Nimesulide is a non-steroidal anti-inflammatory drug (NSAID) used to treat pain and inflammation. This document compiles efficacy results from various clinical studies across different formulations of nimesulide, providing a comprehensive overview of its uses.
Efficacy Results
Dispersible Tablets / Tablets
Comparative studies have assessed nimesulide’s effectiveness against other pain relief medications in different scenarios.
One double-blind study compared nimesulide to naproxen for post-oral surgery pain. Sixty-four patients were divided into two groups, receiving either nimesulide (100 mg) or naproxen (250 mg) every 12 hours. Pain intensity was evaluated at multiple intervals post-medication. Both drugs showed excellent tolerability and significant pain reduction. Notably, the nimesulide group experienced faster pain relief within the first hour of treatment.
Another study investigated nimesulide versus celecoxib in patients with knee osteoarthritis. Forty-four patients were randomized to receive nimesulide (100 mg twice daily) or celecoxib (200 mg once daily) for two weeks. Pain intensity was measured, and synovial fluid analysis was conducted in patients with joint effusion. Nimesulide demonstrated more pronounced effects and a quicker onset of analgesic action compared to celecoxib. Nimesulide significantly reduced substance P and interleukin-6 concentrations in synovial fluid, while celecoxib showed a delayed and less significant reduction in interleukin-6 levels. Both drugs were well-tolerated, and the study concluded nimesulide is effective for symptomatic treatment of osteoarthritis.
Animal studies further explored nimesulide’s analgesic properties. In two studies comparing nimesulide, diclofenac, celecoxib, and rofecoxib for inflammatory pain, nimesulide showed superior efficacy in inhibiting thermal hyperalgesia induced by formalin injection. In mechanical hyperalgesia reduction, nimesulide and diclofenac were more effective than celecoxib and rofecoxib. In rheumatoid arthritis patients, a single oral dose of all drugs reduced inflammatory hyperalgesia, but nimesulide was uniquely effective within 15 minutes of treatment and more effective than rofecoxib (25 mg). These findings suggest nimesulide is particularly effective and fast-acting against inflammatory pain.
In treating acute non-infectious upper respiratory tract inflammation, a randomized single-blind study compared nimesulide (200 mg/day) to flurbiprofen (300 mg/day) over 7 days in 60 patients. Both drugs were equally effective in reducing mucosal congestion, local redness, fever, and sore throat. However, nimesulide treatment resulted in fewer and less severe adverse events compared to flurbiprofen.
Nimesulide has also been shown to alleviate pain associated with uterine contractions in dysmenorrhea. A single 100 mg oral dose of nimesulide distributes to female genital tissues. A double-blind, placebo-controlled crossover study in women with dysmenorrhea showed that two 100 mg doses of nimesulide reduced prostaglandin F2α levels in menstrual blood.
A study evaluating nimesulide, aceclofenac, and diclofenac for traumatic locomotor system disorders involved 19 patients receiving nimesulide (100 mg twice daily), 19 receiving aceclofenac (100 mg twice daily), and 21 receiving diclofenac (50 mg three times daily) over seven days. Nimesulide demonstrated significantly better efficacy in reducing pain on movement, movement limitation, local sensitivity, and pain intensity. Tolerability was also significantly better for nimesulide, suggesting its COX-2 selectivity contributes to both efficacy and safety compared to non-selective agents like aceclofenac and diclofenac. The study concludes nimesulide can be considered a first-choice anti-inflammatory and analgesic for traumatic locomotor system disorders.
For primary dysmenorrhea syndrome, a double-blind, randomized, crossover study involving 67 patients compared nimesulide to placebo over three menstrual cycles. Nimesulide proved more effective than placebo in preventing or relieving symptomatic patterns, with satisfactory tolerability and minimal side effects reported.
In acute upper respiratory tract inflammation, a 4-day double-blind, parallel study with 51 patients compared nimesulide to placebo. Patients receiving nimesulide showed significant improvement in tonsillar swelling, hoarseness, sore throat, headache, and arthralgia compared to placebo, with no associated adverse effects.
Numerous comparative studies have highlighted nimesulide’s effectiveness against other medications. It has been shown to be more effective than piroxicam (osteoarthritis), paracetamol (upper respiratory tract inflammation), benzydamine or naproxen (otorhinolaryngological disease), phenylprenazone (laryngotracheitis/bronchitis, respiratory inflammation, and otorhinolaryngological disease), serrapeptase (post-operative or dental pain, trauma, and phlebitis), ketoprofen (post-operative pain), and mefenamic acid (dysmenorrhea). Nimesulide’s efficacy is comparable to aspirin, with or without vitamin C, and mefenamic acid (respiratory tract infection), ibuprofen (soft tissue disease), naproxen (respiratory tract inflammation, dysmenorrhea, and post-operative pain states), suprofen and paracetamol (post-operative pain states), benzydamine (genitourinary tract inflammation), and dipyrone, paracetamol, or diclofenac (fever).
