Comparison of slow-release indomethacin and diflunisal in patients with arthrosis

Summary

A double-blind, crossover study was carried out in 44 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerability of treatment with a new slow-release formulation of indomethacin (50?mg) with that of diflunisal (250?mg). After a 1-week wash-out period, patients were allocated at random to receive 2 tablets daily of one or other preparation for 6 weeks before being crossed over to the alternative drug for a further 6 weeks. Aspirin was allowed as a rescue analgesic throughout the study. Subjective assessments of pain and objective assessments of joint mobility were made before the start of treatment and at the end of each period, and details were recorded of rescue analgesic usage and any side-effects. Analysis of the results from 42 patients showed that whilst both treatments helped to alleviate pain, patients' overall evaluation of efficacy at the end of the study indicated that indomethacin was slightly more effective than dif lunisal and there was a significant preference for indomethacin. Both drugs were well tolerated and none of the side-effects, reported in about 15% of patients on each drug, resulted in any withdrawals.     

Comparison of a slow-release indomethacin tablet and naproxen in osteoarthrosis

A double-blind, crossover study was performed in 21 out-patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerability of a new slow-release formulation (multiple units dose preparation) of indomethacin (50 mg) with those of naproxen (250 mg). After a wash-out period of 1 week, the patients were randomized to receive 2 tablets daily of one or other preparation for 3 weeks. This was followed by another wash-out period of 1 week, whereafter the patients were crossed over to the alternative drug for another 3 weeks. Subjective assessments of pain and objective assessment of joint mobility and the use of acetylsalicylic acid as rescue analgesic were used to evaluate the efficacy of the treatment. Analysis of results from 19 patients showed that both drugs effectively alleviated pain, and there was no difference between indomethacin and naproxen in this respect. There were 2 withdrawals, 1 on naproxen due to inefficacy and 1 on indomethacin due to gastro-intestinal side-effects. Otherwise, the drugs were well tolerated and side-effects occurred to the same extent on both drugs. This study confirms the good efficacy and tolerability of the new slow-release indomethacin preparation.     

Diflunisal in osteoarthrosis of the hip and knee

Summary

A double-blind randomized trial was carried out in 60 patients with osteoarthrosis of the hip or knee to assess the relative efficacy and tolerance of treatment with diflunisal twice daily (maximum 750?mg per day) or with aspirin given 4-times daily (maximum 3 g per day) over a period of 12 weeks. Clinical assessments were made on entry and at regular intervals of weight-bearing pain, night pain, specific function pain, inactivity stiffness, and range of joint movement. A considerable proportion of patients in both groups showed improvement in all parameters except for limitation of movement. The difference in response between the two groups was not statistically significant, neither was the patients' overall opinion of response to or clinician's assessment of therapeutic efficacy of either drug treatment at the end of the trial. Ten of the 29 patients in the aspirin group had to withdraw because of adverse reactions, mainly gastro-intestinal, compared with 4 of the 31 patients in the diflunisal group. The overall incidence of side-effects in all patients was lower in the diflunisal group, and those that were reported were less disturbing. At the end of the double-blind study, patients were given the option to continue with the particular drug treatment for a further two 13-week periods. More patients chose to remain on diflunisal than on aspirin at the end of each of the three periods and the difference was statistically significant.     

A double-blind comparison of diflunisal and aspirin in the treatment of post-operative pain after episiotomy.

A double-blind randomized trial was carried out in 161 primiparous women suffering from moderate to severe post-episiotomy pain to compare the analgesic efficacy of single doses of diflunisal (125 mg, 250 mg, of 500 mg), aspirin (600 mg), and placebo. The results of pain rating assessments made before and at hourly intervals after drug administration showed that both the active drugs were more effective than placebo and produced similar pain relief over the first 4 hours. The analgesic efficacy of aspirin tailed off after 4 hours but pain relief with 500 mg diflunisal was still evident after 8 hours. Over 65% of patients in the diflunisal group had effective relief of pain at 8 hours whereas there was no significant difference between the aspirin and placebo-treated groups by the seventh and eighth hour.     

Diflunisal in the treatment of osteoarthrosis: a double-blind study comparing diflunisal with ibuprofen.

A double-blind trial was carried out in 37 patients with osteoarthrosis to compare the efficacy and tolerance of 250 mg diflunisal twice daily with that of 400 mg ibuprofen 3-times daily over an 8-week period. Rating scale assessments were made, at the end of a preceding 1-week, wash-out period on placebo and at regular fixed intervals, of weight-bearing pain, night pain, a specific functional activity, and of the duration of inactivity stiffness. Patients' and physician's overall evaluations of response, taking side-effects into account, were made on completion of the study. The data collected indicated that in 30 patients completing the trial both treatments produced similar overall results and, with the exception of weight-bearing pain which appeared to be improved more in the ibuprofen group, diflunisal provided equal therapeutic benefit with fewer side-effects.     

