Etoricoxib: A Highly Selective COX-2 Inhibitor

2005 ◽  
Vol 39 (5) ◽  
pp. 854-862 ◽  
Author(s):  
Shaunta‘ D Martina ◽  
Kimi S Vesta ◽  
Toni L Ripley
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Data Extraction ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Cochrane Library ◽  
Chronic Lower Back Pain ◽  
Acute Gout ◽  
Antiinflammatory Drugs ◽  
Dental Surgery ◽  
Cox 2

OBJECTIVE: To review the available literature evaluating the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of etoricoxib, a highly selective cyclooxygenase-2 (COX-2) inhibitor that is not currently approved for use in the US. DATA SOURCES: Literature retrieval was accessed through MEDLINE (1966–December 2004), Current Contents (1998–December 2004), and Cochrane Library (4th quarter 2004). References from retrieved articles, information from the manufacturer, and abstracts from the American College of Rheumatology and Annual European Congress of Rheumatology meetings were searched. STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in English evaluating etoricoxib were included in this review. An abstract was excluded if it presented preliminary data from trials that are now published, analyzed data previously reported in a published clinical trial, or compared etoricoxib with placebo for an indication with published active-comparator controlled trials. DATA SYNTHESIS: Twelve clinical trials evaluating efficacy were reviewed. Efficacy for acute pain has been evaluated in acute gout, primary dysmenorrhea, and dental surgery and for chronic pain in rheumatoid arthritis, osteoarthritis, and chronic lower back pain. For safety, 3 clinical trials and 6 retrospective analyses of gastrointestinal, renovascular, or cardiovascular adverse effects were reviewed. CONCLUSIONS: Available studies demonstrate the efficacy of etoricoxib compared with nonsteroidal antiinflammatory drugs, but no published studies to date have compared etoricoxib with other selective COX-2 inhibitors. While these agents have demonstrated a significant reduction in gastrointestinal adverse effects, the cardiovascular adverse effects of selective COX-2 inhibition are not well defined. Further study is necessary to delineate the benefits and risks of etoricoxib compared with alternative treatment regimens.

Glucosamine

1998 ◽  
Vol 32 (5) ◽  
pp. 574-579 ◽  
Author(s):  
Teresa Susanne Barclay ◽  
Candy Tsourounis ◽  
Gary M McCart
Keyword(s):  
Adverse Effects ◽  
Data Extraction ◽  
Critical Evaluation ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Control Group ◽  
Antiinflammatory Drugs ◽  
Skin Reactions ◽  
Medline Search ◽  
Degenerative Process ◽  
Gastrointestinal Problems

OBJECTIVE: To review the pharmacology and pharmacokinetics of glucosamine and critically evaluate currently available literature regarding its safety and efficacy. DATA SOURCE: A MEDLINE search was conducted between January 1965 and May 1997. Key words used in the search were osteoarthritis, osteoarthrosis, gonarthrosis, and glucosamine. In addition, references cited in articles obtained from the MEDLINE search were reviewed for additional literature. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for inclusion in the review. Articles were excluded from critical evaluation for lack of randomization, lack of a control group, 30 or fewer study participants, inconsistent treatment regimen, incomplete dosing information, or incomplete reporting of results. DATA SYNTHESIS: Osteoarthritis affects approximately 12% of the US population; the incidence increases with increasing age. Currently used pharmacologic treatments, including acetaminophen and nonsteroidal antiinflammatory drugs, do not slow or reverse the degenerative process in osteoarthritis. Glucosamine has recently received a great deal of attention from the public as a potential treatment of osteoarthritis, prompting healthcare professionals to investigate its clinical usefulness and potential for adverse effects. The drug has been proposed to stop and possibly reverse the degenerative process in osteoarthritis. Following absorption of an oral dose, glucosamine is incorporated into plasma proteins during first-pass metabolism, resulting in 26% bioavailability. Unbound glucosamine is concentrated in the articular cartilage. Each of the three critically evaluated studies reported a decrease in the symptoms of osteoarthritis (e.g., decreased Lequesne index, decreased pain severity, increased range of motion) for the glucosamine group, which was greater than that obtained in the control group. Flaws in study design, however, prevent the use of these results in modifying current clinical practice. Reported short-term adverse effects include mild gastrointestinal problems, drowsiness, skin reactions, and headache. CONCLUSIONS: Improvement in the symptoms of osteoarthritis associated with the use of glucosamine has been observed in clinical trials; however, those trials have flaws in design and data analysis. Further research needs to be conducted before glucosamine can be recommended as a treatment for osteoarthritis.

