Safety Of Nimesulide Research Articles

Some aspects of anti-inflammatory therapy of osteoarthritis

In the article, the authors discuss the therapy of OA as one of the common diseases of the musculoskeletal system, which leads to disability of people of working age. Focusing on modern concepts of pathogenesis, the article draws attention to pain and the mechanisms of its formation in OA. The recommendations of the world’s leading communities (EULAR, ARC OARSI) and the conclusions of the consensus resolution of experts of the Russian Federation on the diagnosis and treatment of osteoarthritis 2022 are also given. The article draws attention to some aspects of pain therapy. The data of studies and meta-analyses demonstrating the effectiveness of NSAIDs in pain associated with OA are presented. Among the variety of NSAIDs, the article provides data on the efficacy and safety of nimesulide, as well as its additional properties such as inhibition of cancer cell proliferation, neuroprotective and gastroprotective effects. The conclusions of the consensus meetings of 2005, the purpose of which was to provide a continuous and up-to-date assessment of the clinical profile and safety profile of nimesulide, and 2014, the purpose of which was to familiarize with the current state of pathophysiology and treatment of acute pain with a special focus on nimesulide, are presented. The article also provides data on the safety and efficacy of nimesulide in the treatment of OA in comparison with drugs such as diclofenac, naproxen and ibuprofen. One of the little-studied aspects of pain therapy is the patient’s preference. The article presents data from studies of the effectiveness of various forms of NSAIDs and patient preferences in therapy. The authors of the article conclude that the most acceptable from the point of view of efficacy, safety, the rate of onset of the effect, as well as the preferences of patients is nimesulide in the form of granules for the preparation of a solution.

Лечение пациентов со скелетно-мышечным болевым синдромом в период пандемии COVID-19

Objective of the Review: To discuss the efficiency and safety of the use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with low back pain (LBP), also during COVID-19 pandemic. Key Points. Musculoskeletal pain syndromes, including LBP, are common; they affect the quality of patients’ life and result in huge medical bills. In a lot of post-COVID-19 patients, LBP appears for the first time or gets worse. Challenges in the management of such patients are caused by involvement of multiple organs and body systems, the need in taking numerous medications at once, which increases the risk of drug interaction. This overview describes the efficiency and safety of nimesulide in patients with low back pain. The use of NSAIDs in patients with COVID-19 is discussed. Beneficial effects and possible risks of nimesulide are analysed. Conclusion. Management of patients with LBP during the COVID-19 pandemic requires thorough selection of an optimal therapy taking into account comorbidities and a high risk of drug-drug interactions. Nimesulide is a potent medication with a favourable safety and tolerability profile. It is advisable to use nimesulide in the management of patients with low back pain, including COVID-19 survivors. Safety of the therapy can be ensured by thorough drug selection taking into account comorbidities and risks of complications. Keywords: musculoskeletal pain syndromes, low back pain, COVID-19, post-COVID syndrome, nonsteroidal anti-inflammatory drugs, nimesulide, management, side effects.

Nonspecific low-back pain: approaches to diagnosis and treatment

This review considers the problem of pain chronification process based on the biopsychosocial model. Treatment of nonspecific low-back pain is specifically highlighted. Algorithms for the management of such patients are described. The efficacy and safety of nimesulide is discussed.

Ankylosing spondylitis and comorbidity: safety of long-term use of nimesulide

Ankylosing spondylitis (AS) is a socially significant rheumatic disease that generally starts in young adults and, if untreated, often leads to temporary incapacitation, and by 40 years, and to disability. Despite the relatively young age of patients, the course of AS is accompanied by a number of comorbidities that most commonly include hypertension, dyslipidemia, and involvement of the gastrointestinal tract and kidney. The main group of drugs recommended for the treatment of the disease is nonsteroidal anti-inflammatory drugs (NSAIDs) that, when used long, exert analgesic, anti-inflammatory, and even disease-modifying effects on the one hand and can cause adverse reactions on the other. When choosing NSAIDs, one should consider not only the activity of the pathological process, but also the presence of comorbidities in the patient. The paper gives data on the efficacy and safety of nimesulide in AS. The drug has proven its efficacy and safety in various rheumatic diseases over nearly a quarter century of its use in Russia.

