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The Cochrane Database of Systematic... Sep 2015This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This is an updated version of the original Cochrane overview published in Issue 9, 2011. That overview considered both efficacy and adverse events, but adverse events are now dealt with in a separate overview.Thirty-nine Cochrane reviews of randomised trials have examined the analgesic efficacy of individual drug interventions in acute postoperative pain. This overview brings together the results of those individual reviews and assesses the reliability of available data.
OBJECTIVES
To summarise the efficacy of pharmaceutical interventions for acute pain in adults with at least moderate pain following surgery who have been given a single dose of oral analgesic.
METHODS
We identified systematic reviews in the Cochrane Database of Systematic Reviews in The Cochrane Library through a simple search strategy. All reviews were overseen by a single review group, had a standard title, and had as their primary outcome the number of participants with at least 50% pain relief over four to six hours compared with placebo. For individual reviews, we extracted the number needed to treat for an additional beneficial outcome (NNT) for this outcome for each drug/dose combination, and also the percentage of participants achieving at least 50% maximum pain relief, the mean of mean or median time to remedication, and the percentage of participants remedicating by six, eight, 12, or 24 hours. Where there was adequate information for pairs of drug and dose (at least 200 participants, in at least two studies), we defined the addition of four comparisons of typical size (400 participants in total) with zero effect as making the result potentially subject to publication bias and therefore unreliable.
MAIN RESULTS
The overview included 39 separate Cochrane Reviews with 41 analyses of single dose oral analgesics tested in acute postoperative pain models, with results from about 50,000 participants in approximately 460 individual studies. The individual reviews included only high-quality trials of standardised design, methods, and efficacy outcome reporting. No statistical comparison was undertaken.Reliable results (high quality information) were obtained for 53 pairs of drug and dose in painful postsurgical conditions; these included various fixed dose combinations, and fast acting formulations of some analgesics. NNTs varied from about 1.5 to 20 for at least 50% maximum pain relief over four to six hours compared with placebo. The proportion of participants achieving this level of benefit varied from about 30% to over 70%, and the time to remedication varied from two hours (placebo) to over 20 hours. Good (low) NNTs were obtained with ibuprofen 200 mg plus paracetamol (acetaminophen) 500 mg (NNT compared with placebo 1.6; 95% confidence interval 1.5 to 1.8), ibuprofen fast acting 200 mg (2.1; 1.9 to 2.3); ibuprofen 200 mg plus caffeine 100 mg (2.1; 1.9 to 3.1), diclofenac potassium 50 mg (2.1; 1.9 to 2.5), and etoricoxib 120 mg (1.8; 1.7 to 2.0). For comparison, ibuprofen acid 400 mg had an NNT of 2.5 (2.4 to 2.6). Not all participants had good pain relief and, for many pairs of drug and dose, 50% or more did not achieve at least 50% maximum pain relief over four to six hours.Long duration of action (eight hours or greater) was found for etoricoxib 120 mg, diflunisal 500 mg, paracetamol 650 mg plus oxycodone 10 mg, naproxen 500/550 mg, celecoxib 400 mg, and ibuprofen 400 mg plus paracetamol 1000 mg.There was no evidence of analgesic effect for aceclofenac 150 mg, aspirin 500 mg, and oxycodone 5 mg (low quality evidence). No trial data were available in reviews of acemetacin, meloxicam, nabumetone, nefopam, sulindac, tenoxicam, and tiaprofenic acid. Inadequate amounts of data were available for nine drugs and doses, and data potentially susceptible to publication bias for 13 drugs and doses (very low quality evidence).
AUTHORS' CONCLUSIONS
There is a wealth of reliable evidence on the analgesic efficacy of single dose oral analgesics. Fast acting formulations and fixed dose combinations of analgesics can produce good and often long-lasting analgesia at relatively low doses. There is also important information on drugs for which there are no data, inadequate data, or where results are unreliable due to susceptibility to publication bias. This should inform choices by professionals and consumers.
