- 79 Downloads
Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) administered orally or rectally twice daily for a variety of inflammatory and pain states. In mostly short term studies (up to 4 weeks), it was effective in reducing pain associated with osteoarthritis, cancer, thrombophlebitis, oral surgery and dysmenorrhea in adults, reducing pain associated with general surgery in adults and children, and pain, fever and inflammation accompanying respiratory tract infections, otorhinolaryngological diseases and traumatic injury in adults and children. Nimesulide appeared to be at least as effective as other NSAIDs in all of these indications.
Nimesulide has been well tolerated by adult, elderly and paediatric patients in clinical trials and large postmarketing surveillance studies. In general qualitative terms nimesulide exhibits the usual adverse events associated with NSAIDs (gastrointestinal, dermatological and neurological). However, it has a pharmacodynamic profile suggestive of a possibly reduced propensity to cause adverse gastrointestinal effects, although this has not been conclusively demonstrated in comparative clinical trials, many of which showed a similar incidence of such effects for nimesulide and the comparator agent. Additionally, nimesulide has been well tolerated by most aspirin (acetylsalicylic acid)- and/or NSAID-intolerant patients and in patients with asthma.
Thus, available evidence indicates that nimesulide is an effective and well tolerated alternative to other NSAIDs in the short term treatment of pain and inflammation of osteoarthritis and various other causes.
The anti-inflammatory, analgesic and antipyretic activities of nimesulide, a non-steroidal anti-inflammatory drug (NSAID) of the sulfonanilide class, have been demonstrated in a number of experimental models and in numerous clinical trials. Nimesulide has exhibited potency similar to or greater than that of indomethacin, diclofenac, piroxicam and ibuprofen in standard animal models of inflammation such as carrageenin-induced rat paw oedema and inflammation, ultraviolet light-induced erythema in guinea-pigs and adjuvant arthritis in rats. The analgesic potency of nimesulide was 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. Nimesulide has shown superior antipyretic potency to indomethacin, ibuprofen, aspirin and paracetamol (acetaminophen) in rats with yeast-induced fever.
Nimesulide is a relatively weak inhibitor of prostaglandin synthesis in vitro and appears to exert its effects through a variety of mechanisms including free-radical scavenging, effects on histamine release, the neutrophil myeloperoxidase pathway, bradykinin activity, tumour necrosis factor-α release, cartilage degradation, metalloprotease synthesis, phosphodiesterase type IV inhibition, platelet aggregation and synthesis of platelet activating factor. Animal studies have suggested that nimesulide is less ulcerogenic than aspirin, indomethacin, naproxen, piroxicam and ibuprofen. Nimesulide appears to have little effect on renal prostaglandin synthesis in rats.
After oral administration of nimesulide 50 to 200mg to healthy adult volunteers, peak serum concentrations of 1.98 to 9.85 mg/L are achieved within 1.22 to 3.17 hours. Compared with values obtained with oral drug administration, peak serum concentrations are slightly lower (2.14 to 2.32 mg/L) and are achieved more slowly (3 to 4.58h) after rectal administration of nimesulide 100 and 200mg. Oral drug absorption is nearly complete and concomitant administration of food may decrease the rate, but not the extent, of absorption of nimesulide. The drug is extensively bound (99%) to plasma proteins and has an estimated apparent volume of distribution of 0.19 to 0.35 L/kg following oral administration.
Nimesulide is extensively metabolised (1 to 3% of a dose is excreted unchanged in the urine) to several metabolites which are excreted mainly in the urine (≈70%) or the faeces (≈20%). The drug is almost completely biotransformed into 4-hydroxy-nimesulide in both free and conjugated forms and this metabolite appears to contribute to the anti-inflammatory activity of the compound. Peak concentrations of 4-hydroxy-nimesulide ranged from 0.84 to 3.03 mg/L and were attained within 2.61 to 5.33 hours after oral administration of nimesulide 50 to 200mg to healthy adult volunteers. The elimination half-life of 4-hydroxy-nimesulide ranges from 2.89 to 4.78 hours and is generally similar to or slightly higher than that of the parent compound (1.56 to 4.95h).
