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Drug Safety Sep 2022Diclofenac has increased cardiovascular risks, but its risk profile compared with other COX-2 inhibitors remains unknown.
Cardiovascular Risks of Diclofenac Versus Other Older COX-2 Inhibitors (Meloxicam and Etodolac) and Newer COX-2 Inhibitors (Celecoxib and Etoricoxib): A Series of Nationwide Emulated Trials.
INTRODUCTION
Diclofenac has increased cardiovascular risks, but its risk profile compared with other COX-2 inhibitors remains unknown.
AIMS
The aim of this study was to compare the cardiovascular risks of diclofenac versus other older and newer COX-2 inhibitors (coxibs).
METHODS
Using Danish nationwide health registries (1999-2020), we conducted a series of emulated trials (n = 264). Eligible adults had no recent NSAID prescriptions, contraindications or conditions with low adherence. We included initiators of diclofenac (n = 1,600,202), meloxicam (n = 10,903), etodolac (n = 238,538), celecoxib (n = 77,591), and etoricoxib (n = 12,122). We computed the adjusted intention-to-treat incidence rate ratio (aIRR) with 95% confidence interval (CI) of major adverse cardiovascular events (MACE) within 30 days of initiation (5562 events).
RESULTS
MACE was 20% increased among initiators of diclofenac compared with other older COX-2 inhibitors (aIRR 1.19, 95% CI 1.10-1.28), driven by cardiac death (aIRR 1.57, 95% CI 1.21-2.03). The effect appeared strongest for women (aIRR 1.28, 95% CI 1.15-1.43), individuals with high baseline cardiovascular risk (aIRR 1.32, 95% CI 1.05-1.66), and when comparing high-dose diclofenac with low doses of the other older COX-2 inhibitors (aIRR 1.31, 95% CI 1.13-1.52). The results reflected increased rates compared with both meloxicam (aIRR 1.46, 95% CI 0.94-2.26) and etodolac (aIRR 1.18, 95% CI 1.09-1.28). Diclofenac initiators had similar increased rates of MACE compared with coxibs (aIRR 0.96, 95% CI 0.85-1.08), consistent for celecoxib (aIRR 1.02, 95% CI 0.88-1.19) and etoricoxib (aIRR 0.85, 95% CI 0.66-1.10).
CONCLUSIONS
The increased cardiovascular risks associated with diclofenac initiation were higher than for other older COX-2 inhibitors (meloxicam/etodolac) and comparable to coxibs (celecoxib/etoricoxib).
Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Cardiovascular Diseases; Celecoxib; Cyclooxygenase 2 Inhibitors; Diclofenac; Etodolac; Etoricoxib; Female; Heart Disease Risk Factors; Humans; Meloxicam; Risk Factors
PubMed: 35909207
DOI: 10.1007/s40264-022-01211-1 -
PloS One 2019Plasma pharmacokinetic profiles and the anti-inflammatory efficacy of meloxicam were determined when administered subcutaneously (SC) or intramuscularly (IM) to sheep....
Plasma pharmacokinetic profiles and the anti-inflammatory efficacy of meloxicam were determined when administered subcutaneously (SC) or intramuscularly (IM) to sheep. Merino ewes were initially injected with 0.1 mL of oil of turpentine into a forelimb to induce inflammation, followed by either 1.0 mg/kg or 2.0 mg/kg of meloxicam administered either SC or IM (n = 6 per treatment group) or followed by no meloxicam administration (control) (n = 4). Ewes were examined to determine skin temperature, limb circumference, limb sensitivity and signs of lameness at 0, 0.5, 1, 2, 4, 6, 8, 10, 12, 24 and 48 h following treatment, with blood collected at these time-points to quantify meloxicam plasma concentrations. Skin temperature of ewes dosed with meloxicam at 1.0 mg/kg SC and 2.0 mg/kg IM at 12 h and 1.0 mg/kg SC at 24 were significantly different to the controls (P < 0.05). Limb circumferences of ewes dosed with 1.0 mg/kg IM were significantly different to controls at 10 h and 12 h (P < 0.05). All meloxicam treatment groups resulted in reduced limb sensitivity compared to controls at 6 h, with the 1.0 and 2.0 mg/kg IM treatments significantly different at 12 h (P < 0.05) and 1.0 and 2.0 mg/kg SC groups, significantly different to controls at 48 h (P < 0.05). No significant difference in lameness scores were detected over 48 h. The 1.0 mg/kg IM treatment had a significantly greater plasma meloxicam concentration than the 1.0 mg/kg SC treatment over 0.5 to 4 h (P < 0.001). Both 1.0 mg/kg SC and IM treatments demonstrated elimination half-lives (mean ± SD) of 10.82 ± 2.46 and 12.63 ± 2.37 h, respectively. Meloxicam at all doses provided some anti-inflammatory and analgesic effects from 6 to 48 h; however no route could be distinguished as more efficacious than the others.