A double-blind comparison of diflunisal and aspirin in the treatment of post-operative pain after episiotomy

Summary

A double-blind randomized trial was carried out in 161 primiparous women suffering from moderate to severe post-episiotomy pain to compare the analgesic efficacy of single doses of diflunisal (125?mg, 250?mg, or 500?mg), aspirin (600?mg), and placebo. The results of pain rating assessments made before and at hourly intervals after drug administration showed that both the active drugs were more effective than placebo and produced similar pain relief over the first 4 hours. The analgesic efficacy of aspirin tailed off after 4 hours but pain relief with 500?mg diflunisal was still evident after 8 hours. Over 65% of patients in the diflunisal group had effective relief of pain at 8 hours whereas there was no significant difference between the aspirin and placebo-treated groups by the seventh and eighth hour.     

Diflunisal in the treatment of osteoarthrosis: a double-blind study comparing diflunisal with ibuprofen

Summary

A double-blind trial was carried out in 37 patients with osteoarthrosis to compare the efficacy and tolerance of 250?mg diflunisal twice daily with that of 400?mg ibuprofen 3-times daily over an 8-week period. Rating scale assessments were made, at the end of a preceding 1-week wash-out period on placebo and at regular fixed intervals, of weight-bearing pain, night pain, a specific functional activity, and of the duration of inactivity stiffness. Patients' and physician's overall evaluations of response, taking side-effects into account, were made on completion of the study. The data collected indicated that in 30 patients completing the trial both treatments produced similar overall results and, with the exception of weight-bearing pain which appeared to be improved more in the ibuprofen group, diflunisal provided equal therapeutic benefit with fewer side-effects.     

A comparative study of flurbiprofen and indomethacin in rheumatoid arthritis.

A double-blind, crossover study was carried out in 30 patients with active, classical or definite rheumatoid arthritis to compare the effect of 200 mg flurbiprofen per day with that of 100 mg indomethacin per day. Patients received, at random, each drug for a period of 2 weeks separated by a weeks' wash-out period on placebo. Assessments were made before the start of the trial and at weekly intervals of pain, morning stiffness, grip strength, articular index, walking time, and finger joint size. Patients' preference for any particular treatment period was recorded at the end of the trial. Laboratory investigations were carried out before and during the trial. Both drugs shows statistically significant improvement over baseline assessments, although there was little difference between the two active treatment periods. More patients preferred the treatment period with flurbiprofen, and this was probably related to the fewer side-effects which were reported with this drug.     

Medical treatment of acute low back pain. Diflunisal compared with indomethacin in acute lumbago

Diflunisal and indomethacin were compared in patients with acute lumbago in a double-blind prospective clinical trial. The dosage of diflunisal was 500 mg twice daily (d-group) and the dosage of indomethacin 50 mg three times daily (i-group). Out of 133 patients, 66 were in the d-group and 67 in the i-group. They were followed up for a week. In addition to the patient's own daily evaluation of pain and functional disability, control visits were performed by the investigators on days 0, 3 and 7. Both of the test drugs were effective in the dosages used. Patients' pain was decreased, functional disability was improved and patients' subjective evaluation of treatment efficacy was very similar to that of the investigators. There were no differences as to the treatment efficacy, but reports of side-effects were slightly less (p less than 0.05) in the d-group than in the i-group. If patients who had no side-effects were compared, the efficacy of diflunisal was better than indomethacin (p less than 0.05). It can be said that indomethacin was essentially as effective as diflunisal, but at the expense of an increased frequency of side-effects. In the d-group two patients (3%) and in i-group six patients (9%) discontinued the therapy because of side-effects. In acute lumbago rapid relief of pain and other harmful symptoms hastens improvement. For such indications the choice of drug therapy in general practice should be based in particular on considerations of safety and lack of potential side-effects in addition to efficacy.     

Diflunisal compared with naproxen in the treatment of osteoarthrosis of hip or knee: a double-blind trial

Summary

A randomized double-blind trial was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerance of treatment with diflunisal or naproxen. During the first 4 weeks, patients received either 250?mg diflunisal or 250?mg naproxen twice daily and this was increased by 250?mg daily in 5 patients on diflunisal and in 3 on naproxen for the second 4 weeks of the trial. The results of subjective assessments made before and at the end of Week 8 showed a trend in favour of diflunisal for improvement of symptoms, except for weight-bearing pain which was improved in only 1 patient in each group. More of the patients receiving diflunisal than naproxen considered treatment to have been satisfactory, and rated their response as equally as good as or better than previous medication. Diflunisal produced significantly fewer side-effects than naproxen, the use of which was associated with a relatively high incidence of gastro-intestinal upsets, leading to the withdrawal of 2 patients at Week 4.     

