A single-dose analgesic study of naproxen sodium and soluble aspirin in patients with rheumatoid arthritis

Summary

Nineteen patients with moderate or severe pain due to rheumatoid arthritis were entered into a double-blind, crossover comparison of single doses of 550?mg naproxen sodium and 900?mg soluble aspirin. Pain relief, measured on a visual analogue scale, showed a rapid onset of action of both drugs. Pain relief reached 50% of its maximum within 1 hour on both drugs. There were no significant differences in the pain relief/time curves. Five patients found no relief of pain with either drug but of the remaining 14 patients 10 reported an onset of action of both drugs within half an hour. Nine patients on naproxen sodium and 7 on soluble aspirin rated pain relief as good or very good. At the end of the study, 7 patients preferred soluble aspirin, 4 preferred naproxen sodium and the remainder gave no preference. There were no side-effects reported on either drug.     

The Effect of Food on Bromfenac,Naproxen Sodium,and Acetaminophen in Postoperative Pain after Orthopedic Surgery

Study Objectives . To evaluate the effect of a standard meal on bioavailability of bromfenac, and on the relative analgesic efficacy and adverse effect liability of bromfenac 25 mg, naproxen sodium 550 mg, and acetaminophen 325 mg in the treatment of pain after orthopedic surgery. Design . Randomized, double-blind, single-dose, parallel-group. Setting . Two wards of the orthopedic surgery department at the Central Hospital, Karlstad, Sweden. Patients . Three hundred ten patients with steady, moderate, or severe pain within 72 hours after orthopedic surgery. Interventions . Patients were randomly assigned both to receive a standard meal or remain in a fasted state, and to treatment with a single oral dose of bromfenac 25 mg, naproxen sodium 550 mg, or acetaminophen 325 mg, when they experienced steady, moderate, or severe pain that required an analgesic. Using a self-rating record, subjects rated their pain and its relief for up to 8 hours after medicating. Blood samples were obtained from all patients using one of two schedules. Measurements and Main Results . The peak plasma bromfenac concentration for fed patients was only 28% of that of fasted patients. Disregarding food intake, bromfenac 25 mg and naproxen sodium 550 mg were significantly superior to acetaminophen 325 mg for all summary measures of analgesia. Bromfenac and naproxen were superior to acetaminophen by hour 1 and this difference persisted for 8 hours. Food reduced bromfenac's analgesic effect, but not that of naproxen or acetaminophen; treatment by meal interaction was significant for five measures of efficacy. Analgesic response for fed bromfenac recipients, compared with those who were fasted, ranged from 37–71%. The percentage of patients reporting an adverse effect was significantly higher for bromfenac (25%) and naproxen (24%) than for acetaminophen (12%). Conclusions . Results of analgesic studies not taking patients' food status into consideration might be misleading. Although bromfenac 25 mg and naproxen sodium 550 mg produced significant analgesia compared with acetaminophen 325 mg, bromfenac's efficacy was significantly reduced when patients ate a standard meal. Adverse effects were transient and consistent with the pharmacologic profiles of the drugs.     

Efficacy of single-dose,extended-release naproxen sodium 660 mg in postsurgical dental pain: two double-blind,randomized, placebo-controlled trials

Objective:

To evaluate the efficacy of a novel formulation of extended-release/immediate-release (ER) naproxen sodium over 24?h in a dental pain model.

Research design and methods:

Two randomized, double-blind, placebo-controlled trials in moderate to severe pain after extraction of one or two impacted third molars (at least one partial mandibular bony impaction). Treatment comprised oral ER naproxen sodium 660?mg (single dose), placebo (both studies) or immediate-release (IR) naproxen sodium 220?mg tid (study 2).

Main outcome measures:

Primary efficacy endpoint: 24-h summed pain intensity difference (SPID). Secondary variables included total pain relief (TOTPAR), use of rescue medication. All treatment-emergent adverse events were recorded.