scholarly journals Adverse Effects of Nonsteroidal Antiinflammatory Drugs: An Update of Gastrointestinal, Cardiovascular and Renal Complications

2014 ◽  
Vol 16 (5) ◽  
pp. 821 ◽  
Author(s):  
Sam Harirforoosh ◽  
Waheed Asghar ◽  
Fakhreddin Jamali
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Gi Tract ◽  
Antiinflammatory Drugs ◽  
Controlled Release Formulations ◽  
Gi Toxicity ◽  
Inflammatory Drugs ◽  
Cox 2

Non-steroidal anti-inflammatory drugs (NSAIDs) are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients. Both therapeutic and adverse effects of NSAIDs are due to inhibition of cyclooxygenase (COX) enzyme. NSAIDs are classified as non-selective and COX-2-selective inhibitors (COXIBS) based on their extent of selectivity for COX inhibition. However, regardless of their COX selectivity, reports are still appearing on the GI side effect of NSAIDs particularly on the lower gastrointestinal (GI) tract and the harmful role of their controlled release formulations. In addition, previously unpublished data stored in the sponsor’s files, question the GI sparing properties of rofecoxib, a COXIB that has been withdrawn due to cardiovascular (CV) side effects. Presently, the major side effects of NSAIDs are the GI complications, renal disturbances and CV events. There is a tendency to believe that all NSAIDs are associated with renal and CV side effects, a belief that is not supported by solid evidence. Indeed, lower but still therapeutics doses of some NSAIDs may be cardioprotective. In this review, we briefly discuss the GI toxicity of the NSAIDs and assess their renal and CV adverse effects in more detail. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Treatment Options for Rheumatoid Arthritis: Celecoxib, Leflunomide, Etanercept, and Infliximab

2000 ◽  
Vol 34 (6) ◽  
pp. 743-760 ◽  
Author(s):  
Brigitte T Luong ◽  
Barbara S Chong ◽  
Dionne M Lowder
Keyword(s):  
Rheumatoid Arthritis ◽  
English Language ◽  
Data Extraction ◽  
Treatment Options ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Safety And Efficacy ◽  
Medline Search ◽  
Pertinent Data

OBJECTIVE: To review new pharmacologic agents approved for use in the management of rheumatoid arthritis (RA). DATA SOURCES: A MEDLINE search (1966–January 2000) was conducted to identify English-language literature available on the pharmacotherapy of RA, focusing on celecoxib, leflunomide, etanercept, and infliximab. These articles, relevant abstracts, and data provided by the manufacturers were used to collect pertinent data. STUDY SELECTION: All controlled and uncontrolled trials were reviewed. DATA EXTRACTION: Agents were reviewed with regard to mechanism of action, efficacy, drug interactions, pharmacokinetics, dosing, precautions/contraindications, adverse effects, and cost. DATA SYNTHESIS: Traditional pharmacologic treatments for RA have been limited by toxicity, loss of efficacy, or both. Increasing discoveries into the mechanisms of inflammation in RA have led to the development of new agents in hopes of addressing these limitations. With the development of celecoxib, a selective cyclooxygenase-2 inhibitor, the potential exists to minimize the gastrotoxicity associated with nonsteroidal antiinflammatory drugs. Leflunomide has been shown to be equal to or less efficacious than methotrexate, and may be beneficial as a second-line disease-modifying antirheumatic drug (DMARD). The biologic response modifiers, etanercept and infliximab, are alternatives that have shown benefit alone or in combination with methotrexate. However, they should be reserved for patients who fail to respond to DMARD therapy. Further studies should be conducted to evaluate the long-term safety and efficacy of these agents as well as their role in combination therapy. CONCLUSIONS: Celecoxib, leflunomide, etanercept, and infliximab are the newest agents approved for RA. Clinical trials have shown that these agents are beneficial in the treatment of RA; however, long-term safety and efficacy data are lacking.

