mobic and Gastrointestinal-Hemorrhage

Topics: Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Gastrointestinal Hemorrhage; Humans; Meloxicam; Risk Assessment; Thiazines; Thiazoles

Meloxicam (Mobic) is a new nonsteroidal anti-inflammatory drug (NSAID) derived from enolic acid, exhibiting selectivity for cyclooxygenase (COX)-2 over COX-1. Meloxicam has shown potent anti-inflammatory and analgesic activity together with low gastrointestinal toxicity in animal models. It is a potent inhibitor not only of acute exudation in adjuvant arthritis in the rat, but also of bone and cartilage destruction. The therapeutic range of meloxicam in the rat, with regard to inhibition of adjuvant arthritis, was several times greater than that of other NSAIDs. Meloxicam in therapeutic doses was found to have no effect on bleeding time or platelet aggregation in healthy volunteers. In clinical studies, meloxicam has shown reliable efficacy against rheumatoid arthritis, osteoarthritis, lumbago (low back pain), scapulohumeral periarthritis, and neck-shoulder-arm syndrome with low gastrointestinal toxicity.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Experimental; Arthritis, Rheumatoid; Clinical Trials as Topic; Cyclooxygenase 2; Enzyme Inhibitors; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Inflammation; Isoenzymes; Meloxicam; Membrane Proteins; Pain; Platelet Aggregation; Prostaglandin-Endoperoxide Synthases; Rats; Thiazines; Thiazoles

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

The diagnosis of NSAID-induced colon ulcers is difficult when the distribution or endoscopic findings are not typical. An 83-year-old woman was transferred to our hospital for hemorrhagic diarrhea. Colonoscopy showed multiple ulcers in the entire colon, particularly longitudinal ulcers in the transverse colon. These were unusual for NSAID-induced colopathy, although she had been on meloxicam. However, capsule endoscopy revealed multiple scars and erosions, characteristic of NSAIDs users. The final diagnosis was NSAID-induced enteropathy, and all lesions were in remission after meloxicam discontinuation. We herein emphasize the value of an endoscopic assessment of the entire digestive tract in the diagnosis of NSAID-induced mucosal lesions.

Topics: Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Capsule Endoscopy; Colon; Colonoscopy; Female; Gastrointestinal Hemorrhage; Humans; Intestine, Small; Meloxicam; Thiazines; Thiazoles; Ulcer

Nonsteroidal anti-inflammatory drugs (NSAID) are well known to induce gastric mucosal damage including bleeding, ulceration and perforation in humans and animals too. These effects are related with the inhibition of the enzyme cyclooxygenase, which is the main established mechanism of action for these drugs. Fasted rats were given piroxicam, preferential COX-1 inhibitor (10-20 mg/kg) or meloxicam, preferential COX-2 inhibitor (7.5-15 mg/kg) orally. Six or nine hours (h) later, respectively, the stomach was excised, the severity of the damage assessed and myeloperoxidase (MPO) activity measured, as well as prostaglandin PGE(2) content. Furthermore, in order to assess the effects of these oxicams over previously damaged gastric mucosa, 1 ml of 0.6 N HCl was administered p.o. followed, 1 h after, of the correspondent dose of each NSAID, and the same parameters were determined. Oral administration of both drugs dose-dependently caused acute gastric haemorrhage erosions. Myeloperoxidase activity was significantly increased by piroxicam administration. In addition, PGE(2) content was significantly reduced. The association between the administration of the acid and NSAID caused a worsening of the damage and, while myeloperoxidase activity did not modify by both piroxicam and meloxicam, PGE(2) levels were reduced. These results suggest that the PG derived from both COX-1 and COX-2 pathway plays a beneficial role in the gastroprotection, and thus caution should be exercise in the clinical use of preferential COX-2 inhibitors.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Dinoprostone; Dose-Response Relationship, Drug; Drug Synergism; Drug Therapy, Combination; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Hydrochloric Acid; Male; Meloxicam; Peroxidase; Piroxicam; Rats; Rats, Wistar; Stomach Ulcer; Thiazines; Thiazoles

