mobic and Kidney-Diseases

Non-steroidal anti-inflammatory drugs (NSAIDs) are known to increase the risk of cardiovascular (CV) and renal incidences, especially at higher doses and upon long term use. However, the available reports are criticized for lack of specificity, grouping of vastly different outcomes together and ignoring the heterogeneity among NSAIDs. In this systematic review, we are reporting CV/renal risks associated with meloxicam, stratified into myocardial, vascular, renal risk categories, to address the differential nature of NSAIDs effects on different body systems. We are also reporting composite CV/renal risk to present overall risk associated with various covariates.. We searched the online healthcare databases for observational studies or randomized controlled trials, reporting myocardial or all-cause mortality outcome (>90 days exposure) and/or vascular/renal outcomes (any exposure) after meloxicam use, published until April 2014. The combined odd ratio values (OR'; 95% CI) were calculated using the random effect inverse variance model.. We found 19 eligible studies out of 2,422 reports. Meloxicam demonstrated a low increase in composite risk (OR' 1.14; CI 1.04-1.25) which was mainly vascular in nature (OR' 1.35; CI 1.18-1.55] as it did not elevate myocardial (OR' 1.13; CI 0.98-1.32) or renal (OR', 0.99; CI 0.72-1.35) risks. Relative to meloxicam, other NSAIDs increased the composite risk, in a dose-dependent fashion, in the following order: rofecoxib > indomethacin > diclofenac > celecoxib > naproxen > ibuprofen. OR' was also influenced by type of disease and the comparator used, and acetylsalicylic acid.. NSAIDs are heterogeneous in increasing CV/renal risks. The low increased risk associated with meloxicam is mainly vascular in origin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Case-Control Studies; Cyclooxygenase 2 Inhibitors; Humans; Kidney Diseases; Meloxicam; Randomized Controlled Trials as Topic; Risk Factors; Thiazines; Thiazoles; Vascular Diseases

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

To determine the effects of meloxicam on values of hematologic and plasma biochemical analysis variables and results of histologic examination of tissue specimens of Japanese quail (Coturnix japonica).. 30 adult Japanese quail.. 15 quail underwent laparoscopic examination of the left kidneys, and 15 quail underwent laparoscopic examination and biopsy of the left kidneys. Quail in each of these groups received meloxicam (2.0 mg/kg, IM, q 12 h; n = 10) or a saline (0.9% NaCl) solution (0.05 mL, IM, q 12 h; control birds; 5) for 14 days. A CBC and plasma biochemical analyses were performed at the start of the study and within 3 hours after the last treatment. Birds were euthanized and necropsies were performed.. No adverse effects of treatments were observed, and no significant changes in values of hematologic variables were detected during the study. Plasma uric acid concentrations and creatine kinase or aspartate aminotransferase activities were significantly different before versus after treatment for some groups of birds. Gross lesions identified during necropsy included lesions at renal biopsy sites and adjacent air sacs (attributed to the biopsy procedure) and pectoral muscle hemorrhage and discoloration (at sites of injection). Substantial histopathologic lesions were limited to pectoral muscle necrosis, and severity was greater for meloxicam-treated versus control birds.. Meloxicam (2.0 mg/kg, IM, q 12 h for 14 days) did not cause substantial alterations in function of or histopathologic findings for the kidneys of Japanese quail but did induce muscle necrosis; repeated IM administration of meloxicam to quail may be contraindicated.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Aspartate Aminotransferases; Coturnix; Creatine Kinase; Kidney Diseases; Meloxicam; Muscle, Skeletal; Muscular Diseases; Poultry Diseases; Thiazines; Thiazoles; Uric Acid

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Bird Diseases; Clonixin; Female; Ketoprofen; Kidney Diseases; Male; Melopsittacus; Meloxicam; Thiazines; Thiazoles

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

To evaluate the effect of Rut-bpy (Cis-[Ru(bpy)2(SO3)(NO)]PF 6), a novel nitric oxide donor, able to modulate the histological changes caused by the NASID (meloxicam).. Wistar rats were assigned into three groups (n=6 rats/group): Sham group (saline solution), NSAID group (meloxicam - 15 mg/kg) and Rut-bpy group (100 mg/kg of Rut-bpy associated with 15mg/kg of meloxicam). At the end of experiments, kidneys were removed for histological study, fractal dimension and lacunarity in all animals.. At the histological examination, all animals (six animals - 100 %) in the NSAID group had membrane thickening and other changes (necrosis, acute tubular congestion and vascular congestion); on the other hand, only one animal (16.6 %) of the Rut-bpy group had congestion. The fractal dimension and lacunarity were greater in the control and Rut-bpy group than in NSAIDs group (p<0.05).. Rut-bpy may prevent renal histological changes in rats caused by meloxicam.