Topics: Animals; Behavior, Animal; Extremities; Gait; Injections, Intramuscular; Injections, Subcutaneous; Meloxicam; Sheep; Skin Temperature; Treatment Outcome; Turpentine
PubMed: 31017959
DOI: 10.1371/journal.pone.0215842 -
The Medical Letter on Drugs and... Sep 2019
Review
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Humans; Meloxicam; Solubility; Tablets
PubMed: 31599868
DOI: No ID Found -
International Immunopharmacology Mar 2023Meloxicam is a selective cyclooxygenase-2 inhibitor and has been widely used in combination with antibiotics to alleviate uterine inflammation and provide analgesia in...
Meloxicam is a selective cyclooxygenase-2 inhibitor and has been widely used in combination with antibiotics to alleviate uterine inflammation and provide analgesia in postpartum cows. Studies have shown that meloxicam has antioxidant and anti-inflammatory effects. However, the link between meloxicam and uterine inflammation and oxidative stress in dairy cows has not been studied. The purpose of this study was to research the effects of meloxicam (0.5 or 5 μM) on oxidative stress and inflammatory response of primary bovine endometrial epithelial cells (BEEC) stimulated by Escherichia coli lipopolysaccharide (1 μg/mL LPS). As a result, LPS stimulated the production of oxidative stress markers and the expression of inflammatory factors, accompanied by a decrease in the activity and the gene transcription of antioxidant enzymes. Co-treatment of meloxicam and LPS reduced the content of oxidative stress markers and the mRNA levels of the pro-inflammatory genes, and improved antioxidant enzyme activities and the corresponding gene expression as compared with the cells treated with LPS alone. Meloxicam attenuated the inhibitory effect of the Nrf2 pathway and the phosphorylation levels of p65 and IκBα caused by LPS. In conclusion, meloxicam alone had no effect on BEEC, but prevented oxidative stress and inflammatory response in LPS-stimulated BEEC.
Topics: Female; Cattle; Animals; NF-kappa B; Meloxicam; Lipopolysaccharides; NF-E2-Related Factor 2; Antioxidants; Oxidative Stress; Inflammation; Epithelial Cells
PubMed: 36750013
DOI: 10.1016/j.intimp.2023.109822 -
Journal of Feline Medicine and Surgery Feb 2021Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival....
OBJECTIVES
Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival. This study aimed to prospectively evaluate the renal effects of low-dose meloxicam treatment (0.02 mg/kg/day) over 6 months in cats with chronic kidney disease (CKD).
METHODS
Twenty-one cats with stable International Renal Interest Society stage 2 or 3 CKD were recruited and randomized to placebo or meloxicam groups. Cats were evaluated at baseline and at 1, 3 and 6 months, including blood pressure, chemistry, symmetric dimethylarginine (SDMA), glomerular filtration rate (GFR), urinalysis, urine protein:creatinine ratio (UPC), urine transforming growth factor-beta (β):creatinine ratio, urine clusterin, urine cystatin B and serum inosine.
RESULTS
No statistical difference was observed in systolic blood pressure, blood urea nitrogen, creatinine, SDMA, GFR, urine transforming growth factor-β:creatinine ratio, urine clusterin, urine cystatin B or serum inosine in cats receiving meloxicam vs placebo. Mean UPC was greater in the meloxicam group (0.33) than the placebo group (0.1) at 6 months ( = 0.006). Four cats had meloxicam discontinued owing to potential (mainly gastrointestinal) adverse effects.
CONCLUSIONS AND RELEVANCE
No decline in renal excretory function was observed when meloxicam was administered to cats with CKD. However, gastrointestinal adverse effects were observed, and cats that received meloxicam had greater proteinuria at 6 months than cats that received placebo. As proteinuria is associated with negative outcomes (progression of azotemia and hypertension) in cats with CKD, this finding suggests that meloxicam should be used with caution in cats with CKD and UPC monitored. Until further research is available, clinicians should weigh the risk of potential increased proteinuria against quality of life benefits when considering meloxicam for analgesia in cats with renal disease.
