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Molecules (Basel, Switzerland) Aug 2021Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were... (Review)
Review
Herein, we review the recent progress in the synthesis of representative nonsteroidal anti-inflammatory drugs (NSAIDs), ibuprofen and naproxen. Although these drugs were discovered over 50 years ago, novel practical and asymmetric approaches are still being developed for their synthesis. In addition, this endeavor has enabled access to more potent and selective derivatives from the key frameworks of ibuprofen and naproxen. The development of a synthetic route to ibuprofen and naproxen over the last 10 years is summarized, including developing methodologies, finding novel synthetic routes, and applying continuous-flow chemistry.
Topics: Electrochemistry; Humans; Hydrogenation; Ibuprofen; Naproxen; Oxidation-Reduction; Stereoisomerism
PubMed: 34443379
DOI: 10.3390/molecules26164792 -
The New England Journal of Medicine Dec 2016The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
The cardiovascular safety of celecoxib, as compared with nonselective nonsteroidal antiinflammatory drugs (NSAIDs), remains uncertain.
METHODS
Patients who required NSAIDs for osteoarthritis or rheumatoid arthritis and were at increased cardiovascular risk were randomly assigned to receive celecoxib, ibuprofen, or naproxen. The goal of the trial was to assess the noninferiority of celecoxib with regard to the primary composite outcome of cardiovascular death (including hemorrhagic death), nonfatal myocardial infarction, or nonfatal stroke. Noninferiority required a hazard ratio of 1.12 or lower, as well as an upper 97.5% confidence limit of 1.33 or lower in the intention-to-treat population and of 1.40 or lower in the on-treatment population. Gastrointestinal and renal outcomes were also adjudicated.
RESULTS
A total of 24,081 patients were randomly assigned to the celecoxib group (mean [±SD] daily dose, 209±37 mg), the naproxen group (852±103 mg), or the ibuprofen group (2045±246 mg) for a mean treatment duration of 20.3±16.0 months and a mean follow-up period of 34.1±13.4 months. During the trial, 68.8% of the patients stopped taking the study drug, and 27.4% of the patients discontinued follow-up. In the intention-to-treat analyses, a primary outcome event occurred in 188 patients in the celecoxib group (2.3%), 201 patients in the naproxen group (2.5%), and 218 patients in the ibuprofen group (2.7%) (hazard ratio for celecoxib vs. naproxen, 0.93; 95% confidence interval [CI], 0.76 to 1.13; hazard ratio for celecoxib vs. ibuprofen, 0.85; 95% CI, 0.70 to 1.04; P<0.001 for noninferiority in both comparisons). In the on-treatment analysis, a primary outcome event occurred in 134 patients in the celecoxib group (1.7%), 144 patients in the naproxen group (1.8%), and 155 patients in the ibuprofen group (1.9%) (hazard ratio for celecoxib vs. naproxen, 0.90; 95% CI, 0.71 to 1.15; hazard ratio for celecoxib vs. ibuprofen, 0.81; 95% CI, 0.65 to 1.02; P<0.001 for noninferiority in both comparisons). The risk of gastrointestinal events was significantly lower with celecoxib than with naproxen (P=0.01) or ibuprofen (P=0.002); the risk of renal events was significantly lower with celecoxib than with ibuprofen (P=0.004) but was not significantly lower with celecoxib than with naproxen (P=0.19).
CONCLUSIONS
At moderate doses, celecoxib was found to be noninferior to ibuprofen or naproxen with regard to cardiovascular safety. (Funded by Pfizer; ClinicalTrials.gov number, NCT00346216 .).
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Cardiovascular Diseases; Celecoxib; Cyclooxygenase 2 Inhibitors; Female; Gastrointestinal Diseases; Humans; Ibuprofen; Intention to Treat Analysis; Kidney Diseases; Male; Middle Aged; Naproxen; Risk
PubMed: 27959716
DOI: 10.1056/NEJMoa1611593 -
Medicine May 2020Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary dysmenorrhea is common and troublesome. The comparative efficacy of over-the-counter analgesics (OTCAs) for dysmenorrhea is unclear. This study was aimed at conducting a network meta-analysis to assess the efficacy and safety of 5 OTCAs - naproxen, ibuprofen,diclofenac, aspirin, and ketoprofen - in patients with primary dysmenorrhea.
METHODS
The study was registered with PROSPERO (number: CRD42019133556). The search strategy involved a review of PubMed, Embase, Cochrane Library, Web of Science, and CINAHL for relative randomized controlled trials of the 5 analgesics from the date of database establishment to July 2019. The outputs are presented as odds ratios (ORs), their corresponding 95% confidence intervals (CIs), and the surface under the cumulative ranking area (SUCRA) probabilities.
