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Diflunisal, a new analgesic/anti-inflammatory monosubstance, has been compared with naproxen in a double-blind study in patients with rheumatoid arthritis. In doses of 1 g diflunisal daily and 750 mg naproxen daily both therapies resulted in significant improvements in subjective and objective parameters measured - day and night pain, morning stiffness, Ritchie index, grip strength, and doctor and patient assessment of overall effect. Side effects were uncommon and of little significance in the diflunisal-treated patients, whereas two patients in the naproxen group were dropped from the study because of clinically significant drug-related side effects. It is concluded that diflunisal should be a very useful addition to the therapies currently available.

One hundred and twelve patients with acute mechanical low back pain were randomly divided into three treatment groups. All patients received ergonomic advice and then either a non-steroidal anti-inflammatory drug or conservative or manipulative types of physiotherapy. Serial assessments of pain and spinal mobility showed similar response rates in all three treatment groups and no significant difference between therapies. The overall improvement ratings, time off work, and economic cost favoured the group treated with the nonsteroidal anti-inflammatory drug, but this group had a better range of spinal flexion at the onset so firm conclusions regarding the preferred management of these patients in general practice cannot be drawn. Treatment failures occurred in all groups highlighting the need for a variety of therapeutic approaches in managing the patient with low back pain.

Fifty college athletes with acute sprains and strains from football-related activities were randomly assigned to treatment with either diflunisal or acetaminophen with codeine for seven days. Additional treatment in both groups included rest, elevation, local application of cold or heat, splinting, and physical therapy, as indicated. Both treatment groups exhibited clinically significant improvements in pain, tenderness, and swelling. The results of this study show that diflunisal, a peripherally acting nonnarcotic nonsteroidal anti-inflammatory agent with analgesic properties, was as effective as acetaminophen with codeine in relieving mild to moderate pain due to musculo-skeletal sprains and strains. The long duration of action of diflunisal permits less frequent dosing, an important consideration when prescribing medication for active young adults.

A clinical study to evaluate the analgesic efficacy of carprofen was conducted at the University of Colorado School of Dentistry. In a 6-month period, 248 patients underwent the surgical removal of wisdom teeth for analysis of postoperative pain relief.

In comprehensive clinical studies, diflunisal--a new nonsteroidal antiinflammatory drug with a long duration of action--was shown to be highly effective and generally well tolerated in the short- and long-term treatment of the pain of osteoarthritis. In double-blind comparison studies, diflunisal was comparable in efficacy to aspirin and better tolerated. In a separate study with ibuprofen, 800 to 1,200 mg daily (manufacturer's present recommended dose, 900 to 2,400 mg daily), diflunisal, 500 to 750 mg daily, was more effective and comparable in tolerability. Diflunisal had a longer duration of action, requiring only twice-a-day dosage.

The efficacy and tolerability of diflunisal (500 mg orally, twice daily) and piroxicam (20 mg orally, once daily) were compared in a 12-week open-label study in 44 patients with active rheumatoid arthritis. Both medications were equally effective and generally well tolerated. No significant differences were found between drug groups. Both groups showed statistically significant improvement in the overall number of swollen and tender joints, painful joint count, and the patients' assessment of pain and disease severity. Two (9%) of 23 patients in the diflunisal group and one (5%) of 21 patients in the piroxicam group reported adverse effects. Only one patient withdrew from the study because of side effects (lightheadedness during use of diflunisal). It is concluded that both diflunisal and piroxicam are highly effective and generally well tolerated in the management of rheumatoid arthritis.

The pharmacologic properties, clinical efficacy and tolerability of the newer non-steroidal anti-rheumatic drugs are compared. Guidelines for a prescribing policy are given in which a safety-first approach is adopted. Propionic acid derivatives or newer drugs with similar properties are proposed as initial therapy to control symptoms of rheumatoid arthritis or osteoarthrosis. Special problems such as compliance in chronic disease, treatment of ulcer patients with anti-rheumatic drugs, therapy in the elderly, treatment for juvenile rheumatoid arthritis and treatment during pregnancy are considered.

