InChI=1S/C14H13N3O4S2/c1- 8-7-15-14(22-8)16-13(19)11-12(18)9-5-3-4-6-10(9)23(20,21)17(11)2/h3-7,18H,1-2H3,(H,15,16,19) |
| ZRVUJXDFFKFLMG-UHFFFAOYSA-N |
| CN1C(C(=O)Nc2ncc(C)s2)=C(O)c2ccccc2S1(=O)=O |
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cyclooxygenase 2 inhibitor
A cyclooxygenase inhibitor that interferes with the action of cyclooxygenase 2.
analgesic
An agent capable of relieving pain without the loss of consciousness or without producing anaesthesia. In addition, analgesic is a role played by a compound which is exhibited by a capability to cause a reduction of pain symptoms.
human metabolite
Any mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
(via benzothiazine )
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non-steroidal anti-inflammatory drug
An anti-inflammatory drug that is not a steroid. In addition to anti-inflammatory actions, non-steroidal anti-inflammatory drugs have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins.
antirheumatic drug
A drug used to treat rheumatoid arthritis.
analgesic
An agent capable of relieving pain without the loss of consciousness or without producing anaesthesia. In addition, analgesic is a role played by a compound which is exhibited by a capability to cause a reduction of pain symptoms.
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View more via ChEBI Ontology
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4-hydroxy-2-methyl-N-(5-methyl-1,3-thiazol-2-yl)-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxide
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meloxicam
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WHO MedNet
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meloxicam
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WHO MedNet
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méloxicam
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WHO MedNet
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meloxicamum
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WHO MedNet
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UNII-VG2QF83CGL
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ChemIDplus
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5886369
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Reaxys Registry Number
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Reaxys
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71125-38-7
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CAS Registry Number
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KEGG COMPOUND
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Keller AN, Eckle SB, Xu W, Liu L, Hughes VA, Mak JY, Meehan BS, Pediongco T, Birkinshaw RW, Chen Z, Wang H, D'Souza C, Kjer-Nielsen L, Gherardin NA, Godfrey DI, Kostenko L, Corbett AJ, Purcell AW, Fairlie DP, McCluskey J, Rossjohn J (2017)
Drugs and drug-like molecules can modulate the function of mucosal-associated invariant T cells.
Nature immunology 18, 402-411 [PubMed:28166217]
[show Abstract]
The major-histocompatibility-complex-(MHC)-class-I-related molecule MR1 can present activating and non-activating vitamin-B-based ligands to mucosal-associated invariant T cells (MAIT cells). Whether MR1 binds other ligands is unknown. Here we identified a range of small organic molecules, drugs, drug metabolites and drug-like molecules, including salicylates and diclofenac, as MR1-binding ligands. Some of these ligands inhibited MAIT cells ex vivo and in vivo, while others, including diclofenac metabolites, were agonists. Crystal structures of a T cell antigen receptor (TCR) from a MAIT cell in complex with MR1 bound to the non-stimulatory and stimulatory compounds showed distinct ligand orientations and contacts within MR1, which highlighted the versatility of the MR1 binding pocket. The findings demonstrated that MR1 was able to capture chemically diverse structures, spanning mono- and bicyclic compounds, that either inhibited or activated MAIT cells. This indicated that drugs and drug-like molecules can modulate MAIT cell function in mammals. | Kluivers-Poodt M, Zonderland JJ, Verbraak J, Lambooij E, Hellebrekers LJ (2013)
Pain behaviour after castration of piglets; effect of pain relief with lidocaine and/or meloxicam.
