mobic and Osteoarthritis

Topics: Animals; Carbazoles; Dog Diseases; Dogs; Meloxicam; Osteoarthritis; Randomized Controlled Trials as Topic; Treatment Outcome

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Diclofenac; Gastrointestinal Diseases; Humans; Meloxicam; Myocardial Infarction; Osteoarthritis; Risk

Topics: Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Drug Interactions; Female; Humans; Male; Meloxicam; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Thiazines; Thiazoles

BestBETs for Vets are generated by the Centre for Evidence-based Veterinary Medicine at the University of Nottingham to help answer specific questions and assist in clinical decision making. Although evidence is often limited, they aim to find, present and draw conclusions from the best available evidence, using a standardised framework. A more detailed description of how BestBETs for Vets are produced was published in a previous issue of Veterinary Record (VR, April 4, 2015, pp 354-356).

Topics: Animals; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Meloxicam; Osteoarthritis; Pain; Randomized Controlled Trials as Topic; Thiazines; Thiazoles

Osteoarthritis (OA) is very common in the cat and in many cases is associated with significant long-term pain, which limits mobility and activity, and severely compromises the animal's quality of life.. The treatment of chronic arthritic pain is a major challenge and many analgesic drugs used in other species are not licensed, not available or not tested for use in the cat. Many older cats with painful OA have some degree of chronic kidney disease (CKD) and many clinicians are reluctant to use non-steroidal anti-inflammatory drugs (NSAIDs) in these animals because of the potential for nephrotoxicity.. There are several publications that show that meloxicam is an effective NSAID for the cat and can be used long-term. It is easy to administer and there is published evidence that meloxicam can actually slow the progression of CKD in this species. Many other drugs are used to treat chronic pain in the cat but there is no documented evidence of their efficacy in OA. Unlike the dog, there is limited evidence for the effectiveness of omega-3 fatty acid-rich diets in managing feline OA and further work is required. There is no published data as yet for the usefulness or otherwise of nutraceuticals (glucosamine and chondroitin) in managing feline OA; studies in the authors' clinic suggest some pain-relieving effect. Research into environmental enrichment as a way of improving quality of life in cats with painful OA is lacking, but it is an approach worth using where possible. Modifications to the environment (eg, provision of comfortable bedding and ramps) are also important.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Evidence-Based Medicine; Meloxicam; Osteoarthritis; Thiazines; Thiazoles

To identify and critically evaluate the quality of evidence of the most commonly used pharmacologic, nutraceutical, and purported slow-acting drugs of osteoarthritis for the management of osteoarthritis in dogs by use of the FDA's evidence-based medicine scoring system.. Systematic review.. 16 clinical trials.. A broad bibliographic search was performed prior to May 2006. Inclusion criteria focused on prospective trials evaluating commonly used medical treatment interventions for the management of osteoarthritis in dogs and published in peer-reviewed journals. The analysis consisted of the following: study design rating, quality factor rating, quantity rating, consistency rating, relevance to disease risk reduction rating, and cumulative strength of evidence ranking.. 4 trials evaluating meloxicam were rated as type I. Three trials evaluating carprofen were rated as type I, and 2 trials were rated as type III. One trial evaluating each of the following agents was rated as type 1: etodolac; P54FP; polysulfated glycosaminoglycan; and a combination of chondroitin sulfate, glucosamine hydrochloride, and manganese ascorbate. Two trials evaluating pentosan polysulphate and 2 trails evaluating green-lipped mussels were rated as type I. One trial evaluating hyaluronan was rated as type III.. A high level of comfort exists for meloxicam that the claimed relationship is scientifically valid and that its use is clinically efficacious for the treatment of osteoarthritis in dogs. A moderate level of comfort exists for carprofen; etodolac; pentosan polysulphate; green-lipped mussels; P54FP; polysulfated glycosaminoglycans; and a combination of chondroitin sulfate, glucosamine hydrochloride, and manganese ascorbate. An extremely low level of comfort exists for hyaluronan.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chondroitin; Clinical Trials as Topic; Dog Diseases; Dogs; Evidence-Based Medicine; Glucosamine; Meloxicam; Osteoarthritis; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome

To observe the rate of efficacy and adverse drug reaction of non-steroidal anti-inflammatory drugs (NSAIDs) in the population with osteoarthritis and rheumatoid arthritis, based on available clinical data.. Using Meta analysis to evaluate the data of effect and safety profile of NSAIDs from 19 articles on randomized clinical trials published from 1990 to 2001 in Chinese journals. The total number of patients enrolled for evaluation on rates of effectiveness and adverse drug reaction were 1 732 and 2 925, respectively.. Data on the effect and safety were comparatively heterogeneous among different kinds of NSAIDs. The effective rates (95% CI) were as follows: nabunetone, 66.7% (61.9% - 71.4%); meloxicam, 68.4% (59.2% - 77.6%); naproxen, 64.5% (59.8% - 69.1%); nimesulide, 79.8% (75.7% - 84.0%); ibuprofen, 77.2% (70.7% - 83.8%); diclofenac, 77.1% (69.2% - 85.0%); oxaprozin, 65.8% (59.5% - 72.0%). Rates of adverse drug reaction (95% CI) were as follows: nabunetone, 16.3% (12.5% - 20.0%); meloxicam, 10.2% (4.2% - 16.2%); naproxen, 29.2% (24.8% - 33.6%); nimesulide, 20.2% (16.0% - 24.3%); ibuprofen, 16.7% (14.7% - 18.8%); diclofenac, 19.3% (11.9% - 26.7%); oxaprozin, 12.7% (8.9% - 16.7%) respectively.. The rates of effect and adverse reaction on patients having osteoarthritis and rheumatoid arthritis with NSAIDs treatment would largely depend on the drugs being used. Within 2 - 8 weeks of treatment, the effective rate and rate of adverse drug reaction with commonly used NSAIDs as nabumeton, meloxicam, etc., were 59.2% - 85.0% and 4.2% - 33.6%, respectively.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Butanones; China; Diclofenac; Humans; Ibuprofen; Meloxicam; Nabumetone; Naproxen; Osteoarthritis; Oxaprozin; Propionates; Randomized Controlled Trials as Topic; Sulfonamides; Thiazines; Thiazoles

Meloxicam (Mobic trade mark, Boehringer Ingelheim) is a relatively new oral non-steroidal anti-inflammatory drug (NSAID) approved for the treatment of osteoarthritis in the US. It has also been evaluated for the treatment of rheumatoid arthritis, ankylosing spondylitis and acute 'rheumatic' pain. Meloxicam has been shown to be COX-2 preferential, particularly at its lowest therapeutic dose, and is anti-inflammatory by inhibiting prostanoid synthesis in inflammatory cells. Since it is COX-2 preferential, it would be expected to have less gastrointestinal toxicity than non-selective NSAIDs. In clinical trials of meloxicam in osteoarthritis, it was found to be as effective as piroxicam, diclofenac and naproxen with less clinical gastrointestinal symptoms and less perforations, obstructions and bleeds by meta-analysis. Adverse events, including peripheral oedema and hypertension, occurred at a similar rate as with traditional NSAIDs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Interactions; Humans; Meloxicam; Osteoarthritis; Pain; Product Surveillance, Postmarketing; Spondylitis, Ankylosing; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Drug Hypersensitivity; Humans; Isoenzymes; Meloxicam; Osteoarthritis; Pain Measurement; Thiazines; Thiazoles; Treatment Outcome

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase Inhibitors; Gastrointestinal Diseases; Humans; Meloxicam; Osteoarthritis; Spondylitis, Ankylosing; Thiazines; Thiazoles

Most studies of nonsteroidal anti-inflammatory drugs (NSAID) do not demonstrate appreciable differences in efficacy. As awareness of the adverse effects associated with NSAID use increases, safety is becoming the primary concern among physicians when selecting NSAID for use by their human patients. However, veterinarians may be less aware of the safety concerns associated with NSAID use. A wide range of NSAID is used to treat human beings with osteoarthrits; however, it is imperative to remember that dogs are especially sensitive to these drugs, and reports of serious, and occasionally fatal, complications are numerous. Carprofen is a propionic acid-derived NSAID that has anti-inflammatory, analgesic, and antipyretic activity. In animals, carprofen is as potent as indomethacina and more potent than aspirin or phenlbutazone, but carprofen appears to be safer than most other NSAID.

Topics: Acetaminophen; Analgesics, Non-Narcotic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Carbazoles; Clonixin; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Ibuprofen; Indomethacin; Ketoprofen; Meclofenamic Acid; Meloxicam; Naproxen; Osteoarthritis; Pain; Phenylbutazone; Piroxicam; Thiazines; Thiazoles

Nonsteroid antiinflammatory drugs (NSAIDs) or aspirin-like drugs act by inhibiting the activity of the cyclooxygenase (COX) enzyme. Two isoforms of COX exist, COX-1, which is constitutively expressed, and COX-2, which is an inducible isoform. Prostaglandins synthesized by the constitutively expressed COX-1 are implicated in the maintenance of normal physiological function and have a 'cytoprotective' action in the stomach. COX-2 expression is normally low but is induced by inflammatory stimuli and cytokines. It is thought that the antiinflammatory actions of NSAIDs are caused by the inhibition of COX-2, whereas the unwanted side effects, such as gastrointestinal and renal toxicity, are caused by the inhibition of the constitutively expressed COX-1. Individual NSAIDs show different selectivities against the COX-1 and COX-2 isoforms. NSAIDs that are selective towards COX-2, such as meloxicam, may have an improved side-effect profile over current NSAIDs. In addition to their use as antiinflammatory agents in the treatment of rheumatoid arthritis and osteoarthritis, selective COX-2 inhibitors may also be beneficial in inhibiting colorectal tumor cell growth and in delaying premature labor.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Aspirin; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Humans; Isoenzymes; Meloxicam; Membrane Proteins; Osteoarthritis; Prostaglandin-Endoperoxide Synthases; Prostaglandins; Thiazines; Thiazoles

Nonsteroidal antiinflammatory drugs (NSAIDs) exert their actions by inhibiting cyclooxygenase (COX). It has recently been postulated that NSAIDs' antiinflammatory efficacy arises from inhibition of the COX-2 isoform of cyclooxygenase, whereas inhibition of the COX-1 isoform produces the troublesome and sometimes serious gastric and renal side effects of NSAIDs. A relatively selective COX-2 inhibitor, such as meloxicam, may combine antiinflammatory efficacy with improved tolerability. In volunteers, indomethacin 75 mg, but not meloxicam 7.5 mg, inhibited renal prostaglandin E2 excretion and platelet aggregation (COX-1 mediated effects). Double-blind, randomized trials in osteoarthritis and rheumatoid arthritis patients have shown equivalent antiinflammatory efficacy among meloxicam 7.5 mg or 15 mg and diclofenac 100 mg, naproxen 750 mg, and piroxicam 20 mg. In a double-blind, placebo-controlled trial, meloxicam (7.5 or 15 mg) caused less endoscopically detected gastrointestinal (GI) damage (Lanza scale) than piroxicam 20 mg. The MELISSA study, a double-blind, randomized, 28-day trial in over 9,000 patients showed that meloxicam 7.5 mg caused statistically less total GI toxicity, dyspepsia, abdominal pain, nausea and vomiting, and diarrhea than diclofenac 100 mg, despite equivalent reductions in pain on movement for each treatment. A global safety analysis of clinical trials, representing over 5,600 patients and comprising 170 and 1,100 patient-years of exposure for meloxicam 7.5 mg and 15 mg, respectively, showed that meloxicam caused less GI toxicity and fewer peptic ulcers and GI bleeds than naproxen, diclofenac, or piroxicam. The renal safety profile and incidence of liver function abnormalities with meloxicam is equivalent to other NSAIDs available for clinical use. In conclusion, relatively selective COX-2 inhibition exemplified by meloxicam may offer effective symptom relief with an improved GI tolerability profile.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Gastrointestinal Diseases; Guinea Pigs; Humans; Isoenzymes; Kidney Diseases; Meloxicam; Membrane Proteins; Mice; Osteoarthritis; Prostaglandin-Endoperoxide Synthases; Thiazines; Thiazoles

Meloxicam is a new once daily non-steroidal anti-inflammatory drug (NSAID). Double-blind trials in over 5000 patients with osteoarthritis and rheumatoid arthritis have shown that meloxicam 7.5 mg and 15 mg are significantly more effective than placebo and comparable in efficacy to standard NSAIDs such as naproxen 750-1000 mg, piroxicam 20 mg and diclofenac 100 mg slow release. In a global safety analysis, both meloxicam doses produced significantly fewer gastrointestinal (GI) side effects than the comparators (p < 0/05). Severe GI side effects, discontinuations due to GI side effects and less serious events such as dyspepsia and abdominal pain were also significantly less frequent with meloxicam. Perforations, ulcerations and bleedings occurred in 0.1%, 0.2%, 1.2%, 0.6% and 2.1% of meloxicam 7.5 mg, 15 mg, piroxicam, diclofenac and naproxen patients respectively (p < 0.05 for piroxicam and naproxen compared with meloxicam). This improved safety profile is likely to be due to meloxicam's selective inhibition of COX-2 relative to COX-1.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Kidney Diseases; Male; Meloxicam; Osteoarthritis; Randomized Controlled Trials as Topic; Thiazines; Thiazoles; Treatment Outcome

Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID) developed for the treatment of rheumatoid arthritis and osteoarthritis. It has greater in vitro and in vivo inhibitory action against the inducible isoform of cyclo-oxygenase (COX-2), which is implicated in the inflammatory response, than against the constitutive form of this enzyme (COX-1), inhibition of which is associated with gastric, renal and other adverse effects. It has anti-inflammatory effects similar to or better than those of other NSAIDs in animal models, and a greater therapeutic ratio (ulcerogenic potential:efficacy in adjuvant arthritis). In healthy volunteers meloxicam 7.5 or 15 mg caused less gastrointestinal mucosal damage on endoscopy than piroxicam 20 mg, with a significant difference between meloxicam 7.5 mg and piroxicam. In comparative clinical trials, meloxicam was at least as effective as piroxicam and naproxen in patients with rheumatoid arthritis, and diclofenac and piroxicam in patients with osteoarthritis. Meloxicam was at least as well tolerated as piroxicam, diclofenac or naproxen overall but had improved gastrointestinal tolerability compared with these agents.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biological Availability; Clinical Trials as Topic; Half-Life; Humans; Meloxicam; Osteoarthritis; Thiazines; Thiazoles

To evaluate the analgesic efficacy of meloxicam oral transmucosal spray (OTMS) alone and with tramadol in cats with osteoarthritis (OA).. Randomized, blinded study.. Fifteen geriatric cats weighing 4.5 ± 1.0 kg.. Healthy cats with OA were randomly administered a placebo (every 12 hours orally) and meloxicam OTMS (approximately 0.05 mg kg. Mean ± standard deviation peak vertical force (percentage of body weight) increased significantly in both groups (p = 0.02), from 47.7 ± 6.5% to 60.5 ± 9.4% in group M, and from 51.8 ± 5.0% to 64.1 ± 6.5% in group TM, with no difference between groups. Motor activity increased in M (from 43 ± 12 to 56 ± 13; p = 0.02), but not in TM. The number of stimulations from RMTS increased in TM only. Cut-off values were reached in a larger number of cats (n = 5) in TM than M (n = 1) (p < 0.05). Gastrointestinal adverse effects were self-limiting in six cats, including five in TM.. Meloxicam OTMS had similar effects on peak vertical force, motor activity and pain sensitization as previously reported for oral meloxicam in OA cats. The tramadol-meloxicam combination provided no evident benefit over meloxicam alone, except for central hypersensitivity (assessed with RMTS). Further assessment of the potential toxicity of the combination is required prior to clinical use. Gingival administration was well accepted overall.