A double-blind, multicenter comparison of nimesulide and diclofenac in 122 patients with acute shoulder pain, along with a meta-analysis of nimesulide studies, indicated that nimesulide was at least as effective as diclofenac after 14 days. Tolerability was significantly better in the nimesulide group, with investigators and patients reporting better overall tolerability compared to diclofenac. The meta-analysis confirmed nimesulide’s efficacy in treating osteoarthritis and a better risk-benefit ratio compared to placebo in terms of safety and tolerability, particularly regarding gastrointestinal adverse events.
Bibliographic References:
- Arbex, ST et al. Avaliação comparativa do nimesulide versus naproxeno no tratamento da dor pós-cirurgia oral. Rev Bras Odontol; 49(1): 15-8, 1992.
- Bianchi M, et al. Effects of nimesulide on pain and on synovial fluid concentrations of substance P, interleukin-6 and interleukin-8 in patients with knee osteoarthritis: comparison with celecoxib. Int J Clin Pract, 61 (8): 1270-7, 2007.
- Bianchi M, Broggini M. Anti-hyperalgesic effects of nimesulide: Studies in rats and humans. Int J Clin Pract Suppl; (128): 11-9, 2002.
- Cadeddu L. et al. Comparison of nimesulide and flurbiprofen in the treatment of non infectious acute inflammation of the upper respiratory tract. J Int Med Res; 16(6): 466-73, 1988.
- Pulkkinen M. Nimesulide in Dysmenorrhoea. Drugs 46 (Suppl. 1): 129-133, 1993.
- Marczyk LR. Estudo randomizado do nimesulide, aceclofenaco e diclofenaco no tratamento de afecções traumáticas do aparelho locomotor. Acta ortop. bras; 5(3): 103-9, 1997.
- Moggian G et al. A new pharmacologic treatment of primary dysmenorrhea. Clin. Ter. 117(6): 481-492, 1986.
- Nouri ME. Nimesulide for treatment of acute inflammation of the upper respiratory tract. Clin Ther; 6(2): 142-50, 1984.
- Ward A et al. Nimesulide. A preliminary review of its pharmacological properties and therapeutic afficacy in inflammation and pain states. Drugs 36 (6): 732-53,1988.
- Wober W. Comparative efficacy and safety of nimesulide and diclofenac in patients with acute shoulder, and a metaanalysis of controlled studies with nimesulide. Rheumatology (Oxford); 38 Suppl 1: 33-8, 1999.
Drops
Studies have also examined the efficacy of nimesulide drops, particularly in pediatric populations.
A double-blind, multicenter study involving 42 hospitalized children (6 months to 8 years old) with acute respiratory tract infections and fever investigated nimesulide’s antipyretic activity. Children were randomized to receive nimesulide oral suspension (5 mg/kg/day) or placebo for five days, alongside antibiotics. Nimesulide significantly reduced temperature within six hours of the first dose, from an average of 38.89 ºC to 37.28 ºC, while no significant change was observed in the placebo group. Temperature normalized by the next day, and nimesulide was well-tolerated, indicating its usefulness for rapid fever reduction before antibiotic therapy takes effect.
In treating minor traumatic soft tissue lesions in children, a double-blind study randomized 40 children to oral nimesulide (50 mg twice daily) or placebo for 5 days. Nimesulide significantly improved symptoms (pain at rest and movement) and signs (immobility, edema, and hematoma) compared to placebo, with good tolerability and no gastrointestinal issues reported.
A controlled clinical study comparing nimesulide and ketoprofen in 71 pediatric patients (7-14 years old) with orthopedic disorders found both drugs effective. However, nimesulide showed better tolerability, with fewer drug-related side effects (8.6%) compared to ketoprofen (33%).
In children with respiratory tract infections, a study comparing ibuprofen, paracetamol, and nimesulide involved 90 children divided into three treatment groups. Nimesulide (2.5 mg/kg twice daily) demonstrated significantly lower body temperature two hours post-administration compared to paracetamol and ibuprofen.
A randomized study comparing nimesulide to paracetamol in 110 children (3-6 years old) with upper respiratory tract inflammation and fever showed nimesulide suspension (1.5 mg/kg three times daily) to be as effective as paracetamol syrup (10 mg/kg four times daily) in reducing fever, local pain, and general discomfort. Tolerability was similar, although slightly fewer withdrawals due to adverse events occurred in the nimesulide group.
Bibliographic References:
- Lecomte J et al. Antipyretic effects of nimesulide in paediatric practice: a double-blind study. Curr Med Res Opin; 12(5): 296-303, 1991.
