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, parallel trial of oxaprozin versus naproxen in the treatment of osteoarthritis

A double-blind trial was carried out in 24 patients with osteoarthritis of the knee or hip to compare the efficacy and tolerance of oxaprozin with that of naproxen. Patients were assigned at random to receive fixed doses of either 1200 mg oxaprozin once daily or 250 mg naproxen 3-times daily over a period of 8 weeks. Assessments made on entry and after 4 and 8 weeks of treatment showed that in the oxaprozin group there were significant mean decreases, indicating improvement in patient's condition, with respect to observer's opinion, patient's opinion, pain intensity and activity impairment at both on-therapy visits. In the naproxen group, there were significant mean decreases with respect to observer's opinion, patient's opinion, pain intensity and time to walk 15 metres. None of the mean differences between the groups was statistically significant. Adverse effects were reported for 3 of the 12 oxaprozin patients and 6 of the 12 naproxen patients. The specific adverse effects noted for more than 1 patient were diarrhoea for oxaprozin and dyspepsia for naproxen. No difference between the groups was statistically significant from this point of view. Laboratory determinations showed no toxicity in either group. It is concluded that once-daily oxaprozin is an effective and well-tolerated form of treatment for osteoarthritis, equivalent to naproxen given 3-times daily.     

Double-blind parallel study of meptazinol versus diflunisal in the treatment of lumbago

Summary

Seventy out-patients with acute back pain participated in a double-blind comparative trial of the clinical efficacy and tolerance of orally administered meptazinol and diflunisal. Half of the patients received 200?mg meptazinol or 250?mg diflunisal 4-times daily for up to 3 weeks, depending on the duration of pain. Patients were examined 4 times at 1-week intervals for their capability to do daily tasks, for their capacity for forward bending, thoraco-lumbar torsion, straight leg raising, static hip flexion and sit-ups, and for subjective assessment of pain. Side-effects were recorded on a questionnaire. Both treatments produced marked improvement in most of the parameters assessed, often within the first week and, overall, the results were similar with the two drugs. Few side-effects were reported and those that were recorded were slight and similar in incidence apart from nausea in 5 meptazinol-treated patients and smarting and burning on urination in 2 patients receiving diflunisal.     

A double-blind,parallel trial of oxaprozin versus naproxen in the treatment of osteoarthritis

Summary

A double-blind trial was carried out in 24 patients with osteoarthritis of the knee or hip to compare the efficacy and tolerance of oxaprozin with that of naproxen. Patients were assigned at random to receive fixed doses of either 1200?mg oxaprozin once daily or 250?mg naproxen 3-times daily over a period of 8 weeks. Assessments made on entry and after 4 and 8 weeks of treatment showed that in the oxaprozin group there were significant mean decreases, indicating improvement in patient's condition, with respect to observer's opinion, patient's opinion, pain intensity and activity impairment at both on-therapy visits. In the naproxen group, there were significant mean decreases with respect to observer's opinion, patient's opinion, pain intensity and time to walk 15 metres. None of the mean differences between the groups was statistically significant. Adverse effects were reported for 3 of the 12 oxaprozin patients and 6 of the 12 naproxen patients. The specific adverse effects noted for more than I patient were diarrhoea for oxaprozin and dyspepsia for naproxen. No difference between the groups was statistically significant from this point of view. Laboratory determinations showed no toxicity in either group. It is concluded that once-daily oxaprozin is an effective and well-tolerated form of treatment for osteoarthritis, equivalent to naproxen given 3–times daily.     

Diflunisal in general practice

Summary

A large-scale, double-blind comparative study was carried out in general practice to assess the relative efficacy and tolerance of diflunisal and aspirin in patients suffering from acute painful conditions such as sprains and strains, osteoarthritis, etc. Patients received either 250?mg or 500?mg diflunisal twice daily, or 600?mg aspirin 4-times daily for 5 days. The results of subjective assessments of pain relief from the daily records of 1902 patients (967 on diflunisal, 935 on aspirin), and the overall assessment of response by both doctors and patients, showed that diflunisal was significantly better than aspirin. Gastric side-effects were more common and more severe in patients receiving aspirin, and more often led to withdrawal of treatment.     