Topics: Administration, Mucosal; Analgesics, Opioid; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Drug Therapy, Combination; Female; Male; Meloxicam; Oral Sprays; Osteoarthritis; Pilot Projects; Single-Blind Method; Thiazines; Thiazoles; Tramadol

To compare the efficacy of meloxicam and a glucosamine-chondroitin (Glu-Ch) supplement in the management of feline osteoarthritis (OA).. Prospective, blinded, randomized clinical trial. Cats over eight years of age with clinical signs of chronic OA were assigned to one of two groups and Glu-Ch or meloxicam was administered orally for 70 days, followed by a placebo until day 98. Cats were assessed by a veterinarian on five occasions and the owner completed an assessment form at the same time.. Data were collected from thirty cats. Pre-treatment disease scores were significantly higher in the meloxicam group for owner mobility (p=0.01) and veterinary lameness (p=0.02). Owner mobility scores at day 14 (p=0.01) and day 42 (p=0.002) were significantly improved compared to pre-treatment scores for the meloxicam group. When meloxicam and Glu-Ch were discontinued and the placebo commenced, a significant proportion of the meloxicam group showed worsening of all the owner-assessed scores between day 70 and day 98, when compared to the Glu-Ch group (mobility p=0.01; activity p=0.02; temperament p=0.04; lifestyle p=0.01).. Treatment with meloxicam resulted in a significant improvement in mobility and activity levels of cats with OA until the placebo was introduced. A greater proportion of cats receiving meloxicam medication showed a significant worsening of owner assessment scores once the placed was introduced, when compared to the Glu-Ch group.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Chondroitin; Dietary Supplements; Female; Glucosamine; Male; Meloxicam; Osteoarthritis; Thiazines; Thiazoles

NSAIDs are the cornerstone of medical management of canine osteoarthritis (OA). Meloxicam is a daily-administered NSAID widely available in a liquid formulation and manufacturer's summary of product characteristics (SPC) advise that it is given at the lowest effective dose. Mavacoxib is a long-acting NSAID given as a monthly tablet. This study compares these drugs in the management of canine OA. In all, 111 dogs with OA of the elbow, hip or stifle were randomly assigned to receive one of these NSAIDs for a 12-week period, and to administer them as per the manufacturer's SPC. Outcomes, including ground reaction forces and three validated clinical metrology instruments, were measured at baseline, 6 and 12 weeks. Improvements were seen in all outcome measures for both groups to a similar degree, and adverse events occurred at a similar rate. There were significant improvements in outcome measures from week 6 to week 12, as well as from baseline. Long-term meloxicam dose was more important than recent dose. Clinical efficacy and adverse event rates are similar for meloxicam and mavacoxib when administered as per their UK SPC. This is relevant information for veterinary surgeons when prescribing NSAID treatment for canine OA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Dog Diseases; Dogs; Female; Male; Meloxicam; Osteoarthritis; Pyrazoles; Thiazines; Thiazoles; Treatment Outcome

This study aimed to characterize osteoarthritis (OA)-related chronic pain and disability in experimental cats with naturally occurring OA. Peak vertical ground reaction force (PVF), accelerometer-based motor activity (MA) and the von Frey anesthesiometer-induced paw withdrawal threshold were used to define OA and to test the efficacy of meloxicam. A diagnosis of OA was based on radiographic and orthopedic examinations. Cats with OA (n=39) and classified as non-OA (n=6) were used to assess the reliability and sensitivity of the parameters to assess OA over 3weeks while being administered placebo medication. A randomised parallel design study was then used to investigate the effects on OA of daily oral meloxicam treatment for 4weeks at different dose rates (0.025mg/kg, n=10mg/kg; 0.04mg/kg, n=10; 0.05mg/kg, n=9), compared to cats administered a placebo (n=10). The test-retest repeatability for each tool was good (intra-class correlation coefficient ⩾0.6). The PVF and the von Frey anesthesiometer-induced paw withdrawal threshold discriminated OA (P<0.05). Meloxicam did not add to the PVF improvement observed in placebo-treated cats during the treatment period (adj-P⩽0.01). The 0.025 and the 0.05mg/kg meloxicam-treated cats experienced a higher night-time (17:00-06:58h) MA intensity during the treatment period compared to the placebo period (adj-P=0.04, and 0.02, respectively) and this effect was not observed in the placebo group. The high allodynia rate observed in the 0.04mg/kg meloxicam-treated group may explain the lower responsiveness to the drug. The von Frey anesthesiometer-induced paw withdrawal threshold demonstrated no responsiveness to meloxicam. The results from this study indicated that daily oral meloxicam administration for 4weeks provided pain relief according to night-time MA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Chronic Pain; Dose-Response Relationship, Drug; Female; Hyperalgesia; Male; Meloxicam; Osteoarthritis; Pain Measurement; Thiazines; Thiazoles

Non-steroidal anti-inflammatory drugs (NSAIDs) are an effective and common treatment for chronic pain disorders, but long-term use is associated with risk of potentially life-threatening gastrointestinal adverse events (AEs). The proton pump inhibitor esomeprazole has been found to be effective for gastroprotection in NSAID users, but few long-term studies have been conducted in Japan.. This was an open-label, multicentre, single-arm, prospective 1-year study of treatment with esomeprazole (20 mg once daily) in Japanese patients (aged ≥20 years) with endoscopic evidence of previous peptic ulcer and receiving daily oral NSAID therapy (at a stable dose) for a chronic condition. Eligibility was not dictated by type of oral NSAID. The primary objective was to determine long-term safety and tolerability of esomeprazole. Efficacy for prevention of peptic ulcers was also determined (Kaplan-Meier method). All statistical analyses were descriptive.. A total of 130 patients (73.1% women, mean age 62.1 years, 43.8% Helicobacter pylori-positive) received treatment with esomeprazole in addition to long-term NSAID therapy (most commonly for rheumatoid arthritis [n=42] and osteoarthritis [n=34]). Loxoprofen, meloxicam and diclofenac were the most commonly used NSAIDs; cyclo-oxygenase (COX)-2 selective agents were used by 16.2% of patients (n=21). Long-term compliance with esomeprazole (capsule counts) was >75% for the majority of patients. Although 16.9% of patients (n=22) experienced AEs judged to be possibly related to treatment with esomeprazole, they were mostly mild and transient. The most commonly reported possibly treatment-related AEs were abnormal hepatic function, headache, increased γ-glutamyltransferase levels and muscle spasms (2 patients each). Overall, 95.9% (95% confidence interval: 92.3, 99.4) of patients remained ulcer free at 1 year.. Long-term treatment with esomeprazole (20 mg once daily) is well tolerated and efficacious for preventing ulcer recurrence in Japanese NSAID users with a history of peptic ulcer.. ClinicalTrials.gov identifier NCT00595517.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diclofenac; Esomeprazole; Female; gamma-Glutamyltransferase; Headache; Humans; Japan; Liver Function Tests; Male; Meloxicam; Middle Aged; Osteoarthritis; Peptic Ulcer; Phenylpropionates; Proton Pump Inhibitors; Secondary Prevention; Spasm; Thiazines; Thiazoles; Time Factors

The clinical safety and efficacy of a transmucosal oral spray (TMOS) formulation of meloxicam was evaluated for the control of pain and inflammation associated with osteoarthritis in dogs. A total of 280 client-owned dogs were enrolled at fourteen veterinary clinics: there were 187 dogs in the meloxicam TMOS group and 93 in the placebo control group. Dogs received placebo or treatment spray once daily for twenty-eight days. Improvement in signs of osteoarthritis was measured using client-specific outcome measures (CSOM) made at days 14 and 28 and veterinary assessments of lameness and pain on palpation made at day 28. A significantly higher number of dogs in the meloxicam TMOS group were treatment successes at 28 days (72.6%) compared with the placebo group (46.9%), based on CSOM scores. Total CSOM scores were significantly lower in the meloxicam TMOS-treated group compared with the placebo group at both 14 and 28 days. Differences between treatment groups were not observed in veterinary assessments. Gastrointestinal effects of meloxicam were observed in some animals. Meloxicam TMOS was found to be safe and effective in dogs for the control of pain and inflammation associated with osteoarthritis.

Topics: Administration, Mucosal; Aerosols; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dog Diseases; Dogs; Female; Male; Meloxicam; Osteoarthritis; Thiazines; Thiazoles

To evaluate the anti-inflammatory effect of Silymarin in patients with knee osteoarthritis (OA) in comparison with piroxicam and meloxicam.. A double-blind clinical trial was performed at the Department of Rheumatology, Baghdad Teaching Hospital, Baghdad, Iraq during the period from October 2004 to September 2005, in which 220 patients (79 males and 141 females) with painful knee osteoarthritis were randomized into 5 groups, treated with either silymarin (300 mg/day), piroxicam (20 mg/day), meloxicam (15 mg), or a combination of silymarin with piroxicam or meloxicam. Serum levels of interleukin-1 alpha, interleukin-8, and the complement proteins C3 and C4 were assessed at zero time, and after 8 weeks.. Silymarin reduces significantly serum levels of IL-1 alpha and IL-8, C3 and C4 after 8 weeks compared to the pre-treatment levels. Piroxicam showed no significant reduction in IL-1 alpha levels, while IL-8 decreased significantly, compared to pre-treatment value. Meloxicam elevates serum levels of IL-1 alpha significantly, while IL-8 did not significantly change compared to the pre-treatment value. Piroxicam or meloxicam produced slight, non-significant increase in serum levels of complement proteins after the 8-week treatment period. Adjunct use of silymarin with piroxicam results in significant reduction in both cytokines (IL-1 alpha and IL-8), and serum levels of C3 and C4. However, its adjunct use with, meloxicam did not reveal any significant changes in this respect.. Silymarin reduces the elevated levels of interleukins and complement proteins, when used alone, or in combination with NSAIDs for the treatment of knee OA.

Topics: Adult; Aged; Anti-Inflammatory Agents; Female; Humans; Knee; Male; Meloxicam; Middle Aged; Osteoarthritis; Piroxicam; Silymarin; Thiazines; Thiazoles

To evaluate the in vivo effects of firocoxib, meloxicam, and tepoxalin on prostaglandin (PG) and leukotriene production in duodenal mucosa and other target tissues in dogs with chronic osteoarthritis (OA).. 8 dogs with chronic, unilateral OA of the stifle joint.. In a crossover design, each dog received placebo (no treatment), firocoxib, meloxicam, or tepoxalin for 7 days, followed by a 21-day washout period. On the first day of treatment (day 0; baseline) and days 2, 4, and 7, samples of whole blood, synovial fluid, and gastric and duodenal mucosae were collected. Prostaglandin E2 concentrations were measured in synovial fluid of the stifle joint and after ex vivo stimulation of whole blood samples. Synthesis of PGE1 and PGE2 was measured in samples of gastric and duodenal mucosae. Concentrations of thromboxane B2 (TxB2) were measured in whole blood samples. Leukotriene B4 (LTB4) concentrations were measured in samples of whole blood (ex vivo stimulation) and gastric and duodenal mucosae.. Firocoxib, meloxicam, and tepoxalin significantly suppressed whole blood concentrations of PGE2, compared with baseline and placebo concentrations, at days 2, 4, and 7. Tepoxalin significantly suppressed serum TxB2 concentrations, compared with baseline, firocoxib, meloxicam, and placebo, at all 3 time points. Production of PGE1 and PGE2 was significantly lower in duodenal versus gastric mucosa. Tepoxalin significantly decreased rates of PGE1 and PGE2 in duodenal and gastric mucosae, compared with baseline rates.. PG production was lower in the duodenum than in the stomach. Firocoxib had a COX-1-sparing effect in vivo.