S.35.04 - Immune factors as biomarkers for stress-related psychiatric and pain disorders

Evidence for a role of immune system in hyperalgesic pain states is increasing. Recent work in neuroimmunology suggests that the immune system does more than simply perform its well known functions of recognizing and removing invading pathogens and tumors. Interest in neuroinflammation and neuroimmune activation has grown rapidly in recent years with the recognition of the role of central nervous system inflammatiom and immune responses in the aetiology of pain states. Among various theories, the role of inflammatory responses of the injured nerve has recently received attention. Cytokines are heterogenous group of polypeptides that activate the immune system and mediate inflammatory responses, acting on a variety of tissue, including the peripheral and central nervous system. Interleukin-6 (IL-6) a pro-inflammatory cytokine, is potentially important in pain aetiology, have pronociceptive actions. Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. Substances released during inflammation from immune cells play an important role in the development and maintenance of chronic pain. Nimesulide, a highly selective cox-2 inhibitor, effectively reduces hyperalgesia due to peripherally administration of inflammatory agents like formalin. The safety of nimesulide was reported for some conditions in which other NSAIDs are contraindicated. Here we have determined the effect of nimesulide on pain behaviour and serum IL-6 level in chronic constriction injury (CCI) model of neuropathic pain.Experiments were carried out on male Wistar rats, (weight 150–200 g, n = 8). Rats were divided into 3 different groups: 1- CCI + saline 0.9% 2- Sham + saline 0.9% (control) 3- CCI + drug. Nimesulide (1.25, 2.5, 5 mg/kg, i.p.) was injected 1h before surgery and continued daily to day 14 post-ligation. 42 °C water for thermal hyperalgesia, von Frey filaments for mechanical allodynia, acetone test for cool allodynia and 10 °C water for cold hyperalgesia were respectively used as pain behavioural tests. Behavioural tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 10, 14 and the serum concentration of IL-6 was determined at the day 14.The results of this study showed a decrease in hyperalgesia and allodynia following nimesulide administration.It appears that nimesulide was able to reduce pain behaviour due to nerve inflammation and a parallel decrease in the serum IL-6 concentration was observed.The immune system is an important mediator in the cascade of events that ultimately results in hyperalgesia. Cytokines contribute to the patheogenesis of neuropathic pain, therefore drugs that inhibit cytokine release from immune cells may reduce inflammatory pain states.

The problem in the evaluation of the efficacy and safety of nonsteroidal anti-inflammatory drugs

The review gives data on the safety of nimesulide used for the treatment of chronic joint diseases. The first-line treatment at its any stage for joint diseases is nonsteroidal anti-inflammatory drugs (NSAIDs). Questions have recently arisen of the safety of nimesulide; however, epidemiological findings and clinical experience confirm a positive benefit/risk profile of nimesulide in the treatment of acute pain. The International Consensus Meeting (Vienna, 2014) noted that the risk of severe adverse hepatic NSAID reactions was low and the rate of liver damage associated with nimesulide was completely similar to that observed with other NSAIDs. There are data available in the literature on the rate of serious adverse liver reactions to different NSAIDs and paracetamol. The rate of such reactions to all NSAIDs per million patientyears was 1.55 and that to nimesulide was 1.88. The members of the International Consensus Group concluded that nimesulide, if properly used, remained a valuable and safe drug for the treatment of various conditions, characterized by the presence of acute inflammatory pain, by virtue of the rapid onset of analgesic action and an evidence-based positive benefit/risk profile. The long successful experience with nimesulide in our country suggests that the agent may be successfully used to treat chronic and acute pain (including dysmenorrhea) in a daily dose of 200 mg/day. The safety profile of the drug is quite satisfactorily for all adverse reactions typical of NSAIDs, including its negative effect on the liver.