RESULTS
Thirty-five trials with 4383 participants were included in our study. As for efficacy outcomes, all the included analgesics except aspirin were more effective than placebo in treating dysmenorrhea [naproxen (OR 3.99, 95% CI 2.18-7.30), ibuprofen (OR 10.08, 95% CI 3.29-30.85), diclofenac (OR 11.82, 95% CI 2.66-52.48), and ketoprofen (OR 5.12, 95% CI 1.57-16.69). The OTCAs were superior to the placebo in terms of pain relief in primary dysmenorrhea. Aspirin was less effective than ibuprofen (OR 0.17, 95% CI 0.04-0.73) and diclofenac (OR 1.17, 95% CI 0.02-0.85). The SUCRA curves showed that diclofenac and ibuprofen were the most and second most effective (85.1% and 83.8%, respectively), followed by ketoprofen, naproxen, and aspirin. Regarding safety, there was no significant difference between the 5 OTCAs included and the placebo. Diclofenac versus ibuprofen (OR 4.31, 95% CI 1.18-15.67), ketoprofen versus diclofenac (OR 0.18, 95% CI 0.04-0.78), and ketoprofen versus aspirin (OR 0.41, 95% CI 0.18-0.97) presented statistically significant differences. Ketoprofen and ibuprofen were ranked the best (SUCRA 90.6% and 79.6%), followed by naproxen, aspirin, and diclofenac.
CONCLUSION
Considering the efficacy and safety, ibuprofen is recommended as the optimal OTCA for primary dysmenorrhea. Further well-designed studies that directly compare these analgesics are needed to support our conclusion.
Topics: Adolescent; Adult; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Diclofenac; Dysmenorrhea; Female; Humans; Ibuprofen; Ketoprofen; Middle Aged; Naproxen; Network Meta-Analysis; Nonprescription Drugs; Treatment Outcome; Young Adult
PubMed: 32384431
DOI: 10.1097/MD.0000000000019881 -
Medicine May 2019The effect of naproxen on the treatment of neoplastic fever is still unclear. A systematic review and meta-analysis were performed to investigate the effect of naproxen... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The effect of naproxen on the treatment of neoplastic fever is still unclear. A systematic review and meta-analysis were performed to investigate the effect of naproxen in the treatment of cancer fever or suspicion. Besides, the latest and most convincing evidence was provided for the earlier use of naproxen in treating cancer patients with fever of unknown origin.
METHODS
A literature review was conducted to identify all published studies on the naproxen for the treatment of neoplastic fever. Electronic databases (eg, PUBMED, EMBASE and the Cochrane Library) were searched until October 2018. Data were extracted, and the risk of bias was assessed by 2 authors independently. Standard meta-analyses on the rate of successful treatment were conducted using a random-effects model, and relative risks were calculated with 95% confidence intervals (CIs).
RESULTS
A total of 15 studies, recruiting 582 participants, were included, which were 1 randomized controlled trial (RCT), 1 non-RCT, 3 cross-sectional studies, and 10 case-series studies. The result of our meta-analysis revealed that the success rate on the treatment of neoplastic fever using naproxen was 94.1% (95% CI: 87.6%-97.3%). The success rate of the suspected neoplastic fever was 79.8%; for fever of unknown origin, it also reached 67.7%. In this meta-analysis, the success rate was 98.1% (95% CI: 95.0%-99.3%) in the dosage of 250 mg twice a day. Besides, a small dose of 125 mg naproxen, 375 mg twice a day and 250 mg 3 times a day were also useful. The result of the subgroup analysis revealed that the difference was not statistically significant in the treatment success rate for solid tumors and hematologic malignant.
CONCLUSIONS
The result of our meta-analysis suggested that naproxen exhibited a highly successful rate for the treatment of neoplastic fever. Besides, naproxen was also satisfactory in improving symptoms of suspected neoplastic fever and fever of unknown origin. The earlier use of naproxen might be able to mitigate cancer patient's suffering and enhanced their quality of life. These findings, however, rely primarily on observational data and should be interpreted rigorously. Further well-conducted trials are required to assess naproxen for the treatment of neoplastic fever.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cross-Sectional Studies; Dose-Response Relationship, Drug; Fever; Humans; Naproxen; Neoplasms; Quality of Life
PubMed: 31145329
DOI: 10.1097/MD.0000000000015840 -
The Science of the Total Environment Oct 2020Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) represent one of the main therapeutic classes of molecules contaminating aquatic ecosystems worldwide. NSAIDs are commonly... (Review)
Review
Toxicity of the Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) acetylsalicylic acid, paracetamol, diclofenac, ibuprofen and naproxen towards freshwater invertebrates: A review.
Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) represent one of the main therapeutic classes of molecules contaminating aquatic ecosystems worldwide. NSAIDs are commonly and extensively used for their analgesic, antipyretic and anti-inflammatory properties to cure pain and inflammation in human and veterinary therapy. After use, NSAIDs are excreted in their native form or as metabolites, entering the aquatic ecosystems. A number of monitoring surveys has detected the presence of different NSAIDs in freshwater ecosystems in the ng/L - μg/L concentration range. Although the concentrations of NSAIDs in surface waters are low, the high biological activity of these molecules may confer them a potential toxicity towards non-target aquatic organisms. The present review aims at summarizing toxicity, in terms of both acute and chronic toxicity, induced by the main NSAIDs detected in surface waters worldwide, namely acetylsalicylic acid (ASA), paracetamol (PCM), diclofenac (DCF), ibuprofen (IBU) and naproxen (NPX), both singularly and in mixture, towards freshwater invertebrates. Invertebrates play a crucial role in ecosystem functioning so that NSAIDs-induced effects may result in hazardous consequences to the whole freshwater trophic chain. Acute toxicity of NSAIDs occurs only at high, unrealistic concentrations, while sub-lethal effects arise also at low, environmentally relevant concentrations of all these drugs. Thus, further studies represent a priority in order to improve the knowledge on NSAID toxicity and mechanism(s) of action in freshwater organisms and to shed light on their real ecological hazard towards freshwater communities.
Topics: Acetaminophen; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Diclofenac; Ecosystem; Fresh Water; Humans; Ibuprofen; Invertebrates; Naproxen
PubMed: 32559537
DOI: 10.1016/j.scitotenv.2020.140043 -
The New England Journal of Medicine Nov 2000Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
BACKGROUND
Each year, clinical upper gastrointestinal events occur in 2 to 4 percent of patients who are taking nonselective nonsteroidal antiinflammatory drugs (NSAIDs). We assessed whether rofecoxib, a selective inhibitor of cyclooxygenase-2, would be associated with a lower incidence of clinically important upper gastrointestinal events than is the nonselective NSAID naproxen among patients with rheumatoid arthritis.
METHODS
We randomly assigned 8076 patients who were at least 50 years of age (or at least 40 years of age and receiving long-term glucocorticoid therapy) and who had rheumatoid arthritis to receive either 50 mg of rofecoxib daily or 500 mg of naproxen twice daily. The primary end point was confirmed clinical upper gastrointestinal events (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcers).
RESULTS
Rofecoxib and naproxen had similar efficacy against rheumatoid arthritis. During a median follow-up of 9.0 months, 2.1 confirmed gastrointestinal events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (relative risk, 0.5; 95 percent confidence interval, 0.3 to 0.6; P<0.001). The respective rates of complicated confirmed events (perforation, obstruction, and severe upper gastrointestinal bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (relative risk, 0.4; 95 percent confidence interval, 0.2 to 0.8; P=0.005). The incidence of myocardial infarction was lower among patients in the naproxen group than among those in the rofecoxib group (0.1 percent vs. 0.4 percent; relative risk, 0.2; 95 percent confidence interval, 0.1 to 0.7); the overall mortality rate and the rate of death from cardiovascular causes were similar in the two groups.
CONCLUSIONS
In patients with rheumatoid arthritis, treatment with rofecoxib, a selective inhibitor of cyclooxygenase-2, is associated with significantly fewer clinically important upper gastrointestinal events than treatment with naproxen, a nonselective inhibitor.
Topics: Adult; Arthritis, Rheumatoid; Cardiovascular Diseases; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Duodenal Obstruction; Female; Gastric Outlet Obstruction; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Isoenzymes; Lactones; Male; Membrane Proteins; Middle Aged; Naproxen; Peptic Ulcer; Proportional Hazards Models; Prostaglandin-Endoperoxide Synthases; Sulfones
PubMed: 11087881
DOI: 10.1056/NEJM200011233432103 -
Journal of Pharmacy & Pharmaceutical... 2021Post-operative pain is a common type of acute pain that can require therapeutic intervention. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage... (Review)
Review
INTRODUCTION
Post-operative pain is a common type of acute pain that can require therapeutic intervention. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to manage post-operative pain and help reduce or eliminate the use of opioids. Current pain management guidelines recommend administration of NSAIDs as first line therapy to all post-operative surgical patients, unless contraindicated, as one method to minimize opioid use.
METHODS
This article is based on previously conducted studies and does not contain any studies with human participants or animals performed by the author. Literature for controlled trials involving naproxen in a peri-procedural setting was included. Comprehensive meta-analyses and individual clinical trial reports were summarized.
RESULTS
Naproxen was shown to have significant efficacy in treating pain following different surgical interventions, eliminating, or reducing the use of rescue opioids in many trials. Importantly, naproxen did not demonstrate an increased rate of bleeding or other adverse events in this elevated-risk population.