Topics: Acute Pain; Administration, Oral; Adult; Analgesics; Humans; Pain, Postoperative
PubMed: 26414123
DOI: 10.1002/14651858.CD008659.pub3 -
The Cochrane Database of Systematic... Jan 2005Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Editor's note: The anti-inflammatory drug rofecoxib (Vioxx) was withdrawn from the market at the end of September 2004 after it was shown that long-term use (greater than 18 months) could increase the risk of heart attack and stroke. Further information is available at www.vioxx.com. Osteoarthritis is a chronic disease of the joints, characterised by joint pain, stiffness and loss of physical function. Its onset is age-related and occurs usually between the ages of 50 and 60. It is the commonest cause of disability in those aged over 65, with OA of the knee and/or hip affecting over 20 per cent of the elderly population.
OBJECTIVES
To establish the efficacy and safety of rofecoxib in the management of OA by systematic review of available evidence.
SEARCH STRATEGY
We searched the following databases up to August 2004: MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, National Research Register, NHS Economic Evaluation Database, Health Technology Assessment Database. The bibliographies of retrieved papers and content experts were consulted for additional references.
SELECTION CRITERIA
All eligible randomised controlled trials (RCTs) were included. No unpublished RCTs were included in this edition of the review.
DATA COLLECTION AND ANALYSIS
Data were abstracted independently by two reviewers. A validated checklist was used to score the quality of the RCTs. Comparable trials were pooled using fixed effects model.
MAIN RESULTS
Twenty-six RCTs were included. The comparators were placebo, diclofenac, ibuprofen, naproxen, nimesulide, nabumetone, paracetamol, celecoxib and Arthrotec. The evidence reviewed indicated that rofecoxib was more effective than placebo (patient global response RR 1.75 95% CI: 1.35, 2.26) but was associated with more adverse events (RR 1.32 95% CI 1.11, 1.56). There were no consistent differences in efficacy between rofecoxib and any of the active comparators at equivalent doses. Endoscopic studies indicated that compared to ibuprofen 800 mg three times a day, rofecoxib caused fewer erosions and gastric ulcers at doses of 25mg and 50mg; the difference in duodenal ulcers was evident only at a dose of 25mg. Rofecoxib 50mg also caused more endoscopically observed ulcers greater than rofecoxib 25mg (RR 2.48 CI: 1.21, 5.11). Very few of the trials reported overall rates of GI adverse events although rofecoxib was found to cause fewer GI events than naproxen. Only one of the nine trials comparing rofecoxib to celecoxib reported on the overall rates of GI events and this was a comparison of the higher recommended dose of rofecoxib with the lower recommended dose of celecoxib. Similarly, the three trials in older hypertensive patients that examined the cardiovascular safety of rofecoxib and celecoxib used non-comparable doses; the results of these studies indicated that rofecoxib caused more patients to have oedema and a clinically significant increase in systolic blood pressure. This difference between rofecoxib and celecoxib was not evident in studies conducted in more general populations.
AUTHORS' CONCLUSIONS
Rofecoxib was voluntarily withdrawn from global markets in October 2004 therefore there are no implications for practice concerning its use. There remains a number of questions over both the benefits and risks associated with Cox II selective agents and further work is ongoing.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Drug Approval; Humans; Lactones; Osteoarthritis; Randomized Controlled Trials as Topic; Sulfones
PubMed: 15654705
DOI: 10.1002/14651858.CD005115 -
The Cochrane Database of Systematic... Oct 2009Nabumetone is a non-steroidal anti-inflammatory drug (NSAID) used mainly in treating pain associated with arthritis. The usual oral dose for osteoarthritis is 1000 mg... (Review)
Review
BACKGROUND
Nabumetone is a non-steroidal anti-inflammatory drug (NSAID) used mainly in treating pain associated with arthritis. The usual oral dose for osteoarthritis is 1000 mg daily, and higher doses are not advised in older patients. There are no known systematic reviews of its analgesic efficacy in acute postoperative pain. This review sought to evaluate the efficacy and safety of oral nabumetone in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish whether drugs have analgesic properties.