The use of nimesulide in the treatment of acute low back pain

The objective is to study the efficacy and safety of nimesulide (nemulex) in the treatment of acute low back pain (LBP). The medical documentation of 54 patients with primary syndrome of LBP, which were treated in a polyclinic with nemulex at a dose of 200 mg per day had been studied. The assessment of patients' condition and efficacy and safety of the treatment was conducted based on the information after three visits (1-st, 5-th and 10-th day). The analysis took into account the data of clinical-neurological examination and the assessment of pain intensity at rest and at movement according to the visual analogue scale (VAS) and the severity of Lasegue symptom and limitation of movements in the lumbar spine. Safety of the therapy was evaluated on the basis of accounting of undesirable side reactions and data analysis and physical examination and laboratory testing. Cardiovascular safety was assessed by blood pressure and blood lipid profile on day 10. The use of nemulex at a dose of 200 mg per day resulted in relief of pain and increase of mobility in the lumbar spine on the 5th day of treatment that indicates the effectiveness of anti-inflammatory therapy to restore the previous functional status of patients with LBP. The use of nemulex was accompanied not only by statistically significant analgesic effect (0,78±0,14 points alone; 1,12±0,18 points when moving by VAS on the 10th day of the treatment) and high security (only 1 of the 54 patients was recorded to have elevation of hepatic transaminases; and 2 patients with dyspepsia without endoscopic changes of gastrointestinal tract).

Efficacy and safety of nimesulide for the treatment of patients with dorsopathy

Efficacy and safety of nimesulide for the treatment of patients with dorsopathy

A phase III trial evaluating the efficacy and tolerability of nimesulide 1% spray in patients with soft-tissue injuries

Aim:To evaluate the efficacy and safety of nimesulide 1% w/w spray in minor soft-tissue injuries in adult Indians through a multicentric, open-labeled, phase III trial.Materials and Methods:125 eligible patients, who met the selection criteria and gave written informed consent, were screened, enrolled, and treated with nimesulide 1% spray for seven days. Patients were assessed at baseline, day 1, day 4, and day 8 for efficacy and safety. Primary efficacy variable pain intensity, was measured using a NRS 1-100 mm (numerical rating scale). Secondary efficacy variables were degree of inflammation and edema and degree of functional impairment; overall assessment of efficacy was done by patient (patient global assessment – PGA) and by investigator (investigator global assessment – IGA) on days 4 and 8.Result:There was a statistically significant reduction in the NRS score, degree of pain, edema (inflammation), and improvement in functional impairment on days 4 and 8 and in serum creatine kinase levels on day 8 in comparison with baseline. Global assessment of efficacy on day 8 was rated as “very good (21%),” “good (67.70%),” and “fair (11.30%)” by investigators and “very good (25%),” “good (58.90%),” and “fair (16.1%)” by patients. Two mild adverse events were reported in two patients, which resolved without any intervention. One (local irritation) was reported as not related, while the other (itching sensation) was probably related to the study drug.Conclusion:Nimesulide 1% spray was effective with a good safety profile and can be considered is a good alternative to oral analgesic therapy in minor soft-tissue injuries.

Once more about the safety of nimesulide

When nonsteroidal anti-inflammatory drugs (NSAIDs) are used, great attention is paid to their safety now. NSAIDs are primarily evaluated for their effects on the gastrointestinal mucosa, also assess the risk from NSAIDs on liver function. The retrospective analysis of 179 case histories of patients with rheumatoid arthritis, made at the Research Institute of Rheumatology, Russian Academy of Medical Sciences, has revealed no hepatotoxic reactions in the treatment with nise alone and in combination with methotrexate or leflunomide, which are known to be hepatotoxic. There was not more than a 2-fold increase in the level of hepatic enzymes in 7.8 and 10.2% of patients receiving nise and diclofenac, respectively.