Clinical trial registration:

NCT00720057 (study 1), NCT01389284 (study 2).

Results:

Primary efficacy analyses: pain intensity was significantly lower over 24?h with ER naproxen sodium vs. placebo (p?<?0.001), with significant relief from 15?min (study 2). In study 2, ER naproxen sodium was non-inferior to IR naproxen sodium, reducing pain intensity to a comparable extent over 24?h. TOTPAR was significantly greater with ER and IR naproxen sodium vs. placebo at all time points, with generally comparable differences between active treatments. Significantly more placebo patients required rescue medication vs. ER and IR naproxen sodium from 2–24?h post-dose. Once daily ER naproxen sodium was generally safe and well tolerated, with a similar safety profile to IR naproxen sodium tid.

Limitations:

The studies were single dose, with limited ability to assess efficacy or safety of multiple doses over time. As the imputed pain score meant that estimated treatment differences may have been biased in favor of ER naproxen sodium, a post hoc analysis evaluated the robustness of the results for pain relief.

Conclusions:

A single dose of ER naproxen sodium 660?mg significantly reduced moderate to severe dental pain vs. placebo and was comparable to IR naproxen sodium 220?mg tid. Significant pain relief was experienced from 15?min and sustained over 24?h, resulting in a reduced need for rescue medication. ER naproxen sodium 660?mg once daily is a convenient and effective therapy providing 24?h relief of pain.     

Bioavailability of naproxen sodium and its relationship to clinical analgesic effects.

1 In the first of a series of trials with naproxen sodium it was shown that patients achieved significantly earlier and higher plasma levels of naproxen when naproxen sodium was administered. 2 In a second study comparing naproxen with naproxen sodium in patients with post-partum pain, pain intensity was consistently lower for the group receiving naproxen sodium. However, statistically significant differences were not seen until 4 to 5 h after medication. 3 A final study documented that a more frequent dosage schedule of every 6 h led to clearly higher plasma levels than those achieved with an every 8 h regimen; plasma levels did not plateau. Doses up to 1,375 mg/day were well tolerated. 4 In conclusion, naproxen sodium appears to be an improved form of naproxen for use as a analgesic agent.     

Comparison of the efficacy of naproxen sodium and dihydrocodeine tartrate in the treatment of post-operative pain

A single-blind, parallel study was carried out in 54 patients with post-operative pain after minor orthopaedic procedures to compare the efficacy and tolerance of naproxen sodium and dihydrocodeine tartrate. Patients were allocated at random to receive oral treatment as soon as analgesia became necessary with an initial dose of either 550 mg naproxen sodium or 30 mg dihydrocodeine tartrate, then doses of 275 mg and 30 mg, respectively, when required up to a maximum of 5 doses per day for 3 days. Assessments were made of pain severity and pain relief 2 and 4 hours after the first dose and at the end of each day. The results indicated that naproxen sodium gave statistically significantly greater pain relief than dihydrocodeine tartrate after the first dose. Both treatments were well tolerated and few side-effects were reported. Three patients in each group were withdrawn due to lack of efficacy (combined with adverse effects in 1 naproxen sodium patient), and 1 patient in each group was withdrawn because of side-effects.     

Effects of a combination of oral naproxen sodium and codeine on experimentally induced pain