OBJECTIVES
To assess the efficacy of single dose oral nabumetone in acute postoperative pain, and any associated adverse events.
SEARCH STRATEGY
We searched The Cochrane Library (Issue 2, 2009), MEDLINE (May 2009); EMBASE via Ovid (May 2009); and the Oxford Pain Relief Database.
SELECTION CRITERIA
Randomised, double-blind, placebo-controlled clinical trials of oral nabumetone for relief of acute postoperative pain in adults.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trial quality and extracted data. The area under the "pain relief versus time" curve was used to derive the proportion of participants with nabumetone and placebo experiencing at least 50% pain relief over 4 to 6 hours, using validated equations. The number needed to treat to benefit (NNT) was calculated using 95% confidence intervals (CI). The proportion of participants using rescue analgesia over a specified time period, and time to use of rescue analgesia, were sought as additional measures of efficacy. Information on adverse events and withdrawals was also collected.
MAIN RESULTS
No studies were identified by the searches that examined oral nabumetone in participants with established postoperative pain.
AUTHORS' CONCLUSIONS
In the absence of evidence of efficacy, at present, for oral nabumetone in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda.
Topics: Acute Disease; Administration, Oral; Adult; Analgesics; Butanones; Cyclooxygenase 2 Inhibitors; Humans; Nabumetone; Pain, Postoperative
PubMed: 19821428
DOI: 10.1002/14651858.CD007548.pub2 -
The Cochrane Database of Systematic... Jun 2017Rheumatoid arthritis is a systemic auto-immune disorder that causes widespread and persistent inflammation of the synovial lining of joints and tendon sheaths.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Rheumatoid arthritis is a systemic auto-immune disorder that causes widespread and persistent inflammation of the synovial lining of joints and tendon sheaths. Presently, there is no cure for rheumatoid arthritis and treatment focuses on managing symptoms such as pain, stiffness and mobility, with the aim of achieving stable remission and improving mobility. Celecoxib is a selective non-steroidal anti-inflammatory drug (NSAID) used for treatment of people with rheumatoid arthritis.
OBJECTIVES
To assess the benefits and harms of celecoxib in people with rheumatoid arthritis.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and clinical trials registers (ClinicalTrials.gov and the World Health Organization trials portal) to May 18, 2017. We also searched the reference and citation lists of included studies.
SELECTION CRITERIA
We included prospective randomized controlled trials (RCTs) that compared oral celecoxib (200 mg and 400 mg daily) versus no intervention, placebo or a traditional NSAID (tNSAID) in people with confirmed rheumatoid arthritis, of any age and either sex. We excluded studies with fewer than 50 participants in each arm or had durations of fewer than four weeks treatment.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration.
MAIN RESULTS
We included eight RCTs with durations of 4 to 24 weeks, published between 1998 and 2014 that involved a total of 3988 adults (mean age = 54 years), most of whom were women (73%). Participants had rheumatoid arthritis for an average of 9.2 years. All studies were assessed at high or unclear risk of bias in at least one domain. Overall, evidence was assessed as moderate-to-low quality. Five studies were funded by pharmaceutical companies. Celecoxib versus placeboWe included two studies (N = 873) in which participants received 200 mg daily or 400 mg daily or placebo. Participants who received celecoxib showed significant clinical improvement compared with those receiving placebo (15% absolute improvement; 95% CI 7% to 25%; RR 1.53, 95% CI 1.25 to 1.86; number needed to treat to benefit (NNTB) = 7, 95% CI 5 to 13; 2 studies, 873 participants; moderate to low quality evidence).Participants who received celecoxib reported less pain than placebo-treated people (11% absolute improvement; 95% CI 8% to 14%; NNTB = 4, 95% CI 3 to 6; 1 study, 706 participants) but results were inconclusive for improvement in physical function (MD -0.10, 95% CI 0.29 to 0.10; 1 study, 706 participants).In the celecoxib group, 15/293 participants developed ulcers, compared with 4/99 in the placebo group (Peto OR 1.26, 95% CI 0.44 to 3.63; 1 study, 392 participants; low quality