The pharmacokinetic profile of nimesulide is not significantly altered in children, elderly volunteers and patients with moderately impaired renal function [creatinine clearance 1.8 to 4.8 L/h (30 to 80 ml/min)]. Slight accumulation of 4-hydroxy-nimesulide was noted in patients with moderate renal impairment; however, the clinical significance of this finding is unknown.
Clinical studies have established the analgesic, anti-inflammatory and antipyretic effectiveness of orally (mostly 200 mg/day) or rectally (400 mg/day) administered nimesulide in the treatment of a variety of painful inflammatory conditions, including those associated with osteoarthritis, oncology, postoperative trauma, sports injuries, ear, nose and throat disorders, dental surgery, bursitis/tendinitis, thrombophlebitis, upper airways inflammation and gynaecological disorders. In these indications, nimesulide is more effective than placebo and is at least as effective as therapeutic dosages of other NSAIDs, including piroxicam, ketoprofen, naproxen, etodolac, mefenamic acid, diclofenac, niflumic acid, fentiazac, feprazone and flurbiprofen. Nimesulide therapy was characterised by a rapid onset of analgesia and symptomatic relief in studies where a significant difference in clinical efficacy between active treatments was observed. However, most of these studies evaluated small numbers of patients and were probably too small to identify any small differences in effectiveness.
In children, nimesulide suspension, granules and suppositories are more effective than placebo and are at least as effective as paracetamol, diclofenac, naproxen, lysine acetylsalicylate, mefenamic acid, ketoprofen and dipyrone in reducing the pain, inflammation and fever associated with respiratory tract infection, postoperative pain and musculoskeletal injury.
Nimesulide has been well tolerated by both young and elderly adults and children in 2 large postmarketing surveillance surveys. As with other NSAIDs, the most common adverse effects are gastrointestinal disturbances (epigastralgia, heartburn, nausea, diarrhoea and vomiting; 5.1 to 8.5% of patients), dermatological reactions (rash, pruritus; 0.2 to 0.6%) and central nervous system effects (dizziness, somnolence, headache; 0.3 to 0.4%). Withdrawal rates associated with short term (up to 30 days) nimesulide treatment range from 1.1 to 2.2% in adult, elderly and paediatric patients.
Available data indicate that the gastrointestinal tolerability of nimesulide in adults and children is similar to that of other NSAIDs. The rate of endoscopically verified gastroduodenal irritation with nimesulide appears to be similar to that with placebo and diclofenac, and less than that with indomethacin. The drug is well tolerated by most patients intolerant of aspirin and/or other NSAIDs and by patients with asthma.
Dosage and Administration
The usual oral and rectal dosages of nimesulide in adults are 100 and 200mg twice daily, respectively. In children, nimesulide dosage is commonly 5 mg/kg/day divided into 2 or 3 daily doses administered in the form of a suspension, granules or suppositories. The drug is contraindicated in patients with active peptic ulcer disease or moderate to severe hepatic impairment. Nimesulide is generally well tolerated in the elderly and patients with moderate renal insufficiency; however, caution should be used in this group of patients. Similarly, although nimesulide does not appear to interact with warfarin in patients and healthy volunteers, interactions with oral anticoagulants or other highly protein bound drugs cannot be ruled out in clinical practice.
KeywordsAdis International Limited Indomethacin Naproxen Piroxicam Ketoprofen
Unable to display preview. Download preview PDF.