Summary The effect of an orally administered combination of naproxen sodium 550 mg and codeine phosphate 60 mg on threshold and tolerance to electrically induced pain, and on the threshold to thermally induced pain, was compared with the effects of naproxen sodium 550 mg alone, codeine phosphate 60 mg alone, and placebo. 16 female and 16 male, healthy young subjects, took part in four experiments on consecutive days of one week. On each day one treatment was administered, in random order, under double blind conditions. The combination increased threshold and tolerance to electrically induced pain and the threshold to thermally induced pain markedly more than did naproxen sodium alone. Naproxen sodium plus codeine was also more effective in increasing threshold and tolerance to electrically induced pain than was codeine alone; the latter increased the threshold and tolerance to electrically induced pain and the threshold to thermally induced pain markedly more than placebo. Naproxen sodium alone had a relatively weak effect on the three pain measures. Reaction time to acoustic stimuli and the side effect profile were not significantly influenced by any of the treatments, and no severe adverse effects occurred. It is concluded that the combination of naproxen sodium 550 mg and codeine phosphate 60 mg, as indicated by its effects on experimentally induced pain, can produce more intense analgesia than the same doses of naproxen sodium and codeine administered alone, and that naproxen sodium and codeine phosphate given in combination enhanced each other's effect in an additive manner.     

Comparison of the efficacy of naproxen sodium and dihydrocodeine tartrate in the treatment of post-operative pain

Summary

A single-blind, parallel study was carried out in 54 patients with post-operative pain after minor orthopaedic procedures to compare the efficacy and tolerance of naproxen sodium and dihydrocodeine tartrate. Patients were allocated at random to receive oral treatment as soon as analgesia became necessary with an initial dose of either 550?mg naproxen sodium or 30?mg dihydrocodeine tartrate, then doses of 275?mg and 30?mg, respectively, when required up to a maximum of 5 doses per day for 3 days. Assessments were made of pain severity and pain relief 2 and 4 hours after the first dose and at the end of each day. The results indicated that naproxen sodium gave statistically significantly greater pain relief than dihydrocodeine tartrate after the first dose. Both treatments were well tolerated and few side-effects were reported. Three patients in each group were withdrawn due to lack of efficacy (combined with adverse effects in 1 naproxen sodium patient), and 1 patient in each group was withdrawn because of side-effects.     

Etoricoxib

Etoricoxib is a cyclo-oxygenase (COX)-2-selective NSAID with a higher COX-1 to COX-2 selectivity ratio than the other COX-2-selective NSAIDs rofecoxib, valdecoxib or celecoxib. In patients with rheumatoid arthritis, improvements in tender and swollen joint counts and patient and investigator global assessment of disease activity were significantly greater in etoricoxib than in placebo recipients in two studies. Etoricoxib was also significantly more effective than naproxen in one of these studies. In patients with osteoarthritis of the hip or knee, etoricoxib was significantly more effective than placebo and had similar efficacy to naproxen with regards to improvements in pain and physical function scores and patient global assessment of disease status scores in two studies. Etoricoxib had similar efficacy to diclofenac in patients with osteoarthritis of the knee. Single-dose etoricoxib relieved pain in patients with postoperative dental pain in two studies. Similar scores assessing total pain relief over 8 hours (TOPAR8) were reported in etoricoxib and naproxen sodium or ibuprofen recipients, and higher TOPAR8 scores were reported with etoricoxib than with paracetamol (acetaminophen)/codeine. Pain relief was significantly better with etoricoxib than placebo in two studies in patients with chronic low back pain. Etoricoxib had similar efficacy to indomethacin in a study in patients with acute gout, and single-dose etoricoxib had similar efficacy to naproxen sodium in a study in women with primary dysmenorrhoea. Compared with non-COX-selective NSAIDs, etoricoxib was associated with significantly fewer upper gastrointestinal (GI) perforations, ulcers or bleeds, and was significantly less likely to result in treatment discontinuation because of NSAID-type GI symptoms or any GI symptoms.     

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.     

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.     

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.     