A double-blind randomised cross-over study to compare 2 regimes of paracetamol and diflunisal for postoperative pain relief following 3rd molar surgery was designed. 35 patients received one of the regimes at one visit and the alternative at the other visit. Both drugs, namely a single dose of 500 mg of diflunisal given preoperatively or 2 doses of 1000 mg of paracetamol, given preoperatively and 4 h postoperatively, produced adequate pain relief, without the need for supplementary analgesics during the 10-h test period. The differences in the mean overall pain scores in the 2 regimes were not statistically significant.

Diflunisal (500 mg orally, twice daily) and naproxen (375 mg orally, twice daily) were compared for efficacy and tolerability in a 12-week open-label study in 33 patients with active rheumatoid arthritis (RA). Both drugs resulted in marked reduction in the number of swollen, tender, and painful joints and comparable improvement in patients' assessment of disease activity and pain. There were no significant differences between the two medications in the measured indices of disease activity. No adverse experiences were reported by patients in either treatment group. The results indicate that both diflunisal and naproxen were equally effective and that both agents are generally well tolerated in this group of patients with RA.

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.

The authors favor conservative treatment of tennis elbow, starting with cessation of the offending activity and prescription of a nonsteroidal anti-inflammatory drug (NSAID) and followed by isometric and isotonic exercises when pain and inflammation have subsided. Two NSAIDs, diflunisal and naproxen, were evaluated in 38 patients with mild-to-moderate pain associated with tennis elbow. The physicians' assessments found no statistically significant differences between the two drugs; both provided effective reduction of pain and swelling. Patients' assessments of pain relief achieved with their respective drugs significantly (P = 0.019) favored diflunisal. Prompt and effective relief of pain and swelling hastens the patient's progression to physical therapy and return to normal activities.

20 patients with elevated serum uric acid levels and osteoarthritis of the hip or knee were given diflunisal 500 mg b.i.d. The joint complaints were influenced good to excellent in all patients. The uric acid levels were decreased from 7.37 to 6.22 mg/dl for the duration of this eight week open study. Diflunisal can be advocated also for the treatment of gout.

The antipyretic efficacy of diflunisal was assessed in rats made febrile by yeast and in rabbits made febrile by bacterial endotoxin. Diflunisal was a more potent antipyretic than aspirin in rats, reducing a maximum fever in doses not producing overt toxic effects. In contrast, submaximal fever in rabbits was not reduced by diflunisal. Fatal hyperthermia of rapid onset was observed in rats and rabbits receiving high doses of diflunisal after administration of microbial pyrogen but not in control animals. These data indicate the toxicity of diflunisal may be potentiated by the presence of pyrogens. It is concluded that the apparent antipyretic efficacy of a drug can depend on the species-pyrogen combination used to screen for antipyresis.

Two-hundred and one outpatients with postoperative pain following oral surgery were randomly assigned, on a double-blind basis, a single oral dose of diflunisal (250, 500, or 1000 mg), aspirin (650 mg), or placebo. Using a self-rating record, the subjects rated their pain and its relief hourly for 12 hours after medication. Measures of peak and total analgesia were derived from the patients' subjective reports. Diflunisal 250 and 1000 mg were significantly superior to aspirin for every measure of total and peak analgesia; the 500-mg diflunisal dose was significantly superior to aspirin for measures of total analgesia only. All doses of diflunisal were significantly superior to aspirin and placebo at each hour from hour 3 through hour 12. Approximately 60 per cent of the patients treated with diflunisal completed the 12-hour observation period without the need for additional analgesic therapy. Adverse effects were mild and transitory and occurred in less than 10 per cent of the patients.

155 patients undergoing surgical removal of lower third molars took part in a parallel group, randomised double-blind study to assess the analgesic effect of single pre-operative doses of ibuprofen (400 mg), codeine phosphate (30 mg), a combination of ibuprofen/codeine (400 mg/30 mg), placebo and post-operative single doses of the same combination or diflunisal (250 mg). Patients receiving the combination or ibuprofen pre-operatively took significantly longer between surgery completion and needing the post-operative study treatment than patients receiving codeine phosphate or placebo. At 1 1/2-2 h after post-operative administration, patients receiving the combination post-operatively reported significantly greater decreases in pain severity than those receiving diflunisal. Patients taking the combination post-operatively experienced significantly better pain relief than patients taking diflunisal at 1 and 2 h, but the reverse was true at 5 h. Side-effects reported were mild with no significant differences between the different treatment groups.

