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.     

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.     

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.     

A controlled comparison of dipyrone and paracetamol in post-episiotomy pain

Summary

A double-blind, placebo-controlled trial was carried out in 299 patients suffering from post-episiotomy pain to compare the analgesic effectiveness and tolerance of single doses of 500?mg dipyrone and 500?mg paracetamol. Assessments of pain relief over a 6-hour period showed that dipyrone produced significantly better results than placebo within half an hour of intake mid maintained this superiority throughout the 6 hours. It also afforded consistently better pain relief than paracetamol and was significantly more effective at the 6-hour assessment. Side-effects were few and mild.     

Analgesic effect of fendosal, ibuprofen and aspirin in postoperative oral surgery pain

The analgesic efficacy of a single 200-mg dose of fendosal, a nonnarcotic, nonsteroidal antiinflammatory analgesic, was compared, in a double-blind study, with aspirin 650 mg, ibuprofen 400 mg and placebo in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Using a self-rating record, patients rated their pain and its relief hourly for up to 12 hours after medicating. Each active medication was significantly superior to placebo. The peak analgesic effect of fendosal 200 mg was similar to that of the aspirin 650-mg standard. Although fendosal's onset of action was slow (3 hours), its effect persisted for 8 hours, substantially longer than that of aspirin. Ibuprofen 400 mg was statistically significantly superior to aspirin 650 mg and fendosal 200 mg for most measures of peak and total analgesia, and its effect persisted for 8 hours. The results of this study raise some questions concerning the comparability of data from studies that employ different criteria for remedication and/or different criteria for the inclusion of data in the analyses of efficacy.     

Diflunisal in the management of sprains.

A double-blind randomized trial was carried out in 31 patients suffering from acute, minor ligamentous injuries to compare the efficacy of diflunisal in the relief of pain with that of oxyphenbutazone. Patients received either 500 mg diflunisal twice daily or 200 mg oxyphenbutazone 3-times daily for 3 days. The results of subjective assessments showed tha by Day 3 spontaneous pain had either completely resolved or markedly improved in all patients, and that diflunisal was significantly better than oxyphenbutazone on Days 1 and 3 in relieving pain on movement of the joint.     

Diflunisal in the management of sprains

Summary

A double-blind randomized trial was carried out in 31 patients suffering from acute, minor ligamentous injuries to compare the efficacy of diflunisal in the relief of pain with that of oxyphenbutazone. Patients received either 500?mg diflunisal twice daily or 200?mg oxyphenbutazone 3-times daily for 3 days. The results of subjective assessments showed that by Day 3 spontaneous pain had either completely resolved or markedly improved in all patients, and that diflunisal was significantly better than oxyphenbutazone on Days 1 and 3 in relieving pain on movement of the joint.     

Analgesic efficacy of low-dose ibuprofen in dental extraction pain

A single-dose, double-blind, randomized, parallel trial was conducted to compare the analgesic efficacy of oral ibuprofen (I) 100, 200, or 400 mg, aspirin (ASA) 650 mg, and placebo in moderate to severe pain after extraction of impacted teeth. Subjective, self-evaluated pain intensity and pain relief reports, hourly for 6 hours, were used as indexes of analgesic response. Data on 227 evaluable patients showed significant differences among the 4 active treatments and placebo (p less than 0.001) by most measurements of analgesia. Although no consistent, significant differences were observed among the active drugs, I 400 mg performed the best, followed by I 200 mg, ASA 650 mg, and I 100 mg. Remedication was required by 59% patients receiving I 400 mg, 67% taking I 200 mg, 73% taking ASA 650 mg, 74% taking I 100 mg, and 96% receiving placebo. Differences between I 400 mg and I 100 mg were significant for remedication data (p less than 0.05). Side effects were minor, infrequent, and not dose related. In this study, I 100 mg was distinctly superior to placebo and probably as effective as ASA 650 mg in relieving pain. Only a shallow dose response of ibuprofen was observed.     