Topics: 2,2'-Dipyridyl; Animals; Anti-Inflammatory Agents, Non-Steroidal; Fractals; Kidney Diseases; Male; Meloxicam; Nitric Oxide Donors; Organometallic Compounds; Random Allocation; Rats, Wistar; Reproducibility of Results; Ruthenium

Topics: Amitriptyline; Animals; Anti-Retroviral Agents; Kidney Diseases; Male; Meloxicam; Quality of Life; Rats; Rats, Wistar; Stavudine

Nonsteroidal anti-inflammatory (NSAI) drugs are the most commonly used group of drugs today. Increase in the use of standard NSAI for treating pain and inflammation was restricted by the fact that these drugs were proven to possibly cause gastrointestinal and renal toxicity. Meloxicam is a NSAI that has anti-inflammatory, analgesic, and antipyretic effects. This study aims to investigate the effects of meloxicam on stomach, kidney, and liver of rats under light microscopy level. Based on the light microscopic observations, mononuclear cell infiltration and pseudolobular formation was established in liver samples of animals in the experimental group. Metaplasia in surface and glandular epithelia and atrophy were observed in stomach samples. Glomerular stasis-related hypertrophy and focal interstitial nephritis were found in kidneys. It was concluded in this study that meloxicam might cause hepatotoxicity, nephrotoxicity, and gastric metaplasia in rats at a used dose and duration.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2; Disease Models, Animal; Dose-Response Relationship, Drug; Inflammation; Kidney; Kidney Diseases; Liver; Meloxicam; Metaplasia; Pain; Rats; Rats, Sprague-Dawley; Stomach; Stomach Diseases; Thiazines; Thiazoles; Toxicity Tests

Unilateral ureteral obstruction (UUO) is a well-established model for the study of interstitial fibrosis in the kidney. In this study, we investigated the effects of a COX-2 inhibitor, meloxicam, on UUO-induced renal interstitial fibrosis in mice. Serum creatinine, blood urea nitrogen and urinary glucose were significantly increased by UUO. However, all of these changes were attenuated by meloxicam (1 mg/kg/day). Masson׳s trichrome staining showed that interstitial fibrosis was significantly increased by UUO, but that meloxicam also significantly diminished the area of UUO-induced fibrosis. Heat shock protein (HSP) 47 protein, a collagen-specific molecular chaperone essential for the biosynthesis of collagen molecules, and type IV collagen mRNA were increased in kidneys of UUO mice. Meloxicam reduced the expression of both HSP47 protein and type IV collagen mRNA. The phosphorylation of extracellular regulated kinase (ERK) and c-jun-N-terminal kinase (JNK) was increased by UUO, but these changes were inhibited by meloxicam. Collectively, these results suggest that COX-2 may be involved in the expression of HSP47 and type IV collagen through the phosphorylation of ERK and JNK, accelerating renal interstitial fibrosis.

Topics: Animals; Collagen; Cyclooxygenase 2 Inhibitors; Fibrosis; HSP47 Heat-Shock Proteins; Kidney; Kidney Diseases; Male; Meloxicam; Mice, Inbred BALB C; Mitogen-Activated Protein Kinase Kinases; RNA, Messenger; Thiazines; Thiazoles

The interaction between oral non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone administered concurrently for 30 days was studied in 18 healthy dogs divided into 3 groups of 6 dogs each: a drug-free negative control group (NC group) given 2 gelatin capsules; a group given meloxicam (0.1 mg/kg) and prednisolone (0.5 mg/kg) (MP group); and a group given a reduced dosage of ketoprofen (0.25 mg/kg, p.o.) and prednisolone (0.5 mg/kg, p.o.) (KP group). The dogs were periodically monitored by physical examinations, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests [effective renal plasma flow (ERPF) and glomerular filtration rate (GFR)], urinalyses [urinary sediments, and urinary micro-albumin to creatinine ratio (UAlb/Cre)], urinary enzyme indices, and haemostatic function tests [buccal mucosa bleeding time (BMBT), cuticle bleeding time (CBT)]. Significant changes were observed in the KP group, including a decrease of ERPF and GFR, an increased UAlb/Cre ratio, prolonged BMBT and CBT, as well as the presence of more severe grades of endoscopic lesions and fecal occult blood. In both the MP and KP groups, abnormal enzymuria with exfoliation of renal tubular epithelial cells in the urine was found. However, no significant changes in any of the other tests were observed in the MP group compared with the NC group. These findings suggest that the combination of NSAIDs, even selective COX-2 inhibitors, with prednisolone may be contraindicated due to the potential for serious adverse effects on the kidneys, the platelets, and the gastrointestinal tract.