Animal : an international journal of animal bioscience 7, 1158-1162 [PubMed:23388116]
[show Abstract]
Behavioural responses and the effect of lidocaine and meloxicam on behaviour of piglets after castration were studied. A total of 144 piglets of 2 to 5 days of age were allocated to one of six treatments: castration (CAST), castration with lidocaine (LIDO), castration with meloxicam (MELO), castration with lidocaine and meloxicam (L + M), handling (SHAM) and no handling (NONE). Behaviour was observed for 5 days after the procedure, growth until weaning was recorded and characteristics of the castration wound noted. MELO piglets showed significantly (P < 0.05) more no pain-related behaviour than CAST and LIDO at the afternoon after castration, and were not significantly different from SHAM and NONE. LIDO piglets showed an increase (P < 0.001) in tail wagging, lasting for 3 days. This increase was not seen in L + M piglets. The occurrence of several behaviours changed with age, independent of treatment. A treatment effect on growth was not found. Wound healing was rapid in all treatments, but thickening of the heal was observed in several piglets, suggesting perturbation in the cicatrization process. Our study showed a pain-relieving effect of meloxicam after castration. Local anaesthesia resulted in piglets performing more tail wagging during the first few days after castration, which was prevented by administering meloxicam in combination with local anaesthesia. | Rätsep MT, Barrette VF, Winterborn A, Adams MA, Croy BA (2013)
Hemodynamic and behavioral differences after administration of meloxicam, buprenorphine, or tramadol as analgesics for telemeter implantation in mice.
Journal of the American Association for Laboratory Animal Science : JAALAS 52, 560-566 [PubMed:24041211]
[show Abstract]
Cannulation of the common carotid artery for chronic, continuous radiotelemetric recording of aortic hemodynamic properties in mice is a highly invasive recovery surgery. Radiotelemetric recording, by its continuous nature, gives the most accurate measurements of hemodynamic variables in experimental animals, and is widely used in the study of cardiovascular diseases including hypertension. The American Heart Association has recommended data acquisition by radiotelemetric recording but did not provide guidelines regarding postoperative analgesic support. We assessed hemodynamic parameters, locomotor activity, food intake, and weight loss in radiotransmitter-implanted CD1 female mice receiving analgesic support during the first 48 h after surgery. The efficacy of analgesic support from the NSAID meloxicam was compared with that of the widely used opioid agonist buprenorphine and the related compound, tramadol. Meloxicam-treated mice recovered lost body weight more rapidly than did tramadol-or buprenorphine-treated mice. Furthermore, meloxicam-treated mice maintained circadian rhythm after surgery and had tighter regulation of mean arterial pressure than did tramadol- or buprenorphine-treated mice. Meloxicam was also superior with regard to food intake, locomotor activity, and limiting variance in hemodynamic parameters. This study indicates that when compared with buprenorphine and tramadol, meloxicam should be the postoperative analgesic of choice for radiotelemeter implantation in mice. | Kimble B, Black LA, Li KM, Valtchev P, Gilchrist S, Gillett A, Higgins DP, Krockenberger MB, Govendir M (2013)
Pharmacokinetics of meloxicam in koalas (Phascolarctos cinereus) after intravenous, subcutaneous and oral administration.
Journal of veterinary pharmacology and therapeutics 36, 486-493 [PubMed:23406022]
[show Abstract]
The pharmacokinetic profile of meloxicam in clinically healthy koalas (n = 15) was investigated. Single doses of meloxicam were administered intravenously (i.v.) (0.4 mg/kg; n = 5), subcutaneously (s.c.) (0.2 mg/kg; n = 1) or orally (0.2 mg/kg; n = 3), and multiple doses were administered to two groups of koalas via the oral or s.c. routes (n = 3 for both routes) with a loading dose of 0.2 mg/kg for day 1 followed by 0.1 mg/kg s.i.d for a further 3 days. Plasma meloxicam concentrations were quantified by high-performance liquid chromatography. Following i.v. administration, meloxicam exhibited a rapid clearance (CL) of 0.44 ± 0.20 (SD) L/h/kg, a volume of distribution at terminal phase (Vz ) of 0.72 ± 0.22 L/kg and a volume of distribution at steady state (Vss ) of 0.22 ± 0.12 L/kg. Median plasma terminal half-life (t(1/2)) was 1.19 h (range 0.71-1.62 h). Following oral administration either from single or repeated doses, only maximum peak plasma concentration (C(max) 0.013 ± 0.001 and 0.014 ± 0.001 μg/mL, respectively) was measurable [limit of quantitation (LOQ) >0.01 μg/mL] between 4-8 h. Oral bioavailability was negligible in koalas. Plasma protein binding of meloxicam was ~98%. Three meloxicam metabolites were detected in plasma with one identified as the 5-hydroxy methyl derivative. This study demonstrated that koalas exhibited rapid CL and extremely poor oral bioavailability compared with other eutherian species. Accordingly, the currently recommended dose regimen of meloxicam for this species appears inadequate. | Borghi B, Aurini L, White PF, Mordenti A, Lolli F, Borghi R, Martignani M, Greggi T (2013)
Long-lasting beneficial effects of periradicular injection of meloxicam for treating chronic low back pain and sciatica.