Clinical therapeutic trial of sodium meclofenamate and naproxen in rheumatoid arthritis, with comments on the use of placebos in clinical trials

Forty patients with active rheumatoid arthritis were entered into a single-blind study of 12-weeks' duration to compare the efficacy and tolerance of 100 mg sodium meclofenamate 3-times daily and 250 mg naproxen twice daily. Disease activity was defined by the presence of a Ritchie Articular Index score of greater than 15. Patients were assessed at 4-week intervals. Analysis of variance of the data from those patients who completed 12 weeks in the trial showed that in the sodium meclofenamate group there was a significant improvement in articular index, left grip strength, pain severity and patients' global assessment over the course of the study. In the naproxen group, there was a significant improvement in articular index, grip strength and pain severity over the study. Pairwise comparisons showed that morning stiffness improved significantly from baseline to 12 weeks only, in both treatment groups. There were no significant differences between the two treatment groups for any of the measurements at any time period during the study. In the sodium meclofenamate group, there were 4 drop-outs due to inadequate efficacy and 6 in the naproxen group. Four patients in the sodium meclofenamate group and 2 patients in the naproxen group dropped out of the study because of side-effects, primarily nausea. These results suggest that sodium meclofenamate was equally well tolerated and as effective as naproxen in the treatment of rheumatoid arthritis in this group of patients.     

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.     

Clinical therapeutic trial of sodium meclofenamate and naproxen in rheumatoid arthritis,with comments on the use of placebos in clinical trials

Summary

Forty patients with active rheumatoid arthritis were entered into a single-blind study of 12-weeks' duration to compare the efficacy and tolerance of 100?mg sodium meclofenamate 3-times daily and 250?mg naproxen twice daily. Disease activity was defined by the presence of a Ritchie Articular Index score of greater than 15. Patients were assessed at 4-week intervals. Analysis of variance of the data from those patients who completed 12 weeks in the trial showed that in the sodium meclofenamate group there was a significant improvement in articular index, left grip strength, pain severity and patients' global assessment over the course of the study. In the naproxen group, there was a significant improvement in articular index, grip strength and pain severity over the study. Pairwise comparisons showed that morning stiffness improved significantly from baseline to 12 weeks only, in both treatment groups. There were no significant differences between the two treatment groups for any of the measurements at any time period during the study. In the sodium meclofenamate group, there were 4 drop-outs due to inadequate efficacy and 6 in the naproxen group. Four patients in the sodium meclofenamate group and 2 patients in the naproxen group dropped out of the study because of side-effects, primarily nausea. These results suggest that sodium meclofenamate was equally well tolerated and as effective as naproxen in the treatment of rheumatoid arthritis in this group of patients.     

Difunisal in general practice.

A large-scale, double-blind comparative study was carried out in general practice to assess the relative efficacy and tolerance of difunisal and aspirin in patients suffering from acute painful conditions such as sprains and trains, osteoarthritis, etc. Patients received either 250 mg or 500 mg difunisal twice daily, or 600 mg aspirin 4-times daily for 5 days. The results of subjective assessments of pain relief from the daily records of 1902 patients (967 on diflunisal, 935 on aspirin), and the overall assessment of response by both doctors and patients, showed that diflunisal was significantly better than aspirin. Gastric side-effects were more common and more severe in patients receiving aspirin, and more often led to withdrawal of treatment.     

A double-blind crossover trial of diflunisal and naproxen in osteoarthritis

Fifty patients with osteoarthritis were studied in a double-blind, crossover trial of diflunisal (1000 mg daily) and naproxen (750 mg daily). In the 45 patients who completed the study, no significant difference was noted between the drugs in most of the parameters studied, including evening pain intensity and effectiveness rating by patient and investigator. There was a trend towards greater patient preference for diflunisal, although this trend did not reach statistical significance. Naproxen produced significantly fewer side-effects, although side-effects with both drugs were mild.     

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.     

Comparison of the efficacy and safety of naproxen CR and nabumetone in the treatment of patients with osteoarthritis of the knee.