Topics: Animals; Cat Diseases; Cats; Glomerular Filtration Rate; Meloxicam; Quality of Life; Renal Insufficiency, Chronic; Retrospective Studies
PubMed: 32594827
DOI: 10.1177/1098612X20935750 -
Current Pain and Headache Reports Jan 2020Acute postoperative pain reduction is a major target against the opioid crisis. While opioids have traditionally been the mainstay for postoperative analgesia, current... (Review)
Review
PURPOSE OF REVIEW
Acute postoperative pain reduction is a major target against the opioid crisis. While opioids have traditionally been the mainstay for postoperative analgesia, current practice has focused on a multimodal approach to pain control, including ultrasound-guided blocks with longer acting local anesthetic agents.
RECENT FINDINGS
Non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, are an important class of medications utilized to manage pain in the perioperative period. An additional treatment used in perioperative or postoperative pain relief is Exparel, a bupivacaine (sodium channel blocker) liposomal injectable suspension with a 3-4-day duration of action. The long-acting mechanism and formulation of Exparel consistently has demonstrated decreased opioid use and pain scores in patients undergoing many different surgical procedures. A concern is that pH negatively alters the efficacy of bupivacaine, as in cases of inflamed tissue and acidic fluid pH. For this reason, a combination medication with both meloxicam and bupivacaine has been developed, which normalizes pH and has anti-inflammatory and anti-pain conduction properties. Clinical studies demonstrate that this combination agent can be extremely beneficial in treating postoperative pain. This manuscript summarizes the newest developments with regard to liposomal bupivacaine and the non-steroidal meloxicam, their roles in effective treatment of postoperative pain, contraindications, special considerations of using these medications, and future considerations. HTX-011 pairs up a new extended-release formulation of the local anesthetic bupivacaine with meloxicam, a well-established non-steroidal anti-inflammatory drug (NSAID).
Topics: Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Bupivacaine; Delayed-Action Preparations; Drug Therapy, Combination; Humans; Liposomes; Meloxicam; Pain Management; Pain, Postoperative
PubMed: 32002676
DOI: 10.1007/s11916-020-0837-2 -
Poultry Science Sep 2023This study aimed to determine the pharmacokinetics of meloxicam in pigeons. Twenty-four 7-wk-old meat pigeons (Columba livia) were randomly divided into 3 groups (PO,...
This study aimed to determine the pharmacokinetics of meloxicam in pigeons. Twenty-four 7-wk-old meat pigeons (Columba livia) were randomly divided into 3 groups (PO, IM, and IV) and given a single dose of 1 mg/kg body weight of meloxicam. Plasma samples were taken at predetermined times, which were then analyzed using a validated high-performance liquid chromatography (HPLC) method and subjected to noncompartmental analysis using Phoenix software. Results indicated that meloxicam was absorbed effectively and quickly after PO and IM dosing. Peak concentrations (0.83 ± 0.21 and 1.59 ± 0.49 μg/mL) were achieved at 2 and 0.26 h, respectively, with mean absorption times of 2.56 ± 1.50 and 1.47 ± 0.89 h. Bioavailability was high at 86.31 ± 43.45% and 81.57 ± 52.58%, respectively, and the area under the concentration-time curve (AUC) was 5.33 ± 2.68 and 5.03 ± 3.26 h·µg/mL. After IV administration, the elimination was faster with a total body clearance (CL) of 188.75 ± 83.23 mL/h/kg, an elimination half-life (t) of 1.76 ± 0.56 h, and a volume of distribution at steady-state (V) of 427.50 ± 188.43 mL/kg. Considering the lack of a precise analgesic threshold of meloxicam in pigeons and the notable differences in its analgesic threshold among various animal species, formulating a dosing regimen in pigeons presented a significant challenge. Based on the previous analgesic threshold (3.5 μg/mL) in parrots, a higher dose (e.g., 2 mg/kg) or shorter dosing interval (e.g., every 6 h) is recommended for treating pain in pigeons. Nonetheless, further pharmacodynamic research is required to verify these recommendations.
Topics: Animals; Meloxicam; Columbidae; Anti-Inflammatory Agents, Non-Steroidal; Thiazines; Thiazoles; Area Under Curve; Half-Life; Chickens; Administration, Oral; Injections, Intravenous; Injections, Intramuscular
PubMed: 37390554
DOI: 10.1016/j.psj.2023.102869 -
AAPS PharmSciTech Aug 2019The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The...