Topics: 4-Butyrolactone; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dog Diseases; Dogs; Duodenum; Female; Intestinal Mucosa; Leukotrienes; Male; Meloxicam; Osteoarthritis; Prostaglandins; Pyrazoles; Sulfones; Synovial Fluid; Thiazines; Thiazoles

Osteoarthritis is a chronic, painful condition that is now recognised as affecting a large proportion of cats. Non-steroidal anti-inflammatory drugs (NSAIDs) have proven efficacy in dogs and humans but there are limited published data on the use of NSAIDs in the long-term management of this condition in cats. This prospective study aimed to assess the long-term safety and palatability of oral meloxicam and its efficacy in treating osteoarthritic pain in cats when given at a dose of 0.01-0.03 mg/kg once daily. Forty cats diagnosed with osteoarthritis completed the trial with a mean treatment duration of 5.8 months. Gastrointestinal upset in 2/46 (4%) cats was the only adverse effect noted. No deleterious effect on renal function was detected in cats studied. Owners subjectively assessed treatment efficacy as good or excellent in 34/40 (85%) of cases. The results of this study showed oral meloxicam to be safe and palatable long-term treatment for osteoarthritis in cats when given with food at a dose of 0.01-0.03 mg/kg.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cat Diseases; Cats; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Female; Male; Meloxicam; Osteoarthritis; Thiazines; Thiazoles; Treatment Outcome

To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs.. 8 client-owned dogs with clinical signs of osteoarthritis.. Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations.. Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib.. At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.

Topics: Animals; Aspirin; Carbazoles; Cross-Over Studies; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Female; Gene Expression Regulation; Hemostasis; Male; Meloxicam; Osteoarthritis; Platelet Aggregation; Prostaglandins; Sulfonamides; Thiazines; Thiazoles

The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Carbazoles; Chondroitin Sulfates; Chronic Disease; Dog Diseases; Dogs; Double-Blind Method; Gait; Glucosamine; Lameness, Animal; Manganese Compounds; Meloxicam; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prospective Studies; Severity of Illness Index; Stifle; Thiazines; Thiazoles; Treatment Outcome

The aim of this study was to evaluate the efficacy and tolerability of meloxicam compared with diclofenac in patients with osteoarthritis of the lumbar spine.. 229 patients with radiologically confirmed osteoarthritis of the lumbar spine.. Once-daily meloxicam 7.5 mg tablet or diclofenac 100 mg slow release tablet. Efficacy and tolerability parameters were assessed at baseline and after 3, 7 and 14 days of treatment.. The two drugs had equal short-term efficacy, with pain on motion of lumbar spine significantly (p<0.05) decreased at Day 3. Secondary efficacy variables were also significantly improved at Days 3, 7 and 14. There were no statistically significant differences between the two drugs, although the global tolerability of meloxicam was significantly better than for diclofenac, as assessed by the investigators (p = 0.0072) and the patients (p = 0.049).. Meloxicam and diclofenac were equivalent in relieving the acute pain associated with osteoarthritis of the lumbar spine. However, meloxicam was much better tolerated.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Diclofenac; Double-Blind Method; Female; Humans; Lumbar Vertebrae; Male; Meloxicam; Middle Aged; Osteoarthritis; Spinal Diseases; Thiazines; Thiazoles

This paper reviews recent studies that have aimed to establish the relative bioavailability of a new oral formulation of meloxicam, and to evaluate its safety and efficacy in a clinical setting. For the bioavailability study, 16 healthy volunteers were randomised to receive either an oral or a solid formulation of meloxicam 15 mg. The performance of the oral suspension was tested in 286 patients with osteoarthritis who were randomised to receive either formulation at 7.5 mg daily. It was found that the new oral suspension was bioequivalent to the capsules formulation, and was more rapidly absorbed after a single dose. No clinical differences were observed in both efficacy and tolerability parameters with either type of formulation in patients with osteoarthritis. The oral suspension was well accepted by the patients. Hence, the oral suspension provides a useful alternative to solid formulations in the treatment of inflammatory joint diseases and painful musculoskeletal disorders.

Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Cyclooxygenase Inhibitors; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis; Suspensions; Thiazines; Thiazoles

A prospective, open trial to evaluate the safety and efficacy of oral meloxicam 7.5 mg once daily over a period of 28 days in Thai patients with osteoarthritis was conducted in 3 major hospitals in Bangkok, Thailand. A total of 137 patients were enrolled and completed the study protocol. The mean age of the patients was 57.6 years and 88 per cent were female. Pain on movement and pain at rest evaluated after treatment by visual analog scale (VAS) were significantly improved with respect to the baseline status (p<0.001). The final efficacy was reported as satisfactory or good in 97 per cent and 94 per cent as determined by patients and physicians respectively. Patient status evaluated at the end of the study reported improvement of their arthritic condition in 84 per cent. Drug tolerability assessed by patients and physicians and was good or satisfactory in 99 per cent and 98 per cent. GI adverse event was reported in 8.8 per cent. Other adverse events were itching/rash in 2.0 per cent and headache/insomnia in 1.5 per cent of patients. No patients withdrew from the study due to adverse events. No GI bleeding or perforation were observed. No hospitalization was observed during the study. There was no significant change of blood chemistry and hematological profile between pre and post treatment examination. Results from this study suggest that oral meloxicam 7.5 mg for 28 days is a safe and effective treatment regimen with high GI tolerability profile for the treatment of osteoarthritis in Thai patients.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis; Pain Measurement; Prospective Studies; Thiazines; Thiazoles

A clinical trial was conducted to evaluate the safety and efficacy of the nonsteroidal anti-inflammatory drug meloxicam in dogs with chronic osteoarthritis. Forty clinical cases were enrolled in the 2-phase study. Phase 1 compared therapeutic efficacy and tolerance of meloxicam or placebo for 1 week. Phase 2 involved a 4-week evaluation of the drug's clinical efficacy and tolerance. Clinical efficacy was evaluated by using a scoring system that assessed specific lameness, general stiffness, painful rise, exercise intolerance, and behavior. Evaluations demonstrated significant reductions (P < 0.05) in clinical signs of osteoarthritis following 4 weeks of drug therapy. Side effects were minimal in extent and duration. The drug was accepted without problems in the majority of cases. The findings of this investigation suggest that the efficacy, tolerance, and formulation of meloxicam oral suspension make it well suited for the treatment of chronic osteoarthritis in the dog.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Dog Diseases; Dogs; Female; Male; Meloxicam; Osteoarthritis; Thiazines; Thiazoles; Treatment Outcome

Meloxicam (Mobic; Boehringer Ingelheim, Ridgefield, Conn) is an enolic acid derivative of the oxicam group of nonsteroidal anti-inflammatory drugs (NSAIDs) whose mechanism of action may be related to prostaglandin (cyclooxygenase) synthetase inhibition. In previous studies, meloxicam has been found to be safe and effective in the treatment of osteoarthritis (OA) at doses of 7.5 to 15 mg daily. To evaluate a lower dose and a different patient population, we evaluated the efficacy and safety of 3 doses of meloxicam vs placebo and diclofenac for the treatment of OA among patients with symptom exacerbations.. In this double-blind, double-dummy, parallel-group, multicenter study, 774 patients with confirmed OA of the hip or knee and a flare were randomized and treated with daily oral administration of meloxicam tablets (at dosages of 3.75, 7.5, or 15 mg/d), diclofenac (100 mg [50 mg twice daily]), or placebo. Treatment was for 12 weeks, with regular assessments for drug safety and efficacy. Safety was assessed by evaluation of adverse events, vital signs, and laboratory data. Primary efficacy variables included the Western Ontario and McMaster University Osteoarthritis (WOMAC) index, the patient's overall assessment of pain, and the patient's and investigator's overall assessment of disease activity.. The incidence of all adverse events was lower at each dosage of meloxicam than for diclofenac but greater than for placebo. However, the incidence of gastrointestinal adverse events and dropout rates because of such events was the same for meloxicam as for placebo and lower than for diclofenac. Meloxicam, at 7.5 and 15 mg/d, and diclofenac were statistically significantly more effective than placebo for all end points, while the 3.75-mg/d dosage of meloxicam did not always reach statistical significance for all end points. Efficacy was evident after 2 weeks of treatment, improved with increasing doses, and was maintained until the end of the trial.. Meloxicam is a safe and effective medication for the symptomatic treatment of OA. The data support consideration of 7.5 to 15 mg of meloxicam once daily to treat the pain and stiffness of OA, with gastrointestinal tolerability comparable to that of placebo. Arch Intern Med. 2000;160:2947-2954

Topics: Adult; Aged; Cyclooxygenase Inhibitors; Diclofenac; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis; Thiazines; Thiazoles; Treatment Outcome

Increasingly, MCOs ask pharmaceutical companies for evidence of a new product's cost effectiveness before adding it to the formulary. This article examines a research partnership between a pharmaceutical company and 14 MCOs to assess the cost effectiveness of a new medication for osteoarthritis. The research partnership, a study protocol, and research activities are discussed.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cooperative Behavior; Cost-Benefit Analysis; Cyclooxygenase Inhibitors; Drug Industry; Formularies as Topic; Humans; Managed Care Programs; Meloxicam; Osteoarthritis; Research; Thiazines; Thiazoles; United States

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Drug Hypersensitivity; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis; Thiazines; Thiazoles; Treatment Outcome

Response and tolerance study of a novel nonspecific antiinflammatory drug meloxikam (movalis) in patients with osteoarthrosis (OA).. 630 OA patients entered a multicenter trial in 29 hospitals. Movalis was given in a dose 7.5 mg or 15 mg (groups 1 and 2, respectively). In poor response the dose 7.5 mg was raised to 15 mg. The course of treatment took 2-4 weeks. The effect was assessed in scores by changes in the complaints.. Movalis has a significant antiinflammatory and analgetic effect, improved joint function, diminished severity of arthralgia and synovitis. Side effects were occasional.. Movalis introduction in wide rheumatological practice will raise effectiveness of OA treatment and reduce the risk of side effects.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Female; Humans; Isoenzymes; Male; Meloxicam; Osteoarthritis; Pain Measurement; Russia; Safety; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome

To test effectiveness of a new nonsteroid antiinflammatory drug movalis in osteoarthritis.. 113 patients aged 30-85 years from 8 Moscow clinics were treated with movalis. All the patients had long-standing osteoarthritis, 26 patients had concomitant gastric or duodenal ulcers. Movalis was given in daily dose from 7.5 to 15 mg for 1-4 weeks.. None case of ulcer onset or recurrence was observed. The response was rated as good in 44.2, satisfactory in 47.0% and bad in 8.8% of the cases. Tolerance was good in 99.1% of patients and bad in 0.9%.. Movalis has a definite antiinflammatory and analgetic activity in patients with osteoarthritis and spondylarthrosis.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Isoenzymes; Male; Meloxicam; Middle Aged; Moscow; Osteoarthritis; Pain Measurement; Retrospective Studies; Thiazines; Thiazoles; Treatment Outcome

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID), with a favourable ratio of inhibition of cyclooxygenase-2 (COX-2)/cyclooxygenase-1 (COX-1), giving the drug the potential to produce few gastric adverse effects. The aim of this study was to investigate the efficacy and safety of meloxicam in patients with osteoarthritis (OA) of the knee. Five hundred and thirteen patients were treated in a double-blind trial comparing once-daily meloxicam 7.5 mg, 15mg, 30mg, or placebo (140, 134, 102 and 137 patients, respectively). Outcome measures included scores on Visual Analogue Scales (VAS) for pain on movement (primary endpoint) and pain at rest in the target joint as well as global efficacy. Lesquesne's index of severity and paracetamol consumption were also measured. Global tolerability and the occurrence of adverse events were monitored. Both meloxicam 7.5 mg and 15 mg were significantly more effective than placebo with respect to pain on movement (p < 0.01 and p < 0.03, respectively). Both doses of meloxicam compared favourably with placebo with respect to pain of the target joint at rest, although only the 15 mg dose achieved statistical significance (p < 0.02). Global efficacy showed a significant difference for both doses of meloxicam (p < 0.05 and p < 0.002 for 7.5 mg and 15 mg doses, respectively). Once daily meloxicam 7.5 and 15 mg is effective and well tolerated in the short term symptomatic treatment of OA of the knee.