Diflunisal, a nonacetylated salicylate preparation with a prolonged duration of action, was compared with ibuprofen for the treatment of rheumatoid arthritis in a multicenter trial comprising 210 patients. Diflunisal was administered twice a day (500 to 750 mg/day) and ibuprofen was administered four times a day (1,600 to 2,400 mg/day). To maintain double-blind conditions, all patients ostensibly followed the same regimen, ingesting their assigned drug and a matching placebo of their nonassigned drug. Disease activity assessments and laboratory tests were done periodically throughout the 12 weeks of the study, and results were compared with pretreatment findings. Efficacy evaluations in 187 patients showed that both treatments were similarly efficacious. Safety and tolerability also were similar in the two groups. Diflunisal, however, offers a more acceptable BID treatment schedule.

A double-blind study of 43 patients undergoing excision of haemorrhoids under spinal anaesthesia was carried out to compare the analgesic effects of diflunisal (DFL, 21 patients) and dextropropoxyphene napsylate (DPN, 22 patients) on post-operative pain. Eleven patients (25%) reported no significant pain during the study indicating that they had needed no analgesic medication (4 in the DFL group and 7 in the DPN group). Thus 17 patients in the DFL group and 15 patients in the DPN group contributed to the analysis data. Seven patients in the DFL group and 9 patients in the DPN group needed additional analgesic therapy on the day of surgery. After the day of surgery the analgesic effect of both of the test medications was sufficient but DFL proved to provide slightly better pain relief than DPN. Two patients in each study group had mild adverse reactions including vomiting and epigastric pain, which were probably drug related. It is concluded that both DFL and DPN are safe and sufficiently effective treatments for pain after haemorrhoidectomy but not until one day after surgery.

Sixteen hyperuricemic gouty patients were treated with diflunisal, a novel salicylate, 500 mg BID. Serum and urine uric acid along with uric acid clearances were studied before and after a 7-day treatment. A clear hypouricemic action was observed, but 2 different mechanisms of action were seen when overexcretor patients and normoexcretor patients were analyzed separately. In overexcretors an allopurinol-like action was evident, whereas in normoexcretors a uricosuric action occurred. In vitro experiments showed a competitive inhibition of xanthine-oxidase exerted by diflunisal at low concentrations.

A double-blind, completely randomized study was carried out on 169 patients to compare the analgesic efficacy and tolerability of diflunisal with that of Veralgin after surgical removal of impacted third molars. One group received 1000 mg diflunisal (Donobid, MSD) 2 h preoperatively and then 500 mg twice daily for 2.5 days, and the other group Veralgin (aminophenazon. 286 mg, barbital. 114 mg, aethylmorph. hydrochlorid. 20 mg, Orion), a fixed combination widely used in Finland, 1 tablet twice daily beginning 2 h prior to operation. Visual analogue scales were used to estimate pain. Diflunisal was found to be superior in relieving pain in the early postoperative period, the associated frequency of adverse clinical experiences was lower and the final evaluation of analgesic efficacy by both the patients and the investigators, was in its favour. The study confirms that postoperative pain after third molar surgery can be controlled well without the use of mainly centrally acting combination analgesics.

Sixty-two patients with osteoarthrosis entered a 10-week double-blind cross-over trial of diflunisal and naproxen. Eight patients withdrew for drug-related reason, and seven for other reasons. There was no statistically significant difference in parameters of disease activity on each treatment period, but naproxen produced fewer withdrawals due to drug-related side-effects.

The emergency physician treats many patients with mild to moderate pain due to musculoskeletal injury. The physician must consider the extent of injury, the patient's medication history, and the potential for abuse when prescribing an oral analgesic. A study was designed to compare the efficacy of two oral analgesics, one containing a narcotic and one nonnarcotic, in relieving mild to moderate pain associated with grade 2 ankle sprain. Forty patients were enrolled--all with moderate pain--and were randomly allocated to treatment with either diflunisal or acetaminophen with codeine. Both analgesic agents were equally effective in relieving the pain. Side effects were experienced by six patients, all of whom were receiving acetaminophen with codeine; none of the patients given diflunisal noted side effects. Global assessments of the efficacy and tolerability of the study drugs showed that 89% of 19 patients given diflunisal and 43% of 21 patients given acetaminophen with codeine considered their respective analgesics excellent or very good.