The purpose of the present investigation was to analyze devitrification of amorphous drugs such as lornoxicam, meloxicam, and felodipine in the presence of sericin. The binary solid dispersions comprising varying mass ratios of drug and sericin were subject to amorphization by spray drying, solvent evaporation, ball milling, and physical mixing. Further, obtained solid dispersions (SDs) were characterized by HPLC, ATR-FTIR, HNMR, molecular docking, accelerated stability study at 40°C and 75 ± 2% RH (XRD and DSC), and in vitro dissolution studies. The HPLC analysis indicated no decomposition of the drugs during the spray drying process. From ATR-FTIR, NMR, and molecular docking study, it was revealed that H-bonding played a vital role in amorphous drug stabilization. An excellent devitrification inhibition was observed in case of lornoxicam (SDLS3) and meloxicam (SDMS3) SDs prepared by spray drying. On the other hand, spray-dried SD of felodipine (SDFS3) showed traces of microcrystals. The percent crystallinity of SDLS3, SDMS3, and SDFS3 was found to be 7.4%, 8.23%, and 18.31% respectively indicating adequate amorphization. The dissolution performance of SDLS, SDMS, and SDFS after 3 months showed > 85% than SDs prepared by other methods. Thus, sericin significantly inhibited crystallization and was responsible for amorphous state stabilization of pharmaceuticals.
Topics: Chemistry, Pharmaceutical; Crystallization; Desiccation; Drug Stability; Felodipine; Meloxicam; Molecular Docking Simulation; Piroxicam; Sericins; Solubility; Solvents
PubMed: 31407105
DOI: 10.1208/s12249-019-1475-z -
Journal of Veterinary Pharmacology and... Sep 2022The objective of this study was to determine the pharmacokinetics of meloxicam after a single intravenous (IV), intramuscular (IM), and oral (PO) dose at 1 mg/kg body...
The objective of this study was to determine the pharmacokinetics of meloxicam after a single intravenous (IV), intramuscular (IM), and oral (PO) dose at 1 mg/kg body weight in Jing Hong laying hens. Blood samples were collected at predetermined time points. Plasma meloxicam concentrations were determined using a validated high-performance liquid chromatography (HPLC) assay method and then subjected to a non-compartmental analysis. After IV administration, meloxicam had a mean (±SD) volume of distribution at steady-state (Vd ) of 206.50 ± 25.23 ml/kg, a terminal half-life (t ) of 5.45 ± 0.53 h, and a total body clearance (Cl) of 26.48 ± 4.13 ml/h/kg. After PO and IM administration, meloxicam was absorbed relatively rapidly: the peak concentrations (C s) of 3.04 ± 0.56 and 8.94 ± 2.31 μg/ml were observed at 3.08 and 0.80 h, respectively. After PO and IM administration, the absolute bioavailability (F) was determined as 70.13% and 125.50%, respectively. Assuming that hens shared the same analgesic threshold of meloxicam (0.5 μg/ml) with humans, the plasma concentrations after three different routes (PO, IM, and IV) of administration were above this value for 16.7, 19.2, and 14.9 h, respectively.
Topics: Administration, Intravenous; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Biological Availability; Chickens; Female; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Meloxicam
PubMed: 35717631
DOI: 10.1111/jvp.13081 -
Journal of the American Academy of... Apr 2022Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as part of multimodal analgesia in total knee arthroplasty (TKA). Selective cyclooxygenase (COX)-2...
INTRODUCTION
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as part of multimodal analgesia in total knee arthroplasty (TKA). Selective cyclooxygenase (COX)-2 inhibitors (e.g., celecoxib) are believed to have fewer gastrointestinal (GI) adverse effects than nonselective NSAIDS. Meloxicam is less selective for COX-2 than celecoxib is and partially inhibits COX-1 at higher doses. Nonetheless, some surgeons prefer using nonselective NSAIDs because of their lower expense.
METHODS
Four thousand nine hundred ninety-four patients who underwent TKA between January 2015 and February 2020 and took either celecoxib (n = 3,174), meloxicam 15 mg/d (n = 1,819), or meloxicam 7.5 mg/d (n = 451) were studied. Mutlimodal postoperative analgesia protocols were otherwise similar. GI bleeding and wound complication incidence were determined, as well as average 30-day prescription costs.
RESULTS
GI bleeding incidence was similar in the three cohorts (P = 0.4). The incidence of wound complications did not significantly differ between the groups: 0.06%, 0.07%, and 0.22% in the celecoxib, meloxicam 15 mg/d, and meloxicam 7.5 mg/d groups, respectively (P = 0.06). Subsituting meloxicam for celecoxib results in an average savings of $183 per prescription.
DISCUSSION
Meloxicam used at higher doses (15 mg/d) does not markedly increase the risk of GI or wound complications associated with COX-1 inhibition and is less costly for multimodal analgesia after TKA.
Topics: Analgesia; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Knee; Celecoxib; Cyclooxygenase 2 Inhibitors; Humans; Meloxicam
PubMed: 35389917
DOI: 10.5435/JAAOSGlobal-D-22-00032