OBJECTIVE: To comparre the safety and efficacy of naproxen CR (1,000 mg once daily) with that of nabumetone (1,000 mg once daily) in the treatment of patients with symptomatic knee osteoarthritis(OA). METHODS: A total of 159 Korean patients (80 in the naproxen CR group and 79 in the nabumetone group) were enrolled in this 4-week, single-blind, controlled, randomized, parallel study and an intention-to-treat model was used for data analysis. Six efficacy parameters were measured: Lequesne index, visual analogue pain scale at rest and atactivity, patient's and physician's global assessment, and time to walk 50 feet. RESULTS: Significant improvement in all efficacy parameters except time to walk 50 feet occurred at Week 2 and Week 4 in both groups. Themean improvement from baseline at Week 2 and Week 4 for the efficacy variables was not different between naproxen CR and nabumetone group. Twenty-four patients (30%) in the naproxen CR group and 18 patients (22.8%) in the nabumetone group withdrew from the study. Among them, only 1patient in the naproxen CR group terminated the study prematurely due to an adverse event of dyspepsia. No statistically significant difference in the frequency of adverse events, including gastrointestinal symptoms, was observed between these 2 groups during the treatment period. Significant laboratory abnormalities also did not occur during the study period in both groups. CONCLUSIONS: Naproxen CR is an effective and tolerable drug in the treatment of knee OA. Efficacy and safety profiles are comparable to those of nabumetone.     

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.     

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

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 diflunisal 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.     

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.     

High-performance liquid chromatographic analysis of diflunisal in plasma and urine: application to pharmacokinetic studies in two normal volunteers

A high-performance liquid chromatographic (HPLC) assay with fluorescence detection has been developed for the determination of diflunisal in plasma and urine. The plasma or urine, containing naproxen as the internal standard, was extracted with ether-hexane (1:1). The samples were analyzed on a microparticulate column, and the compounds were eluted using a mobile phase of 0.05 M phosphate buffer (pH 3) and methanol. Plasma samples were analyzed from two healthy male subjects who received a 250- and 750-mg oral dose of diflunisal 3 weeks apart. The data were analyzed according to a two-compartment open model. There was a disproportionate increase in the area under the plasma concentration-time curves (AUC 750 mg/AUC 250 mg was 3.84 for subject A and 4.22 for subject B) and a reduction in plasma clearance after the 750-mg dose of diflunisal. These data suggest that the kinetics of diflunisal may be dose dependent.     

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.     

Diclofenac sodium: a review of its pharmacological properties and therapeutic use in rheumatic diseases and pain of varying origin

Diclofenac sodium, a phenylacetic acid derivative, is a non-steroidal, anti-inflammatory, analgesic agent advocated for use in rheumatoid arthritis, degenerative joint disease, ankylosing spondylitis and allied conditions, and in the treatment of pain resulting from minor surgery, trauma and dysmenorrhoea. Published data indicate that diclofenac 75 to 150mg daily (25 to 50mg 3 times daily) is comparable in efficacy with ordinary aspirin 3 to 5g daily and indomethacin 75 to 150mg daily in rheumatoid arthritis and with indomethacin in osteoarthritis. Available data suggest that in patients with osteoarthritis diclofenac sodium is comparable in efficacy and tolerability with naproxen, ibuprofen, sulindac and diflunisal. As oral diclofenac is generally given in 3 divided daily doses it may be at a disadvantage relative to less frequent administration with naproxen, diflunisal and sulindac in rheumatoid arthritis, although there is some evidence of diclofenac's efficacy when administered twice daily, or once daily as a slow release tablet. The drug is also available as suppositories and ampoules for intramuscular injection. No one of the non-steroidal anti-inflammatory agents is the most suitable drug for all patients requiring such therapy, and diclofenac should be considered along with other drugs of its type in the arthritic patient.     

The efficacy and tolerability of enteric and non-enteric coated naproxen tablets: a double-blind study in patients with osteoarthritis.

A double-blind, crossover study was undertaken to compare the efficacy and tolerability of a novel enteric coated 500 mg naproxen tablet with normal release 500 mg naproxen in patients with osteoarthritis. Eighty-eight patients were randomly allocated to receive enteric coated naproxen as a single daily dose of 2 tablets at night or 1 normal release naproxen tablet twice daily for a period of 3 weeks, followed by the alternative treatment for a further period of 3 weeks. The results of patient and doctor assessments showed that both treatments were increasingly efficacious, with a significant period effect found in the measures for pain on passive movement and duration of morning stiffness. No significant treatment differences were seen in any of the measures of efficacy and tolerability, although there were more withdrawals on normal release than on enteric coated naproxen (p = 0.07). It was concluded that enteric coated naproxen given as a single 1 g dose at night and normal release 500 mg naproxen given twice daily are equally efficacious and well tolerated.