The attenuation of pain behaviour and serum interleukin-6 concentration by nimesulide in a rat model of neuropathic pain

Background Evidence for a role of immune system in hyperalgesic pain states is increasing. Recent work in neuroimmunology suggests that the immune system does more than simply perform its well known functions of recognizing and removing invading pathogens and tumors. Interest in neuroinflammation and neuroimmune activation has grown rapidly in recent years with the recognition of the role of central nervous system inflammatiom and immune responses in the aetiology of pain states. Among various theories, the role of inflammatory responses of the injured nerve has recently received attention. Cytokines are heterogenous group of polypeptides that activate the immune system and mediate inflammatory responses, acting on a variety of tissue, including the peripheral and central nervous system. Interleukin-6 (IL-6) a pro-inflammatory cytokine, is potentially important in pain aetiology, have pronociceptive actions. Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. Substances released during inflammation from immune cells play an important role in the development and maintenance of chronic pain. Nimesulide, a highly selective cox-2 inhibitor, effectively reduces hyperalgesia due to peripherally administration of inflammatory agents like formalin. The safety of nimesulide was reported for some conditions in which other NSAIDs are contraindicated. Here we have determined the effect of nimesulide on pain behaviour and serum IL-6 level in chronic constriction injury (CCI) model of neuropathic pain. Methods Experiments were carried out on male Wistar rats, (weight 150–200 g, n = 8). Rats were divided into 3 different groups: 1- CCI + saline 0.9% 2- Sham + saline 0.9% (control) 3- CCI + drug. Nimesulide (1.25, 2.5, 5 mg/kg, i.p.) was injected 1h before surgery and continued daily to day 14 post-ligation. 42 °C water for thermal hyperalgesia, von Frey filaments for mechanical allodynia, acetone test for cool allodynia and 10 °C water for cold hyperalgesia were respectively used as pain behavioural tests. Behavioural tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 10, 14 and the serum concentration of IL-6 was determined at the day 14. Results The results of this study showed a decrease in hyperalgesia and allodynia following nimesulide administration. Conclusions It appears that nimesulide was able to reduce pain behaviour due to nerve inflammation and a parallel decrease in the serum IL-6 concentration was observed. Implications The immune system is an important mediator in the cascade of events that ultimately results in hyperalgesia. Cytokines contribute to the patheogenesis of neuropathic pain, therefore drugs that inhibit cytokine release from immune cells may reduce inflammatory pain states.

Efficacy and safety of nimesulide long term administration in patients with osteoarthritis: results of 12-months open controlled study DINAMO (long term administration of nimesulide in osteoarthritis multifactor assessment)

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Safety of Selective COX‐2 Inhibitors in Aspirin/Nonsteroidal Anti‐inflammatory Drug‐Intolerant Patients: Comparison of Nimesulide, Meloxicam, and Rofecoxib

Background. Intolerance to acetylsalicylic acid (ASA) and other nonsteroidal anti‐inflammatory drugs (NSAIDs) is a crucial problem in clinical practice. There is, therefore, a need for safer NSAIDs in patients with analgesic intolerance. Objective. To assess the safety of nimesulide, meloxicam, and rofecoxib, selective COX‐2 inhibitors, in a group of ASA/NSAIDs‐intolerant patients. Method. Tolerances to nimesulide, meloxicam, and rofecoxib were assessed by single‐blind placebo‐controlled oral challenges. One hundred twenty‐seven subjects with history of adverse reaction to ASA/NSAIDs received oral challenges with nimesulide, 61 subjects were challenged with meloxicam, 51 subjects were challenged with rofecoxib, and 37 subjects were challenged with all three drugs. Placebos were given to all patients on the first day of the study. On the second day, one‐fourth and three‐fourths of the therapeutic doses of the active drugs (nimesulide 100 mg, meloxicam 7.5 mg, or rofecoxib 25 mg) were given at 60‐minute intervals. There was at least a 3‐day interval between challenge tests. Erythema, pruritus accompanied by erythema, urticaria/angioedema, rhinorrhea, nasal obstruction, sneezing, dyspnea, or cough associated with a decrease of at least 20% in the forced expiratory volume (FEV1) and hypotension were considered as positive reactions. Results. Positive reactions to the nimesulide, meloxicam, and rofecoxib challenges were observed in 18/127 (14.3%), 5/61 (8.1%), and 1/51 (2.0%) patients, respectively. In each group of nine patients, there were two patients with asthma and four who developed skin type reactions and asthmatic reactions, respectively, to the nimesulide challenge. Among five patients who reacted to the meloxicam challenge, asthmatic type reactions were detected in two asthmatics. Only one urticarial type reaction was observed with rofecoxib challenge in one patient who presented with anaphylaxis to ASA/NSAIDs. All patients with asthma tolerated rofecoxib without any adverse effects. None of the patients reacted to the placebo. Among 37 patients challenged with all three drugs, 11 reacted to nimesulide, and one patient reacted only to meloxicam. Three patients reacted to more than one of the drugs tested, and one of them reacted to all drugs. Conclusion. This is the first placebo‐controlled report comparing these three drugs. The results indicate that among these alternative drugs for ASA/NSAIDs‐intolerant patients, rofecoxib seems to have the most favorable tolerability.