- 2.Magni E. Nimesulide an overview. Drug Invest 1991; 3 Suppl. 2: 1–3Google Scholar
- 7.Roos D. The respiratory burst of phagocytic leukocytes. Drug Invest 1991; 3 Suppl. 2: 48–53Google Scholar
- 9.Southorn PA, Powis G. Free radicals in medicine. II. Involvement in human diseases. Mayo Clin Proc 1988; 63: 390–408Google Scholar
- 11.Bevilacqua M, Vago T, Beretta A. Nimesulide as inhibitor of superoxide anions (02-) production by human polymorphonuclear leukocytes. Pain Reproduct 1988; 31: 265–72Google Scholar
- 12.Capecchi PL, Ceccatelli L, Beermann U, et al. Inhibition of neutrophil function in vitro by nimesulide. Preliminary evidence of an adenosine-mediated mechanism. Arzneimittel Forschung 1993; 43: 992–6Google Scholar
- 14.Bevilacqua M, Vago T, Baldi G. Nimesulide inhibits cyclic nucleotide specific phosphodiesterase (PDE; type IV) in human neutrophils; a clue for its inhibitory effect on 02 production? [abstract]. 4th Interscience World Conference on Inflammation, Geneva, April 15-18 1991Google Scholar
- 15.Bevilacqua M, Vago T, Baldi G, et al. Nimesulide decreases superoxide production by inhibiting phosphodiesterase type IV Eur J Pharmacol. In pressGoogle Scholar
- 16.Dallegri F, Patrone F, Ballestrero A, et al. Inactivation of neu-trophil-derived hypochlorous acid by nimesulide: a potential mechanism for the tissue protection during inflammation. Int J Tissue React 1990; 12 (2): 107–11Google Scholar
- 17.Dallegri F, Ottonello L, Gatti F, et al. Neutrophil oxidative responses. Cell-directed and scavenging actions of the anti-inflammatory drug nimesulide. Drug Invest 1991; 3 Suppl. 2: 71–4Google Scholar
- 18.Maffei Facino R, Carini M, Aldini G. Antioxidant activity of nimesulide and its main metabolites. Drugs 1993; 46 Suppl. 1: 15–21Google Scholar
- 21.Casolaro V, Meliota S, Marino O, et al. Nimesulide, a sul-fonanilide nonsteroidal anti-inflammatory drug, inhibits mediator release from human basophils and mast cells. J Pharmacol Exp Ther 1994; 267: 1375–85Google Scholar
- 22.Genovese A, Spadaro G, Ciccarelli A, eds. Modulation of mediator release from human FcRI+ cells. New York: Plenum Publishing Co., 1992 (Olivieri D, Barnes P, Hurd S, Folco G, eds.)Google Scholar
- 23.Marino O, Casolaro V, Meliota S, et al. Inhibition of histamine release from FcRI+ cells by nimesulide. Agents Actions 1992; 32: C311–4Google Scholar
- 29.Swingle KF, Moore GGI. Pre-clinical pharmacological studies with nimesulide. Drugs Exp Clin Res 1984; 10: 587–97Google Scholar
- 31.Tanaka K, Shimotori T, Makino S, et al. Pharmacological studies of the new antiinflammatory agent 3-formylamino-7-methylsulfonylamino-6-phenoxy 4H-1-benzopyran-4-one. Antiinflammatory, analgesic and other related properties. Arzneimittel Forschung 1992; 42: 935–44Google Scholar
- 33.Cunietti E, Monti M, Viganö A, et al. Nimesulide in the treatment of hyperpyrexia in the aged. Double-blind comparison with paracetamol. Arzneimittel Forschung 1993; 43: 160–2Google Scholar
- 34.Ceserani R, Casciarri I, Cavalletti E, et al. Action of nimesulide on rat gastric prostaglandins and renal function. Drug Invest 1991; 3 Suppl. 2: 14–21Google Scholar
- 35.Tofanetti O, Casciarri I, Cipolla PV. Effect of nimesulide on cyclo-oxygenase activity in rat gastric mucosa and inflammatory exudate. Med Sci Res 1989; 17: 745–6Google Scholar
- 36.Carr DP, Henn R, Green JR. Comparison of the systemic inhibition of thromboxane synthesis, anti-inflammatory activity and gastro-intestinal toxicity of nonsteroidal anti-inflammatory drugs in the rat. Agents Action 1986; 19: 374–5Google Scholar
- 37.Velo GP. The anti-inflammatory, analgesic and antipyretic activity of nimesulide in experimental models. Drug Invest 1991; 3 Suppl. 2: 10–3Google Scholar