scholarly journals Factors Associated with Celecoxib and Rofecoxib Utilization

2005 ◽  
Vol 39 (4) ◽  
pp. 597-602 ◽  
Author(s):  
Nigel SB Rawson ◽  
Parivash Nourjah ◽  
Stella C Grosser ◽  
David J Graham
Keyword(s):  
Cardiovascular Disease ◽  
Disease Burden ◽  
Multiple Logistic Regression Analysis ◽  
Underlying Disease ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Nonselective Nsaid ◽  
Antiinflammatory Drugs ◽  
The Past ◽  
Increased Risk ◽  
Cox 2

BACKGROUND: The cyclooxygenase-2 (COX-2) selective nonsteroidal antiinflammatory drugs (NSAIDs) celecoxib and rofecoxib (before its removal) are marketed as having fewer gastrointestinal (GI)-related complications than nonselective NSAIDs. However, adverse reaction data suggest that the use of COX-2 selective NSAIDs is associated with clinically significant GI events. OBJECTIVE: To assess whether patients receiving celecoxib and rofecoxib have a greater underlying disease burden than patients prescribed nonselective NSAIDs. METHODS: The study population consisted of members of 11 health plans, aged >34 years, with a pharmacy claim for celecoxib or rofecoxib or a nonselective NSAID dispensed between February 1, 1999, and July 31, 2001, who had been continuously enrolled for >364 days before the dispensing date. Celecoxib and rofecoxib patients were randomly selected without replacement from a pool of eligible users in each of the 30 months. Nonselective NSAID users were randomly chosen without replacement within each month on a 2:1 ratio to cases; they could be chosen in more than one month. Univariate analyses comparing 9000 cases and 18 000 controls were performed, followed by a multiple logistic regression analysis conditioned on time. RESULTS: Increasing age, treatment by a rheumatologist or an orthopedic specialist, treatment with a high number of different medications in the past year, treatment with oral corticosteroids in the past year, and having had a previous GI bleed increased the likelihood of receiving celecoxib or rofecoxib, whereas treatment with a high number of nonselective NSAID prescriptions in the past year decreased it. Treatment with a high number of different medications was a predictor of increased prevalence of underlying diabetes mellitus and cardiovascular disease. CONCLUSIONS: Patients having a greater underlying disease burden were more likely to receive COX-2 selective NSAIDs than nonselective ones. Paradoxically, patients at higher risk for cardiovascular disease were channeled toward treatment with COX-2 selective NSAIDs, many of which may confer an increased risk of acute myocardial infarction and other adverse cardiovascular outcomes.

Lactulose in the Management of Constipation: A Current Review

1992 ◽  
Vol 26 (10) ◽  
pp. 1277-1282 ◽  
Author(s):  
Theresa V. Kot ◽  
Ngaire A. Pettit-Young
Keyword(s):  
Clinical Trials ◽  
Adverse Effects ◽  
Clinical Studies ◽  
Data Extraction ◽  
Point Of View ◽  
Data Synthesis ◽  
Study Selection ◽  
Beneficial Response ◽  
A Current

OBJECTIVE: To review the current published clinical studies evaluating the clinical efficacy and safety of lactulose compared with other laxatives or placebo. Adverse effects associated with lactulose are also reported. DATA SOURCES: Information was retrieved by searching the MEDLINE and EMBASE databases for clinical trials, abstracts, conference proceedings, and review articles dealing with lactulose. STUDY SELECTION: Emphasis was placed on clinical trials where lactulose was compared with other laxatives or placebo in patient populations where the diagnosis of constipation was reasonably established. DATA EXTRACTION: The methodology and results from clinical studies were evaluated. Assessment of the studies was made based on diagnosis of constipation, prior management of patients, follow-up of patients, dosage, and adverse effects. DATA SYNTHESIS: Clinical trials in geriatric patients, terminally ill patients, children, and normal and constipated subjects were reviewed. In most instances, lactulose was compared with a placebo, without incorporating the current education on dietary techniques for improving defecation. CONCLUSIONS: Generally, clinical trials have demonstrated a beneficial response compared with placebo, although sometimes that response has been only marginally better, from a clinical point of view.