Nimesulide versus Ibuprofen for Postoperative Tonsillectomy Pain

Nonsteroidal anti-inflammatory drugs are effective analgesics but their use during tonsillectomy is controversial because of the risk of postoperative bleeding. The aim of this study was to compare the analgesic efficacy and safety of nimesulide, a preferential cyclo-oxygenase type-2 inhibitor, with ibuprofen in the treatment of pain after tonsillectomy. A prospective, double-blind, randomised clinical trial. A total of 80 consenting generally healthy patients, aged 14-58 years, undergoing tonsillectomy were randomly assigned to receive either nimesulide 100mg or ibuprofen 800mg orally 60 minutes before surgery. Subsequent doses of the same study medication were administered at 12-hour intervals for the first 7 days, and thereafter when needed. During the first 24 postoperative hours in hospital oxycodone was used for rescue analgesia, and after discharge patients were allowed to use a paracetamol-codeine combination for breakthrough pain. Recovery was recorded up to 3 weeks after surgery. The need for rescue analgesia during the first 24 hours was similar in the two study groups; 0-7 doses (mean +/- SD 3.3 +/- 1.7 doses) in the nimesulide group and 0-11 doses (3.3 +/- 2.4 doses) in the ibuprofen group. After discharge significant differences were found between the two study groups in favour of the nimesulide-treated patients. Cessation of significant pain while swallowing occurred after 3-19 (10.9 +/- 3.8) days in the nimesulide group versus 7-20 (12.9 +/- 3.3) days in the ibuprofen group (p = 0.041), and return to normal daily activities occurred after 3-21 (10.3 +/- 4.9) days in the nimesulide group versus after 3-19 (12.7 +/- 4.2) days in the ibuprofen group (p = 0.048). At 3 weeks, six of 33 patients in the nimesulide group versus 15 of 37 patients in the ibuprofen group had pain during swallowing (p = 0.049). One patient (3%) in the nimesulide group and five patients (12%) [p = 0.22] in the ibuprofen group needed electrocautery to stop postoperative bleeding. Oral nimesulide was as effective as ibuprofen in pain management after tonsillectomy, and nimesulide improved the recovery after discharge.

DOUBLE‐BLIND STUDY COMPARING THE LONG‐TERM EFFICACY OF THE COX‐2 INHIBITOR NIMESULIDE AND NAPROXEN IN PATIENTS WITH OSTEOARTHRITIS

SUMMARYThis double‐blind one‐year study compares the long‐term efficacy and safety of nimesulide with naproxen in patients with osteoarthritis (OA) of the knee or hip. Patients were randomised to nimesulide 100 mg twice daily (n=183) or naproxen 250 mg morning, 500 mg evening (n=187). The primary efficacy variable was change in pain intensity (WOMAC A scale) at 6 months. Nimesulide tablets showed at least equivalent efficacy to naproxen tablets in reducing pain intensity at 6 and 12 months (nimesulide ‐22.5% at 6 and 12 months; naproxen ‐22.4% at 6 months, ‐19.9% at 12 months; non‐inferiority proven). At 6 months the investigator assessed efficacy as ‘good’ or ‘excellent’ in 59.3% of nimesulide and 56.4% of naproxen‐treated patients, with corresponding values for patient assessment of 57% and 52.7%. Both treatments were well tolerated, with fewer related gastrointestinal adverse events reported with nimesulide (77 cases, 47.5%) than with naproxen (96 cases, 54.5%). This study shows nimesulide to be as effective as naproxen in the long‐term treatment of OA and to be associated with fewer gastrointestinal side‐effects.