A single-dose study of the efficacy and safety of FS 205-397 (250 mg or 500 mg) versus aspirin and placebo in the treatment of postsurgery dental pain

The efficacy and safety of two dose levels of FS 205-397 (either 250 or 500 mg) were compared with the efficacy and safety of aspirin 650 mg and placebo in a 6-hour, single-dose, double-blind study in 161 patients who had undergone extraction of third molars. Each of the doses of FS 205-397, as well as aspirin, produced analgesia. However, the analgesic effects of both the 500 mg dose of FS 205-397 and aspirin were at times significantly better and more prolonged than those produced by the lower dose of FS 205-397. On the other hand, both doses of FS 205-397 had a significantly faster onset of action than aspirin. Side effects, reported by 17% of the 161 patients, did not differ significantly among the four treatment groups with respect to frequency, type, or severity. The most commonly reported side effects were nausea (7%) and drowsiness (6%). The results indicated that FS 205-397, administered in single doses of either 500 or 250 mg, is a safe and effective analgesic for the relief of pain following dental surgery, and may offer particular advantages in terms of onset of effects.     

The effects of fendosal, aspirin and placebo on postoperative dental pain. A dose-ranging and efficacy study

The purpose of this study was to characterize the analgesic dose-effect curve of orally administered fendosal, relative to aspirin 650 mg and placebo. A total of 153 patients experiencing moderate to severe pain due to extraction of impacted molar teeth completed this two-part, single-dose, double-blind, randomized trial. In part I, the possible treatments were placebo, aspirin 650 mg, fendosal 100 mg and fendosal 200 mg. In part II, fendosal 400 mg replaced the fendosal 100 mg treatment. A nurse-observer collected subjective reports of pain intensity and relief at 30 minutes and hourly for eight hours. Fendosal 100 mg was not an analgesic dose but 200 and 400 mg were on the ascending portion of the dose-effect curve. Fendosal 200 mg was superior to placebo and about equal to aspirin in total effect but not peak effect. Fendosal 400 mg was statistically superior to both fendosal 200 mg and placebo. Fendosal 400 mg appears to provide analgesia similar to that of aspirin 650 mg but with a substantially longer duration. Only a few mild side effects were reported.     

The relative analgesic efficacy of propiram fumarate, codeine, aspirin, and placebo in post-impaction dental pain

To evaluate the analgesic efficacy of orally administered 50 mg propiram fumarate, 650 mg aspirin, 60 mg codeine phosphate, and placebo in acute post-impaction dental pain, 159 patients with moderate or severe pain were randomly allocated to the four treatments in this single-dose double-blind, stratified, parallel-group study. A research nurse questioned the patients at 1/2 hour and hourly for 6 hours after medicating. A standard format was used to question subjects about their pain intensity and relief from the starting pain. Propiram, 50 mg, produced a level of analgesia approaching that of 650 mg aspirin in peak effect, total effect, and duration of action and was statistically superior to 60 mg codeine and placebo for every measure of analgesic efficacy. Several mild adverse effects were observed; however, they appeared to be evenly distributed among the active treatments.     

Analgesic effect of naproxen sodium, codeine, a naproxen-codeine combination and aspirin on the postoperative pain of oral surgery

In a double-blind study, 198 outpatients with pain after oral surgery were randomly assigned to treatment with a single oral dose of naproxen sodium 550 mg, codeine sulfate 60 mg, a combination of naproxen sodium 550 mg with codeine sulfate 60 mg, aspirin 650 mg or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Orthogonal contrasts for the four treatments making up the factorial component showed that the naproxen effect was significant for every measurement of total and peak analgesia; the codeine effect was significant for total and peak pain relief and patients' overall evaluation. The naproxen-codeine interaction was not statistically significant for any measure, which suggests that the analgesic effect of the combination represents the additive effect of its constituents. Based on pairwise comparisons, aspirin was significantly superior to placebo for most measures of effect, naproxen was significantly superior to both aspirin and codeine for all measures and the combination was significantly superior to naproxen for patients' overall evaluation. No more patients experienced adverse effects with aspirin or naproxen than with placebo, but significantly more patients receiving the codeine-containing treatments experienced adverse effects than those receiving aspirin and naproxen.     