Minerva anestesiologica 79, 370-378 [PubMed:23306395]
[show Abstract]
BackgroundChronic low back pain (LBP) and sciatica can occur without obvious structural causes and are often resistant to conventional analgesic drugs. The effect of periradicular injection of meloxicam on LBP with or without a radicular component was assessed. A secondary objective of this prospective observational study was to assess the effect of meloxicam on functional recovery.MethodsSeventy-two patients (30 men, 42 women) with LBP and/or sciatica were followed for 90 days to six years after injecting 10 mg meloxicam in 10 mL saline at each of the involved dermatomal levels. A standard verbal rating scale (VRS) from 0=no pain to 10=severe pain was used for assessing LBP before the injection of meloxicam (at baseline) and at 1, 5, 10, 30 and 60 min, and 1, 5, 15, 30 and 90 days intervals after the injection. The meloxicam injection was repeated only if the VRS score remained >3. Rescue analgesic requirements and functional activity levels were also assessed from 30-90 days after the last injection of meloxicam.ResultsThe mean baseline LBP score was 8.60 ± 1.50 (SD) despite the use of multi-modal analgesic regimens (NSAIDs, glucocorticosteroids, paracetamol, oral opioids, gabapentanoid compounds, epidural or periradicular steroid and/or local anesthetics) as well as laser treatments and physical therapy. The majority of patients reported that their pain intensity decreased by ~50% 1-2 min after the meloxicam injection was completed. Thirty-six patients (50%) required no further injections, 25 patients (35%) required a second injection after seven days, and 11 patients (15%) required a total of three injections. After the meloxicam treatment(s), only 10 patients (14%) required "rescue" analgesia with oral NSAIDs. All patients were able to increase their level of functional activity after the meloxicam treatment(s).ConclusionPeriradicular injections of meloxicam (10 mg) appear to be a useful alternative to opioid and non-opiod analgesics for patients with intractable LBP due to nerve root inflammation. | Wen ZH, Tang CC, Chang YC, Huang SY, Chen CH, Wu SC, Hsieh SP, Hsieh CS, Wang KY, Lin SY, Lee HL, Lee CH, Kuo HC, Chen WF, Jean YH (2013)
Intra-articular injection of the selective cyclooxygenase-2 inhibitor meloxicam (Mobic) reduces experimental osteoarthritis and nociception in rats.
Osteoarthritis and cartilage 21, 1976-1986 [PubMed:24084190]
[show Abstract]
ObjectiveTo study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes.MethodsOA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes.ResultsOA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage.ConclusionsIntra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression. | Moore RA, Derry S, McQuay HJ (2009)
Single dose oral meloxicam for acute postoperative pain in adults.