Topics: Acetylglucosaminidase; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bleeding Time; Cyclooxygenase Inhibitors; Dogs; Drug Interactions; Endoscopy; Female; gamma-Glutamyltransferase; Gastrointestinal Diseases; Glomerular Filtration Rate; Ketoprofen; Kidney Diseases; Meloxicam; Occult Blood; Prednisolone; Random Allocation; Renal Plasma Flow, Effective; Statistics, Nonparametric; Thiazines; Thiazoles; Urinalysis

Cyclo-oxygenase inhibitors have different selectivity for inhibitory action on the isoforms of the enzyme. Our purpose was to compare the tocolytic and maternal toxic effects of various cyclo-oxygenase inhibitors in the lipopolysaccharide-induced preterm birth in pregnant mice.. We randomly assigned 50 ICR pregnant mice into five groups of 10 mice each and treated them intraperitoneally with either phosphate-buffered saline solution or lipopolysaccharide (50 microg) on day 15 of pregnancy. Of the four groups that received lipopolysaccharide, three groups also were treated either with nonselective cyclo-oxygenase inhibitors (indomethacin [1 mg/kg/d] or diclofenac [2 mg/kg/d]) or with the cyclo-oxygenase-2 preferential inhibitor, meloxicam (2 mg/kg/d), with a gavage tube on days 15 through 18 of pregnancy or until maternal death. The mice were killed immediately after preterm birth or on day 21 of pregnancy. Preterm birth rates and maternal side effect profiles were evaluated.. Preterm birth occurred in 90% of mice after intraperitoneal lipopolysaccharide injection and in 20% of mice after phosphate-buffered saline solution injection. Indomethacin and meloxicam, but not diclofenac, significantly decreased the incidence of preterm birth that was induced by lipopolysaccharide (33.3% and 33.3%, respectively; P =.028). Although the overall incidence of maternal gastric and/or renal toxicities was not significantly increased in the indomethacin or meloxicam groups, a significant increase was noticed in the diclofenac group compared with the lipopolysaccharide-treated control group (P =.006).. Indomethacin and meloxicam, but not diclofenac, inhibit the lipopolysaccharide-induced preterm birth in an animal model. Meloxicam appears to have no advantage over indomethacin with regard to tocolysis and maternal side effects.

Topics: Animals; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Diclofenac; Female; Indomethacin; Isoenzymes; Kidney Diseases; Lipopolysaccharides; Meloxicam; Mice; Mice, Inbred ICR; Obstetric Labor, Premature; Pregnancy; Pregnancy Outcome; Prostaglandin-Endoperoxide Synthases; Stomach Diseases; Thiazines; Thiazoles

Topics: Administration, Sublingual; Adult; Anti-Inflammatory Agents, Non-Steroidal; Colic; Humans; Kidney Diseases; Male; Meloxicam; Thiazines; Thiazoles; Ureteral Calculi

The aim of the present study was to determine how the pharmacokinetics of meloxicam are affected by kidney dysfunction and consequently to define the appropriate dose for the use of meloxicam in patients with mild or moderate renal impairment.. Meloxicam was administered to subjects with mild (creatinine clearance 41-60 ml min-1) to moderate (20-40 ml min-1) renal impairment compared with normal renal function (> 60 ml min-1). Thirty-eight subjects received meloxicam 15 mg once daily over 9 days. Meloxicam plasma concentrations were determined from blood samples taken during the study and pharmacokinetic parameters calculated according to noncompartmental methods.. Subjects with no or mild renal impairment showed similar pharmacokinetic profiles (geometric mean AUCSS (%gCV) 55 (33%) vs 55 (38%) micrograms ml-1 h). Subjects with moderate renal impairment demonstrated lower total plasma meloxicam concentrations (AUCSS 35 (50%) micrograms ml-1 h, with corresponding higher plasma clearance (P = 0.013) compared with subjects with no renal impairment. However, this was combined with higher meloxicam free fractions in moderately impaired subjects such that free meloxicam concentrations were similar in all three groups. Meloxicam was well tolerated with few adverse events occurring and no difference in incidence observable between groups.. On the basis of these results there is no necessity for a dosage adjustment when administering meloxicam to patients with mild to moderate renal impairment.

Topics: Administration, Oral; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Kidney Diseases; Linear Models; Male; Meloxicam; Middle Aged; 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