Despite a wide range of study designs, a multiplicity of international trials of diclofenac in osteoarthritis have disclosed similar results. These include double-blind comparisons with indomethacin, aspirin, naproxen, ibuprofen, sulindac, and diflunisal, as well as open trials from European field studies. The results of this review document that diclofenac is as effective as other nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis.

In a clinical study the blood levels of dehydroepiandrosterone sulphate (DHEAS), pregnenolone sulphate (5-PS), testosterone sulphate (TS) and their respective unconjugated steroids were measured in: 20 patients with systemic lupus erythematosus (SLE) who were receiving either no treatment (11 patients) or else treatment with chloroquine (9 patients), in some cases combined with non-steroidal anti-inflammatory drugs (NSAIDs); in 26 patients receiving corticosteroid (Prednisolone) treatment; and in healthy men and women. The patients not on corticosteroid exhibited substantially reduced DHEAS, 5-PS and TS levels (geom. mean: 2300 vs. normal 4300 nmol/l DHEAS; 200 vs. 320 nmol/l 5-PS; and 120 vs. 360 nmol/l TS; p less than 0.001), irrespective of the difference in sex, age or chloroquine treatment. The patients on corticosteroid treatment displayed a similar pattern of levels, but the reduction was much more marked than in the patients not on the steroid (geom. mean: 610 nmol/l DHEAS, 55 nmol/l 5-PS; and 35 nmol/l TS; p less than 0.001). No consistent changes were observed in the unconjugated steroid levels, although they were also reduced by the treatment with prednisolone. The data indicate that a deficiency in sulpho-conjugated steroids is a permanent feature of patients with SLE and that this is accentuated by the administration of corticosteroid derivatives. Further studies are needed to establish the pathophysiological significance of these findings.

We conducted an open-label randomized clinical trial comparing the efficacy and tolerability of diflunisal and dextropropoxyphene napsylate with acetaminophen (DPN-A) in the management of mild to moderate pain following arthroscopic surgery of the knee. Patients used a self-rating pain scale to evaluate the analgesia provided by each medication. Twenty-six patients completed the study; 12 received diflunisal and 14 received DPN-A. The physicians found no significant differences between the two groups in their preoperative or postoperative assessment of pain, tenderness, swelling, and active range of motion. There were no statistically significant differences between the two groups' mean pain scores or assessment of the overall efficacy of their respective drugs. No patient in either treatment group reported any adverse effects.

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.

Ninety patients with active rheumatoid arthritis took part in a cross-over trial comparing diclofenac sodium, diflunisal and naproxen. The efficacy of the three drugs was similar though there were trends in favour of diclofenac sodium in some measurements. The incidence of side-effects was similar with the three drugs and each was chosen by a significant group of patients as continuation therapy at the end of the study.

In a single-dose, double-blind randomized study, the analgesic efficacy of suprofen 200, suprofen (alpha-methyl-4-(2-thienylcarbonyl)-benzene acetic acid; Suprol) 400 mg and diflunisal 750 mg capsules was determined in comparison to placebo capsules. A total of 130 patients participated in the study, all of them requiring analgesic treatment on the first post-operative day following meniscectomy. The treatment groups were homogeneous with respect to their demographic data. With the chosen pain model all active test substances were statistically significantly superior to placebo as far as pain intensity differences (SPID), pain relief (TOTPAR) and global evaluation of efficacy were concerned. Despite great differences in dosage and half-life, the active test substances must be regarded as equipment. Side effects were reported by 2 patients each in the diflunisal 750 mg and the placebo group, and by 1 patient treated with suprofen 200 mg.

A randomized, double-blind trial was carried out in 47 hospital out-patients, with classical rheumatoid arthritis, to compare the efficacy and tolerance of diflunisal with that of naproxen. After an initial one week washout period the patients received diflunisal 1000 mg daily or naproxen 750 mg daily using a double placebo, crossover method. Each drug was administered for a three week period separated by a one week between treatment washout. With both drugs there was an improvement in objective and subjective assessments of response indicating that they each had an effective anti-inflammatory action. Diflunisal produced a significantly greater improvement in evening pain (p = 0.03), morning stiffness (p = 0.01) and the average total grip strength (p = 0.05). Nearly 60% of patients preferred diflunisal to naproxen but this was not of statistical significance. Frequency and severity of side-effects were similar. The similarity of diflunisal to aspirin in urate lowering is commented upon.