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

Although clinical trial results suggest that meloxicam has less gastrointestinal toxicity than most other non-steroidal anti-inflammatory drugs (NSAIDs), in practice it has been associated with a large number of yellow card reports of gastrointestinal complications.. To estimate whether meloxicam and the coxibs, rofecoxib and celecoxib, have been channelled towards high risk patients, and to estimate the risk of hospitalisation for gastrointestinal haemorrhage associated with the use of these drugs, allowing for the effects of channelling.. Using the UK General Practice Research Database, 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.. Cohort study of patients who received a prescription for an NSAID between June 1987 and January 2001. Exposure to newer NSAIDs (meloxicam, rofecoxib, celecoxib) and to older non-specific NSAIDs was identified. Channelling was assessed on factors including: demographic variables; diagnosis of arthritis; history of NSAID use or gastrointestinal events, including gastrointestinal haemorrhage; and use of ulcer healing drugs.. Most risk factors for gastrointestinal haemorrhage were more prevalent among patients prescribed the newer NSAIDs. Adjusting for these risk factors reduced the relative risks of gastrointestinal haemorrhage on meloxicam and coxibs versus older non-specific NSAIDs to 0.84 (95% confidence interval 0.60, 1.17) and 0.36 (0.14, 0.97), respectively.. Channelling towards high risk gastrointestinal patients occurred in the prescribing of newer NSAIDs. After attempting to correct for channelling bias, coxib exposure, but not meloxicam exposure, was associated with a significantly lower risk of gastrointestinal haemorrhage than older non-specific NSAID exposure.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Bias; Celecoxib; Cohort Studies; Databases, Factual; Family Practice; Female; Gastrointestinal Hemorrhage; Humans; Lactones; Male; Meloxicam; Middle Aged; Pyrazoles; Risk Factors; Sulfonamides; Sulfones; Thiazines; Thiazoles

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known to induce gastrointestinal damage including bleeding, ulceration and perforation in humans and animals. The aim of this study was to compare the effects of two oxicams, preferential cyclooxygenase (COX)-1 or COX-2 inhibitors, on both gastric mucosa and some biological parameters (hematological, hepatic and renal) after subchronic administration (14 and 28 days) in rats. Neutrophil infiltration was also assessed. Equipotent doses of meloxicam (3.75 and 7.5 mg/kg) and piroxicam (5 and 10 mg/kg) were administered. Both drugs dose-dependently caused multiple gastric erosions and hemorrhage in rats after 14 and 28 days of administration. Treatment with meloxicam led to a higher gastric damage than with piroxicam on day 14 although these results were not significant. The levels of myeloperoxidase activity (as an index of neutrophil infiltration) were not changed compared with control after drug treatment. All the hematological parameters obtained after drugs administration for 14 and 28 days were in the range of normal values, and a significant increase in platelet levels could be observed in the group treated with 5 mg/kg of piroxicam for 14 days. Aspartate aminotransferase (AST or GOT) increased significantly after 14 days, but after 28 days the values returned to normality. Creatinine and urea did not undergo significant changes except for the piroxicam 14-day 5 mg/kg group, in which uremia increased significantly over normal values. In conclusion, our results show that meloxicam, a preferential COX-2 inhibitor, causes rates of gastric lesion comparable to those seen with traditional NSAIDs, without inducing important changes in biological parameters.

Topics: Animals; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Isoenzymes; Male; Meloxicam; Membrane Proteins; Piroxicam; Prostaglandin-Endoperoxide Synthases; Rats; Rats, Wistar; Thiazines; Thiazoles

To obtain formally quantified data on the relation of meloxicam to newly diagnosed gastrointestinal problems, myocardial infarction, or treated hypertension.. Nested case-control study.. United Kingdom-based General Practice Research Database.. Patients who received prescriptions for meloxicam, diclofenac, naproxen, or piroxicam formed the study population. Cases were people who developed gastrointestinal problems, myocardial infarction, or hypertension.. Relative risk estimates for developing the study outcomes were provided for each study nonsteroidal antiinflammatory drug (NSAID), with diclofenac as the reference drug. In no instance was meloxicam associated with an increased risk for a study outcome.. Compared with the other NSAIDs, meloxicam was not materially associated with any study outcomes. This study provides reassurance to those prescribing this newer class of NSAIDs.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Databases, Factual; Diclofenac; Gastrointestinal Hemorrhage; Humans; Hypertension; Isoenzymes; Meloxicam; Membrane Proteins; Myocardial Infarction; Naproxen; Piroxicam; Prostaglandin-Endoperoxide Synthases; Risk Assessment; Thiazines; Thiazoles; United Kingdom

