Meloxicam: a reappraisal of pharmacokinetics, efficacy and safety

Gates, Brian J.; Nguyen, Trang Thi; Setter, Stephen M.; Davies, Neal M.

doi:10.1517/14656566.6.12.2117

Cited by 76 publications

(45 citation statements)

References 48 publications

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“…Meloxicam is a preferential cyclooxygenase‐2 inhibitor with analgesic, antipyretic, and anti‐inflammatory properties . An oral dosage form of the drug has demonstrated efficacy for the treatment of pain and inflammation in patients with rheumatoid arthritis and osteoarthritis and is associated with fewer gastrointestinal adverse events compared with nonselective NSAIDs . Oral meloxicam is metabolized in the liver to 4 inactive metabolites that are excreted in urine and feces with an elimination half‐life of ∼20 hours .…”

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confidence: 99%

A Phase 3, Randomized, Placebo‐Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery

Bergese

Melson

Candiotti

et al. 2019

Clinical Pharm in Drug Dev

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An intravenous (IV) formulation of meloxicam is being studied for moderate to severe pain management. This phase 3, randomized, multicenter, double‐blind, placebo‐controlled trial evaluated the safety of once‐daily meloxicam IV 30 mg in subjects following major elective surgery. Eligible subjects were randomized (3:1) to receive meloxicam IV 30 mg or placebo administered once daily. Safety was evaluated via adverse events, clinical laboratory tests, vital signs, wound healing, and opioid consumption. The incidence of adverse events was similar between meloxicam IV– and placebo‐treated subjects (63.0% versus 65.0%). Investigators assessed most adverse events as mild or moderate in intensity and unrelated to treatment. Adverse events of interest (injection‐site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound‐healing events) were similar between groups. Over the treatment period, meloxicam IV was associated with a 23.6% (P = .0531) reduction in total opioid use (9.2 mg morphine equivalent) compared to placebo‐treated subjects. The results suggest that meloxicam IV had a safety profile similar to that of placebo with respect to numbers and frequencies of adverse events and reduced opioid consumption in subjects with moderate to severe postoperative pain following major elective surgery.

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confidence: 99%

A Phase 3, Randomized, Placebo‐Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery

Bergese

Melson

Candiotti

et al. 2019

Clinical Pharm in Drug Dev

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“…Meloxicam is a nonsteroidal anti‐inflammatory drug (NSAID) with preferential COX2 inhibitory activity . Meloxicam is a U.S. Food and Drug Administration–approved drug for rheumatoid arthritis and osteoarthritis .…”

Section: Introductionmentioning

confidence: 99%

Modulator Effects of Meloxicam against Doxorubicin-Induced Nephrotoxicity in Mice

Hassan

Ghobara

Abd‐Allah

2014

J Biochem Mol Toxicol

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Doxorubicin-induced renal toxicity overshadows its anticancer effectiveness. This study is aimed at assessing the possible modulator effects of meloxicam, a cyclooxigenase-2 inhibitor, on doxorubicin-induced nephrotoxicity in mice and exploring some of the modulator mechanisms. Forty male mice were divided for treatment, for 2 weeks, with saline, meloxicam (daily), doxorubicin (twice/week), or both meloxicam and doxorubicin. Doxorubicin induced a significant increase in relative kidney weight to body weight, kidney lipid perooxidation, plasma levels of interleukin-6 and tumor necrosis factor-α, kidney caspase-3 activity, and kidney prostaglandin E2 (PGE2) content. Doxorubicin disturbed kidney histology, abrogated renal function tests (serum creatinine, uric acid, and blood urea nitrogen), induced a significant decrease in antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase, and catalase) and reduced glutathione (GSH) content. The administration of meloxicam with doxorubicin mitigated all doxorubicin-disturbed parameters. Meloxicam ameliorated doxorubicin-induced renal injury via inhibition of inflammatory PGE2, inflammatory cytokines, caspase-3 activity, antioxidant effect, and free radical scavenging activity.