evidence). Nine (of 475) participants in the celecoxib group developed short-term serious adverse events, compared with five (of 231) in the placebo group (Peto OR 0.87 (0.28 to 2.69; 1 study, 706 participants; low quality evidence).There were fewer withdrawals among people who received celecoxib (163/475) compared with placebo (130/231) (22% absolute change; 95% CI 16% to 27%; RR 0.61, 95% CI 0.52 to 0.72; 1 study, 706 participants).Cardiovascular events (myocardial infarction, stroke) were not reported. However, regulatory agencies warn of increased cardiovascular event risk associated with celecoxib. Celecoxib versus tNSAIDsSeven studies (N = 2930) compared celecoxib and tNSAIDs (amtolmetin guacyl, diclofenac, ibuprofen, meloxicam, nabumetone, naproxen, pelubiprofen); one study included comparisons of both placebo and tNSAIDs (N = 1149).There was a small improvement, which may not be clinically significant, in numbers of participants achieving ACR20 criteria response in the celecoxib group compared to tNSAIDs (4% absolute improvement; 95% CI 0% less improvement to 8% more improvement; RR 1.10, 95% CI 0.99 to 1.23; 4 studies, 1981 participants). There was a lack of evidence of difference between participants in the celecoxib and tNSAID groups in terms of pain or physical function. Results were assessed at moderate-to-low quality evidence (downgraded due to risk of bias and inconsistency).People who received celecoxib had a lower incidence of gastroduodenal ulcers ≥ 3 mm (34/870) compared with those who received tNSAIDs (116/698). This corresponded to 12% absolute change (95% CI 11% to 13%; RR 0.22, 95% CI 0.15 to 0.32; 5 studies, 1568 participants; moderate quality evidence). There were 7% fewer withdrawals among people who received celecoxib (95% CI 4% to 9%; RR 0.73, 95% CI 0.62 to 0.86; 6 studies, 2639 participants).Results were inconclusive for short-term serious adverse events and cardiovascular events (low quality evidence). There were 17/918 serious adverse events in people taking celecoxib compared to 42/1236 among people who received placebo (Peto OR 0.71; 95% CI 0.39 to 1.28; 5 studies, 2154 participants). Cardiovascular events were reported in both celecoxib and placebo groups in one study (149 participants).
AUTHORS' CONCLUSIONS
Celecoxib may improve clinical symptoms, alleviate pain and contribute to little or no difference in physical function compared with placebo. Celecoxib was associated with fewer numbers of participant withdrawals. Results for incidence of gastroduodenal ulcers (≥ 3 mm) and short-term serious adverse events were uncertain; however, there were few reported events for either.Celecoxib may slightly improve clinical symptoms compared with tNSAIDs. Results for reduced pain and improved physical function were uncertain. Particpants taking celecoxib had lower incidence of gastroduodenal ulcers (≥ 3 mm) and there were fewer withdrawals from trials. Results for cardiovascular events and short-term serious adverse events were also uncertain.Uncertainty about the rate of cardiovascular events between celecoxib and tNSAIDs could be due to risk of bias; another factor is that these were small, short-term trials. It has been reported previously that both celecoxib and tNSAIDs increase cardiovascular event rates. Our confidence in results about harms is therefore low. Larger head-to-head clinical trials comparing celecoxib to other tNSAIDs is needed to better inform clinical practice.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Celecoxib; Humans; Myocardial Infarction; Pain Measurement; Randomized Controlled Trials as Topic; Stomach Ulcer; Stroke; Treatment Outcome
PubMed: 28597983
DOI: 10.1002/14651858.CD012095.pub2 -
Ugeskrift For Laeger Feb 2015Pseudoporphyria is a photosensitive bullous disease, which resembles porphyria cutanea tarda. Normal porphyrin levels in urine, stool and blood define pseudoporphyria.... (Review)
Review
Pseudoporphyria is a photosensitive bullous disease, which resembles porphyria cutanea tarda. Normal porphyrin levels in urine, stool and blood define pseudoporphyria. Pseudoporphyria is associated with chronic renal failure, haemodialysis, a variety of drugs (e.g. naproxen, nabumetone, furosemide, ciprofloxacin, voriconazole, acitretin), tanning beds and UVA exposure. Treatment consists of UV protection and cessation of suspected agents. Patients in haemodialysis can benefit from treatment with N-acetylcysteine or glutathione.