- 39.Lücker PW. Pharmacokinetic comparison in 12 healthy volunteers after three different oral doses. Helsinn data on file. TSD No. 5781E; 1993Google Scholar
- 40.Lückner PW. Bioavailability after single administration to 18 subjects of the tablets or granules. Influence of food. Helsinn data on file. TSD No. 5565E; 1992Google Scholar
- 44.Lücker PW. Report on the pharmacokinetics and relative bio-availability/bioequivalence of three different nimesulide formulations in 18 healthy volunteers. Helsinn data on file. TSD No. 5356; 1991Google Scholar
- 45.De Caro G. A comparison of the pharmacokinetics and bioavailability in man of single and repeated doses of formulations of nimesulide to be taken by mouth (100mg) tablets and per rectum (200mg suppositories). Helsinn data on file. TSD No. 5473; 1989Google Scholar
- 46.Maffei Facino R. Determination of metabolites in urine and feces of 8 healthy volunteers. Helsinn data on file. TSD No. 5578E; 1989Google Scholar
- 49.Chérié Lignière G, Tamborini U, Panarace G. La nimesulide nel liquido sinoviale di pazienti con artrite reumatoide. Farmaci Terapia 1990; 7: 173–6Google Scholar
- 51.Maffei Facino R, Carini M, Brambilla A, et al. Metabolism of nimesulide in man and radical scavenging activity of its main metabolites. In: 3rd Interscience World Conference on Inflammation; 1989 Mar 30–31: Monte Carlo, 1989: 244Google Scholar
- 52.Marrei Facino R, Carini M, Stefani R, et al. In vivo metabolism of nimesulide in man and in the rat. Arzneimittel-Forschung. In pressGoogle Scholar
- 53.Pontiroli AE et al. Nimesulide and aging: the role of physiologic and pharmacokinetic factors in drug response. 4th Interscience World Conference on Inflammation, Geneva (Switzerland), 1991Google Scholar
- 54.Lücker PW. Study on the pharmacokinetics (single and multiple dose) of nimesulide in 10 elderly patients. Helsinn data on file. TSD No. 5619; 1991Google Scholar
- 56.Fillastre JP. Pharmacokinetics of nimesulide in patients with impaired renal function. Helsinn data on file. TSD No. 4871; 1989Google Scholar
- 57.Fourage M. Pharmacokinetic profile of nimesulide and its 40H-metabolite in plasma and urine in 10 subjects with moderate renal failure during repeat oral administration. Helsinn data on file. TSD No. 5611; 1992Google Scholar
- 58.Olive G. Pharmacokinetics of nimesulide after single oral administration to healthy subjects and those with hepatic insufficiency. Helsinn data on file. Study No. 5498; 1993Google Scholar
- 59.Mele G, Memeo A, Mellesi L, et al. Post-marketing surveillance on nimesulide in the treatment of 8,354 patients over 60 years old affected with acute and chronic musculo-skeletal diseases [in Italian]. Arch Med Interna 1992; 44: 213–21Google Scholar
- 60.Pochobradsky MG, Mele G, Beretta A. Post-marketing survey of nimesulide in the short-term treatment of osteoarthritis. Drugs Exper Clin Res 1991; 17(3): 197-204Google Scholar
- 61.Dreiser RL. Open long term study in 133 osteoarthritic patients. Helsinn data on file. TSD No. 483IE; 1992Google Scholar
- 62.Bourgeois P, Dreiser RL, Lesquesna M, et al. Multicentre double-blind study to define the most favourable dose of nimesulide in terms of efficacy/safety ratio in the treatment of osteoarthritis. Eur J Rheumatol Inflammat. In pressGoogle Scholar
- 63.Quattrini M. Nimesulide 100mg tablets in the treatment of osteoarthritis of the hip at the painful-inflamed stage. Double-blind comparison with naproxen 500mg tablets. Helsinn data on file. Study No. 5716; 1992Google Scholar
- 64.Dreiser RL, Riebenfeld D. Nimesulide in the treatment of osteoarthritis. Double-blind studies in comparison with Piroxicam, ketoprofen and placebo. Drugs 1993; 46 Suppl. 1: 191–5Google Scholar
