Tolerability of nimesulide in aspirin-sensitive patients.

In most patients with aspirin and nonsteroidal antiinflammatory drug (NSAID) intolerance, antiinflammatory treatment is a clinical problem. In this study we evaluated the tolerance to a new nonsteroidal antiinflammatory drug, nimesulide (Aulin, Boehringer Mannheim, Italia), in 429 patients presenting with clear histories of intolerance to NSAIDs. Nimesulide has been chosen due to its weak inhibitory action on cyclooxygenase and its peculiar mechanism of action. We carried out a single-blind challenge with cumulative doses of nimesulide administered on three different days, until the therapeutic dose of 200 mg or intolerance symptoms were reached. Nimesulide has been well tolerated in 418 subjects and only 11 patients (3.3%) showed a positive test. Our study demonstrates that nimesulide seems to be a suitable drug in aspirin hypersensitivity.

Use of a novel non-steroidal anti-inflammatory drug, nimesulide, in the treatment of abacterial prostatovesiculitis.

Nimesulide, a novel non-steroidal anti-inflammatory drug, was used in cases of abacterial prostato-vesiculitis. Thirty patients with a mean age of 33.7 years (range 18-58) were studied. Nimesulide was administered orally 100 mg b.i.d. for three cycles of 10 d each. Dysuric symptoms, semen analysis, and transrectal ultrasound were examined during the study. The concentration-time curves of nimesulide (NIM) and its metabolite, hydroxynimesulide (OH-NIM) in seminal fluid were also evaluated after single oral administration (100 mg) using an HPLC technique. Following administration of the drug, the Cmax was reached in seminal fluid at the second hour for NIM (with a mean value +/- SD of 0.58 +/- 0.13 micrograms ml-1) and at the fourth hour for OH-NIM (2.98 +/- 0.38 micrograms ml-1). Maximal seminal fluid concentrations compared to blood plasma levels were observed at the fourth hour for both substances (31.73 +/- 2.34% for NIM; 31.87 +/- 8.66% for OH-NIM. Dysuric symptoms were relieved in 20 (66%) patients. A clear amelioration of inflammatory signs were observed at transrectal ultrasound evaluation in 16 (54%) patients. No statistically significant changes of sperm count and motility in the whole sample were observed, while a significant reduction in the number of abnormal forms occurred. From these results, nimesulide appears to be an effective anti-inflammatory drug with a good diffusion into the genital apparatus and low side-effects.

Nimesulide in the treatment of hyperpyrexia in the aged. Double-blind comparison with paracetamol.

The efficacy and safety of nimesulide (Aulin, CAS 51803-78-2) in a new pharmaceutical suppository form (200 mg) were assessed in a double-blind study versus paracetamol suppositories (500 mg). The study was conducted in a sample of aged in-patients suffering from viral or bacterial infections of upper and lower respiratory tract with fever. Thirty-nine patients were randomly assigned to treatment with nimesulide or paracetamol (18 nimesulide, 21 paracetamol). Both drugs, administered t.i.d. for 2 consecutive days followed by observation without therapy on the 3rd day, showed an adequate control of hyperpyrexia with significant reduction of body temperature from baseline. Tolerability was good for both drugs. Only one patient of the nimesulide group could not complete the study because of an adverse reaction consisting in cutaneous erythema with itching that regressed spontaneously. It is concluded that nimesulide is as active and safe as paracetamol in treating hyperpyrexia of the aged.

Double-blind study of nimesulide in divers with inflammatory disorders of the ear, nose and throat.

200 divers of either sex, aged 18 to 54 years, entered a double-blind study to compare the efficacy and tolerability of nimesulide 200 mg/day with those of seaprose S 60 mg/day in the treatment of nonbacterial inflammatory disorders of the ear, nose, and throat. At the end of the 1-week treatment period, both drugs were judged to be effective, with improvements and, in most cases, complete remission of all symptoms observed. Nimesulide showed greater clinical efficacy, and both drugs were well tolerated.

Nimesulide in the treatment of chronic bronchitis.

Hypersecretion of mucus is the main feature of chronic bronchitis and is associated with an increased susceptibility to bronchial infections. Although airway inflammation is present in patients with chronic bronchitis and is recognised as a contributing factor in the development of bronchial hyper-reactivity and obstruction, the role of anti-inflammatory drugs in the treatment of chronic bronchitis has not been established. Nimesulide is a nonsteroidal anti-inflammatory drug that can modulate the function of neutrophils and block the effects of several inflammatory mediators. We found that a 3-week treatment course of nimesulide in patients with chronic mucus hypersecretion decreased sputum viscosity, thus significantly improving symptoms. The effect of nimesulide on the rheological properties of mucus was slower and weaker than that of classic mucolytics and was more likely to be related to a reduction in bronchovascular permeability. The clinical usefulness of nimesulide in chronic bronchitis deserves further investigation.

Nimesulide does not interfere with airway responsiveness in allergic asthma.

The clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) in asthmatic patients is limited by the possibility that these drugs may aggravate asthma by increasing the production of leukotrienes. Nimesulide, an NSAID with a weak inhibitory activity on prostaglandin synthetase, has been hypothesised to be safer than other NSAIDs in asthma. We have recently demonstrated in asthmatics who were allergic to the house dust mite that nimesulide neither alters the bronchial response to allergen nor aggravates the allergen-induced increase in airway responsiveness.

A comparison of nimesulide vs paracetamol in the treatment of pyrexia in the elderly.

The efficacy and safety of rectally administered nimesulide 200mg and paracetamol 500mg were assessed in a double-blind study. The study was conducted in 39 elderly inpatients with infections of the upper or lower respiratory tract associated with fever; 18 patients received nimesulide and 21 received paracetamol. Both treatments were given for 2 consecutive days and provided adequate therapy for pyrexia, with significant reductions in body temperature being observed. Both drugs were well tolerated. Only 1 patient in the nimesulide-treated group could not complete the study because cutaneous erythema occurred with itching; this resolved spontaneously upon treatment withdrawal. It is concluded that nimesulide is as active and safe as paracetamol for the treatment of pyrexia in the elderly.

Nimesulide in the treatment of pelvic inflammatory diseases. A multicentre clinical trial conducted in Campania and Sicily.

400 patients aged 18 to 71 years took part in a multicentre noncomparative study designed to assess the clinical efficacy and tolerability of nimesulide in gynaecological inflammatory disease: adnexitis (72 patients), cervicitis (78 patients), endometritis (18 patients), myometritis (22 patients), and combined disorders (210 patients). All patients were treated with nimesulide 100mg twice daily in granular form for an average of 19.5 days. The treatment produced good results in all types of diseases considered, with a significant decrease in severity of symptoms being observed. The drug was well tolerated.

Nimesulide in the treatment of mastalgia.

Sixty patients with mastalgia, either idiopathic or secondary to dysplastic lesions, were treated with oral nimesulide (100mg tablets twice daily) for 15 days. Breast tension and pain, assessed at baseline and on completion of the treatment period, improved or resolved with therapy. Indeed, breast pain (which most likely manifests as a consequence of periductal inflammation) was most noticeably reduced. The drug was well tolerated in nearly all patients. These results support the usefulness of nimesulide and other nonsteroidal anti-inflammatory drugs in the treatment of mastalgia.

Nimesulide in the treatment of menstrual migraine.

In a controlled double-blind clinical trial, 30 patients aged 18 to 45 years, with menstrual migraine, were randomly assigned to 2 parallel treatment groups of 15 patients each. One group received granular nimesulide 100mg 3 times daily and the other group received placebo. Each treatment was given for 10 days, starting from the onset of migraine symptoms, and was repeated for the 2 following menstrual cycles. The overall assessment of efficacy in the 2 groups was based on hourly self-evaluation of pain during each study day. In patients treated with nimesulide, pain intensity and duration were significantly reduced compared with placebo (p = 0.0001) during all the menstrual cycles in the study.

Controlled clinical studies of nimesulide in the treatment of urogenital inflammation.

Two double-blind, randomised studies were conducted to compare the efficacy and tolerability of nimesulide (200 mg/day) with those of placebo or bromeline (240 mg/day). Treatments were administered orally to patients of either sex (aged 19 to 70 years) with acute infection and inflammation of the urogenital tract, and were given concomitantly with antimicrobial therapy for approximately 9 days. In both studies, a clinically significant improvement in symptoms, leading to complete remission, was achieved in most patients treated with nimesulide. Furthermore, treatment with nimesulide resulted in a more rapid improvement in symptoms and complete remission in a greater number of patients than did treatment with bromeline. Both nimesulide and bromeline were well tolerated.

Treatment of abacterial prostato-vesiculitis with nimesulide.

The efficacy and tolerability of nimesulide were assessed in the treatment of patients with prostato-vesiculitis. In a noncomparative investigation, 30 patients received oral nimesulide 100mg twice daily for three 10-day cycles. Micturition-related symptoms were resolved in 20 patients and clear amelioration of inflammatory signs was observed with transrectal ultrasound in 16 patients. Abnormal sperm forms decreased from 57 to 49% (p < 0.001). In a comparative investigation, 40 patients received nimesulide 200mg twice daily or ketoprofen 100mg twice daily via the rectal route. Patients and physicians expressed an overall opinion on efficacy in favour of nimesulide. In a pharmacokinetic study of healthy volunteers who received oral nimesulide 100mg as a single dose, the mean maximum nimesulide concentration (0.58 +/- 0.13 mg/L) in seminal fluid was achieved after 2 hours while the maximum seminal fluid: blood plasma ratio 0.32 +/- 0.02 was observed after 4 hours. These data suggest that nimesulide is an effective NSAID in the treatment of abacterial prostato-vesiculitis and also demonstrate that this drug has a favourable disposition within the genital tract.