Risankizumab for the Treatment of Moderate to Severe Plaque Psoriasis

2019 ◽  
Vol 54 (4) ◽  
pp. 380-387 ◽  
Author(s):  
Wendy Li ◽  
Rima Ghamrawi ◽  
Wasim Haidari ◽  
Steven R. Feldman
Keyword(s):  
Clinical Trials ◽  
Phase Ii ◽  
Plaque Psoriasis ◽  
Data Extraction ◽  
Severity Index ◽  
Phase Iii ◽  
Cochrane Library ◽  
Severe Plaque Psoriasis ◽  
Phase Iii Clinical Trials ◽  
Interleukin 23

Objective: Risankizumab (Skyrizi), an interleukin-23 (IL-23) antagonist, was approved by the Food and Drug Administration (FDA) for the treatment of moderate to severe plaque psoriasis in April 2019. This article will review phase II and III clinical trials to assess the efficacy, safety, and clinical application of this drug. Data Sources: A systematic literature review was performed using the terms “psoriasis AND risankizumab” in the OVID MEDLINE, PubMed, Cochrane Library, EMBASE, and Web of Science databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies. Study Selection and Data Extraction: Articles written in English between January 2000 and October 2019 discussing phase II and phase III clinical trials were evaluated. Data Synthesis: By the primary end point at week 16 in phase III trials, more patients achieved Psoriasis Area and Severity Index 90 receiving 150 mg risankizumab (72%-75%) compared with placebo (2.0%-4.9%, P < 0.001), 45 or 90 mg ustekinumab (42.0%-48%, P < 0.0001), and 40 mg adalimumab (47%, P < 0.0001). More patients achieved a static Physician’s Global Assessment score of 0 or 1 receiving 150 mg risankizumab (84%-88%) compared with placebo (5.1%-7.8%, P < 0.001), 45 or 90 mg ustekinumab (62%-63%, P < 0.0001), and 40 mg adalimumab (60%, P < 0.0001). Risankizumab was well tolerated across all studies. Conclusion: Risankizumab is a newly FDA-approved IL-23 inhibitor that shows particular promise in the treatment of plaque psoriasis. Based on this review, it is an effective and safe addition to the armamentarium of biologics that are currently available.

Recombinant human thyrotropin stimulated 131I treatment for multinodular goiter

2016 ◽  
Vol 55 (06) ◽  
pp. 228-235 ◽  
Author(s):  
Limin Tang ◽  
Tiekun Ma ◽  
Fengyu Wu
Keyword(s):  
Adverse Effects ◽  
Data Extraction ◽  
Thyroid Volume ◽  
131I Therapy ◽  
Cochrane Library ◽  
131I Treatment ◽  
Significant Difference ◽  
High Doses ◽  
Recombinant Human Thyrotropin ◽  
The Cochrane Library

SummaryThe aim of the study was to investigate the effects of rhTSH stimulation before 131I treatment in patients with MNG. Methods: Sources included the Cochrane Library, MEDLINE, EMBASE, and SCOPUS database (all until January 2016). Randomized controlled trials (RCTs) that assessed the efficacy of rhTSH-stimulated 131I treatment compared to placebo or 131I treatment alone were collected. Two authors performed the data extraction independently. Results: Six RCTs involving 294 patients with MNG were included in this review. Altogether 168 patients were randomized to rhTSH-stimulated 131I therapy, and 126 to either placebo and 131I or 131I alone. rhTSH-stimulated 131I vs placebo and 131I or 131I alone for MNG showed no statistically significant difference in quality of life and all-cause mortality. rhTSH- (at a dose of 0.03 mg and above) stimulated 131I treatment for MNG showed significant benefits in thyroid volume reduction. 131I treatment with rhTSH stimulation at high doses (0.03 mg, 0.1 mg, 0.3 mg and 0.45 mg) for MNG caused significantly higher adverse effects and hypothyroidism. Conclusions: The overall results indicated that using rhTSH at high doses of 0.03–0.45 mg before 131I therapy resulted in a greater TVR than 131I therapy alone for patients with non-toxic MNG. However, an increased incidence of adverse effects and hypothyroidism was observed in patients receiving highdose of rhTSH pretreatment than in patients who received low-dose rhTSH pretreatment. Therefore, a dose of 0.03 mg rhTSH pretreatment before 131I therapy may be more potent than 131I alone in treating patients with non-toxic MNG who either had a contraindication for or declined surgery.