Topics: Administration, Oral; Aged; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Female; Humans; Knee Joint; Male; Meloxicam; Middle Aged; Osteoarthritis; Pain Measurement; Safety; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome

Although widely used, non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a high incidence of gastrointestinal (GI) side-effects. Inhibition of the cyclooxygenase (COX) enzyme is the basis for both the efficacy and toxicity of NSAIDs. The discovery of two COX isoforms, constitutive COX-1 and inducible COX-2, has led to the hypothesis that selective inhibition of COX-2 will minimize the potential for GI toxicity without compromising efficacy. The Meloxicam Large-scale International Study Safety Assessment (MELISSA) trial reported here was therefore set up to investigate the tolerability of meloxicam, a preferential inhibitor of COX-2, compared to diclofenac. MELISSA was a large-scale, double-blind, randomized, international, prospective trial, conducted over 28 days in patients with symptomatic osteoarthritis. Patients received either meloxicam 7.5 mg or diclofenac 100 mg slow release, the recommended doses for the treatment of osteoarthritis. Evaluation of the profile of adverse events was the main aim of the trial, together with assessment of efficacy. A total of 9323 patients received treatment (4635 and 4688 in the meloxicam and diclofenac groups, respectively). Significantly fewer adverse events were reported by patients receiving meloxicam. This was attributable to fewer GI adverse events (13%) compared to diclofenac (19%; P < 0.001). Of the most common GI adverse events, there was significantly less dyspepsia (P < 0.001), nausea and vomiting (P < 0.05), abdominal pain (P < 0.001) and diarrhoea (P < 0.001) with meloxicam compared to diclofenac. Five patients on meloxicam experienced a perforation, ulcer or bleed vs seven on diclofenac (not significant). No endoscopically verified ulcer complication was detected in the meloxicam group compared to four with diclofenac. There were five patient days of hospitalization in patients on meloxicam compared to 121 with diclofenac. Adverse events caused withdrawal from the study in 254 patients receiving meloxicam (5.48%) compared to 373 (7.96%) on diclofenac (P < 0.001). These differences were attributable to differences in reported GI adverse events (3.02% on meloxicam vs 6.14% on diclofenac; P < 0.001). Differences in efficacy, as assessed by visual analogue scales, consistently favoured diclofenac. In all instances, 95% confidence intervals did not cross zero, suggesting a statistically significant effect. However, differences were small (4.5-9.01% difference) and did not reach pre-determined

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Diclofenac; Double-Blind Method; Female; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Isoenzymes; Male; Meloxicam; Middle Aged; Osteoarthritis; Patient Dropouts; Peptic Ulcer; Prospective Studies; Thiazines; Thiazoles; Treatment Outcome

SELECT is a large-scale, prospective, international, multicentre, double-blind, double-dummy, randomized, parallel-group trial. Patients with exacerbation of osteoarthritis were treated with the recommended dose of meloxicam (7.5 mg) or piroxicam (20 mg) once daily for 28 days; 4320 patients were administered meloxicam and 4336 piroxicam. The incidence of adverse events was significantly lower in the meloxicam group (22.5%) compared with the piroxicam group (27.9%; P < 0.001), mainly due to the significantly lower incidence of gastrointestinal (GI) adverse events in the meloxicam than in the piroxicam group (10.3% vs 15.4%,; P < 0.001), while the efficacy of both drugs was equivalent. Individual GI events occurred significantly less often with meloxicam than piroxicam: dyspepsia (3.4% vs 5.8%; P < 0.001), nausea/vomiting (2.5% vs 3.4%; P < 0.05) and abdominal pain (2.1% vs 3.6%; P < 0.001). There were 16 patients with perforations, ulcerations or bleeding (PUBs) of the upper GI tract in the piroxicam group compared with seven in the meloxicam group (relative risk piroxicam:meloxicam = 1.4). Four PUBs were complicated (perforations or bleedings); none of these occurred in the meloxicam group (relative risk piroxicam:meloxicam = 1.9). The outcome of SELECT is consistent with that of the large-scale clinical trial of similar design and size which compared 7.5 mg meloxicam with 100 mg diclofenac in patients with osteoarthritis, and with a previous global analysis of the safety of meloxicam. It adds further data to the proposed relationship between selective inhibition of cyclooxygenase-2 and improved GI tolerability of non-steroidal anti-inflammatory drugs.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Isoenzymes; Male; Meloxicam; Middle Aged; Osteoarthritis; Piroxicam; Prospective Studies; Thiazines; Thiazoles; Treatment Outcome

Meloxicam is a new nonsteroidal anti-inflammatory drug (NSAID), which, in animal tests, displays a high potency for anti-inflammatory and analgesic action. The aim of this study was to investigate the efficacy and tolerability of 15 mg meloxicam in comparison with 100 mg slow-release diclofenac in patients with osteoarthritis of the knee. Two hundred and fifty-eight patients were included in the intent-to-treat analysis; these were randomized into two groups to receive either 15 mg meloxicam (N = 128) or 100 mg diclofenac (N = 130) for a period of 6 weeks. The results with respect to efficacy showed a trend in favor of meloxicam regarding pain on movement, global efficacy and paracetamol consumption, although these differences did not reach statistical significance. The most frequently-occurring adverse events in both groups were of a gastrointestinal (GI) nature. However, there was a higher incidence (26 vs 16%) of GI adverse events in the diclofenac group compared with the meloxicam group. Both drugs were well tolerated when assessed by the patients on a visual analog scale (VAS). Thus, 15 mg meloxicam is an effective and well-tolerated therapy for osteoarthritis and compares favorably with diclofenac 100 mg, a well-established treatment for this indication.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Double-Blind Method; Female; Humans; Knee Joint; Male; Meloxicam; Osteoarthritis; Pain Measurement; Thiazines; Thiazoles

A multicentre, double-blind, randomized study was conducted in patients with osteoarthritis (OA) of the hip or knee in order to compare the efficacy and safety of the new cyclooxygenase-2 (COX-2) inhibitor, meloxicam, with diclofenac sodium, a conventional treatment for this condition. Three hundred and thirty-six patients were treated with oral meloxicam 7.5 mg once daily or diclofenac 100 mg slow release once daily for 6 months. There were no significant differences between the treatment groups with respect to overall pain, pain on movement, global efficacy or quality of life scores at the end of treatment, all of which showed good levels of improvement. Sixty-six patients were withdrawn after the start of the double-blind phase due to adverse events (n = 21, meloxicam; n = 31, diclofenac) or to lack of efficacy (seven in each group). The median of dose paracetamol taken concomitantly was statistically significantly lower in the meloxicam group than in the diclofenac group (185 vs 245 mg/day; P = 0.0123) with a comparable proportion of patients taking concomitant paracetamol therapy in both groups. Both drugs were well tolerated, although severe adverse events, treatment withdrawal and clinically significant laboratory abnormalities were more common with diclofenac than with meloxicam. Thus, meloxicam 7.5 mg is a safe and effective treatment for OA of the hip and knee which demonstrates a trend towards an improved safety profile compared with diclofenac.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Diclofenac; Double-Blind Method; Drug Tolerance; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis; Quality of Life; Thiazines; Thiazoles; Time Factors; Treatment Outcome

This multicentre, randomized, open controlled study compared the local and overall tolerability of i.m. meloxicam with i.m. piroxicam in 211 patients with rheumatoid arthritis (RA) (n = 95) or osteoarthritis (OA) (n = 116). Of these, 210 patients were randomized (2:1) to receive meloxicam 15 mg (n = 144) or piroxicam 20 mg (n = 66) for 7 days. Local tolerability of meloxicam was significantly better than piroxicam with respect to occurrence of redness after the first injection (P = 0.03) and global assessment after the first and final injections (P < 0.05). No rise in creatinine phosphokinase levels (a marker of muscle fibre damage) was observed with meloxicam, in contrast to piroxicam (P = 0.0001). The overall tolerability of both treatments was good. Significant differences in favour of meloxicam were observed for global efficacy assessed by the patient in RA (P < 0.05) and for overall pain intensity in OA patients (P = 0.02). In conclusion, i.m. meloxicam is safe and effective for the treatment of acute rheumatic pain and shows some superiority over piroxicam.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Tolerance; Female; Humans; Injections, Intramuscular; Male; Meloxicam; Middle Aged; Osteoarthritis; Piroxicam; Thiazines; Thiazoles; Treatment Outcome

Meloxicam is a new non-steroidal anti-inflammatory drug (NSAID) which has shown potent anti-inflammatory properties but good gastrointestinal (GI) renal tolerability. The safety and tolerability profile of orally administered meloxicam 15 mg given once daily over a 28 day treatment period in renally impaired patients with rheumatic disease is presented here. A total of 25 patients (aged 43-78 yr, mean age 70 yr) with rheumatic disease and mild renal impairment were enrolled in this multicentre, open-label study, with 22 patients completing the 28 day treatment period. The median estimated creatinine clearance and N-acetyl-beta-glucosaminidase/creatinine ratios (a marker of renal tubular damage) recorded at day 14, day 28 or 4-7 days after meloxicam treatment was terminated, were not statistically significantly different from baseline values. There was no evidence of accumulation of meloxicam. Overall, meloxicam was well tolerated. The most common adverse events were GI complaints of abdominal pain and dyspepsia. No adverse events related to the urinary system, or increases in serum urea or potassium were recorded. The results suggest that meloxicam, 15 mg once daily, does not further compromise renal function or result in accumulation of meloxicam over this treatment period in patients with pre-existing mild renal impairment.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Drug Tolerance; Female; Humans; Kidney Diseases; Male; Meloxicam; Middle Aged; Osteoarthritis; Thiazines; Thiazoles; Treatment Outcome

The local tolerability, safety and efficacy of meloxicam 15 mg suppositories were compared with piroxicam 20 mg suppositories over a 3-week period in a single-blind, randomized study in patients with osteoarthritis. Patients were randomized 2:1 to receive meloxicam (n = 216) or piroxicam (n = 109). More than 90% of patients and investigators assessed local tolerability of both treatments as good or very good (primary endpoint). There was no significant difference between the groups. Global efficacy was reported by approximately 80% of patients in both groups to be good or very good. Pain on movement and at rest and joint mobility showed statistically significant improvements compared with baseline with both meloxicam and piroxicam; there were no statistically significant differences between treatment groups. Piroxicam and meloxicam suppositories were equally well tolerated, with no serious adverse events recorded in either treatment group. Local adverse events occurred in 11.9% of patients receiving piroxicam and 6.9% of those receiving meloxicam. Overall, gastrointestinal adverse events were the most frequent of all 11.9% of piroxicam-treated patients). In both groups, about 90% of global tolerability assessments were classified, by the investigator and the patient, as either very good or good. In conclusion, meloxicam 15 mg suppositories showed excellent local tolerability accompanied by good safety and efficacy in osteoarthritis, which was comparable to that of an established non-steroidal anti-inflammatory drug (NSAID) administered by the rectal route, and to that previously observed with oral formulations of meloxicam 15 mg.

Topics: Adult; Aged; Aged, 80 and over; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Tolerance; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis; Piroxicam; Range of Motion, Articular; Single-Blind Method; Thiazines; Thiazoles; Treatment Outcome

Anterior cruciate ligament (ACL) tear leads to post-traumatic osteoarthritis (PTOA), a significant clinical burden worldwide that currently has no cure. Recent studies suggest a role of subchondral bone adaptations in the development of PTOA. Particularly, microstructural changes in the rod-and-plate microstructure of subchondral bone may precede and contribute to OA progression. In this study, we quantified microstructural changes in subchondral trabecular rods and plates after ACL-transection for the first time in the well-established preclinical canine model of PTOA and investigated the therapeutic potentials of a bisphosphonate (zoledronate) and NSAID treatment (meloxicam). Unilateral hindlimb ACL transection was performed on skeletally-mature (2-year-old, N = 20) and juvenile (10-month-old, N = 20) male beagles. Animals were assigned to 4 groups (N = 5): ACLT, un-operated control, ACLT with zoledronate, and ACLT with meloxicam treatment. Subchondral bone microstructure was evaluated by micro-computed tomography and cartilage integrity was evaluated histologically. We found that ACL-induced subchondral bone changes depended on skeletal maturity of animals. In mature animals, significant loss of trabecular plates that resulted in reduced PR ratio occurred at Month 1 and persisted until Month 8. Zoledronate treatment prevented trabecular plate loss while meloxicam treatment did not. Whether cartilage degeneration is also attenuated warrants further investigation. In juvenile animals that have not reached skeletal maturity, transient changes in trabecular plate and rod microstructure occurred at Month 3 but not Month 9. Neither zoledronate nor meloxicam treatment attenuated bone microstructural changes or cartilage damages. Findings from this study suggest that early inhibition of bone resorption by bisphosphonate after injury may be a promising therapeutic approach to prevent alterations in subchondral bone microstructure associated with PTOA. Our results further demonstrate that pathogenesis of PTOA may differ between adolescent and adult patients and therefore require distinct management strategies.

Topics: Animals; Anterior Cruciate Ligament Injuries; Bone and Bones; Cartilage, Articular; Disease Models, Animal; Dogs; Male; Meloxicam; Osteoarthritis; X-Ray Microtomography; Zoledronic Acid

Osteoarthritis (OA) pain is the number one cause of chronic pain in dogs. Multimodal treatment, including combining safe and effective nutritional interventions with non-steroidal anti-inflammatory drugs (NSAIDs), is currently considered one of the most appropriate choices for managing OA pain. Palmitoyl-glucosamine is a feed material belonging to the ALIAmide family, whose parent molecule is the prohomeostatic lipid amide N-palmitoyl-ethanolamine. Curcumin is a promising plant antioxidant. The present study aimed at investigating whether 18-week dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain pain relief in dogs with OA-associated chronic pain receiving meloxicam (1.5 mg/ml oral suspension) on a tapering regimen (progressive 25% decrease of the original 0.1 mg/kg/day dose, on a biweekly basis) during the first 8 weeks of treatment. Pain was assessed both by the owners and veterinary surgeons, with the first using both subjective evaluation and validated metrology instruments-i.e., Helsinki Chronic Pain Index (HCPI) and Canine Brief Pain Inventory (CBPI)-while the second rating the severity of lameness and pain on palpation on two previously used 5-point scales.. A total of fifty-eight dogs with OA chronic pain entered the uncontrolled study. Pain on HCPI was considered severe at baseline (range 18-39). Based on owner's assessment, 90% of dogs who responded to meloxicam at the full-dose regimen could reduce meloxicam up to 25% of the original dose without experiencing pain worsening. Moreover, 75% of dogs was assessed as having no pain increase ten weeks after meloxicam withdrawal. A statistically significant decrease of pain severity as scored by HCPI (P < 0.0001) was observed two and ten weeks after meloxicam withdrawal compared to study entry (17.0 ± 1.05 and 15.1 ± 1.02, respectively, vs 29.0 ± 0.74; mean ± SEM). After meloxicam withdrawal, no statistically significant change in the CBPI scores was recorded. Pain on palpation and lameness significantly changed to less severe distributions along the study period (P < 0.0001).. The findings appear to suggest that dietary integration with palmitoyl-glucosamine co-micronized with curcumin was able to maintain meloxicam-induced pain relief in dogs with severe OA chronic pain.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chronic Pain; Curcumin; Dog Diseases; Dogs; Glucosamine; Lameness, Animal; Meloxicam; Osteoarthritis

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Osteoarthritis; Pain; Rats; Rats, Wistar; Thiazines

