NIMM Tablet Ref.[28287] Active ingredients: Nimesulide

Nimesulide is well absorbed after oral administration. After a single dose of 100 mg peak plasma levels of 3-4 mg/ml are reached within 2 to 3 hours. AUC = 20 to 35 mgxh/lt. No statistically significant difference has been found between these figures and those seen after 100 mg given twice daily for 7 days.

Up to 97.5% binds to plasma proteins.

Nimesulide is extensively metabolized in the liver following multiple pathways, including cytochrome P450 (CYP) and 2C9 isoenzymes. Therefore a potential for a drug interaction in case of combined administration with drugs which are metabolised by CYP2C9 is envisaged (see section 4.5). The main metabolite of nimesulide is the para-hydroxy derivative which is also pharmacologically active. The lag time before the appearance of this metabolite in the circulation is short (about 0,8 hours) but its constant formation is not high and is considerably lower than nimesulide absorption constant. Hydroxynimesulide is the only metabolite found in plasma and it is almost completely conjugated. Half life is between 3.2 and 6 hours.

Nimesulide is excreted mainly in the urine (approximately 50% of the administered dose). Only 1 to 3% is excreted as the unmodified compound. Hydroxynimesulide, the main metabolite is found only as a glucuronate. Approximately 29% of the dose is excreted after metabolism in the faeces.

The pharmacokinetic profile of nimesulide remains unchanged in the elderly after single or repeated administration.

In a clinical trial conducted in patients with mild to moderate renal impairment (creatinine clearance 30 to 80 ml/min) versus healthy volunteers the administration of a single dose of nimesulide showed that peak plasma levels of nimesulide and its main metabolite were the same in both group of patients. AUC and t ½ beta were 50% higher in patients with renal failure, however always within the range of kinetic values observed with nimesulide for healthy volunteers. Repeated administration did not cause accumulation.

The administration of nimesulide is contraindicated in patients with hepatic impairment (see section 4.3).

Preclinical data reveal no special hazards for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential. No signs of teratogenic or embryotoxic potential were seen in rats dosed with nimesulide in reproduction toxicity studies up to maternally toxic dose levels.
In rats, nimesulide affected fertility and increased mortality of the offspring in the early post natal period.