双氯芬酸钠栓和坦索罗辛及两药联用治疗输尿管远端结石的疗效比较

目的：比较双氯芬酸钠栓和坦索罗辛及两药联用治疗输尿管远端结石的效果。方法：将输尿管远端结石患者150例,随机分为A组、B组和C组,各50例,A组给予双氯芬酸钠栓治疗,B组给予坦索罗辛胶囊治疗;C组给予两种药物联合治疗。以结石排出及疼痛发作情况为主要的比较指标,以结石排出或治疗2周为观察终点。结果：A、B、C 3组结石排出例数分别为30例、32例、43例;A、B、C组用药后肾绞痛的发作例数分别为14例、17例、6例,均具有统计学差异（P＜0.05）;A、B、C组不良反应发生例数分别为5例、6例、8例,无统计学差异（P＞0.05）。结论：双氯芬酸钠栓和坦索罗辛两种药物联用时可以提高排石效果,缩短排石时间,减少肾绞痛发作,而且不良反应并没有明显增加,建议两种药物联用治疗输尿管远端结石。     

Sodium naproxen versus sodium diclofenac in cancer pain control

In a single-blind random study, simultaneously carried out by five Pain Therapy and Palliative Care Centres, the analgesic power and side-effects of sodium naproxen (CAS 26159-34-2) and sodium diclofenac (CAS 15307-86-5) by mouth were compared in a group of 100 advanced cancer patients. The patients complained of somatic and/or visceral pain and were treated with non-steroid anti-inflammatories as required. The dose administered amounted to 550 mg every 12 h for sodium naproxen and to 100 mg every 12 h for sodium diclofenac. The study stressed the similar analgesic effect of the two drugs--pain intensity and duration decreased by half in the first week of treatment--and a comparatively low morbidity rate.     

Controlled-release naproxen compared with isoxicam in patients with osteoarthritis

The therapeutic efficacy and tolerability of a new controlled-release 1000 mg tablet of naproxen (naproxen CR) were compared with 200 mg isoxicam in 100 out-patients with osteoarthritis. Medications were administered once daily for 4 weeks in a controlled, randomized, double-blind, parallel trial. Patients were assessed for duration of stiffness, global pain, pain in the worst affected joint, night pain, pain on full passive movement, and pain on selected activity. No statistically significant differences were found between naproxen CR and isoxicam for any of the efficacy variables. Only 3 patients (2 with naproxen CR, 1 with isoxicam) reported adverse events, all mild to moderate; no patient withdrew from the study. At the conclusion of the study, patients and physician evaluated therapeutic response independently; both drugs provided steady improvement as judged by patients and physician. Both physician and patients evaluated naproxen CR as very good or good for 36 (72%) patients, and isoxicam as good or very good for 35 (73%) patients. Naproxen CR and isoxicam proved equally effective and well-tolerated for the treatment of osteoarthritis in this study.     

多沙唑嗪治疗输尿管下段结石的疗效观察

目的:观察多沙唑嗪治疗输尿管下段结石的疗效。方法:50例输尿管下段结石患者随机分为两组,各25例,对照组予常规抗炎、解痉治疗,疼痛时给予双氯酚酸钠缓释片50mg,po;治疗组在对照组基础上加用甲磺酸多沙唑嗪控释片4mg,qd,睡前服。治疗时间不超过14d,其间每周复查B超和腹部平片,记录排石时间和药物不良反应。结果:治疗组排石率72%(18/25),明显高于对照组排石率40%(10/25),差异有统计学意义(P<0.05)。两组患者排石所用时间比较,差异有统计学意义(P<0.01)。治疗中未见药品不良反应。结论:多沙唑嗪可有效提高输尿管下段结石的排出率、排石时间短,安全性好。     

尼美舒利对成人斯蒂尔病退热作用的临床研究

目的　比较尼美舒利和萘普生对成人斯蒂尔病 (AOSD)的退热效果和安全性。方法　 36例AOSD患者随机分为两组 :观察组 2 0例 ,用尼美舒利 10 0mg ,2次 /d ;对照组 16例 ,用萘普生 30 0mg ,2次 /d ,两组均同时服用甲氨蝶呤 10mg/周 ,共 4周。 2周不退热者均加服泼尼松 10mg/d。 结果　观察组于 2 4h退热者 13例(6 5 % ) ,1周和 2周退热者分别为 16例 (80 % )和 17例 (85 % ) ,与对照组比较差异有显著性 (P <0 0 5 ) ,同时关节症状及血沉 (ESR)、C反应蛋白 (CRP)较治疗前差异有显著性 (P <0 0 5 )。结论　尼美舒利对AOSD的退热作用明显优于萘普生 ,对关节症状及ESR、CRP的改善与萘普生相当 ,副反应小 ,是现阶段治疗AOSD值得推荐的药物。     

A study of non-articular rheumatic disorders and their response to treatment with naproxen sodium.

