COX-2 participates in the pathogenesis of IFS-induced HC and the treatment with COX and TNF-alpha inhibitors reduced COX-2 expression. The addition of COX-inhibitors to the last two doses of Mesna represents a new therapeutic strategy of preventing HC.
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Etoricoxib, a selective inhibitor of cyclooxygenase 2, is increasingly used in pain relief. Here, we report the first case of etoricoxib-induced immune hemolytic anemia.
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Amorphous solid dispersions (ASDs) of etoricoxib were prepared with polyvinyl alcohol (PVA), polyvinyl pyrrolidone (PVP) and hydroxyethyl cellulose (HEC) at 70:30w/w ratio and characterized for glass transition temperature (Tg), miscibility and intermolecular interactions. Kinetic solubility profiles of amorphous etoricoxib and its ASDs were determined in water at 37 °C. Solid-state stability was assessed by enthalpy relaxation studies at a common degree of undercooling of around 19.0 °C at 0% RH. Recrystallization behavior of supersaturated drug solution was evaluated in the absence and presence of pre-dissolved polymer at 37 °C.
A systematic literature search was carried out for randomised, well controlled clinical trials comparing the efficacy of diclofenac with other pain relief medications in OA (reviews, meta-analyses and n = 1 trials were excluded). The databases searched were EMBASE, Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, and Ovid MEDLINE Daily Update. Articles were included from 1999 onwards. Retrieved articles were discussed by comparator medication.
Etoricoxib in 50 and 100 mg/kg doses changed the levels of oxidant/antioxidant parameters such as MDA, MPO, tGSH, GSHRd, GST, SOD, NO, and 8-OH/Gua in favour of antioxidants. Furthermore, etoricoxib prevented increase of COX-2 gene expression and ALT and AST levels. This important protective effect of etoricoxib on the rat liver I/R can be tested in the clinical setting.
There are many theories about why selective inhibitors of the second isoform of cyclooxygenase (COX-2) increase cardiovascular risk. Although torcetrapib raises blood pressure and cardiovascular risk, it has been difficult to prove such a link for COX-2 inhibitors in randomized clinical trials. This review shows a significant correlation in placebo-controlled trials between the five agents' elevations in blood pressures and their rate ratios for cardiovascular events. A larger body of evidence arises from randomized clinical trial comparisons of selective versus nonselective inhibitors of COX-2, but these results are heterogeneous for naproxen versus other traditional agents. The best current trial evidence comes from the centrally adjudicated placebo-controlled trials of celecoxib for colonic polyps: If the blood pressure did not rise at 1 or 3 years after randomization, cardiovascular risk did not significantly increase. Many more data will become available in 2013, after the only prospective clinical trial involving cardiovascular end points is completed.
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To evaluate the efficacy of 12 weeks of treatment with etoricoxib, a selective COX-2 inhibitor, in patients with osteoarthritis (OA) of the knee or hip.
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This study evaluated two doses of etoricoxib (60 and 90 mg) vs. naproxen 1000 mg in subjects with ankylosing spondylitis (AS).
Pleural effusion caused by drug is an uncommon event in clinical practice. Etoricoxib induced pleural effusion is an extremely rare. We describe a patient with pleural effusion as an adverse drug reaction of etoricoxib.
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After oral co-administration of APE (200mg/Kg) and AN (60mg/kg) with ETO (10mg/kg) in rats, drug concentrations in plasma were determined using HPLC method. The main pharmacokinetic parameters of Cmax, tmax, t1/2, MRT, Vd, CL, and AUC were calculated by non-compartment model. Change in paw volume, mechanical nociceptive threshold, mechanical hyperalgesia, histopathology and hematological parameters were evaluated to study antiarthritic activity.
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A total of 1158 COX-2 inhibitor users were identified; 96 refused to participate and 129 were excluded. The mean (SD) age of the remaining 933 COX-2 inhibitor users was 69 (15) years with 528 women (56.6%) and 405 men (43.4%). Mean time of follow-up was 12.4 months. The annual incidence of clinical upper GI events in these patients taking COX-2 inhibitors was 4.6% (44 events/959 patient-years), with symptomatic ulcers in 3.6% and ulcer complications in 1.0%. Multivariate logistic regression analysis found that a history of peptic ulcer disease (PUD) (odds ratio [OR = 4.61; 95% CI, 1.86-11.40; P = 0.001), concomitant use of steroids (OR = 2.99; 95% CI, 1.39-6.46; P = 0.005), aspirin (OR = 13.47; 95% CI, 5.89-30.82; P < 0.001), and other NSAIDs (OR = 60.49; 95% CI, 11.93-306.64; P < 0.001) were significant independent risk factors for clinical upper GI events in these patients taking COX-2 inhibitors. Age >60 years was not found to be a risk factor.
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Etoricoxib is a selective cyclo-oxygenase-2 (COX-2) inhibitor prescribed for the relief of chronic pain in osteoarthritis and rheumatoid arthritis, and acute pain. The drug is believed to be associated with fewer upper gastrointestinal adverse effects than conventional non-steroidal anti-inflammatory drugs (NSAIDs). A number of studies in acute postoperative pain have now been published.
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Both doses of etoricoxib were non-inferior to naproxen. All treatments were well tolerated. Etoricoxib 60 and 90 mg effectively control pain in patients with AS, with 60 mg once daily as the lowest effective dose for most patients.