16 healthy patients requiring removal of bilateral symmetrically-impacted mandibular third molars participated in a double-blind randomised crossover trial to test the effectiveness of postoperative pain control using a long-acting anti-inflammatory agent (diflunisal) in combination with a long-acting local anaesthetic agent (bupivacaine). Results were compared to the more traditional method of using an oral analgesic with shorter duration of action (paracetamol with codeine) with lignocaine as the local anaesthetic. Using a visual analogue pain scale, patients reported that significantly reduced pain was experienced over the first 4 days postoperatively with the diflunisal/bupivacaine treatment and patient preference for this treatment was highly significant. This report represents the first such study of diflunisal used for an extended course in oral surgery with pain assessment over the same period. No significant side-effects or adverse reactions were encountered.

Standard multiple comparison techniques do not adequately address the situation in which one must demonstrate a combination therapy's superiority to both of its components. This paper proposes several alternative tests to deal with this situation, and evaluates the tests with a Monte Carlo sampling experiment that compares the actual with the nominal significance levels of the tests. Data from a clinical trial that compares the efficacy of a combination analgesic/muscle relaxant to its components and placebo in the treatment of low back pain and spasm illustrate the tests.

Diflunisal is a salicylic acid derivative with analgesic and anti-inflammatory activity. It has been studied in osteoarthritis, pain resulting from musculoskeketal sprains and strains and from minor surgery and cancer. The duration of its analgesic effect is longer than that of aspirin and diflunisal is effective when given twice daily. Diflunisal is not metabolised to salicylic acid and has a lesser effect than aspirin on platelet function in vivo. In osteoarthritis, diflunisal appears comparable in efficacy to moderate doses of aspirin (2 to 3g daily), but is better tolerated. It has not been compared with the most active phenylalkanoic acid derivatives such as naproxen in adequate numbers of patients. Diflunisal is comparable with glafenine in pain and with propoxyphene/paracetamol combinations and oxyphenbutazone in pain and in musculoskeletal strains and sprains. As with other non-steroidal agents, gastrointestinal complaints are the most frequently reported side effects.

An open trial with diflunisal (500 mg twice daily) in 766 outpatients consulting their doctor for low back pain, was carried out as part of the project "Back Pain 1981" in Finland. Of the patients (mean age 41 years), 460 had acute lumbago, 144 sciatica and 162 had chronic low back pain as a clinical diagnosis. In each diagnostic group there was a control group of patients receiving no drug therapy. Of the patients 65 percent were men and 35 percent women and the groups did not differ from this distribution in any diagnosis. The efficacy of the treatment was evaluated using four criteria: change of pain at rest and during exercise, patient's evaluation of the efficacy of the treatment, and the need for any supportive treatment. Side-effects of the drug therapy were registered. In all diagnostic groups the relief of pain both at rest and during exercise was greater in patients receiving diflunisal than in the controls. The greatest difference was found in lumbago. The patient's evaluation did not differ between the groups. The drug therapy diminished the need for supportive physical therapy. The frequency of side-effects was 8.6%. They led to the discontinuation of medication in 14 cases (3%). No severe side-effects were found. Diflunisal therapy for the relief of low back pain is therefore considered to be indicated in outpatient care.

The analgesic efficacy of single 500- and 1,000-mg doses of diflunisal (Dolobid), a new nonsteroidal anti-inflammatory analgesic, was compared in a double-blind study with that of acetaminophen, 600 mg, the combination of acetaminophen, 600 mg, with codeine phosphate, 60 mg, and placebo in 159 oral surgery outpatients. Using a self-rating record, patients rated their pain and its relief hourly for 12 hours after medication. Both doses of diflunisal were significantly more effective than acetaminophen alone and produced peak analgesia comparable to that of the acetaminophen-codeine combination. Diflunisal proved to have an unusually long duration of analgesic action. Acetaminophen and the combination were significantly superior to placebo through hours 2 and 5, respectively; both doses of diflunisal were significantly superior through the end of the 12-hour observation period. None of the active treatments produced more side effects than the placebo.