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“…It is widely used in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other rheumatological conditions. Meloxicam has an oral bioavailability of 89%, and its maximum plasma concentrations (C max ) are achieved within 4 to 11 h (10,26). It is extensively bound to plasma proteins (Ͼ99%), mainly to albumin (24).…”

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confidence: 99%

Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations

Hynninen

Olkkola

Kurkinen

et al. 2009

Antimicrob Agents Chemother

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This study investigated the effect of voriconazole, an inhibitor of cytochrome P450 2C9 (CYP2C9) and CYP3A4, and itraconazole, an inhibitor of CYP3A4, on the pharmacokinetics and pharmacodynamics of meloxicam. Twelve healthy volunteers in a crossover study ingested 15 mg of meloxicam without pretreatment (control), after voriconazole pretreatment, and after itraconazole pretreatment. The plasma concentrations of meloxicam, voriconazole, itraconazole, and thromboxane B 2 (TxB 2 ) generation were monitored. Compared to the control phase, voriconazole increased the mean area under the plasma concentration-time curve from 0 to 72 h (AUC 0-72 ) of meloxicam by 47% (P < 0.001) and prolonged its mean half-life (t 1/2 ) by 51% (P < 0.01), without affecting its mean peak concentration (C max ). In contrast, itraconazole decreased the mean AUC 0-72 and C max of meloxicam by 37% (P < 0.001) and by 64% (P < 0.001), respectively, and prolonged its t 1/2 and time to C max . The plasma protein unbound fraction of meloxicam was unchanged by voriconazole and itraconazole. Lowered plasma meloxicam concentrations during the itraconazole phase were associated with decreased pharmacodymic effects of meloxicam, as observed by weaker inhibition of TxB 2 synthesis compared to the control and voriconazole phases. Voriconazole increases plasma concentrations of meloxicam, whereas itraconazole, unexpectedly, decreases plasma meloxicam concentrations, possibly by impairing its absorption.Meloxicam is a nonsteroidal anti-inflammatory drug (NSAID) of the oxicam class with selectivity toward cyclo-oxygenase 2 (COX-2) compared to 19). It is widely used in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and other rheumatological conditions. Meloxicam has an oral bioavailability of 89%, and its maximum plasma concentrations (C max ) are achieved within 4 to 11 h (10, 26). It is extensively bound to plasma proteins (Ͼ99%), mainly to albumin (24). The elimination half-life (t 1/2 ) of meloxicam ranges from 13 to 20 h, and it is suitable for once-daily dosing (24,26). Meloxicam is extensively metabolized in the liver, primarily by polymorphic cytochrome P450 2C9 (CYP2C9) enzyme, and to a minor extent by CYP3A4 enzyme, to four pharmacologically inactive metabolites (6, 24). Only negligible amounts of the parent drug are found in urine and in feces (24). The effect of different genotypes on the pharmacokinetics of meloxicam is not known.Voriconazole is a triazole antifungal agent used both intravenously and orally to treat invasive fungal infections. Voriconazole undergoes extensive oxidative metabolism involving CYP enzymes CYP2C19, CYP2C9, and CYP3A4 (13). Voriconazole is also an inhibitor of CYP2C9, CYP3A4, and CYP2C19 catalyzed reactions both in vitro and in vivo (17,21,23,25). Another triazole antifungal, itraconazole, is a potent inhibitor of CYP3A4 (18, 28), but it is without effect on CYP2C9 in humans (15,27).Because both voriconazole and itraconazole inhibit CYP enzymes involved in the metabolism of meloxicam, ...

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Meloxicam: a reappraisal of pharmacokinetics, efficacy and safety

Cited by 76 publications

References 48 publications

A Phase 3, Randomized, Placebo‐Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery

A Phase 3, Randomized, Placebo‐Controlled Evaluation of the Safety of Intravenous Meloxicam Following Major Surgery

Modulator Effects of Meloxicam against Doxorubicin-Induced Nephrotoxicity in Mice

Voriconazole Increases while Itraconazole Decreases Plasma Meloxicam Concentrations

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