A double-blind crossover study comparing tolmetin and indomethacin in the treatment of rheumatoid arthritis

Summary

A double-blind crossover trial was carried out in 21 patients with classical or definite rheumatoid arthritis to compare the efficacy of tolmetin (1600 mgper day) with that of indomethacin (100?mg per day) and placebo. After a 1-week wash-out period on paracetamol, patients were treated for 1 week with either tolmetin or indomethacin and then for 1 week on placebo before being crossed over to the alternative drug for a final week. At the end of each treatment period, assessments were made of the severity of morning stiffness and pain, articular index, digital joint size, grip strength, andpatients assessment of well-being and treatment period preference. Tolmetin and indomethacin showed comparable efficacy, and both proved significantly superior to placebo and paracetamol in all parameters, except digital joint size and patients' well-being. One patient was withdrawn because of side-effects on both drugs, but few other side-effects were reported.     

A comparative study of flurbiprofen and indomethacin in rheumatoid arthritis

Summary

A double-blind, crossover study was carried out in 30 patients with active, classical or definite rheumatoid arthritis to compare the effect of 200?mg flurbiprofen per day with that of 100?mg indomethacin per day. Patients received, at random, each drug for a period of 2 weeks separated by a week's wash-out period on placebo. Assessments were made before the start of the trial and at weekly intervals of pain, morning stiffness, grip strength, articular index, walking time, and finger joint size. Patients' preference for any particular treatment period was recorded at the end of the trial. Laboratory investigations were carried out before and during the trial. Both drugs show statistically significant improvement over baseline assessments, although there was little difference between the two active treatment periods. More patients preferred the treatment period with flurbiprofen, and this was probably related to the fewer side-effects which were reported with this drug.     

Relationship of plasma salicylate levels to pain relief with two different salicylates.

In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250 mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects.     

The use of diflunisal in post-operative pain: a report of double-blind comparative trials in patients after meniscectomy.

A series of double-blind randomized trials was carried out in patients suffering from moderate to severe pain after meniscectomy to assess the analgesic effectiveness of diflunisal. In a single-dose study, 150 patients received either diflunisal (125 mg, 250 mg or 500 mg), aspirin (600 mg), or placebo, and hourly assessments were made of pain severity over an 8-hour period. The results showed that 500 mg diflunisal produced comparable relief to aspirin within 3 to 4 hours, but the analgesic effect continued for longer and was still very marked after 8 hours. A multi-dose study in 120 patients receiving doses of diflunisal (375 mg or 500 mg) or placebo confirmed the overall effectiveness of twice daily treatment with diflunisal. In a comparative study against oxyphenbutazone (200 mg t.i.d.), hourly pain scores made on the first post-operative day showed that a single dose of 500 mg diflunisal produced comparable relief over a 12-hour period to that with 2 doses of 200 mg oxyphenbutazone. Overall response to multiple doses was assessed as excellent or good by all the patients receiving diflunisal. Preliminary results are reported on the use of diflunisal in other painful conditions.     

The use of diflunisal in post-operative pain: a report of double-blind Comparative trials in patients after meniscectomy

Summary

A series of double-blind randomized trials was carried out in patients suffering from moderate to severe pain after meniscectomy to assess the analgesic effectiveness of diflunisal. In a single-dose study, 150 patients received either diflunisal (125?mg, 250?mg or 500?mg), aspirin (600?mg), or placebo, and hourly assessments were made of pain severity over an 8-hour period. The results showed that 500?mg diflunisal produced comparable relief to aspirin within 3 to 4 hours, but the analgesic effect continued for longer and was still very marked after 8 hours. A multi-dose study in 120 patients receiving doses of diflunisal (375?mg or 500?mg) or placebo confirmed the overall effectiveness of twice daily treatment with diflunisal. In a comparative study against oxyphenbutazone (200?mg t.i.d.), hourly pain scores made on the first postoperative day showed that a single dose of 500?mg diflunisal produced comparable relief over a 12-hour period to that with 2 doses of 200?mg oxyphenbutazone. Overall response to multiple doses was assessed as excellent or good by all the patients receiving diflunisal. Preliminary results are reported on the use of diflunisal in other painful conditions.     