Pain syndromes, acute and chronic, against the background of inflammatory diseases (such as osteoarthritis (OA)), degenerative-dystrophic changes (involutive process, trauma) or systemic diseases (rheumatoid arthritis, etc.) dictate a steady increase in the intake of nonsteroidal anti-inflammatory drugs (NSAIDs). The choice of the most «safe NSAID» is based on the assessment of the toxicity index (the ratio when blocking cyclooxygenase (COX)) and the development of relative risks (the benefit/risk ratio). As well as those adverse events that can be detected with individual sensitivity to a specific NSAIDs, taking into account the anamnesis of previous diseases and intolerance to NSAIDs, existing chronic diseases (gastrointestinal tract, cardiovascular system, type 2 diabetes mellitus), limiting the appointment of NSAIDs. Considering these circumstances, the NSAID meloxicam (Amelotex) can be recommended for the treatment of various genesis pain syndromes. A number of studies have demonstrated the efficacy and safety of meloxicam with different methods of its administration (per oral (p/o), intramuscularly (i/m)) in the treatment of pain syndrome in the lower back, with OA, etc. Recent studies concern intravenous (i/v) meloxicam (30 mg) administration with moderate and severe postoperative pain syndrome. Today, the most commonly pain therapy scheme using meloxicam includes step-by-step administration of injectable and oral forms: meloxicam i/m (1.5 ml) for 3-5 days, followed by a transition to p/o (7.5-15 mg) intake for 14 days, or complex therapy with meloxicam (Amelotex), with muscle relaxant and B vitamins.. Болевые синдромы, острые и хронические, на фоне воспалительных (таких как остеоартрит (ОА)), дегенеративно-дистрофических изменений (инволютивный процесс, травма) или системных заболеваний (ревматоидный артрит и др.) диктуют неуклонный рост приема нестероидных противовоспалительных препаратов (НПВП). Выбор наиболее безопасного НПВП основан на оценке показателей токсичности (соотношение при блокировании циклооксигеназы — ЦОГ), относительных рисков (соотношение польза/риск), а также нежелательных явлений (НЯ), обусловленных индивидуальной чувствительностью к конкретному НПВП. Для лечения пациентов с болевыми синдромами различного генеза широко используется мелоксикам (Амелотекс). В ряде исследований были продемонстрированы эффективность и безопасность мелоксикама при разных способах его назначения при лечении боли в нижней части спины, при ОА и др. Последние исследования касаются внутривенного введения мелоксикама (30 мг) при умеренном и выраженном послеоперационном болевом синдроме. Сегодня наиболее часто применяется схема терапии боли с последовательным назначением инъекционной и пероральной (п/о) форм мелоксикама — внутримышечно по 1,5 мл (15 мг) в течение 3—5 дней с последующим переходом на п/о прием (7,5—15 мг) в течение 14 дней и комплексная терапия мелоксикамом (Амелотекс), миорелаксантом, витаминами группы B.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diabetes Mellitus, Type 2; Humans; Meloxicam; Osteoarthritis

Background Osteoarthritis (OA) is the most prevalent joint disease and a common cause of joint pain, functional loss, and disability. The severity of this disease is always associated with increased levels of proinflammatory cytokines, which play an important role in cartilage damage, synovitis, and other damage to joint tissues. The discovery that many soluble mediators such as cytokines or prostaglandins can increase the production of matrix metalloproteinases by chondrocytes led to the first steps of an inflammatory state. Several studies show that cytokines, such as interleukin 1ß, have a major role in the development of inflammation that occurs in these joints. The use of glucosamine as an adjuvant to meloxicam therapy is expected to inhibit the development of inflammatory OA. Methods The OA model in rat was induced by single injection of intraarticular monosodium iodoacetate (MIA). The development of OA was observed for 21 days. Furthermore, the evaluation of glucosamine potency as an adjuvant of meloxicam therapy for reducing IL-1ß was done by combined treatment at a low dose of meloxicam 1 mg/kg BW with glucosamine at a dose of 125, 250, or 500 mg/kg BW orally for 28 days. Response to hyperalgesia and knee joint diameter was measured on days 0, 7, 14, 21, 28, 35, 42, and 49. IL-1ß levels were measured on day 21 and day 49 after MIA injection. Results MIA injection successfully induced OA as marked by a significant difference in the time of latency to heat stimulus (p < 0.01) and a significant increase in joint diameter (p < 0.01). On day 21, IL-1ß levels showed a significant decrease in MIA injection (p = 0.05). The administration of meloxicam and glucosamine did not induce significant decrease in knee joint diameter (p > 0.10), but was able to significantly increase the latency time to heat stimulus (p < 0.01). IL-1ß levels also showed a significant decrease after administering a combination of glucosamine and meloxicam (p < 0.01). Conclusions Taken together, the use of glucosamine as an adjuvant in meloxicam therapy may be caused by the synergistic mechanism of meloxicam for the attenuation of OA development through systemically reducing IL-1ß.

Topics: Adjuvants, Pharmaceutic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Drug Therapy, Combination; Glucosamine; Interleukin-1beta; Meloxicam; Osteoarthritis; Rats

In humans, pain due to osteoarthritis has been demonstrated to be associated with insomnia and sleep disturbances that affect perception of pain, productivity, and quality of life. Dogs, which develop spontaneous osteoarthritis and represent an increasingly used model for human osteoarthritis, would be expected to show similar sleep disturbances. Further, these sleep disturbances should be mitigated by analgesic therapy. Previous efforts to quantify sleep in osteoarthritic dogs using accelerometry have not demonstrated a beneficial effect of analgesic therapy; this is despite owner-reported improvements in dogs' sleep quality. However, analytic techniques for time-series accelerometry data have advanced with the development of functional linear modeling. Our aim was to apply functional linear modeling to accelerometry data from osteoarthritic dogs participating in a cross-over non-steroidal anti-inflammatory (meloxicam) drug trial. Significant differences in activity patterns were seen dogs receiving drug (meloxicam) vs. placebo, suggestive of improved nighttime resting (sleep) and increased daytime activity. These results align with owner-reported outcome assessments of sleep quality and further support dogs as an important translational model with benefits for both veterinary and human health.

Topics: Analgesics; Animals; Dog Diseases; Dogs; Female; Humans; Male; Meloxicam; Osteoarthritis; Pain; Sleep; Sleep Initiation and Maintenance Disorders

Drug induced linear IgA bullous dermatosis (LABD) is a rare blistering disease that has been shown to be associated with the use of various medications. Although rarely seen together, some of the medications associated with LABD can lead to the syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which presents with fever, cutaneous eruption, and multi-organ involvement. We present a patient who developed fever and a generalized vesiculobullous eruption after recently starting amlodipine and meloxicam. Initial laboratory tests demonstrated elevated liver function tests, leukocystosis, and eosinophilia. Histopathologic examination of the punch biopsy revealed a bulla with sub-epidermal split and numerous neutrophils. Direct immunofluorescence demonstrated broad deposition of IgA along the dermal-epidermal junction. These findings were consistent with an overlap between LABD and DRESS. Drug induced LABD and DRESS are independently both rare diseases. It is even more uncommon to see the two concurrently in the same patient. In this patient, these two conditions were thought to be triggered by either amlodipine or meloxicam. Given the high mortality rate associated with DRESS, it is important to recognize the presentation and initiate the appropriate treatment plan as soon as possible.

Topics: Amlodipine; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Arthralgia; Drug Hypersensitivity Syndrome; Female; Humans; Hypertension; Linear IgA Bullous Dermatosis; Meloxicam; Middle Aged; Osteoarthritis

Osteoarthritis (OA) is a common progressive joint disease in dogs and cats. The goal of OA treatment is to reduce inflammation, minimize pain, and maintain joint function. Currently, non-steroidal anti-inflammatory drugs (e.g., meloxicam) are the cornerstone of treatment for OA pain, but side effects with long-term use pose important challenges to veterinary practitioners when dealing with OA pain. Palmitoylethanolamide (PEA) is a naturally-occurring fatty acid amide, locally produced on demand by tissues in response to stress. PEA endogenous levels change during inflammatory and painful conditions, including OA, i.e., they are typically increased during acute conditions and decreased in chronic inflammation. Systemic treatment with PEA has anti-inflammatory and pain-relieving effects in several disorders, yet data are lacking in OA. Here we tested a new composite, i.e., PEA co-ultramicronized with the natural antioxidant quercetin (PEA-Q), administered orally in two different rat models of inflammatory and OA pain, namely carrageenan paw oedema and sodium monoiodoacetate (MIA)-induced OA. Oral treatment with meloxicam was used as benchmark.. PEA-Q decreased inflammatory and hyperalgesic responses induced by carrageenan injection, as shown by: (i) paw oedema reduction, (ii) decreased severity in histological inflammatory score, (iii) reduced activity of myeloperoxidase, i.e., a marker of inflammatory cell infiltration, and (iv) decreased thermal hyperalgesia. Overall PEA-Q showed superior effects compared to meloxicam. In MIA-treated animals, PEA-Q exerted the following effects: (i) reduced mechanical allodynia and improved locomotor function, (ii) protected cartilage against MIA-induced histological damage, and (iii) counteracted the increased serum concentration of tumor necrosis factor alpha, interleukin 1 beta, metalloproteases 1, 3, 9 and nerve growth factor. The magnitude of these effects was comparable to, or even greater than, those of meloxicam.. The present findings shed new light on some of the inflammatory and nociceptive pathways and mediators targeted by PEA-Q and confirm its anti-inflammatory and pain-relieving effects in rodent OA pain models. The translatability of these observations to canine and feline OA pain is currently under investigation.

Topics: Administration, Oral; Amides; Animals; Anti-Inflammatory Agents; Carrageenan; Drug Combinations; Edema; Ethanolamines; Hyperalgesia; Inflammation; Male; Meloxicam; Osteoarthritis; Pain; Palmitic Acids; Quercetin; Rats, Sprague-Dawley; Thiazines; Thiazoles

The purpose of the study was to evaluate the influence of long-term non-steroidal anti-inflammatory drugs (NSAID) therapy on the dynamics of the severity of cognitive deficits and its association with changes in the level of cytokines in elderly patients with osteoarthritis (OA). The authors performed a prospective observational study during 540±5,5 days, presented in two stages: phase I - the stage of active NSAID therapy; phase II - the stage of non-pharmacological correction of OA. The first stage included 128 patients with OA from 65 to 75 years (average age 70±4,6 years, 10,2% of males and 89,8% female). Patients from the main group were divided into four subgroups: patients of the 1st group (n=30) received the drug etoricoxib at a dose of 60 mg per day; patients of the 2nd group (n=32) - celecoxib at a dose of 200 mg daily, patients of the 3rd group (n=32) - nimesulide in dose of 100 mg per day; patients of the 4th group (n=34) - meloxicam at a dose of 7,5 mg per day. The comparison group consisted of 40 patients with similar clinical and demographic characteristics of OA, not taking NSAIDs in the previous 6 months or during the study. It was determined the pain and stiffness indexes by the WOMAC initially and evaluated the patient status at the MoCA scale and carried out laboratory diagnosis of contents in serum TGF-β1, IL-1β and IL-6 at all visits. Statistically significant decrease in the level of cytokines was detected during the period of 1st-3rd visits for all patients in the groups receiving NSAID, also there was an increase in cognitive function on a scale of MoCA with a high degree of correlation in relation to the performance of cytokines to the end of the study. The results of our research allow us to speak about possible influence on cognitive functions of NSAID therapy in elderly patients with OA in real clinical practice.. Цель исследования — изучение влияния длительной терапии нестероидными противовоспалительными препаратами (НПВП) на динамику степени выраженности когнитивного дефицита и ее ассоциацию с изменением уровня цитокинов у пациентов пожилого возраста с остеоартрозом (ОА). Проспективное наблюдательное исследование в течение 540±5,5 дня проходило в два этапа: I — этап активной лекарственной терапии НПВП; II — этап немедикаментозной коррекции ОА. В исследование были включены 128 больных 65–75 лет (средний возраст 70±4,6 года, 10,2% мужчин, 89,8% женщин) с ОА. Пациентов основной группы разделили на четыре подгруппы: 1-я (n=30) — получала эторикоксиб (60 мг/сут); 2-я (n=32) — целекоксиб (200 мг/сут); 3-я (n=32) — нимесулид (200 мг/сут); 4-я (n=34) — мелоксикам (7,5 мг/сут). Контрольную группу составили 40 человек с ОА и аналогичными клинико-демографическими характеристиками, не принимавших НПВП в течение предыдущих 6 мес и в ходе исследования. Исходно определяли индексы боли и скованности по WOMAC, а также во время всех визитов оценивали состояние пациентов по Монреальской шкале когнитивной оценки (MoCA) и проводили лабораторную диагностику содержания в сыворотке крови трансформирующего ростового фактора β1, IL-1β и IL-6. У всех пациентов основной группы отмечено статистически значимое снижение уровня цитокинов в период 1-3-го визита, также наблюдали увеличение показателя когнитивных функций по шкале MoCA с высокой степенью корреляции по отношению к показателям цитокинов к концу исследования. Результаты исследования позволяют говорить о возможности влияния на когнитивные функции терапии НПВП у пациентов пожилого возраста с ОА в условиях реальной клинической практики.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Celecoxib; Cognition; Cognition Disorders; Cytokines; Etoricoxib; Female; Humans; Interleukin-1beta; Interleukin-6; Male; Meloxicam; Osteoarthritis; Prospective Studies; Pyridines; Sulfonamides; Sulfones; Thiazines; Thiazoles; Transforming Growth Factor beta1

Medications can cause photosensitivity. Several of these medications, specifically the nonsteroidal anti-inflammatory medications (NSAIDs), may be taken by athletes to treat joint and muscle discomfort. Many athletic events occur outdoors, which in turn exposes athletes to sunlight. Athletes taking NSAIDs and performing extensive outdoor activities may be at higher risk for phototoxic drug reactions. Clinicians may wish consider the potential for patient photosensitivity when recommending prescription and non-prescription medications to outdoor athletes.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Bicycling; Dermatitis, Phototoxic; Female; Humans; Meloxicam; Middle Aged; Osteoarthritis; Photosensitizing Agents; Thiazines; Thiazoles