The Cochrane database of systematic reviewsCD007552 [PubMed:19821429]
[show Abstract]
BackgroundMeloxicam is a non-steroidal anti-inflammatory drug (NSAID) used mainly in treating pain associated with arthritis. The usual oral dose for osteoarthritis is 15 mg daily, but lower doses of 7.5 mg are advised in older patients. This review sought to evaluate the efficacy and safety of oral meloxicam in acute postoperative pain, using clinical studies of patients with established pain, and with outcomes measured primarily over 6 hours using standard methods. This type of study has been used for many decades to establish that drugs have analgesic properties.ObjectivesTo assess the efficacy of single dose oral meloxicam in acute postoperative pain, and any associated adverse events.Search strategyWe searched Cochrane CENTRAL (Issue 2, 2009), MEDLINE (June 2009); EMBASE (June 2009); the Oxford Pain Relief Database.Selection criteriaRandomised, double-blind, placebo-controlled clinical trials of oral meloxicam for relief of acute postoperative pain in adults.Data collection and analysisTwo review authors independently assessed trial quality and extracted data. We planned to use area under the "pain relief versus time" curve to derive the proportion of participants with meloxicam experiencing least 50% pain relief over 4 to 6 hours, using validated equations; to use number needed to treat to benefit (NNT); the proportion of participants using rescue analgesia over a specified time period; time to use of rescue analgesia; information on adverse events and withdrawals.Main resultsNo studies were identified by the searches that examined oral meloxicam in patients with established postoperative pain.Authors' conclusionsIn the absence of evidence of efficacy, at present, for oral meloxicam in acute postoperative pain, its use in this indication is not justified. Because trials clearly demonstrating analgesic efficacy in the most basic of acute pain studies is lacking, use in other indications should be evaluated carefully. Given the large number of available drugs of this and similar classes, there is no urgent research agenda. | Chen YF, Jobanputra P, Barton P, Bryan S, Fry-Smith A, Harris G, Taylor RS (2008)
Cyclooxygenase-2 selective non-steroidal anti-inflammatory drugs (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis and rheumatoid arthritis: a systematic review and economic evaluation.
Health technology assessment (Winchester, England) 12, 1-278, iii [PubMed:18405470]
[show Abstract]
ObjectivesTo review the clinical effectiveness and cost-effectiveness of cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drugs (NSAIDs) (etodolac, meloxicam, celecoxib, rofecoxib, etoricoxib, valdecoxib and lumiracoxib) for osteoarthritis (OA) and rheumatoid arthritis (RA).Data sourcesElectronic databases were searched up to November 2003. Industry submissions to the National Institute for Health and Clinical Excellence (NICE) in 2003 were also reviewed.Review methodsSystematic reviews of randomised controlled trials (RCTs) and a model-based economic evaluation were undertaken. Meta-analyses were undertaken for each COX-2 selective NSAID compared with placebo and non-selective NSAIDs. The model was designed to run in two forms: the 'full Assessment Group Model (AGM)', which includes an initial drug switching cycle, and the 'simpler AGM', where there is no initial cycle and no opportunity for the patient to switch NSAID.ResultsCompared with non-selective NSAIDs, the COX-2 selective NSAIDs were found to be equally as efficacious as the non-selective NSAIDs (although meloxicam was found to be of inferior or equivalent efficacy) and also to be associated with significantly fewer clinical upper gastrointestinal (UGI) events (although relatively small numbers of clinical gastrointestinal (GI) and myocardial infarction (MI) events were reported across trials). Subgroup analyses of clinical and complicated UGI events and MI events in relation to aspirin use, steroid use, prior GI history and Helicobacter pylori status were based on relatively small numbers and were inconclusive. In the RCTs that included direct COX-2 comparisons, the drugs were equally tolerated and of equal efficacy. Trials were of insufficient size and duration to allow comparison of risk of clinical UGI events, complicated UGI events and MIs. One RCT compared COX-2 (celecoxib) with a non-selective NSAID combined with a gastroprotective agent (diclofenac combined with omeprazole); this included arthritis patients who had recently suffered a GI haemorrhage. Although no significant difference in clinical GI events was reported, the number of events was small and more such studies, where patients genuinely need NSAIDs, are