- 66.Lücker PW. Double-blind, randomized, multicentre clinical study evaluating the efficacy and tolerability of nimesulide in comparison with etodolac in patients suffering from osteoarthritis of the knee. Eur J Rheumatol Inflammat. In pressGoogle Scholar
- 67.Arbex ST, Wassal T, Nunes EL. An assessment of nimesulide by comparison with naproxen in the treatment of pain following oral surgery [in Portuguese]. Rev Bras Odontol 1992; 1: 15–8Google Scholar
- 68.Ragot J-P, Giorgi N, Marinoni N, et al. Acute activity of nimesulide in the treatment of pain after oral surgery — double blind, placebo and mefenamic acid controlled study. Eur J Clin Res 1994; 5: 39–50Google Scholar
- 69.Bucci E, Mignogna MD, Scaricabarozzi I, et al. Clinical study of therapeutic activity and tolerability of nimesulide in suppository formulation in odontostomatology [in Italian]. Minerva Stomatolgica 1990; 39: 13–7Google Scholar
- 77.Di Marco C, Fesi P, Letizia GA. Acomparison of the therapeutic effects and tolerability of nimesulide in the treatment of painful disorders following injury [in Italian]. Minerva Ortopedica 1989; 40: 111–6Google Scholar
- 79.Gusso MI, Innocenti M. Nimesulide (a latest generation NSAID) in the treatment of painful inflammatory disorders following injury [in Italian]. Ortopedia e Traumatologica Oggi 1989; 9: 162–8Google Scholar
- 80.Zarraga Corrales J, Lopez Torres D, Cruz Cruz M. Comparative study of nimesulide vs diclofenac in the management of soft parts acute trauma [in Spanish]. Invest Med Int 1992; 19: 133–41Google Scholar
- 81.Bacarat EC, Alves da Motta EL, de Lima GR. A clinical evaluation of the effectiveness and tolerability of nimesulide by comparison with piroxicam in the treatment of primary dysmenorrhoea [in Portuguese]. Rev Bras Ginecol 1991; 101: 467–70Google Scholar
- 83.Di Leo S, Meli MT, Dal Pra ML. Clinical trial of nimesulide in the treatment of inflammatory gynaecological disorders [in Italian]. Minerva Ginecol 1988; 40: 119–24Google Scholar
- 84.Rosales CL, Cisneros Lugo JH. Nimesulide in the treatment of primary dysmenorrhoea. Comparative clinical evaluation against mefenamic acid and against fentiazac [in Spanish]. Ginecol Obstet Mexico 1989; 57: 196–201Google Scholar
- 85.Valdes EF. Comparative evaluation of nimesulide in the treatment of low back pain [in Spanish]. Prens Med Argent 1992; 79: 469–73Google Scholar
- 88.Zanetta M, Martelli E, Corsi G, et al. The use of nimesulide in the treatment of thrombophlebitis of the lower limbs [in Italian]. Minerva Angiol 1988; 13: 49–52Google Scholar
- 91.Gananca MM, Munhoz MSL, Caovilla HH, et al. Comparative study of nimesulide versus potassium diclofenac in the acute otitis media [in Portugese]. Rev Bras Med 1990; 47: 373–6Google Scholar
- 92.Miniti A, Dieb Miziara I. A comparison of nimesulide with naproxen in patients with tonsillitis [in Portugese]. Arqu Bras Med 1991; 65: 511–4Google Scholar
- 93.Munhoz MSL, Gananca MM, Munhoz MLGS. Comparative study with nimesulide versus potassium diclofenac in ENT disease [in Portugese]. Rev Bras Med 1990; 7: 591–4Google Scholar
- 95.Passàli D, Bellussi L, Ciferri G, et al. Prospectitiva terapeutica nelle otiti medie secretive: nimesulide. Otorinolaringol 1988; 38: 169–75Google Scholar
- 97.Corli O, Cozzolino A, Scaricabarozzi I. Nimesulide and diclofenac in the control of cancer-related pain. Comparison between oral and rectal administration. Drugs 1993; 46 Suppl. 1: 152–5Google Scholar
- 98.Gallucci M, Toscani F, Mapelli A, et al. Nimesulide in the treatment of advanced cancer pain. Double-blind comparison with naproxen. Arzneimittel Forschung 1992; 42: 1028–30Google Scholar
- 99.Lecomte J. Double-blind study in 206 patients with extraarticular inflammations. Comparison with naproxen. Eur J Rheumatol Inflammat. In pressGoogle Scholar