122 patients with osteoarthrosis, who have in the past medical history verified chronic gastritis (50 males and 72 females) at the age from 42 to 64 have been examined. Control group was comprised of 40 patients with osteoarthrosis without gastroduodenal zone pathology in the past medical history. For arthralgia relief patients were prescribed meloxicam (average dose--12.5 - 1.39 mg daily) or nimesulide (average dose--150 ± 14.91 mg daily). As a result of this research it was determined that administration of selective NSAID (meloxicam and nimesulide) in patients with chronic gastritis in the past medical history raised the risk of NSAID gastropathy/dyspepsia 2.9 times (P < 0.03) than in patients without associated gastroduodenal zone pathology. Atrophy of gastric mucosa is associated with higher risks (P > 0.05) of erosive gastropathy. Patients with chronic gastritis in the past medical history when taking NSAID with the purpose of gastropathy prevention are recommended to undergo gastroprotective therapy.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Chronic Disease; Female; Gastritis; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis; Protective Agents; Sulfonamides; Thiazines; Thiazoles

To assess effects of in vitro meloxicam exposure on metabolism in articular chondrocytes from dogs with naturally occurring osteoarthritis.. Femoral head cartilage from 16 dogs undergoing total hip replacement.. Articular cartilage samples were obtained. Tissue sulfated glycosaminoglycan (SGAG), collagen, and DNA concentrations were measured. Collagen, SGAG, chondroitin sulfate 846, NO, prostaglandin E2 (PGE2), and matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, and MMP-13 concentrations in culture medium were analyzed. Aggrecan, collagen II, MMP-2, MMP-3, MMP-9, MMP-13, ADAM metallopeptidase with thrombospondin type 1 motif (ADAMTS)-4, ADAMTS-5, tissue inhibitor of metalloproteinase (TIMP)-1, TIMP-2, TIMP-3, interleukin-1β, tumor necrosis factor-α, cyclooxygenase-1, cyclooxygenase-2, and inducible nitric oxide synthase gene expression were evaluated. Comparisons between tissues cultured without (control) and with meloxicam at concentrations of 0.3, 3.0, and 30.0 μg/mL for up to 30 days were performed by means of repeated-measures analysis.. Meloxicam had no effect on chondrocyte SGAG, collagen, or DNA concentrations. Expression of ADAMTS-5 was significantly decreased in all groups on all days, compared with the day 0 value. On day 3, culture medium PGE2 concentrations were significantly lower in all meloxicam-treated groups, compared with values for controls, and values remained low. Culture medium MMP-3 concentrations were significantly lower on day 30 than on day 3 in all meloxicam-treated groups.. Results suggested that in vitro meloxicam treatment of osteoarthritic canine cartilage for up to 30 days did not induce matrix degradation or stimulate MMP production. Meloxicam lowered PGE2 release from this tissue, and effects on tissue chondrocyte content and matrix composition were neutral.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Chondrocytes; Collagen; Dog Diseases; Dogs; Female; Glycosaminoglycans; In Vitro Techniques; Male; Matrix Metalloproteinases; Meloxicam; Osteoarthritis; Real-Time Polymerase Chain Reaction; RNA; Thiazines; Thiazoles; Tissue Inhibitor of Metalloproteinases

The study sought to examine the effect of long-term meloxicam treatment on the survival of cats with and without naturally-occurring chronic kidney disease at the initiation of therapy. The databases of two feline-only clinics were searched for cats older than 7 years that had been treated continuously with meloxicam for a period of longer than 6 months. Only cats with complete medical records available for review were recruited into the study.The median longevity in the renal group was 18.6 years [95% confidence interval (CI) 17.5-19.2] and the non-renal group was 22 years [95% CI 18.5-23.8]. The median longevity after diagnosis of CKD was 1608 days [95% confidence interval 1344-1919] which compares favourably to previously published survival times of cats with CKD. In both groups the most common cause of death was neoplasia. Long-term treatment with oral meloxicam did not appear to reduce the lifespan of cats with pre-existent stable CKD, even for cats in IRIS stages II and III. Therefore, to address the need for both quality of life and longevity in cats with chronic painful conditions, meloxicam should be considered as a part of the therapeutic regimen.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Australia; Cat Diseases; Cats; Kidney Function Tests; Longevity; Meloxicam; Osteoarthritis; Renal Insufficiency, Chronic; Retrospective Studies; Risk Factors; Thiazines; Thiazoles

Medical records (2005-2009) of a feline-only practice were searched for cats with degenerative joint disease (DJD) treated using meloxicam. DJD was diagnosed by the presence of at least two of the following: (i) altered mobility (observed by the owner), (ii) abnormal physical findings, (iii) characteristic radiographic changes. The primary study cohort consisted of cats older than 7 years that had received meloxicam for variable intervals in excess of 6 months, and for which complete records were available. These cats were subdivided according to whether detectable chronic kidney disease (CKD) was present ('renal group'), or not ('non-renal group'), and, for the 'renal group', according to the cat's IRIS category. Serum biochemistry, urinalysis (including urine specific gravity [USG]), body mass and condition score were monitored regularly. Progression of CKD in the 'renal group' and 'non-renal group' of cats was compared to two groups of age- and IRIS-matched control cats not receiving meloxicam (from the same clinic, over the same time period). The study was thus a case-control design, with two study groups. Thirty-eight cats with DJD receiving long-term meloxicam therapy met the inclusion criteria. Of these, 22 cats had stable CKD at the start of treatment (stage 1, eight cats; stage 2, 13 cats; stage 3, one cat). No cats initially had an elevated urinary protein to creatinine ratio. The remaining 16 cats initially had normal renal analytes and adequately concentrated urine. The median age of the 'renal' and 'non-renal' meloxicam groups was 15.5 and 13.4 years, respectively. The median treatment duration was 467 days in the 'renal group' and 327 days in the 'non-renal group'. After titration (to the lowest effective dose), the median maintenance dose was 0.02 mg/kg/day in both groups (range 0.015-0.033 mg/kg/day). There was no difference in sequential serum creatinine concentration or USG measurements between the 'non-renal group' treated with meloxicam compared to control cats not treated with meloxicam. There was less progression of renal disease in the 'renal group' treated with meloxicam compared to the age- and IRIS-matched cats with CKD not given meloxicam. These results suggest that a long-term maintenance dose of 0.02 mg/kg of meloxicam can be safely administered to cats older than 7 years even if they have CKD, provided their overall clinical status is stable. Long-term meloxicam therapy may slow the progression of renal disease in some cats s

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Cat Diseases; Cats; Female; Kidney Function Tests; Male; Meloxicam; New South Wales; Osteoarthritis; Renal Insufficiency, Chronic; Retrospective Studies; Thiazines; Thiazoles

A monolithic drug-in-adhesive (MDIA) type patch containing meloxicam (MX) was designed with an acrylic adhesive, a solubility modulator increasing MX solubility, and enhancers. MDIA patches having one adhesive layer between the backing and the release liner give high productivity and improve patient compliance. The biggest problem to prepare MDIA patch including MX was poor solubility of MX. In this research, solubility modulators to increase solubility of MX and acrylic adhesives and skin permeation enhancers were investigated through solubility tests, in vitro skin permeation tests, and stability tests. Consequently, the composition of sodium methoxide (SM), an acrylic adhesive containing poly(vinyl pyrrolidone) blocks (MAS683), polyoxyethylene cetylether (BC-2), and diisopropanolamine (DIPA) made it possible for MX to be contained in an adhesive layer at a concentration of as much as 15 wt% without MX crystal and with high skin permeation over 400 microG/cm(2). Finally, the patch formulation containing MX (MX-patch) selected through our in vitro study was characterized by in vivo using an animal study to acquire pharmacokinetic (PK) parameters and to confirm the anti-inflammatory efficacy of MX-patch. In the animal study, MX-patch was compared with a commercially available piroxicam patch (PX-patch). The amount of MX delivered from MX-patch to the skin surface was believed to be higher than the amount of MX diffused from the skin tissue to circulatory system because the plasma concentration of MX continuously increased up to 32 h, the end time of PK study, although the patch samples were detached at 24 h. PX-patch produced a C(max) at 8 h. MX-patch showed better significant efficacy than PX-patch in adjuvant arthritis model.

Topics: Acrylic Resins; Administration, Cutaneous; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Carrageenan; Chemistry, Pharmaceutical; Diffusion; Disease Models, Animal; Dosage Forms; Drug Compounding; Drug Stability; Edema; Excipients; Freund's Adjuvant; Meloxicam; Mice; Mice, Hairless; Mycobacterium; Osteoarthritis; Permeability; Piroxicam; Povidone; Rats; Rats, Sprague-Dawley; Skin; Skin Absorption; Solubility; Technology, Pharmaceutical; Thiazines; Thiazoles; Tissue Adhesives

Sodium urate (SU) synovitis was evaluated as a model for feline arthritic pain using a placebo- and positive-controlled (meloxicam) randomized blinded controlled single crossover design. Monosodium urate crystals [20 mg (1 mL) rod-shaped] were injected into alternate stifles of trained anesthetized cats (n = 3) with a 28 day washout. During the first trial phase, two cats received meloxicam (0.1 mg/kg, PO), a nonsteroidal anti-inflammatory drug (NSAID), for three days before and on the day of SU injection; the third cat received placebo. Treatments and stifles were switched for the second trial. Total force, contact pressure and area of the fore and hind limbs were measured using a pressure mat one day and 0.5 h before, and 2, 4, 6, 8, 10, 24, and 30 h post-SU injection. Skin temperature, joint circumference, analgesia, lameness, and visual analogue scale (VAS) pain scores, were measured at the same times. Comparisons were made for each time and for areas under the curve (AUC) using original and change from baseline; P < 0.05 was significant. Significant differences in force mat data and subjective data were found for the hind limb data (total force and total contact pressure at 6, 10, and 30 h; analgesia and VAS for pain at 4 h; lameness at 10, 24, and 30 h) and for AUC(0)-->(24h) and AUC(0)-->(30 h) (total force, total contact pressure, and mean lameness score) and for differences from BL AUC(0)-->(10h) (total contact area) and AUC(0)-->(24h) (total contact area and mean lameness score) and AUC(0)-->(30 h) (total force, total contact area, and mean lameness). No cats required rescue analgesia. Injection of 1 mL of monosodium urate into the stifle of a cat causes moderate transitory pain and was suitable for assessing analgesic efficacy of an NSAID with a pressure mat and subjective criteria.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Area Under Curve; Cats; Female; Inflammation; Lameness, Animal; Meloxicam; Osteoarthritis; Pain; Pain Measurement; Pilot Projects; Severity of Illness Index; Synovitis; Thiazines; Thiazoles; Uric Acid

To test the hypothesis that naproxen, meloxicam and methylprednisolone down-regulate the plasminogen activator (PA)/plasmin system and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] expression during early development of osteoarthritis (OA).. Samples of human OA articular cartilage, meniscus and synovium were obtained at knee arthroscopy and cultured ex vivo with or without naproxen, meloxicam or methylprednisolone. MMP-2 and MMP-9 levels were evaluated by gelatin zymography and urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) levels were measured by enzyme-linked immunosorbent assay (ELISA).. Gelatin zymography revealed that naproxen, meloxicam and methylprednisolone could suppress MMP-2 secretion in all tissue cultures and MMP-9 production in meniscal and synovial cultures. ELISA showed that naproxen and meloxicam reduced u-PA secretion in chondral and synovial cultures at 48 h except in naproxen-treated chondral cultures. On PAI-1 secretion, naproxen and meloxicam had the suppressive effects in all cultures at 48 h but not in naproxen-treated meniscal cultures. Methylprednisolone also decreased u-PA secretion in chondral and synovial cultures and PAI-1 production in synovial cultures at 48 h.. Naproxen, meloxicam and methylprednisolone can down-regulate the PA/plasmin system and gelatinases expression in the early osteoarthritic knee of humans, thereby possibly have a potential structure-modifying activity in a limited use.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Gelatinases; Humans; Meloxicam; Methylprednisolone; Naproxen; Osteoarthritis; Thiazines; Thiazoles; Urokinase-Type Plasminogen Activator

To describe a method to study joint pain in experimental osteoarthritis (OA) and to study nitric oxide (NO) participation in experimental OA.. Rats were subjected to anterior cruciate ligament transection (ACLT) (OA group) of the right knee and evaluated during 28 days. A sham group was false operated and a naive group received no manipulation. Joint pain was measured by recording the time the right hind paw fails to touch the surface while walking. Cell influx (CI) and nitrite levels were measured in joint exudates. Expression of inducible NO synthase (iNOS) in synovia was detected by immunostaining. For the specific purpose of pharmacological manipulation, groups received either indomethacin (2 mg/kg/day s.c. (subcutaneous)), meloxicam (6 mg/kg/day s.c.), morphine (200 microg intra-articularly), the non-selective NOS inhibitor L-N(G)-nitroarginine methyl ester (L-NAME; 30 mg/kg/bid i.p. (intra-peritoneal)) or the selective iNOS inhibitor 1400W (0.5 mg/kg/day s.c.), given 30 min prior (prophylactic) or 4 days after (therapeutic) ACLT, until sacrifice, at 7 days. The respective non-treated groups received the vehicles.. The OA group developed joint pain, as compared to sham and control groups (P<0.05). Significantly increased nitrite levels and iNOS immunostaining were seen in the OA group. Both indomethacin and meloxicam inhibited joint pain (P<0.05). Morphine inhibited joint pain, whereas this effect was blocked by co-administration of the mu-opioid receptor naloxone. CI was similar among all groups. Prophylactic but not therapeutic L-NAME or 1400W reduced joint pain.. We describe a method to quantitate joint pain associated to weight bearing in the ACLT model. The joint pain is sensitive to classical antinociceptive compounds. NO release is associated to joint pain though NOS inhibition does not inhibit ongoing pain.