required to confirm these data. A second trial showed that rofecoxib was associated with fewer diarrhoea events than a combination of diclofenac and misoprostol (Arthrotec). Previously published cost-effectiveness analyses indicated a wide of range of possible incremental cost per quality-adjusted life-year (QALY) gained estimates. Using the simpler AGM, with ibuprofen or diclofenac alone as the comparator, all of the COX-2 products are associated with higher costs (i.e. positive incremental costs) and small increases in effectiveness (i.e. positive incremental effectiveness), measured in terms of QALYs. The magnitude of the incremental costs and the incremental effects, and therefore the incremental cost-effectiveness ratios, vary considerably across all COX-2 selective NSAIDs. The base-case incremental cost per QALY results for COX-2 selective NSAIDs compared with diclofenac for the simpler model are: celecoxib (low dose) 68,400 pounds; celecoxib (high dose) 151,000 pounds; etodolac (branded) 42,400 pounds; etodolac (generic) 17,700 pounds; etoricoxib 31,300 pounds; lumiracoxib 70,400 pounds; meloxicam (low dose) 10,300 pounds; meloxicam (high dose) 17,800 pounds; rofecoxib 97,400 pounds; and valdecoxib 35,500 pounds. When the simpler AGM was run using ibuprofen or diclofenac combined with proton pump inhibitor (PPI) as the comparator, the results change substantially, with the COX-2 selective NSAIDs looking generally unattractive from a cost-effectiveness point of view (COX-2 selective NSAIDs were dominated by ibuprofen or diclofenac combined with PPI in most cases). This applies both to 'standard' and 'high-risk' arthritis patients defined in terms of previous GI ulcers. The full AGM produced results broadly in line with the simpler model.ConclusionsThe COX-2 selective NSAIDs examined were found to be similar to non-selective NSAIDs for the symptomatic relief of RA and OA and to provide superior GI tolerability (the majority of evidence is in patients with OA). Although COX-2 selective NSAIDs offer protection against serious GI events, the amount of evidence for this protective effect varied considerably across individual drugs. The volume of trial evidence with regard to cardiovascular safety also varied substantially between COX-2 selective NSAIDs. Increased risk of MI compared to non-selective NSAIDs was observed among those drugs with greater volume of evidence in terms of exposure in patient-years. Economic modelling shows a wide range of possible costs per QALY gained in patients with OA and RA. Costs per QALY also varied if individual drugs were used in 'standard' or 'high'-risk patients, the choice of non-selective NSAID comparator and whether that NSAID was combined with a PPI. With reduced costs of PPIs, future primary research needs to compare the effectiveness and cost-effectiveness of COX-2 selective NSAIDs relative to non-selective NSAIDs with a PPI. Direct comparisons of different COX-2 selective NSAIDs, using equivalent doses, that compare GI and MI risk are needed. Pragmatic studies that include a wider range of people, including the older age groups with a greater burden of arthritis, are also necessary to inform clinical practice. | Curtiss FR (2006)
Relative value of the NSAIDs, including COX-2 inhibitors and meloxicam.
Journal of managed care pharmacy : JMCP 12, 265-268 [PubMed:16623613] | Ahmed M, Khanna D, Furst DE (2005)
Meloxicam in rheumatoid arthritis.
Expert opinion on drug metabolism & toxicology 1, 739-751 [PubMed:16863437]
[show Abstract]
Rheumatoid arthritis (RA), a chronic inflammatory multisystem disorder marked by joint pain, stiffness, swelling and multiple systemic involvements, requires a multifaceted approach for its management. It includes symptomatic treatment with analgesics as well as disease-modifying medications to alter the course of RA over time. NSAIDS have been widely used for their symptomatic effects, but their use is not free from adverse effects, which may include life-threatening adverse events such as gastrointestinal (GI) bleeding and perforation. Meloxicam, an oxicam derivative that is a member of the enolic acid group of NSAIDs, has recently been approved by the US FDA for use in RA and osteoarthritis. At the FDA-recommended doses meloxicam is COX-2 preferential. By virtue of this COX-2 preferential activity it is expected to have lower GI toxicity as compared with COX-2 nonselective NSAIDs. Clinical trials have shown that meloxicam at 7.5 - 15 mg/day is as effective as diclofenac, piroxicam and naproxen as an anti-inflammatory and analgesic, and was associated with fewer GI adverse effects. | Gates BJ, Nguyen TT, Setter SM, Davies NM (2005)
Meloxicam: a reappraisal of pharmacokinetics, efficacy and safety.
