was present, the liver found to be three-fingers enlarged and firm, simultaneously the spleen was also palpable; other systems were normal on examination. Following investigation were advised and their outcome: S. Bilirubin - 8.70 mg/dl; SGOT/AST - 293 U/L; SGPT/ALT - 785 U/L and Alkaline Phosphatase - 22 KAU; Australia Antigen [Hbs Ag] and Malaria Parasite [ELISA] - negative. One week after dechallenge of the suspected drug nimesulide, LFT was again advised: S. Bilirubin – 0.8 mg/dl; SGOT/AST – 45 U/L; SGPT/ALT – 40 U/L and Alkaline Phosphatase - 16 KAU. Causal relationship could thus be made on the basis of temporal sequence and positive dechallenge.
Conclusion: Nimesulide, similar to other nonsteroidal anti-inflammatory drugs (NSAIDs), has been associated with rare and unpredictable but serious hepatic adverse reactions (2). Many studies showed that nimesulide causes the most frequent dermatological and hepatic side effects in nature, including fatal Reyes syndrome (3). Concomitant therapy with other drugs (amoxicillin/clavulanic acid, lysine salicylate) in many of these cases prohibits a definitive causal link of the adverse reaction to nimesulide therapy. Authors believe when more safer drugs as paracetamol are already available it is irrational to prescribe me-too drugs of doubtful efficacy. It is high time that Drug Control Authorities in India review their policy for granting permission to drugs and drug formulations. India has more than 65000 formulations approved by Drug Controller of India, which is highest for any country in the world.
Even if the Indian drug control agencies are reluctant to impose a total ban on nimesulide, they should immediately forbid its use for treatment of fever or pain. It will be unfortunate if the Indian government waits for another "committee" report before stopping the use of nimesulide, even for the treatment of pain or fever, and lets more innocent patients suffer needlessly. Remember, in September 2002, the Drugs Controller General of India, ordered a review of the drug in view of concerns of hepatotoxicity and the review committee came with the distrustful results.
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