In addition to a deficiency of endogenous prostaglandins due to inhibition of cyclo-oxygenase and a host of prostaglandin-mediated effects on mucosal protection, it has recently been proposed that neutrophil- and oxygen radical - dependent microvascular injuries may be important prime events that lead to mucosal injury induced by non-steroidal anti-inflammatory drugs. Therefore, we evaluated the role of oxygen free radicals in the pathogenesis of acute gastric ulceration induced by meloxicam, a preferential COX-2 inhibitor.. Studies were performed in Wistar rats.. Meloxicam was given by oral administration (3.75-30 mg/kg body weight).. Determinations were made of gastric mucosal injury, xanthine-oxidase, myeloperoxidase and superoxide dismutase activities, as well as the effect of meloxicam on gastric prostaglandin synthesis (PGE2 levels) and glutathione homeostasis.. Oral administration of meloxicam dose-dependently (3.75-30 mg/kg) caused acute gastric haemorrhage erosions. The total area of gastric lesions increased with time until 24 hours after dosing. Xanthine-oxidase activity increased significantly after administration of the drug. Myeloperoxidase activity, as an index of neutrophil infiltration, as well as glutathione peroxidase, an important enzyme that scavenges lipid peroxides, were unaffected by meloxicam administration. In addition, superoxide dismutase activity, PGE2 and glutathione levels were significantly reduced.. These results support the hypothesis that in addition to suppression of prostaglandin synthesis, oxygen free radicals, probably derived via the action of xanthine oxidase, the decrease in superoxide dismutase activity, and the depletion of mucosal glutathione contribute to the pathogenesis of meloxicam-induced ulceration.

Topics: Animals; Dinoprostone; Female; Free Radicals; Gastric Mucosa; Gastrointestinal Hemorrhage; Glutathione; Glutathione Peroxidase; Male; Meloxicam; Neutrophils; Peroxidase; Rats; Rats, Wistar; Reactive Oxygen Species; Superoxide Dismutase; Thiazines; Thiazoles; Xanthine Oxidase

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Gastrointestinal Hemorrhage; Humans; Male; Meloxicam; Middle Aged; Thiazines; Thiazoles

Endoscopy was undertaken to examine the gastroduodenal mucosa of 24 healthy dogs after seven days and again after 28 days of oral non-steroidal anti-inflammatory drug (NSAID) administration. The dogs were divided into four groups. One group received ketoprofen (1 mg/kg every 24 hours), one group carprofen (2 mg/kg every 12 hours for seven days followed by 2 mg/kg every 24 hours), a third group meloxicam suspension (0.2 mg/kg every 24 hours), and the last group gelatin (one capsule every 24 hours). Serum biochemical and complete blood count parameters did not change significantly after NSAID administration. Gastroduodenal lesions were observed in 17 dogs, but in all cases these were mild to moderate. The dogs receiving gelatin or carprofen showed the fewest and the least severe lesions, although there was no statistically significant difference between the three test drugs and the control group (P < or = 0.05). None of the dogs showed any clinical signs related to the gastrointestinal lesions.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Dogs; Endoscopy, Gastrointestinal; Gastric Mucosa; Gastrointestinal Hemorrhage; Gelatin; Ketoprofen; Meloxicam; Stomach Ulcer; Thiazines; Thiazoles

Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Gastrointestinal Diseases; Gastrointestinal Hemorrhage; Humans; Intestinal Perforation; Meloxicam; Prospective Studies; Thiazines; Thiazoles; Ulcer

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Butanones; Cyclooxygenase Inhibitors; Digestive System; Gastrointestinal Hemorrhage; Humans; Meloxicam; Nabumetone; Thiazines; Thiazoles