- 101.Catti A, Monti T. Treatment of infants with acute upper respiratory tract inflammations. A double-blind comparison between nimesulide and paracetamol suppositories. Clin Trials J 1990; 27 (5): 327–35Google Scholar
- 102.Gananca MM, Munhoz MSL, Caovilla HH, et al. Comparative study of nimesulide oral suspension versus diclofenac resinate in children suffering from pharyngo-tonsillitis [in Portugese]. Rev Bras Med 1991; 8: 120–2Google Scholar
- 104.Salmòn Rodriguez LE, Arista Viveros HA, Lujan ME, et al. Assessment of the efficacy and safety of nimesulide vs naproxen in paediatric patients with respiratory tract infections. A comparative single-blind study. Drugs 1993; 46 Suppl. 1: 226–30Google Scholar
- 107.Kierszenbaum JS, Guerra Vitrai B, Longo Kierszenbaum AM, et al. Assessment of nimesulide oral suspension by comparison with diclofenac resinate in upper respiratory tract infection in children [in Portuguese]. Pediatr Mod 1991; 27: 560–2Google Scholar
- 108.Lecomte J, Monti T, Pochobradsky MG. Antipyretic effects of nimesulide in paediatric practice: a double-blind study. Curr Med Res Opin 1991; 12 (5): 296–303Google Scholar
- 111.Facchini R, Selva G, Peretti G. Tolerability of nimesulide and ketoprofen in paediatric patients with traumatic or surgical fractures. Drugs 1993; 46 Suppl.: 238-41Google Scholar
- 117.De Lucia F, Bonavia M, Crimi E, et al. Antiinflammatory-antioxidant treatment with a methane sulfonanilide in allergen-induced asthma. Ann Allergy 1991; 66: 424–9Google Scholar
- 118.Fusetti G, Magni E, Armandola MC. Tolerability of nimesulide. Epidemiological data. Drugs 1993; 46 Suppl. 1: 277–80Google Scholar
- 119.Dreiser RL, Bourgeois P. 3-Month tolerability profile of nimesulide granules in the treatment of osteoarthritis. Helsinn data on file. Study No. 5591; 1993Google Scholar
- 121.Marini U, Spotti D, Magni E, et al. Double-blind endoscopic study comparing the effect of nimesulide and placebo on gastric mucosa of dyspeptic patients. Drug Invest 1990; 2 (3): 162–6Google Scholar
- 122.Porto A. Double-blind multicentre study evaluating by endoscopy the tolerability of nimesulide and diclofenac on gastric mucosa in osteoarthritic patients. Eur J Rheumatol Inflammat. In pressGoogle Scholar
- 123.Cipollini F, Mecozzi V, Altilia F. Endoscopic assessment of the effects of nimesulide on the gastric mucosa: comparison with indomethacin. Curr Ther Res 1989; 45: 1042–8Google Scholar
- 124.Chiantera A, Tesauro R, Di Leo S, et al. Nimesulide in the treatment of pelvic inflammatory diseases. A multicentre clinical trial conducted in Campania and Sicily. Drugs 1993; 46 Suppl. 1: 134–6Google Scholar
- 125.Christanini S, Cutrupi S, Crivelli P, et al. The liver and NSAIDs: results of a multicentric investigation [in Italian]. V Convegno nazionale di informazione epatologica, Cormons-giugno, 1987Google Scholar
- 128.Stillman MT, Schlesinger PA. Nonsteroidal anti-inflammatory nephrotoxicity: should we be concerned?. Arch Int Med 1990; 150: 268–70Google Scholar
- 130.Theiss U, Timmer W, Wieckhorst G, et al. Investigation into a possible drug-drug interaction between warfarin and nimesulide in healthy volunteers. Methods Find Exp Clin Pharmacol 1993; 15: 629–35Google Scholar
- 131.Auteri A, Bruni F, Blardi P, et al. Clinical study on pharmacological interaction between nimesulide and warfarin. Int J Clin Pharmacol Res 1991; 11 (6): 267–70Google Scholar
- 133.Auteri A, Blardi P, Bruni F, et al. Pharmacokinetics and pharmacodynamics of slow-release theophylline during treatment with nimesulide. Int J Clin Pharmacol Res 1991; 11 (5): 211–8Google Scholar
- 135.Dettwiler W. Evaluation of the possible influence of nimesulide treatment on glucose loading test in patients under oral antidiabetic therapy. Helsinn data on file. TSD No. 5004; 1988Google Scholar