Topics: Amidines; Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Benzylamines; Exudates and Transudates; Indomethacin; Male; Meloxicam; Models, Animal; Morphine; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Osteoarthritis; Rats; Rats, Wistar; Stress, Mechanical; Synovial Membrane; Thiazines; Thiazoles

An adult male white Bengal tiger (Panthera tigris tigris) with pronounced atrophy of the pelvic musculature was diagnosed with degenerative osteoarthritis of the coxofemoral joints. Initial management with the nonsteroidal anti-inflammatory drug meloxicam and a semisynthetic sodium pentosan polysulfate resulted in clinical improvement and radiographic stabilization of the arthritic condition over several months. However, because pain was still evident, bilateral denervation of the coxofemoral joints was performed, successfully ameliorating the signs of osteoarthritic pain in the tiger. Meloxicam has shown good clinical efficacy for the treatment of osteoarthritis and other painful conditions in large felids. Coxofemoral joint denervation offers many advantages for the treatment of osteoarthritis in exotic carnivore species, and should be considered a viable treatment modality.

Topics: Animals; Animals, Wild; Anti-Inflammatory Agents, Non-Steroidal; Combined Modality Therapy; Denervation; Hip Joint; Male; Meloxicam; Osteoarthritis; Pain; Thiazines; Thiazoles; Tigers; Treatment Outcome

To evaluate in vivo effects of tepoxalin, an inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX), on prostaglandin (PG) and leukotriene production in osteoarthritic dogs.. 7 mixed-breed adult dogs with chronic unilateral arthritis of a stifle joint.. Dogs were treated in accordance with a randomized 3-way crossover design. Each dog received an inert substance, meloxicam, or tepoxalin for 10 days. On day 0 (baseline), 3, and 10, dogs were anesthetized and samples of blood, stifle joint synovial fluid, and gastric mucosa were collected. Concentrations of PGE2 were measured in synovial fluid and after lipopolysaccharide stimulation of whole blood; PGE1 and PGE2 synthesis was measured in gastric mucosa. Thromboxane B2 (TxB2) concentration was measured in whole blood. Leukotriene B4 (LTB4) concentration was determined in gastric mucosa and in whole blood after ex vivo stimulation with a calcium ionophore.. Tepoxalin significantly decreased LTB4 concentrations in the blood and gastric mucosa at day 10 and TxB2 concentrations in the blood and PGE2 in the gastric mucosa and synovial fluid at days 3 and 10, compared with baseline values. Meloxicam significantly decreased PGE2 concentrations in the blood at days 3 and 10 and synovial fluid at day 3. Meloxicam also decreased PGE1 and PGE2 synthesis in the gastric mucosa at day 3. Meloxicam did not affect LTB4 synthesis in the blood or LTB4 concentrations in the gastric mucosa.. Tepoxalin has in vivo inhibitory activity against COX-1, COX-2, and 5-LOX in dogs at the current approved recommended dosage.

Topics: Analysis of Variance; Animals; Cross-Over Studies; Cyclooxygenase Inhibitors; Dog Diseases; Dogs; Leukotrienes; Lipoxygenase Inhibitors; Meloxicam; Osteoarthritis; Prostaglandins; Pyrazoles; Thiazines; Thiazoles

Although during treatment of arthrosis with meloxicam the level of thromboxan A2 decreases, thrombocyte functions are not affected. Meloxicam in therapeutic doses doesn't increase the risk of haemorrhage. Previously it was suspected that co-administration of salicylates with certain other non-steroid antiinflammatory drugs (NSAIDs) will suppress the effect of salicylate. Van Ryn et al have proved that this is not the case with salicylate plus meloxicam therapy. It is hypothesized that meloxicam loosely binds to the cyclooxygenase-1 (COX-1) enzyme and salicylate can easily replace it.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Hemorrhage; Humans; Meloxicam; Osteoarthritis; Salicylates; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Contusions; Fasciitis, Plantar; Female; Hematoma; Humans; Meloxicam; Middle Aged; Osteoarthritis; Partial Thromboplastin Time; Thiazines; Thiazoles; Treatment Outcome

The study was to screen the possible risk factors of adverse drug reaction (ADR) induced by non-steroidal anti-inflammatory drugs (NSAIDs) in Shanghai patients with arthropathy.. The subjects were randomly selected from a database of outpatients with arthropathy from 9 main hospitals in Shanghai. A door to door retrospective epidemiological survey was used to collect demographic information about the patients, both individual and familial. This included data on their medical histories, lifestyle and dietary habits, history of smoking and alcohol consumption, history of drug therapy, quality of life (QOL) prior to NSAIDs intake, history of NSAIDs therapy and its ADR events, etc. Descriptive statistical methods and univariate analysis were also used to identify possible risk factors for ADRs induced by NSAIDs.. Of the 1002 patients surveyed, the average length of NSAIDs intake was 2 years. ADR incidence from different NSAIDs was high, in a range from 46.7 %-66.2 %. In general, the candidate risk factors for ADRs were different for each NSAID. Each of the candidate risk factors were defined and studied in order to evaluate its role in the determination of ADRs from NSAIDs. "Family history of ADRs caused by NSAIDs" was found to be a significant risk factor for the four commonly used NSAIDs: meloxicam, diclofenac, nimesulide, and nabumetone.. A retrospective epidemiological survey was useful in detecting the risk factors for ADRs caused by NSAIDs. The study found that different NSAIDs might have different risk factors and that there is no single risk factor universally applicable to all NSAIDs.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Butanones; Child; Diclofenac; Dizziness; Exanthema; Female; Gastrointestinal Hemorrhage; Humans; Male; Meloxicam; Middle Aged; Nabumetone; Osteoarthritis; Retrospective Studies; Risk Factors; Spondylitis, Ankylosing; Stomach Diseases; Thiazines; Thiazoles

To compare the relative risks of upper GI haemorrhage (UGIH) in users of Newer versus Older, non-specific NSAIDs when adjusted for channelling bias by regression on individual covariates, a propensity score and both.. Cohort study of patients prescribed NSAIDs between June 1987 and January 2000. Exposure to Newer and Older non-specific NSAIDs was identified, and risk factors evaluated for each patient. Results of multiple covariate analyses and the propensity scoring technique to assess potential channelling bias in comparisons between Newer and Older non-specific NSAIDs were compared.. This study included 7.1 thousand patient years (tpy) exposure to meloxicam, 1.6 tpy exposure to coxibs, and 628 tpy exposure to Older non-specific NSAIDs. Patients receiving Newer NSAIDs were older, more likely to have a history of GI symptoms, and at higher risk for GI complications. Adjusting for these risk factors reduced the relative risks of UGIH on meloxicam and coxibs versus Older non-specific NSAIDs to 0.84 (95%CI 0.60, 1.17) and 0.36 (0.14, 0.97) respectively.. Channelling towards high GI risk patients occurred in the prescribing of Newer NSAIDs. Propensity scores highlighted the markedly different risk profiles of users of Newer and Older non-specific NSAID. Correcting for channelling bias, coxib exposure, but not meloxicam exposure, was associated with less UGIH than Older non-specific NSAID exposure. In the present study, corrections made by regression on a propensity score and on individual covariates were similar.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Cohort Studies; Cyclooxygenase Inhibitors; Databases, Factual; Drug Utilization Review; Family Practice; Female; Gastrointestinal Hemorrhage; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis; Pharmacoepidemiology; Regression Analysis; Risk Factors; Sex Factors; Thiazines; Thiazoles; United Kingdom

To evaluate effects of meloxicam on severity of lameness and other clinical signs in dogs with osteoarthritis (OA).. Randomized, controlled, multicenter clinical trial.. 217 client-owned dogs with clinical and radiographic signs of OA.. Dogs were randomly assigned to be treated with meloxicam (n = 105; 0.2 mg/kg [0.09 mg/lb], SC, once on day 1, then 0.1 mg/kg [0.045 mg/lb], PO, q 24 h, for 13 days) or a placebo (n = 112). A general clinical score was assigned by investigators on days 1 (ie, prior to initiation of treatment), 8, and 15 on the basis of severity of lameness, extent of weight bearing, and severity of signs during palpation of the affected joint. Owners and investigators provided overall evaluations on days 8 and 15.. Dogs treated with meloxicam had significantly greater improvements in general clinical scores, compared with baseline scores, on days 8 and 15 than did dogs treated with placebo. On days 8 and 15, percentages of dogs treated with meloxicam in which owners and investigators considered treatment to be successful were significantly higher than percentages of control dogs in which treatment was considered to be successful. No abnormalities in hematologic and serum biochemical test results were detected.. Results suggest that compared with administration of a placebo, administration of meloxicam for 14 days significantly improved the clinical condition of dogs with OA without causing adverse effects.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dog Diseases; Dogs; Injections, Subcutaneous; Lameness, Animal; Meloxicam; Osteoarthritis; Random Allocation; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome

To assess the economic efficiency of meloxicam, a cyclo-oxygenase (COX)-2 selective inhibitor, versus diclofenac and piroxicam in the UK for the treatment of patients with osteoarthritis and the impact on the NHS budget of substituting nonselective NSAIDs with meloxicam. Methods and perspective: A decision analytical model was used to compare the effects of 4 weeks' treatment of osteoarthritis with meloxicam (7.5 mg/day), diclofenac (100 mg/day) and piroxicam (20 mg/day). The decision tree was derived by combining best practice and clinical reality. Analysis was from the NHS perspective. The study considered only the direct costs. These included costs for drug acquisition and management of all adverse events, both serious gastrointestinal events requiring hospitalisation, and non-serious events that required maintenance. Resource use and treatment costs were obtained from local and published sources. A range of sensitivity analyses was carried out.. Based on two 4-week large-scale trials, the Meloxicam Large-scale International Study Safety Assessment (MELISSA) and Safety and Efficacy Large-scale Evaluation of COX-inhibiting Therapies (SELECT) trials, and a decision analytical model, the findings suggested that meloxicam had the lowest cost per patient ( pound 30 versus pound 35 for piroxicam and pound 51 for diclofenac [costs presented as 1998 values except for drug costs which were in 2000 values]). The results of the Monte Carlo probabilistic sensitivity analysis, using 4000 samples, suggested that meloxicam was the optimal strategy in the drug treatment of patients with osteoarthritis compared with nonselective NSAIDs both individually and as a group. The cost savings were due to lower levels of serious adverse events accompanied by fewer days in intensive care units and shorter overall duration of hospital stay observed with meloxicam compared with diclofenac and piroxicam in the 4-week trials.. Based on the 4-week trial period, meloxicam was predicted to be the lowest cost drug therapy, and thus the optimal drug therapy, in the management of patients with osteoarthritis compared with nonselective NSAIDs such as diclofenac and piroxicam. Applying the cost savings per patient derived from the model, switching patients from piroxicam and diclofenac to meloxicam would indicate a cost saving of over pound 25 million per annum. Models such as this can facilitate better clinical guidance and is a useful way of assessing treatment outcomes.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Decision Support Techniques; Diclofenac; Humans; Meloxicam; Monte Carlo Method; Osteoarthritis; Piroxicam; Thiazines; Thiazoles

Celecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2 selective inhibitors, and were developed to minimize the risk of gastrointestinal (GI) toxicity commonly associated with non-steroidal anti-inflammatory drugs (NSAIDs). The Drug Safety Research Unit (DSRU) monitored the safety of these drugs immediately after launch in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM). Our objective was to investigate whether there is a clinically relevant difference in incidence of reported symptomatic (acid/peptic) and complicated upper GI conditions (perforations/bleeding) between celecoxib and meloxicam during use in general practice.. Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996 to March 1997) and celecoxib (May to December 2000). Simple questionnaires requesting details of events occurring during/after treatment and potential risk factors (including age, sex, history of upper GI problems, and NSAIDS prescribed within 3 months of treatment) were posted to prescribing GPs at least 6 months after the first prescription for each patient. Incidence rates of the first event were calculated; crude and adjusted rate ratios (RR) obtained using regression modelling.. For celecoxib and meloxicam, respectively, 1054 (6.0%) and 1376 (7.2%) patients had symptomatic (acid/peptic) upper GI events whereas 42 (0.2%) and 67 (0.4%) had complicated upper GI conditions (perforations/bleeding). A higher proportion of the celecoxib cohort had an indication for osteoarthritis (28.1 vs 23.2%), were female (68.3 vs 67.1%), were aged 60 yr or more (59.5 vs 55.0%), were prescribed NSAIDs within 3 months of starting treatment (49.4 vs 47.9%), and had a past medical history of upper GI conditions (54.7 vs 29.2%) than those prescribed meloxicam. This suggests differential channelling of groups at higher risk of such events on to celecoxib compared with meloxicam. There was no difference between the two drugs in the time to occurrence of either group of event. The RR over the 270-day study period for celecoxib compared with meloxicam were 0.77 (95% CI 0.69, 0.85) and 0.56 (95% CI 0.32, 0.96) for symptomatic (acid/peptic) upper GI events and complicated upper GI conditions (perforations/bleeding), respectively, adjusted for age, age2, sex, indication, medical history of upper GI problems and whether NSAIDs were prescribed within 3 months prior to starting treatment.. This study reports a relative reduction (23%) in the incidence of symptomatic (acid/peptic) GI events, and a relative reduction (44%) in the incidence rate of complicated upper GI conditions (perforations/bleeding) for celecoxib compared with meloxicam.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Celecoxib; Cohort Studies; Cyclooxygenase Inhibitors; England; Family Practice; Female; Gastrointestinal Diseases; Humans; Incidence; Male; Meloxicam; Middle Aged; Osteoarthritis; Poisson Distribution; Pyrazoles; Regression Analysis; Retrospective Studies; Risk Factors; Sulfonamides; Thiazines; Thiazoles