- Giovannini M et al. A comparison of nimesulide and placebo in the treatment of minor traumatic soft tissue lesions in children. Drugs; 46 Suppl 1: 212-4, 1993.
- Facchini R et al. Tolerability of nimesulide and ketoprofen in paediatric patients with traumatic or surgical fractures. Drugs; 46 Suppl 1: 238-41, 1993.
- Ulukol B et al. Assessment of the efficacy and safety of paracetamol, ibuprofen and nimesulide in children with upper respiratory tract infections. Eur J Clin Pharmacol; 55(9): 615-8, 1999.
- Polidori G et al. A comparison of nimesulide and paracetamol in the treatment of fever due to inflammatory diseases of the upper respiratory tract in children. Drugs; 46 Suppl 1: 231-3, 1993.
Suppository
Efficacy studies also cover nimesulide suppositories for targeted relief.
An open, non-comparative study evaluated nimesulide suppositories in 40 adults with upper respiratory tract infections. Patients received one 100mg nimesulide suppository every 12 hours for 7 days, alongside amoxicillin. Significant symptom regression was observed from the second day of treatment, with excellent or good tolerability in 92.5% of patients. The study concluded nimesulide suppositories offer rapid and intense therapeutic action, improving symptoms quickly.
A double-blind study compared nimesulide suppositories to flurbiprofen in obstetric-gynecological inflammatory pain conditions. Both drugs provided rapid and effective analgesia and anti-inflammatory activity with good tolerability. Nimesulide demonstrated significantly greater analgesic effect than flurbiprofen in the first two hours of treatment.
Pharmacokinetic studies of rectal nimesulide administration in children showed rapid absorption, with peak plasma concentration reached around 3 hours post-administration and a half-life of 3.15 hours. A randomized, double-blind study comparing nimesulide suppositories to dipyrone in 50 children with post-operative pain found both drugs effective, with similar pain reduction and good tolerability.
Bibliographic References:
- Ganança M M Avaliação do nimesulide supositórios na afecções das vias aéreas superiores/ Evaluation of nimesulide suppositories in upper respiratory trract infections Arq Bras Med; 68(6): 441-2, 1994.
- Montoneri C., et al. Studio clinic sull’efficacia e la tollerabilità della nimesulide in formulazione supposte in confront al flurbiprofen in ginecologia. Minerva Ginecol, 42:413-9, 1990.
- Schärli AFet al. Pharmacokinetics and therapeutic study with nimesulide suppositories in children with post-operative pain and inflammation. J Int Med Res.18(4):315-21, 1990.
Capsule
Nimesulide capsules are designed for systemic relief of pain, inflammation, and fever.
Clinical studies evaluating a single daily 200mg dose of nimesulide over 10 days showed significant symptom remission in patients. Improvements were noted in pain (94.7% remission), edema (97.9%), erythema (98.8%), and stiffness (92.9%). Overall treatment was considered successful by physicians (86.6%) and patients (92.5%), with excellent tolerability reported in 87.5% of cases.
Oral administration of nimesulide capsules typically provides pain relief within approximately one hour. Treatment duration should be as short as possible, generally 5 to 10 days, and not exceeding 15 days.
Gel
Topical nimesulide gel provides localized relief for pain and inflammation.
Clinical studies have evaluated nimesulide gel at both 2% and 1% concentrations. A non-comparative study assessed 2% nimesulide gel for treating sports-related injuries in 47 patients. Topical application twice daily for 7 days resulted in statistically significant improvements in pain at rest and on movement, local sensitivity, functional limitation, and overall pain intensity as per medical evaluations. Patient diaries also reported significant improvements in spontaneous pain at rest and on movement, and pain on pressure.
Studies evaluating 1% nimesulide gel also demonstrated efficacy. A study comparing 1% nimesulide gel to 1% diclofenac and 0.5% piroxicam in 36 healthy male volunteers using a modified Hollander test showed nimesulide provided superior analgesia compared to diclofenac and piroxicam, particularly at 15, 30, and 120 minutes post-stimulus.
A study in 70 patients with knee osteoarthritis compared 1% nimesulide gel to placebo over 30 days. Nimesulide gel significantly improved WOMAC scores (pain, stiffness, physical function, and global score), quality of life (NHPD), and patient and physician satisfaction compared to placebo.
Bibliographic References:
- Marczyk LRS, et al. Multicentric study of Nimesulide gel 2% in the topic treatment of sportive injuries. RBM – Rev Bras Med. 2001;58(1-2):79-85.
- Sengupta S, et al. Analgesic eficacy and pharmacokinetics of topical nimesulide gel in healthy human volunteers: double-blind comparison with piroxicam, diclofenac and placebo. Eur J Clin Pharmacol. 1998;54:541-7.