Angioedema Associated with Aspirin and Rofecoxib

2005 ◽  
Vol 39 (5) ◽  
pp. 944-948 ◽  
Author(s):  
Leisa L Marshall
Keyword(s):  
White Woman ◽  
Skin Testing ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Aspirin Therapy ◽  
Probability Scale ◽  
Antiinflammatory Drugs ◽  
Case Summary ◽  
Cox 2 ◽  
Cox 2 Inhibitors ◽  
Auto Injector

OBJECTIVE: To report the probable association of angioedema with aspirin therapy and the selective cyclooxygenase-2 (COX-2) inhibitor rofecoxib. CASE SUMMARY: A 44-year-old white woman, previously tolerant to aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs), developed angioedema of the lips after ingesting two 325-mg aspirin tablets during one day. The reaction occurred 3 hours after taking the second aspirin and resolved within 3 hours. Two weeks later, the patient took a 25-mg rofecoxib tablet for a sore throat, and she developed angioedema 51/2 hours later. Although the woman took 50 mg of diphenhydramine, the swelling did not subside. She repeated the diphenhydramine dose in the evening and, by noon the next day, 261/2 hours after the angioedema began, it was resolved. The patient's internist prescribed an epinephrine auto-injector and advised her to consult an allergist. With skin testing and oral rechallenge with aspirin, but not rofecoxib, the allergist determined the cause of the reactions to be aspirin-induced angioedema and selective COX-2 inhibitor intolerance. The Naranjo probability scale indicated that aspirin was a highly probable cause and rofecoxib was a probable cause of this patient's angioedema. DISCUSSION: Aspirin-induced angioedema and NSAID intolerance have been well documented. There are reports of both tolerance and intolerance to selective COX-2 inhibitors in patients with documented allergy-like reactions to aspirin and NSAIDs. CONCLUSIONS: Patients with aspirin and NSAID intolerance may develop intolerance to COX-2 inhibitors, especially with repeated exposure.

Effect of Structural Modification of Enol−Carboxamide-Type Nonsteroidal Antiinflammatory Drugs on COX-2/COX-1 Selectivity

1997 ◽  
Vol 40 (6) ◽  
pp. 980-989 ◽  
Author(s):  
Edward S. Lazer ◽  
Clara K. Miao ◽  
Charles L. Cywin ◽  
Ronald Sorcek ◽  
Hin-Chor Wong ◽  
...  
Keyword(s):  
Structural Modification ◽  
Nonsteroidal Antiinflammatory Drugs ◽  
Antiinflammatory Drugs ◽  
Cox 2 ◽  
Cox 1

scholarly journals Immediate Rescue Designs in Pediatric Analgesic Trials

2015 ◽  
Vol 122 (1) ◽  
pp. 150-171 ◽  
Author(s):  
Joe Kossowsky ◽  
Carolina Donado ◽  
Charles B. Berde
Keyword(s):  
Clinical Trials ◽  
Rescue Medication ◽  
Study Groups ◽  
Cochrane Library ◽  
Future Research ◽  
Control Groups ◽  
Antiinflammatory Drugs ◽  
Assay Sensitivity ◽  
Pain Scores ◽  
Opioid Sparing

Abstract Background: Designing analgesic clinical trials in pediatrics requires a balance between scientific, ethical, and practical concerns. A previous consensus group recommended immediate rescue designs using opioid sparing as a surrogate measure of analgesic efficacy. The authors summarize the performance of rescue analgesic designs in pediatric trials of four commonly used classes of analgesics: opioids, nonsteroidal antiinflammatory drugs, acetaminophen, and local anesthetics. Methods: MEDLINE, Embase, CINAHL, The Cochrane Library, and Web of science were searched in April 2013. The 85 studies selected were randomized or controlled clinical trials using immediate rescue paradigms in postoperative pain settings. A random-effects meta-analysis was used to synthesize predefined outcomes using Hedges’ g. Difference between the means of the treatment arms were also expressed as a percentage of the corresponding value in the placebo group (placebo-treatment/placebo). Distributions of pain scores in study and control groups and relationships between opioid sparing and pain scores were examined. Results: For each of the four study drug classes, significant opioid sparing was demonstrated in a majority of studies by one or more of the following endpoints: (1) total dose (milligram per kilogram per hour), (2) percentage of children requiring rescue medication, and (3) time to first rescue medication (minutes). Pain scores averaged 2.4/10 in study groups, 3.4/10 in control groups. Conclusions: Opioid sparing is a feasible pragmatic endpoint for pediatric pain analgesic trials. This review serves to guide future research in pediatric analgesia trials, which could test whether some specific design features may improve assay sensitivity while minimizing the risk of unrelieved pain.

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