Non steroidal anti inflammatory drugs.

Nimesulide is a non-steroidal anti-inflammatory drug of the sulphonanilide class. The anti-inflammatory, analgesic and antipyretic activities of the Nimesulide have been demonstrated in a number of experimental models and in numerous clinical trials. The anti-inflammatory potency of Nimesulide is similar or greater than that if Indomethacin, Diclofenac, Piroxicam and Ibuprofen as shown in standard animal models of inflammation such as carrageenin-induced rat paw edema and inflammation, UV light induced erythema in guinea pigs and adjuvant arthritis in rats. Nimesulide has an analgesic potency similar to that of Ibuprofen and less than that of Indomethacin in an acetic acid writhing test in rats, and acetic acid and acetylcholine writhing tests in mice. The antipyretic potency of Nimesulide is superior to that of Indomethacin, Ibuprofen, Asprin and paracetamol in rats with yeast-induced fever.

On oral adminstration of Nimesulide 50-200 mg tablets to healthy volunteers, peak serum concentration of 1.98 to 9.85 mg/L are achieved within 1.22 to 3.17 hours. Oral absorption of Nimesulide is nearly complete. Concomitant adminstration of food may decrease the rate but not the extent of absorption of Nimesulide. Plasma binding was high (99%) and the apparent volume of distribution ranged from 0.19 to 0.35 L/kg. Nimesulide is extensively metabolized to several metaboloties which are excreted mainly in the urine (70% and in faeces (20%).

In patients with moderately impaired renal function (creatinine clearance 1.8 to 4.8 L/h, (30 to 80 ml/min), also in children and elderly volunteers, the pharmacokinetic profile of Nimesulide is not significantly altered. In patients which moderate renal impairment, slight accumulation of 4-Hydroxy Nimesulide was noted, however, the clinical significance of this finding is unknown.

In children, compared with values of adult healthy volunteers, tmax and t1/2 values were similar for the granule for formulation and lower for the suppository formulation in children suggesting a faster absorption and elimination of this formulation in children.

However, additional well-designed studies are needed for further comments on this matter.

Adults – Nimesulide is indicated in the treatment of a variety of painful inflammatory conditions including those associated with Osteoathritis, Postoperative trauma, Sports injuries, Ear, nose and Throat disorders, Dental surgery, Bursitis/TendinitisThrombophlebitis Pharyngitis and Gynaecological disorders.

Children – Nimesulide is indicated for fever and inflammatory symptoms associated with upper respiratory tract infections (viral or bacterial origin) and at reducing pain of various origins in children like post operative pain, pain due to musculoskeletal injury, pain due to minor traumatic soft tissue injury etc.

Adults: Usual oral dose of Nimesulide in adults is 100 mg tablet given twice daily.

Children: 5mg divided in 2 or 3 daily doses or as directed by the physician or pharmacist.

The clinical signs and symptoms of following acute overdosage of NSAIDs and methods of treatment have been reviewed. In general, symptoms of NSAID poisoning are mild, and usually include nausea and vomiting, headache, drowsiness, blurred vision and dizziness. There have been isolated case reports of more serious toxicity, including seizures, hypotension, apnoea, coma and renal failure, although usually after ingestion of substantial quantities. Seizures are a particular problem with mefenamic acid overdosage.

Treatment of NSAID overdosage is entirely supportive. GAtric lavage and activated charcoal may be of benefit within 1 hour of ingestion. Multiple doses of activated charcoal may be useful in enhancing elimination of NSAIDs with long half-lives such as piroxicam and sulindac. Forced diuresis, haemodialysis or haemoperfusion are unlikely to be of benefit for NSAID overdosage, although haemodialysis may be required if oliguric renal failure develops.

Nimesulide has a good tolerability profile. Gastrointestinal disturbances (epigastric pain, heartburn, nausea, diarrhoea, vomiting), skin reactions (rash,pruritus) and CNS effects (dizziness, somnolence, headache) are the most commonly reported adverse events.

Although Nimesulide appears to have minimal potential for renal toxicity in young healthy volunteers, caution is advised with use of Nimesulide in patients with compromised renal function (particularly elderly patients), congestive heart failure or cirrhosis, or those patients who are volume – or salt- depleted (since these groups of patients are more sensitive to the renal effects of NSAIDs).

Nsaids should be used with caution in patients with infections, since symptoms such as fever and inflammation may be masked, and also used with caution in patients with asthma or allergic disorders. NSAIDs are contra-indicated in patients with a history of hypersensitivity reactions to aspirin or other NSAIDs, including those in whom attcks of asthma, angiodema, urticaria or rhinitis have been precipitated by aspirin or any other NSAID.

Other general precautions to be observed include administration to patients with haemorrhagic disorders, hypertension and impaired renal, hepatic or cardiac function. PAtinets undergoing therapy with some NSAIDs may need to be monitored for te development of blood, kidney, liver or eye disorders. NSAIDs should be used with caution in the elderly and may need to be given in reduced doses.

Pregnant and lactating women.

Keep in cool, dry place and protect from moisture and light. Store at a temperature of 25°C.