Nimesulide and diclofenac in the control of cancer-related pain. Comparison between oral and rectal administration.

64 patients with pain associated with advanced cancer were treated with either nimesulide or diclofenac as initial analgesia. Patients were randomly allocated to 1 of 4 treatment groups: oral nimesulide 300 mg/day; oral diclofenac 150 mg/day; rectal nimesulide 400 mg/day; and rectal diclofenac 200 mg/day. After 1 week of treatment, both drugs provided an adequate degree of pain relief and allowed an increase in sleep duration. There were no significant differences in efficacy between the drugs or routes of administration. Fewer side effects were observed with nimesulide, giving this agent a better therapeutic index than the reference compound.

Nimesulide in the treatment of advanced cancer pain. Double-blind comparison with naproxen.

The analgesic efficacy and tolerability of nimesulide and naproxen were compared in 68 patients with advanced cancer who needed to be treated with nonsteroidal anti-inflammatory drugs according to the first step of the pharmacological analgesic scale of the WHO. Patients received either nimesulide 200mg or naproxen 500mg twice daily. The analgesic efficacy and tolerability of the 2 drugs appeared to be similar. Both drugs were effective and were associated with a low incidence of adverse reactions.

Comparison of nimesulide and diclofenac in the prevention and treatment of painful inflammatory postoperative complications of general surgery.

In a double-blind study, 40 patients scheduled for saphenectomy or inguinal hernioplasty were randomly assigned to treatment with nimesulide (200mg 3 times daily) or diclofenac (100mg 3 times daily) administered rectally. Therapy with either drug resulted in significantly less pain, oedema and hyperaemia, and resolution of mild fever. No adverse reactions attributable to treatment were observed.

A double-blind comparison of nimesulide and ketoprofen in dental surgery.

The efficacy and tolerability of nimesulide were compared with those of ketoprofen when administered rectally in a double-blind investigation of 46 patients scheduled for dental surgery. Nimesulide was more effective and more rapid than ketoprofen in ameliorating the painful inflammatory symptoms (pain at rest and upon mastication) and signs (swelling and hyperaemia) associated with the operation. These effects were accompanied by improved quality of sleep and recovery of masticatory and swallowing function, which was superior for nimesulide-treated patients.

A controlled clinical study of the efficacy and tolerability of nimesulide vs naproxen in maxillo-facial surgery.

The anti-inflammatory and analgesic efficacy of nimesulide was assessed and compared with that of naproxen in the postoperative treatment of inflammatory complications of maxillo-facial surgery in a double-blind study. A total of 60 patients were randomly assigned to treatment with nimesulide (100mg twice daily) or naproxen (250mg twice daily) for 6 to 14 days. Treatment with either drug prevented the development of, or ameliorated the signs and symptoms associated with, the inflammatory process (spontaneous pain, difficulty in chewing and swallowing, swelling, hyperaemia, muscle contracture, poor sleep quality). Indeed, most patients experienced complete resolution of their signs and symptoms. The efficacy of nimesulide was considered to be superior to that of naproxen, although both drugs were tolerated equally well.

A comparison of nimesulide and ketoprofen in the prevention and treatment of painful postoperative inflammatory complications of ear, nose and throat surgery.

In a randomised double-blind clinical study, 76 patients undergoing major ear, nose or throat (ENT) surgery (including 45 for cancer) were treated with nimesulide (200mg twice daily) or ketoprofen (100mg twice daily) administered rectally for 5 days. Pain intensity was significantly and similarly reduced in both treatment groups compared with baseline (p = 0.0001). A significant reduction in oedema and hyperaemia was observed on the second day for nimesulide-treated patients and on the third day for those treated with ketoprofen, with complete relief being noted for almost all patients by the fifth day. Fever was resolved in all patients. Adverse events attributable to treatment were observed for 1 patient in each group. These results suggest that nimesulide provides a worthwhile alternative to other NSAIDs in the treatment of postoperative pain and inflammation associated with ENT surgery.

Efficacy of nimesulide in the prevention of inflammatory complications after laser treatment of ocular diseases.

A total of 40 patients with various ocular diseases were treated with nimesulide 200 mg/day or ketoprofen 150 mg/day for 7 days after laser therapy. The incidence of ocular complications was lower in patients treated with nimesulide than with ketoprofen. With regard to posterior segment changes, retinal oedema was reduced in patients treated with nimesulide. After laser treatment, anterior segment changes were modest. These preliminary results stress the efficacy of nimesulide in preventing oedema and also its anti-inflammatory effects on the retina after ocular laser therapy.

Clinical efficacy and tolerability of nimesulide compared with naproxen in the treatment of posthaemorrhoidectomy pain and inflammation.

The efficacy and tolerability of nimesulide and naproxen were compared in a randomised double-blind study of patients with pain and inflammation after haemorrhoidectomy. Both drugs appeared similarly effective in reducing pain and oedema and no adverse reaction was detected. These data extend the information on the anti-inflammatory and analgesic efficacy of nimesulide in the postoperative setting.