Can a cyclo-oxygenase type-2 selective tocolytic agent avoid the fetal side effects of indomethacin?

We evaluated the efficacy and safety of nimesulide (100 mg orally twice daily for > 48 hours) in a pilot series of five women (two with twin pregnancies) at 24(+6) weeks (range 21(+3) - 27(+2)) in preterm labour which was unresponsive to intravenous ritodrine. Nimesulide therapy was continued for eight days (5-16) and was associated with a prolongation of pregnancy of 27 days (6-69). Oligohydramnios occurred in all seven fetuses after three to nine days of therapy, and in the five pregnancies that continued after discontinuation of nimesulide, it resolved within four days (2-7). None of the babies manifested permanent renal damage.

Can a cyclo-oxygenase type-2 selective tocolytic agent avoid the fetal side effects of indomethacin?

We evaluated the efficacy and safety of nimesulide (100 mg orally twice daily for > 48 hours) in a pilot series of five women (two with twin pregnancies) at 24 +6 weeks (range 21 +3–27 +2) in preterm labour which was unresponsive to intravenous ritodrine. Nimesulide therapy was continued for eight days (5–16) and was associated with a prolongation of pregnancy of 27 days (6–69). Oligohydramnios occurred in all seven fetuses after three to nine days of therapy, and in the five pregnancies that continued after discontinuation of nimesulide, it resolved within four days (2–7). None of the babies manifested permanent renal damage.

Interaction between NSAIDs and steroid in rat stomach: safety of nimesulide as a preferential COX-2 inhibitor in the stomach.

The relative risk of development of peptic ulcer with the use of nonsteroidal antiinflammatory drugs (NSAIDs) has been reported to increase when these drugs are administered in combination with steroids. We investigated the ulcerogenic potential of a combination of NSAIDs and steroids in rats and the underlying pathogenic mechanisms. Indomethacin alone produced gastric lesions, and the severity of the lesions markedly increased with concomitant administration of prednisolone. However, nimesulide, even in excessive doses, did not produce any gastric lesions, regardless of concomitant administration with prednisolone. Furthermore, we showed that the ulcerogenic potential of indomethacin administered in combination with prednisolone may be related to the induction of physiological changes, such as endogenous prostaglandin deficiency, an increase in neutrophil activation, and gastric hypermotility, by indomethacin and alteration of normal epithelial renewal by the steroid. These results suggest that the ulcerogenic potential of preferential a COX-1 inhibitor increases following concomitant administration with a steroid, whereas, nimesulide, a preferential COX-2 inhibitor, is nonulcerogenic, even when administered concomitantly with a steroid, and is therefore a clinically useful antiinflammatory agent.

A large, open-label trial of nimesulide in patients with osteoarticular conditions treated in a general practice setting

In an uncontrolled, open-label trial, 885 patients with painful osteoarticular conditions—(738 patients with nonarticular rheumatism, including 167 with painful spinal problems [cervical, dorsal, or low-back pain, or several of these problems combined] and 571 with soft-tissue rheumatism [194 with tendinitis and bursitis, 117 with painful shoulder, and 260 with minor traumas such as strains, sprains, and tears], and 147 patients with other painful conditions)—received nimesulide 100 mg twice daily (BID) for a maximum of 14 days. Patients had the opportunity to stop treatment after 7 days if symptoms were relieved. The efficacy and safety of nimesulide were assessed for all patients on an intent-to-treat basis. In addition, each subgroup of patients was assessed separately. After 7 days of treatment, a significant improvement in locomotor function and a significant reduction in pain, as well as significant reductions in swelling, heat, and redness, were observed in the entire group of patients as well as in each subgroup. The incidence of side effects (11.2%), mainly gastrointestinal (9.2%), was low compared with that described in the literature for nonsteroidal anti-inflammatory drugs (NSAIDs). At the end of the study, a significant percentage of patients and investigators estimated that, globally, both the efficacy and tolerability of nimesulide were satisfactory or excellent. Results of the present study suggest that nimesulide 100 mg BID is a safe and effective NSAID for the treatment of painful osteoarticular conditions, especially nonarticular rheumatism.