Controlled-release indomethacin and sustained-release diclofenac sodium in the treatment of rheumatoid arthritis: a comparative controlled clinical trial

The efficacy and tolerability of a new, controlled-release indomethacin (75 mg) tablet was compared to that of a sustained-release diclofenac sodium (100 mg) tablet in 84 patients with rheumatoid arthritis. The study was designed as a double-blind, double-dummy crossover trial, patients being allocated at random to receive 1 active tablet and 1 placebo tablet of the alternative medication at night for 4 weeks before being crossed over to the alternative treatment for a further 4 weeks. Patient and clinical assessments on entry and at the end of each treatment period showed that pain scores for day and night, duration of morning stiffness, requirement for escape analgesia (paracetamol) and treatment preference were similar for both treatments. Both preparations also significantly improved the degree of joint tenderness compared to baseline (p less than 0.001), as measured by a modified Ritchie Articular Index. Incidence and severity of side-effects were comparable, with a significant improvement in degree of constipation reported for both treatments compared to baseline (p less than 0.05). The incidence and severity of headache was statistically significantly worse (p less than 0.05) for controlled-release indomethacin; however, there was no difference in any other parameter of tolerability. It was concluded that controlled-release indomethacin tablets (75 mg) given as a single night-time dose were as efficacious and well tolerated as sustained-release diclofenac sodium (100 mg).     

Diflunisal compared with naproxen in the treatment of osteoarthrosis of hip or knee: a double-blind trial.

A randomized double-blind trial was carried out in 20 patients with osteoarthrosis of the hip or knee to compare the efficacy and tolerance of treatment with diflunisal or naproxen. During the first 4 weeks, patients received either 250 mg diflunisal or 250 mg naproxen twice daily and this was increased by 250 mg daily in 5 patients on diflunisal and in 3 on naproxen for the second 4 weeks of the trial. The results of subjective assessments made before and at the end of Week 8 showed a trend in favour of diflunisal for improvement of symptoms, except for weight-bearing pain which was improved in only 1 patient in each group. More of the patients receiving diflunisal than naproxen considered treatment to have been satisfactory, and rated their response as equally as good as or better than previous medication. Diflunisal produced significantly high incidence of gastro-intestinal upsets, leading to the withdrawal of 2 patients at Week 4.     

Evaluation of tolmetin in the treatment of active chronic rheumatoid arthritis open and controlled double-blind studies

Summary

In a 6-week open study in 24 patients with rheumatoid arthritis, tolmetin was shown to have analgesic and anti-inflammatory activity at daily doses in excess of 1200 mg per day and produced statistically significant reductions in overall joint pain, walking time and articular index. The drug was well tolerated, but 2 patients were withdrawn because of persistent indigestion and 1 because of an urticarial type rash.

In a double-blind crossover comparison against indomethacin and placebo in 22 patients, 1400 mg tolmetin daily showed efficacy comparable with that of 150 mg indomethacin daily. Few side-effects were reported and did not necessitate any patients being withdrawn.     

Relationship of plasma salicylate levels to pain relief with two different Salicylates

Summary

In a preliminary open study of salsalate (3 g daily for 4 weeks) in 61 patients with rheumatoid arthritis or osteoarthrosis, it was found that although the drug produced satisfactory analgesia in 64% of patients, the incidence of side-effects was high (57% of patients): most were symptoms of salicylism and probably related to the high plasma salicylate levels achieved. In a second open study, 20 patients with osteoarthrosis were treated for 4 weeks with 250?mg diflunisal twice daily and then crossed over to salsalate (3 g daily) for a further 2 weeks. The results of subjective assessments of pain relief showed that both drugs produced satisfactory analgesia, and neither was associated with a significant level of gastro-intestinal bleeding. During the diflunisal treatment period there were no reports of salicylism, and plasma salicylate levels were very much lower than those measured after salsalate. The pain-relieving effects of both drugs, assessed from patient preference for one or the other treatment, were unrelated to the plasma salicylate levels and it is suggested that plasma levels may have more relationship to the incidence of side-effects than with therapeutic effects.     

Controlled-release indomethacin and sustained-release diclofenac sodium in the treatment of rheumatoid arthritis: A comparative controlled clinical trial

Summary

The efficacy and tolerability of a new, controlled-release indomethacin (7.5?mg) tablet was compared to that of a sustained-release diclofenac sodium (100?mg) tablet in 84 patients with rheumatoid arthritis. The study was designed as a double-blind, double-dummy crossover trial, patients being allocated at random to receive 1 active tablet and 1 placebo tablet of the alternative medication at night for 4 weeks before being crossed over to the alternative treatment for a further 4 weeks. Patient and clinical assessments on entry and at the end of each treatment period showed that pain scores for day and night, duration of morning stiffness, requirement for escape analgesia (paracetamol) and treatment preference were similar for both treatments. Both preparations also significantly improved the degree of joint tenderness compared to baseline (p<0.001), as measured by a modified Ritchie Articular Index. Incidence and severity of side-effects were comparable, with a significant improvement in degree of constipation reported for both treatments compared to baseline (p<0.05). The incidence and severity of headache was statistically significantly worse (p<0.05) for controlled-release indomethacin; however, there was no difference in any other parameter of tolerability. It was concluded that controlled-release indomethacin tablets (75?mg) given as a single night-time dose were as efficacious and well tolerated as sustained-release diclofenac sodium (100mg).