Topics: Drug Eruptions; Humans; Porphyria Cutanea Tarda; Porphyrins; Skin Diseases, Vesiculobullous; Ultraviolet Rays
PubMed: 25650579
DOI: No ID Found -
Journal of Pharmacological Sciences Nov 2005The effects of indomethacin and nabumetone on urine and electrolyte excretion in conscious rats were examined. Male Sprague-Dawley rats were housed individually for a... (Comparative Study)
Comparative Study
The effects of indomethacin and nabumetone on urine and electrolyte excretion in conscious rats were examined. Male Sprague-Dawley rats were housed individually for a five-week duration, consisting of acclimatization, control, experimental, and recovery phases. During the experimental phase, rats were given either indomethacin (1.5 mg . kg(-1) body weight . day(-1) in 0.5 ml saline, n = 10), nabumetone (15 mg . kg(-1) body weight . day(-1) 0.5 ml saline, n = 10), or 0.5 ml saline alone (n = 10) for a period of two weeks. Water and food intake, body weight, urine output, and electrolyte excretions were estimated. Data were analyzed using two-way ANOVA. Urine output in the indomethacin- and nabumetone-treated groups was not different from the controls, but was significantly different between the drug-treated groups (P<0.01). Sodium, potassium, calcium, and magnesium excretions were not different between nabumetone-treated and control rats. However, sodium and potassium excretion was significantly lower in rats receiving indomethacin when compared to the control rats. Calcium and magnesium outputs, although did not differ from the controls, nevertheless decreased significantly with indomethacin (P<0.01). It appears that indomethacin and nabumetone when given at maximum human therapeutic doses may affect urine and electrolyte output in conscious rats.
Topics: Animals; Butanones; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Electrolytes; Indomethacin; Kidney; Male; Membrane Proteins; Nabumetone; Rats; Rats, Sprague-Dawley; Urination
PubMed: 16293937
DOI: 10.1254/jphs.fpj05008x -
Pharmaceutics May 2020Photostability studies were performed on topical formulations containing the anti-inflammatory drug Nabumetone and an analog newly synthesized in order to achieve better...
Photostability studies were performed on topical formulations containing the anti-inflammatory drug Nabumetone and an analog newly synthesized in order to achieve better photostability and pharmacokinetic profile. Stability tests, according to the International Conference on Harmonization rules, were applied on ethanol solutions and topical gel formulations of both compounds. The photodegradation profiles were monitored by Multivariate curve resolution applied to the UV spectral data. The inclusion of the compounds in microemulsion was investigated to improve light stability and, at the same time, to ensure a sustained release system for skin delivery. All the formulations in solution, gel, microemulsion, and microemulsion-in-gel were exposed to a forced irradiation of 350 W/m, corresponding to a 21 kJ/m min, for up to 300 min. Photostability increased significantly for both drugs in the liquid microemulsion and microemulsion-in-gel, compared to the ethanol solution and plain gel, reaching a residual drug of 97% and 98% for Nabumetone and analog in microemulsion-in-gel, respectively. Permeation experiments on the microemulsion-in-gel showed a better performance of the analog formulated at 0.2%, compared to the same formulation of Nabumetone at 0.7%. These results highlight the potential of the designed matrices as delayed drug delivery systems along with the use of lower drug doses leading to reduced side effects.
PubMed: 32380748
DOI: 10.3390/pharmaceutics12050423