A group of 85 patients suffering from non-articular rheumatic disorders was studied in an open trial of naproxen sodium in general practice. Patients were assessed and then treated for 7 days with naproxen sodium at a dosage of 275 mg 3 or 4-times daily depending on the severity of pain. Patients were asked to keep a daily record of symptoms and were re-assessed by the doctor after 7 days and, in some cases, after 14 days. Pain and limitation of movement were the predominant symptoms at admission. Patients' daily records showed statistically significant reductions in pain from Day 1 and significant reductions of limitation of movement from Day 2 of the study. At the 7-day follow-up, 27 were cured, 35 improved, 19 not changed or worse, and 4 were not assessed. Thirty patients were given a second weeks' therapy and at the end of this period 24 were cured or improved. Indigestion was the most common side-effect, but only 1 patient withdrew from the trial because of this. One patient developed a rash and was withdrawn from the trial. Both patients were taking the lower dose.     

Valdecoxib: a review of its use in the management of osteoarthritis, rheumatoid arthritis, dysmenorrhoea and acute pain

Valdecoxib is an orally administered, highly selective cyclo-oxygenase (COX)-2 inhibitor with anti-inflammatory and analgesic properties. In well designed trials, valdecoxib demonstrated efficacy versus placebo in patients with osteoarthritis (OA), rheumatoid arthritis (RA), primary dysmenorrhoea and postoperative pain. Initial results in patients with migraine headache were promising. The efficacy of valdecoxib appears dose dependent up to 40 mg/day. Valdecoxib 10 mg/day was as effective as naproxen and rofecoxib in improving signs and symptoms of OA. The American College of Rheumatology 20% response rate was similar in recipients of valdecoxib, naproxen and diclofenac in patients with RA. In patients with dysmenorrhoea, valdecoxib 20 or 40 mg up to twice daily provided as effective pain relief as naproxen sodium 550 mg twice daily. In acute post-surgical pain, single-dose valdecoxib 40 mg had a rapid onset of action, provided similar analgesia to oxycodone 10 mg plus paracetamol (acetaminophen) 1000 mg and provided a longer time to rescue medication than rofecoxib or oxycodone/paracetamol after oral surgery. Pre-emptive administration of valdecoxib 10-80 mg was particularly effective in dental pain. Valdecoxib had opioid-sparing effects after hip or knee arthroplasty and reduced pain after laparoscopic cholecystectomy. Valdecoxib is generally well tolerated. The incidence of gastroduodenal ulcers was generally lower than with nonselective NSAIDs (i.e. NSAIDs not specifically developed as selective COX-2 inhibitors). With concomitant aspirin, the ulcer rate in valdecoxib recipients increased significantly, but was still lower than that in recipients of aspirin plus nonselective NSAIDs. In conclusion, valdecoxib, a COX-2-selective inhibitor, is as efficacious in pain relief as nonselective NSAIDs, with better gastrointestinal tolerability. It was as effective in RA, OA and primary dysmenorrhoea (the approved indications) as nonselective NSAIDs and as effective as rofecoxib in RA flare. In acute post-surgical pain, valdecoxib provided similar pain relief to oxycodone/paracetamol, had a long duration of action, a rapid onset of analgesia and was opioid-sparing. Valdecoxib provides a valuable alternative in the treatment of chronic arthritis pain and acute pain.