Rofecoxib and meloxicam are classified as cyclo-oxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit (DSRU) monitored the post-marketing safety of these drugs in England using the non-interventional observational cohort technique of prescription-event monitoring (PEM).. To compare the incidence rates of selected thromboembolic (TE)(cardiovascular, cerebrovascular and peripheral venous thrombotic) events reported for patients prescribed rofecoxib and meloxicam in general practice.. Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996 to March 1997) and rofecoxib (July to November 1999). Simple questionnaires requesting details of events recorded during/after treatment, indication and potential risk factors (including age, sex and NSAIDs prescribed within 3 months of treatment) were posted to prescribing GPs approximately 9 months after the first prescription for each patient. Incidence rates of the first event within each TE group were calculated; crude and age- and sex-adjusted rate ratios (RR) obtained using regression modelling.. During the 9 months after starting treatment, 21 (0.14%) and 19 (0.10%) patients were reported to have cardiovascular TE events, and 74 (0.48%) and 52 (0.27%) cerebrovascular TE events, and 6 (0.05%) and 20 (0.10%) were reported to have peripheral venous thrombotic events for rofecoxib and meloxicam, respectively. Regarding time to first event, there was a persistent divergence between the two drugs from the start of treatment for both the cerebrovascular TE event group (log rank test P = 0.0063) and the peripheral venous thrombotic event group (log rank test P = 0.0264). Indication and use of a NSAID within 3 months prior to starting treatment had no statistically significant effect on the relative risk estimates of the event groups and was excluded from subsequent analyses. Adjusting for the two identified risk factors of age (age2) and sex, for rofecoxib the adjusted cerebrovascular TE event group rate was higher than for meloxicam [RR 1.68 (95% CI 1.15, 2.46)]; lower than meloxicam for the peripheral venous thrombotic event group [RR 0.29 (95% CI 0.11, 0.78)], and not different for the cardiovascular TE event group [RR 1.38 (95% CI 0.71, 2.67)].. This study reports a relative increase in the rate of cerebrovascular TE events and a relative reduction in peripheral venous thrombotic events in users of rofecoxib compared with meloxicam. There was no difference in the rate of cardiovascular thromboembolic events. The incidence of these three groups of events reported in each of these two drug cohorts was low (less than 0.5%), therefore the relevance of our findings needs to be taken into consideration with other clinical and pharmacoepidemiological studies.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Chi-Square Distribution; Cohort Studies; Cyclooxygenase Inhibitors; England; Family Practice; Female; Humans; Incidence; Lactones; Male; Meloxicam; Middle Aged; Osteoarthritis; Risk Factors; Sulfones; Survival Analysis; Thiazines; Thiazoles; Thromboembolism

The purpose of this study was to evaluate the effect of the administration of meloxicam; carprofen; and a slow-acting disease modifying osteoarthritis agent, that contains chondroitin sulfate, purified glucosamine, and manganese ascorbate (CS-G-M), on thyroid function in dogs. Forty-six healthy (except for osteoarthritis) euthyroid dogs were blindly assigned to 3 treatment groups: meloxicam, carprofen, and CS-G-M. Each group received the recommended dose of the drug for 60 days. Sixteen other osteoarthritic euthyroid dogs, which received a placebo, were used as a control group to validate the study. For all groups, blood samples were collected on days 0, 30, and 60 to evaluate the serum total and free thyroxine, and endogenous thyrotropin concentrations. There were no significant differences among the treatment groups at each time or within each group over a 60-day period for all parameters. Moreover, none of these values were within the hypothyroid range. Based on the results of this study, the administration of meloxicam, carprofen, and CS-G-M did not affect canine thyroid function evaluation.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Autoantibodies; Carbazoles; Chondroitin Sulfates; Dog Diseases; Dogs; Female; Glucosamine; Longitudinal Studies; Male; Manganese Compounds; Meloxicam; Osteoarthritis; Random Allocation; Thiazines; Thiazoles; Thyroid Function Tests; Thyroid Gland; Thyrotropin; Thyroxine; Treatment Outcome

Celecoxib and meloxicam are classified as cyclooxygenase (COX)-2 selective inhibitors. The Drug Safety Research Unit monitored the post marketing safety of these drugs in England using the non-interventional observational cohort technique of Prescription-Event Monitoring (PEM).. To compare the incidence rates of selected thromboembolic (TE) (cardiovascular, cerebrovascular and peripheral venous thrombotic) events reported for patients prescribed celecoxib and meloxicam in general practice.. Patients were identified from dispensed prescriptions written by general practitioners (GPs) for meloxicam (December 1996-March 1997) and celecoxib (May and December 2000). Simple questionnaires requesting details of events occurring during/after treatment, indication and potential risk factors (including age, sex and whether NSAIDs had been prescribed within 3 months of treatment) were posted to prescribing GPs at least 6 months after the first prescription for each patient. Incidence rates of the first event were calculated; crude and adjusted rate ratios (RRs) were obtained using Poisson regression modelling.. During the 9 months after starting treatment, 28 (0.16%) and 19 (0.10%) of patients were reported to have experienced cardiovascular TE events, 68 (0.39%) and 52 (0.27%) cerebrovascular TE events, and 17 (0.10%) and 20 (0.10%) experienced peripheral venous thrombotic events for celecoxib and meloxicam, respectively. Regarding time to first event, there was a persistent divergence between the two drugs from 30 days after the start of treatment for both the cardiovascular TE event group (log rank test P = 0.0153) and cerebrovascular TE event group (log rank test P = 0.0055). Indication and use of an NSAID within 3 months prior to starting treatment had no effect on the relative risk estimates of the event groups and was excluded in subsequent analyses. Adjusting for the two identified risk factors of age (age2) and sex, the cerebrovascular TE event group rate was higher for celecoxib than for meloxicam, RR 1.66 (95% CI 1.10-2.51), over the study period and no different for the cardiovascular TE event group, RR 1.72 (95% CI 0.87-3.40) or peripheral venous thrombotic group, RR 1.06 (95% CI 0.51-2.19).. This study reports a relative increase in the rate of cerebrovascular TE events in users of celecoxib compared to meloxicam. There was no difference in the rate of cardiovascular TE events or peripheral venous thrombotic events between users of these two drugs. The incidence of these three groups of events reported in each of these two drug cohorts was low (<0.5%), therefore the relevance of our findings need to be taken into consideration with other clinical and pharmacoepidemiological studies.

Topics: Adult; Adverse Drug Reaction Reporting Systems; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Celecoxib; Cerebrovascular Disorders; Chi-Square Distribution; Cohort Studies; Cyclooxygenase Inhibitors; England; Family Practice; Female; Humans; Incidence; Male; Meloxicam; Middle Aged; Osteoarthritis; Peripheral Vascular Diseases; Pyrazoles; Risk Factors; Sulfonamides; Survival Analysis; Thiazines; Thiazoles; Thromboembolism

When new drugs with improved safety or efficacy are introduced, they may be preferentially prescribed to specific populations of patients. Safety and efficacy may be underestimated if such channelling effects are not recognized. Meloxicam and cyclooxygenase (COX)-2-specific inhibitors were developed as safer alternatives to non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of osteoarthritis and rheumatoid arthritis. Studies of the use of meloxicam and COX-2-specific inhibitors demonstrate that both of these drugs are being prescribed to patients at increased risk of gastrointestinal adverse drug events. In the case of COX-2-specific inhibitors, this channelling appears to represent a prescribing pattern consistent with current recommendations. Subsequent analysis of the data, after adjusting for channelling bias, showed that the risk of gastrointestinal toxicity for meloxicam was similar to that for other NSAIDs, while COX-2-specific inhibitors reduced the risk of developing gastrointestinal adverse drug events by approximately 60%. These studies serve as examples of observed channelling bias and highlight the need for adjusting for channelling in order to provide a valid assessment of relevant outcomes for drugs likely to be preferentially prescribed to specific populations.

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Drug Utilization; Female; Gastrointestinal Diseases; Humans; Isoenzymes; Male; Meloxicam; Membrane Proteins; Osteoarthritis; Prognosis; Prostaglandin-Endoperoxide Synthases; Risk Factors; Selection Bias; Thiazines; Thiazoles

To evaluate in vivo activity in dogs of meloxicam or aspirin, previously shown in vitro to be a selective cyclooxygenase-2 (COX-2) inhibitor (COX-1 sparing drug), or a nonselective COX inhibitor, respectively.. 12 male dogs with unilateral osteoarthritis of the stifle joint.. Each dog was treated in a crossover design with aspirin or meloxicam for 21 days. Prostaglandin E2 (PGE2) concentrations were measured at days 0 (baseline), 7, and 21 of each treatment period in lipopolysaccharide (LPS)-stimulated blood, synovial fluid collected by arthrocentesis, and endoscopic gastric mucosal biopsy specimens. Thromboxane B2 (TXB2) was evaluated in blood on days 0, 7, and 21 of each treatment period.. Aspirin administration significantly suppressed PGE2 concentrations in blood, gastric mucosa, synovial fluid, and suppressed TXB2 concentration in blood at days 7 and 21. Meloxicam administration significantly suppressed PGE2 concentrations in blood and synovial fluid at days 7 and 21, but had no effect on concentrations of TXB2 in blood or PGE2 in gastric mucosa. Suppression of LPS-stimulated PGE2 concentrations in blood and synovial fluid by aspirin and meloxicam administration is consistent with activity against the COX-2 isoenzyme. Suppression of concentrations of PGE2 in the gastric mucosa and TXB2 in blood by aspirin administration is consistent with activity against COX-1. Meloxicam, in contrast, had a minimal effect on functions mediated by COX-1.. Meloxicam acts in vivo in dogs as a COX-1 sparing drug on target tissues by sparing gastric PGE2 synthesis while retaining antiprostaglandin effects within inflamed joints.

Topics: Animals; Aspirin; Cross-Over Studies; Cyclooxygenase 1; Cyclooxygenase Inhibitors; Dinoprostone; Dog Diseases; Dogs; Gastric Mucosa; Isoenzymes; Male; Meloxicam; Osteoarthritis; Prostaglandin-Endoperoxide Synthases; Stifle; Synovial Fluid; Thiazines; Thiazoles; Thromboxane B2

The safety of cyclo-oxygenase 2 (COX-2) preferential inhibitors such as meloxicam is debated. We describe a patient who presented with bloody diarrhoea after 15 mg meloxicam daily for 10 days for osteoarthritis. The endoscopic and histological features were consistent with the diagnosis of ischaemic colitis. Symptoms and endoscopic lesions quickly regressed within 1 week of meloxicam withdrawal. There was no evidence of another cause of colonic ischaemia. We suggest that meloxicam might have intestinal toxic effects when taken in high doses, because of reduced COX-2 selectivity.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Colitis, Ischemic; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Female; Humans; Isoenzymes; Meloxicam; Membrane Proteins; Middle Aged; Osteoarthritis; Prostaglandin-Endoperoxide Synthases; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Cyclooxygenase Inhibitors; Diarrhea; Dose-Response Relationship, Drug; Drug Interactions; Humans; Meloxicam; Nausea; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Thiazines; Thiazoles

1. Since nonsteroidal anti-inflammatory drugs (NSAIDs) may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan and hyaluronan (HA) molecules produced by aceclofenac, diclofenac and meloxicam in human osteoarthritic (OA) cartilage. 2. Explants were sampled from the medial femoral condyle and were classified by use of the Mankin's histological-histochemical grading system. Cartilage specimens exhibited moderate (M) OA in 20 subjects and had severe (S) OA in 20. 3. Cartilage explants were pulsed with [-3H]-glucosamine and chased in the absence or in the presence of 0.3 - 3 microg ml(-1) of either aceclofenac, diclofenac or meloxicam. After papain digestion, the labelled chondroitin sulphate ([-3H]-proteoglycans) and [-3H]-HA molecules present in the tissue and media were purified by anion-exchange chromatography. 4. In cartilage with MOA and SOA, the metabolic balance of proteoglycan and HA was unaffected by diclofenac. In contrast, and in a dose-dependent manner, aceclofenac and meloxicam both increased the synthesis of proteoglycans and HA in explants with MOA and SOA; these two NSAIDs also reduced significantly the net loss of [-3H]-proteoglycans and [-3H]-HA molecules from cartilage explants. 5. The data obtained in short-term in vitro cultures indicate that, at the concentrations found in synovial fluid, aceclofenac and meloxicam may exert a favourable effect on the overall metabolism of proteoglycans and HA in cartilage with MOA and SOA.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cartilage, Articular; Culture Techniques; Diclofenac; Dose-Response Relationship, Drug; Extracellular Matrix; Humans; Hyaluronic Acid; Meloxicam; Osteoarthritis; Proteoglycans; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Diclofenac; Humans; Meloxicam; Osteoarthritis; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Long-Term Care; Meloxicam; Osteoarthritis; Peptic Ulcer; Risk Factors; Spondylitis, Ankylosing; Thiazines; Thiazoles

Meloxicam is a new preferential cyclooxygenase-2 (COX-2) inhibitor for the treatment of rheumatic disease. This paper presents a global safety analysis of data from meloxicam clinical studies, focusing on gastrointestinal (GI) adverse events. Meloxicam 7.5 and 15 mg (n = 893 and 3282) were compared with piroxicam 20 mg (n = 906), diclofenac 100 mg slow release (n = 324) and naproxen 750-1000 mg (n = 243). With respect to all GI adverse events, meloxicam 7.5 and 15 mg were significantly better than all comparators in a pooled analysis of double-blind studies in rheumatoid arthritis (RA) and osteoarthritis (OA). When examining non-serious GI events, severe GI events, discontinuous due to GI events, dyspepsia, abdominal pain and upper GI events, both meloxicam doses were significantly better than comparator non-steroidal anti-inflammatory drugs (NSAIDs) in most cases. Where statistical significance was not demonstrated, there was generally a trend in favour of meloxicam. With respect to upper GI perforations, ulcerations and bleedings, the most serious of NSAID-associated side-effects, meloxicam was better tolerated than the comparators, reaching statistical significance for piroxicam and naproxen. Meloxicam's improved GI safety profile is likely to be due to its preferential inhibition of inducible COX-2 relative to constitutive COX-1.

Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Clinical Trials as Topic; Double-Blind Method; Female; Gastrointestinal Diseases; Humans; Kidney Diseases; Male; Meloxicam; Middle Aged; Multicenter Studies as Topic; Osteoarthritis; Thiazines; Thiazoles