- Ergün H, etal. Efficacy and safety of topical nimesulide in the treatment of knee osteoarthritis. J Clin Rheumatol. 2007;13:251–5.
Pharmacological Characteristics
Dispersible Tablet / Tablet / Drops / Suppository
Pharmacodynamic Properties
Nimesulide is an NSAID of the sulfonanilide class, exhibiting anti-inflammatory, antipyretic, and analgesic effects. It demonstrates more potent anti-inflammatory activity than aspirin, phenylbutazone, and indomethacin, and comparable or potentially superior antipyretic activity to diclofenac and dipyrone, and acetaminophen.
Nimesulide’s unique mechanism of action involves selective inhibition of cyclooxygenase-2 (COX-2), the enzyme involved in prostaglandin synthesis during inflammation, with minimal impact on COX-1, which protects the gastric mucosa. Additional biochemical properties contribute to its clinical effects, including inhibition of phosphodiesterase type IV, reduction of superoxide anion formation, scavenging of hypochlorous acid, inhibition of proteinases, prevention of alpha-1-protease inhibitor inactivation, inhibition of histamine release, and histamine activity inhibition.
Pre-clinical Data
Pre-clinical studies indicate no special risks for humans based on conventional safety pharmacology, repeated-dose toxicity, genotoxicity, and carcinogenicity studies. Repeated-dose toxicity studies revealed gastrointestinal, renal, and hepatic toxicity. Embryotoxicity studies in rats showed no teratogenic or embryotoxic potential at non-maternally toxic doses. In rabbits, marginal maternal toxicity doses led to slight increases in post-implantation loss and skeletal malformations, but no dose-response relationship was observed for specific malformation types. Few clinical cases of intentional overdose have been reported without signs of intoxication.
Pharmacokinetic Properties
Dispersible Tablet / Tablet / Drops:
Orally administered nimesulide is well absorbed, reaching peak plasma concentrations in 2-3 hours in adults. It exhibits high plasma protein binding (>97.5%). Pharmacokinetic parameters in children are comparable to adults, with similar Cmax and tmax values. Nimesulide is metabolized in the liver, primarily to the pharmacologically active hydroxynimesulide. Excretion is mainly renal, with approximately 50% of the dose excreted in urine. The elimination half-life is around 1.8 to 4.73 hours in adults and 2.36 hours in children. The kinetic profile is unchanged in elderly patients. In moderate renal insufficiency, peak plasma levels are not significantly elevated. Nimesulide is contraindicated in hepatic insufficiency due to accumulation risk. Pain relief onset is approximately 15 minutes, and fever reduction starts within 1-2 hours, lasting about 6 hours.
Suppository:
Rectal administration of nimesulide suppositories in adults leads to peak plasma concentrations around 7.2 to 9 hours post-administration. Other pharmacokinetic properties are generally consistent with oral formulations, including metabolism, excretion, and half-life.
Capsule
Nimesulide in capsule form is a selective COX-2 inhibitor, reducing prostaglandin synthesis and thus alleviating pain, inflammation, and fever. It also inhibits platelet aggregation. Nimesulide’s chemical structure suggests a free radical scavenging mechanism, neutralizing reactive oxygen species produced during inflammation. This mechanism, along with COX-2 inhibition, contributes to its potent anti-inflammatory action in vivo. Some studies suggest better tolerability and fewer side effects compared to other NSAIDs. Metabolism is hepatic, primarily to hydroxynimesulide, and elimination is predominantly renal, without accumulation upon repeated administration.
Gel
Pharmacodynamics
Topical nimesulide gel delivers nimesulide’s anti-inflammatory, analgesic, and antipyretic effects locally. It selectively inhibits COX-2 and exhibits additional mechanisms like scavenging free radicals, inhibiting neutrophil oxygen metabolite release, reducing histamine release, inhibiting platelet-activating factor production, and blocking metalloproteinase activity.
Pharmacokinetics
Topical application of nimesulide gel results in very low systemic absorption compared to oral administration. Peak plasma levels after a single 200mg application are minimal and reached after 24 hours, with no detectable metabolite. However, nimesulide is well-absorbed through the skin, with absorption proportional to contact time and application area. It is metabolized in the liver and primarily eliminated renally, with an elimination half-life of approximately 275 minutes for the 2% gel. Bioavailability compared to oral forms is low, around 20% for the 2% gel, maximizing local effect and minimizing systemic side effects. Topical and oral nimesulide can be combined within therapeutic ranges. Nimesulide gel effectively controls neutrophil-produced oxidases at inflammation sites, allowing for dose adjustment and potential reduction of oral anti-inflammatory dosage. It provides pain relief, reduces edema, and accelerates recovery in the affected area.
Pre-clinical Safety Data
Pre-clinical tolerance and irritation studies in animals indicate nimesulide gel is well-tolerated topically.