Expert opinion on pharmacotherapy 6, 2117-2140 [PubMed:16197363]
[show Abstract]
The discovery of two distinct isoenzymes of COX has led to the development and clinical introduction of COX-2 inhibitors with increased selectivity onto the market. Meloxicam is a non-steroidal anti-inflammatory drug (NSAID) of the oxicam class, and is a preferential inhibitor of COX-2, demonstrating effectiveness with anti-inflammatory, analgesic and antipyretic activity. Meloxicam is therapeutically utilised in the management of osteoarthritis and rheumatoid arthritis. Trials have examined the risk of gastrointestinal ulceration of meloxicam when compared with traditional non-specific COX-inhibiting NSAIDs with mixed results; meloxicam seems to have a greater gastrointestinal risk than the highly specific COX-2 NSAIDs. Meloxicam has a plasma half-life of approximately 20 h and is convenient for once daily administration. Neither moderate renal nor hepatic insufficiency significantly alters the pharmacokinetics of meloxicam in short-term studies. Furthermore, dose adjustment is not required in the elderly. Recent drug-drug interaction studies have demonstrated that meloxicam interacts with some medications, including cholestyramine, lithium and some inhibitors of cytochrome P450 -2C9 and -3A4. Consequently, increased clinical vigilance should be maintained when coprescribing some medications with meloxicam. Concentration-dependent therapeutic and toxicological effects have yet to be extensively elucidated for meloxicam. Long-term safety in various organ systems, especially in the heart and vascular system and with concomitant drug administration, remains to be proven. The pharmacokinetics of meloxicam enables once daily application, which increases compliance compared with some shorter acting NSAIDs; however, long-term clinical data clearly demonstrating safety and efficacy advantages are lacking. | Fleischmann R, Iqbal I, Slobodin G (2002)
Meloxicam.
Expert opinion on pharmacotherapy 3, 1501-1512 [PubMed:12387696]
[show Abstract]
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. | Davies NM, Skjodt NM (1999)
Clinical pharmacokinetics of meloxicam. A cyclo-oxygenase-2 preferential nonsteroidal anti-inflammatory drug.
Clinical pharmacokinetics 36, 115-126 [PubMed:10092958]
[show Abstract]
Meloxicam [4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-1,2-benzothiazine -3-carboxamide-1, 1-dioxide] is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class which shows preferential inhibition of cyclo-oxygenase-2. Meloxicam has a plasma half-life of approximately 20 hours, making it convenient for once-daily administration. Meloxicam is eliminated after biotransformation to 4 pharmacologically inactive metabolites, which are excreted in urine and faeces. Meloxicam and its metabolites bind extensively to plasma albumin. Substantial concentrations of meloxicam are attained in synovial fluid, the proposed site of action in chronic inflammatory arthropathies. Neither moderate renal nor hepatic insufficiency significantly alter the pharmacokinetics of meloxicam. Dosage adjustment is not required in the elderly. Drug-drug interaction studies are available for some commonly co-prescribed medications. Concentration-dependent therapeutic and toxicological effects have yet to be extensively elucidated for this NSAID. | Furst DE (1997)
Meloxicam: selective COX-2 inhibition in clinical practice.
Seminars in arthritis and rheumatism 26, 21-27 [PubMed:9219316]
[show Abstract]
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. | Noble S, Balfour JA (1996)
Meloxicam.
Drugs 51, 424-30; discussion 431-32 [PubMed:8882380]
[show Abstract]
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. |
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