The adverse effects of rofecoxib, celecoxib and other NSAIDs are reviewed. Relevant literature was identified on Medline and in the reference lists in key articles.
Pain is the main reason why people decide to see a doctor; hence, the widespread use of anti-inflammatory drugs which were specifically developed to control pain and inflammation. One of the main causes of pain is represented by osteoarticular conditions, the most common one being arthrosis. Paracetamol is universally indicated as the therapy of first choice in degenerative pathologies of the joints, although it is often insufficient to control adequately the clinical picture and less efficacious than anti-inflammatory drugs. These latter, however, especially when taken chronically, exhibit an unfavourable safety profile. The most common side effect of anti-inflammatory drugs is gastric discomfort; coxibs - COX-2 selective inhibitors - were developed to solve this problem. The use of these drugs, relative to conventional NSAIDs, is associated to a significantly lesser gastroduodenal ulcer rate and to fewer clinically relevant complications, as well as to a smaller rate of treatment discontinuation due to gastrointestinal (GI) symptoms. From a clinical and practical standpoint, the use of coxibs is associated to a remarkably reduced risk of gastroduodenal lesions, similar as the one resulting from the combination of a conventional NSAID and a proton-pump inhibitor. By adding a proton-pump inhibitor to a coxib, such risk seems to become virtually non-existent, even in a high risk population and regardless of ASA administration. It is important to stress that the better tolerability of coxibs does not imply an inferior anti-inflammatory and pain-relieving efficacy, especially with regard to etoricoxib, whose efficacy is at least equivalent as other competing NSAIDs, even in quite severe and complex musculoskeletal pain models. This clear-cut advantage of coxibs at gastric level clashed against a documented increased cardiovascular (CV) risk, which led to the much-talked-about withdrawal of rofecoxib from the market. The most credited pathogenetic hypothesis to explain the association between chronic use of coxibs and CV risk seems to be related to a trombophilic effect due to an imbalance of prothrombotic and antithrombotic factors. Several observational and case-control studies, however, led to suspect that conventional NSAIDs share with coxibs an increased cardiovascular risk; such suspicion was experimentally confirmed by the MEDAL trial. In this trial, the cardiovascular risk of thrombosis among patients who were treated on a long-term basis with a coxib (etoricoxib) was shown to be similar as the risk observed in patients receiving a conventional NSAID (diclofenac). In conclusion, coxibs represent a valid therapeutic option in the treatment of patients with osteoarticular conditions. In terms of cardiovascular risk their efficacy is associated to a similar safety profile as conventional NSAIDs, whereas the gastrointestinal risk related to coxibs seems to be significantly lesser.
Data were pooled from two identical 26-week double-blind, randomized flare design trials comparing etoricoxib 30 mg/day (N=475), celecoxib 200 mg/day (N=488), and placebo (N=244) in patients with OA of the hip or knee. This analysis was limited to the 12-week placebo-controlled period. Response at Week 12 was defined using Outcome Measures in Rheumatology Clinical Trials and Osteoarthritis Research Society International (OMERACT-OARSI) criteria. Factors were analyzed using logistic regression and included age, race, gender, body mass index, index joint, screening (pre-washout) and baseline (post-washout) Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index pain, physical function, and stiffness, and patient global assessment of disease status, prior NSAID/coxib or acetaminophen use, American Rheumatology Association functional class, and disease duration.
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The patient's red blood cells (RBCs) were found to be strongly coated with immunoglobulin G and C3d. Eluted antibodies and dialyzed serum from the patient were not reactive with untreated RBCs, but with etoricoxib-treated RBCs, RBCs in the presence of etoricoxib, urine containing drug metabolites (ex vivo antigen), and two of four additional COX inhibitor drugs analyzed.
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The market withdrawals of rofecoxib (Vioxx) and valdecoxib (Bextra) have focused considerable attention on the side effect profiles of cyclooxygenase (COX) inhibitors. As a result, attempts will be made to identify risk factors in the hope that physicians might be able to ensure patient safety. At first glance, CYP2C9 genotype might be considered a risk factor because many COX inhibitors are CYP2C9 substrates in vitro. This observation has led some to hypothesize that a reduction in clearance, in subjects expressing variant forms of the enzyme (e.g., CYP2C9*1/*3 or CYP2C9*3/*3 genotype), will lead to increased exposure and a greater risk of cardiovascular or gastrointestinal side effects. For any drug, however, one has to consider all clearance pathways. Therefore, a number of COX inhibitors were surveyed and it was determined that CYP2C9 plays a relatively minor role in the overall clearance (
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Proper gout management requires changes to the physician's attitude towards the disease; essentially: (1) an unequivocal diagnosis based in urate crystal identification, (2) a clearly settled aim of the treatment: crystal elimination from the joints and elsewhere, and (3) proper use of the available therapeutic alternatives. Promoting a proper lifestyle appears to be especially important.
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We investigated the effectiveness of oral etoricoxib 90 mg for seven days in a prospective two-stage study design for phase-2 clinical trials in a small sample of patients (n = 42). A cemented primary total hip arthroplasty was implanted for osteoarthritis. Six months after surgery, heterotopic ossification was determined on anteroposterior pelvic radiographs using the Brooker classification.