CONCLUSION
As a generally safe and effective medication, clinical consideration should be given to naproxen when developing any comprehensive, patient-specific, pain management plan.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Humans; Naproxen; Pain, Postoperative
PubMed: 33600307
DOI: 10.18433/jpps31629 -
Journal of Cardiovascular Pharmacology... Mar 2018Over-the-counter analgesics are used globally for the relief of acute pain. Although effective, these agents can be associated with adverse effects that may limit their... (Review)
Review
Over-the-counter analgesics are used globally for the relief of acute pain. Although effective, these agents can be associated with adverse effects that may limit their use in some people. In the early 2000s, observations from clinical trials of prescription-strength and supratherapeutic doses of nonselective and cyclooxygenase-2-selective nonsteroidal anti-inflammatory drugs (NSAIDs) raised safety concerns regarding the risk of cardiovascular adverse effects with the use of these medications. Subsequently, the US Food and Drug Administration mandated additional study of the cardiovascular safety of NSAIDs for a more comprehensive understanding of their risk. As these data were being collected, and based on a comprehensive review of prescription data and the recommendations of the US Food and Drug Administration Advisory Committee, the warning labels of over-the-counter NSAIDs were updated to emphasize the potential cardiovascular risks of these agents. The recently reported "Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen or Naproxen" (PRECISION) trial, in which participants with osteoarthritis or rheumatoid arthritis and underlying cardiovascular risk factors were treated with prescription-strength celecoxib, ibuprofen, or naproxen, revealed similar rates of cardiovascular events (death from cardiovascular causes including hemorrhagic death, nonfatal myocardial infarction, or nonfatal stroke) among the 3 treatment groups. Although informative, the cardiovascular safety findings derived from PRECISION cannot be extrapolated to the safety of the over-the-counter pain relievers ibuprofen and naproxen, given that the doses used were higher (mean [standard deviation]: ibuprofen, 2045 [246] mg; naproxen, 852 [103] mg) and the durations of use longer (∼20 months) than recommended with over-the-counter use of NSAIDs, which for ibuprofen is up to 10 days. This review discusses the cardiorenal safety of the most commonly used over-the-counter analgesics, ibuprofen, naproxen, and acetaminophen. Available data suggest that there is little cardiovascular risk when over-the-counter formulations of these agents are used as directed in their labels.
Topics: Acetaminophen; Analgesics; Drug Labeling; Heart Diseases; Humans; Ibuprofen; Kidney Diseases; Naproxen; Nonprescription Drugs; Patient Safety; Risk Assessment; Risk Factors
PubMed: 29421936
DOI: 10.1177/1074248417751070 -
American Journal of Cardiovascular... Apr 2017The voluntary withdrawal of Vioxx (rofecoxib) from the market in 2004, as well as the 2005 and 2014 US FDA Advisory Committee meetings about non-steroidal... (Review)
Review
The voluntary withdrawal of Vioxx (rofecoxib) from the market in 2004, as well as the 2005 and 2014 US FDA Advisory Committee meetings about non-steroidal anti-inflammatory drugs (NSAIDs) and cardiovascular risk, have raised questions surrounding the use of NSAIDs in at-risk populations. This paper discusses the cardiovascular safety profile of naproxen in the context of the NSAID class. The balance of evidence suggests that cardiovascular risk correlates with cyclooxygenase (COX)-2 selectivity, and the low COX-2 selectivity of naproxen results in a lower cardiovascular risk than that of other NSAIDs. The over-the-counter (OTC) use of naproxen is expected to pose minimal cardiovascular risk; however, the benefit-risk ratio and appropriate use should be considered at an individual patient level, particularly to assess underlying conditions that may increase the risk of events. Likewise, regulatory authorities should revisit label information periodically to ensure labeling reflects the current understanding of benefits and risks.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Humans; Naproxen; Substrate Specificity
PubMed: 27826802
DOI: 10.1007/s40256-016-0200-5 -
Swiss Dental Journal 2016This script gives a pragmatic advice for dentists on pain control and anti-inflammation treatment considering current literature and state of the art of analgesic...
This script gives a pragmatic advice for dentists on pain control and anti-inflammation treatment considering current literature and state of the art of analgesic treatment. Naproxen seems to be the feasible anti-inflammatory painkiller as it has a lower cardio-vascular risk profile compared to other NSAID. The higher gastrointestinal bleeding risk can be mitigated using proton-pump inhibitors. Additionally, the duration of the drug effect of about 1215 hours allows excellent patient compliance and comfort in comparison to other NSAID.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Dental Care; Humans; Naproxen; Pain Management
PubMed: 27808350
DOI: No ID Found