An evaluation of flurbiprofen, aspirin, and placebo in postoperative oral surgery pain

One hundred sixty-four outpatients with postoperative pain after the removal of impacted third molars were randomly assigned on a double-blind basis, to receive oral doses of flurbiprofen 25, 50, or 100 mg; aspirin 600 mg; or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 8 hours after medicating. Estimates of sum of pain differences (SPID), peak pain intensity difference (PID), total relief, peak relief, and hours of 50% relief were derived from these subjective reports. All active medications were significantly superior to placebo. Analgesia was similar for flurbiprofen 25 mg and aspirin 600 mg. Flurbiprofen 50 and 100 mg were significantly superior to aspirin for every measure of analgesia except peak PID. There was a significant dose-response regression between flurbiprofen 25 mg and both of the higher dosages. Flurbiprofen 50 and 100 mg did not differ significantly, suggesting a plateau in flurbiprofen's analgesia. The analgesic effect of flurbiprofen was significant by hour 1 and persisted for 8 hours. The frequency of adverse effects was similar for the active medications.     

A comparative oral analgesic study of indoprofen, aspirin, and placebo in postpartum pain

The purpose of this study was to evaluate the analgesic efficacy and adverse effect liability of single oral doses of indoprofen, 50 mg, 100 mg, and 200 mg, compared with aspirin, 300 mg and 600 mg, and placebo in the relief of moderate to severe postpartum pain. Two hundred-ten patients entered a randomized, double-blind, parallel group study and were evaluated over a six-hour period by a single nurse-observer. There was a significant imbalance in the distribution of pain types across treatments that compromises the interpretation of the results. In addition to analyzing the data from all patients, the subsets with episiotomy/cesarean section pain and uterine cramp pain were examined separately. The latter group had too few patients to permit distinction between drugs. The 100 mg and 200 mg doses of indoprofen were significantly (P less than or equal to .05) more effective than placebo for many variables including the following summary values: sum of pain intensity difference (SPID), sum of hourly relief values (TOTPAR), and % SPID for all patients as well as in the subset of patients with episiotomy/cesarean section pain. Aspirin, 600 mg, was also significantly more effective than placebo for many of the same measures of analgesia in the episiotomy/cesarean section subset. Pairwise differences were also seen between placebo and aspirin, 300 mg, but on fewer variables. Indoprofen, 100 mg, was significantly more effective than aspirin, 600 mg, at hour 6 for pain intensity difference (PID) in the episiotomy/cesarean section subset. The effect of indoprofen appeared to plateau above 100 mg.(ABSTRACT TRUNCATED AT 250 WORDS)     

Onset and duration of analgesia for low-dose ketoprofen in the treatment of postoperative dental pain

The objective of this single dose, double-blind study was to determine the relative analgesic efficacy of low-dose ketoprofen (6.25 mg, 12.5 mg, and 25 mg) compared with ibuprofen (200 mg) and placebo in 175 patients with moderate to severe postoperative pain secondary to extraction of impacted third molars. Analgesia was measured during the 6-hour period after administration based on onset of relief, hourly and summary variables, and duration of treatment effect. All active treatments were significantly more effective than placebo for many hourly measures and for the summary measures sum of pain intensity differences (SPID), sum of hourly pain relief values (TOTPAR), time to peak pain relief, and patient global assessment of study medication. The three ketoprofen doses were significantly more effective than placebo beginning at 30 minutes, whereas ibuprofen was significantly better than placebo beginning at 1 hour. A dose-response relationship was observed for ketoprofen, with the two higher doses providing significantly greater analgesia than the lower dose. However, a plateau effect was seen between the 12.5-mg and 25-mg dose levels. A significantly greater proportion of patients treated with each of the active treatments (ranging from 0.83 to 0.88) reported onset of relief compared with placebo (0.20). The distribution functions of onset of relief differed significantly among treatments, with ketoprofen 12.5 mg and 25 mg having a faster onset than ibuprofen 200 mg and ketoprofen 6.25 mg. The duration of effect was generally shorter for ketoprofen than for ibuprofen, and these difference were significant. This study provides evidence that at the dose levels of 12.5 mg and 25 mg, ketoprofen is an effective analgesic in providing relief of postoperative dental pain. Ketoprofen 12.5 mg and 25 mg provide significantly greater relief in the earlier time period, with a faster onset and shorter duration of effect than ibuprofen 200 mg. The two higher doses of ketoprofen provided similar analgesia, and no additional benefit was obtained by increasing the dose of ketoprofen to 25 mg. Therefore, we conclude that ketoprofen 12.5 mg is an appropriate dose for over-the-counter use.     

Analgesic effect of ciramadol in patients with chronic pain

Summary

A double-blind, crossover study was carried out in 15 patients with chronic pain due to cancer to assess the effectiveness of two different doses of a new analgesic, ciramadol, compared with placebo. Patients received single oral doses of the three medications, in random order, on successive days. Assessments of pain intensity and relief were made on a 4-point rating scale at hourly intervals for 4 hours after the dose. The results showed that ciramadol produced significantly more pain relief than did placebo and this analgesic effect increased with the dose administered. Peak activity was observed at about 2 hours, and pain relief was still marked at 4 hours. No side-effects were reported.     

Analgesic effect of graded doses of flurbiprofen in post-episiotomy pain

Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25, 50 and 100 mg, aspirin 600 mg, and placebo in the relief of moderate to severe post-episiotomy pain. One hundred and fifty-two evaluable patients completed a randomized, double-blind, stratified, parallel groups study. They were observed over a six hour period by one nurse-observer. Based upon each of the summary efficacy measures SPID, TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief, each of the four active treatments were statistically superior to placebo. Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg, but the differences were not statistically significant. Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg. There were no observed or reported adverse effects.     

Comparison of etodolac, aspirin and placebo for pain after oral surgery

Single oral doses of etodolac 50, 100 and 200 mg were compared with aspirin 650 mg and placebo in a double-blind, parallel group study of 189 outpatients reporting moderate or severe pain after oral surgery. Overall efficacy of test drugs was evaluated by sum of pain intensity difference (SPID) scores and total pain relief (TOTPAR) scores over 0.5-3, 0.5-6, 0.5-8 and 0.5-12 hours. Etodolac 200 mg provided significantly greater analgesia than aspirin by these measurements over all SPID and all but one TOTPAR interval, and was significantly more effective than placebo over all intervals. Etodolac 100 mg was superior to aspirin for SPID 0.5-8 and 0.5-12 hours, and superior to placebo for both SPID and TOTPAR over all time intervals. Onset of analgesia for etodolac 100 mg, 200 mg and aspirin was 1 hour or less for the majority of patients in each group; 42% receiving etodolac 200 mg reported onset of analgesia within 0.5 hour. Duration of analgesia for etodolac 200 mg appeared twice that of aspirin. A significant positive dose-response relationship was obtained for the three doses of etodolac. A low frequency of side effects was observed in all treatment groups.     

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.     

A 12-hour Evaluation of the Analgesic Efficacy of Diflunisal,Propoxyphene, A Propoxyphene-Acetaminophen Combination,and Placebo in Postoperative Oral Surgery Pain

One-hundred thirty-two outpatients with pain following oral surgery were randomly assigned, on a double-blind basis, to a single oral dose of diflunisal 500 or 1000 mg, propoxyphene napsylate 100 mg, a combination of propoxyphene napsylate 100 mg with acetaminophen 650 mg, or placebo. Using a self-rating record, subjects rated their pain and its relief hourly for 12 hours after medication. Measures of total and peak analgesia were derived from the patient's subjective reports. Diflunisal 500 and 1000 mg were significantly superior to placebo and propoxyphene alone for every measure of total and peak analgesia, and the effect of diflunisal persisted for 12 hours. Diflunisal 1000 mg was significantly superior to the propoxyphene-acetaminophen combination for all measures of analgesia. Although the propoxyphene-acetaminophen combination was significantly superior to placebo for most measures of analgesia, propoxyphene alone was significantly superior for only two measures. Adverse effects attributed to all drugs were mild and transitory.