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Paediatric Drugs Nov 2022Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in infants, children, and adolescents worldwide; however, despite sufficient evidence of the beneficial... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in infants, children, and adolescents worldwide; however, despite sufficient evidence of the beneficial effects of NSAIDs in children and adolescents, there is a lack of comprehensive data in infants. The present review summarizes the current knowledge on the safety and efficacy of various NSAIDs used in infants for which data are available, and includes ibuprofen, dexibuprofen, ketoprofen, flurbiprofen, naproxen, diclofenac, ketorolac, indomethacin, niflumic acid, meloxicam, celecoxib, parecoxib, rofecoxib, acetylsalicylic acid, and nimesulide. The efficacy of NSAIDs has been documented for a variety of conditions, such as fever and pain. NSAIDs are also the main pillars of anti-inflammatory treatment, such as in pediatric inflammatory rheumatic diseases. Limited data are available on the safety of most NSAIDs in infants. Adverse drug reactions may be renal, gastrointestinal, hematological, or immunologic. Since NSAIDs are among the most frequently used drugs in the pediatric population, safety and efficacy studies can be performed as part of normal clinical routine, even in young infants. Available data sources, such as (electronic) medical records, should be used for safety and efficacy analyses. On a larger scale, existing data sources, e.g. adverse drug reaction programs/networks, spontaneous national reporting systems, and electronic medical records should be assessed with child-specific methods in order to detect safety signals pertinent to certain pediatric age groups or disease entities. To improve the safety of NSAIDs in infants, treatment needs to be initiated with the lowest age-appropriate or weight-based dose. Duration of treatment and amount of drug used should be regularly evaluated and maximum dose limits and other recommendations by the manufacturer or expert committees should be followed. Treatment for non-chronic conditions such as fever and acute (postoperative) pain should be kept as short as possible. Patients with chronic conditions should be regularly monitored for possible adverse effects of NSAIDs.
Topics: Adolescent; Infant; Child; Humans; Meloxicam; Naproxen; Celecoxib; Ibuprofen; Ketoprofen; Diclofenac; Ketorolac; Flurbiprofen; Niflumic Acid; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Anti-Inflammatory Agents; Chronic Disease; Pain
PubMed: 36053397
DOI: 10.1007/s40272-022-00514-1 -
Drugs & Aging Apr 2019Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in... (Review)
Review
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely recommended and prescribed to treat pain in osteoarthritis. While measured to have a moderate effect on pain in osteoarthritis, NSAIDs have been associated with wide-ranging adverse events affecting the gastrointestinal, cardiovascular, and renal systems. Gastrointestinal toxicity is found with all NSAIDs, which may be of particular concern when treating older patients with osteoarthritis, and gastric adverse events may be reduced by taking a concomitant gastroprotective agent, although intestinal adverse events are not ameliorated. Cardiovascular toxicity is associated with all NSAIDs to some extent and the degree of risk appears to be pharmacotherapy specific. An increased risk of acute myocardial infarction and heart failure is observed with all NSAIDs, while an elevated risk of hemorrhagic stroke appears to be restricted to the use of diclofenac and meloxicam. All NSAIDs have the potential to induce acute kidney injury, and patients with osteoarthritis with co-morbid conditions including hypertension, heart failure, and diabetes mellitus are at increased risk. Osteoarthritis is associated with excess mortality, which may be explained by reduced levels of physical activity owing to lower limb pain, presence of comorbid conditions, and the adverse effects of anti-osteoarthritis medications especially NSAIDs. This narrative review of recent literature identifies data on the safety of non-selective NSAIDs to better understand the risk:benefit of using NSAIDs to manage pain in osteoarthritis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Diclofenac; Gastrointestinal Diseases; Humans; Meloxicam; Myocardial Infarction; Osteoarthritis; Risk
PubMed: 31073921
DOI: 10.1007/s40266-019-00660-1 -
PloS One 2020In veterinary medicine, the administration of nonsteroidal anti-inflammatory analgesics (NSAIDs) for the control of postsurgical pain in dogs and cats is common given... (Comparative Study)
Comparative Study
Clinical evaluation of postoperative analgesia, cardiorespiratory parameters and changes in liver and renal function tests of paracetamol compared to meloxicam and carprofen in dogs undergoing ovariohysterectomy.
BACKGROUND
In veterinary medicine, the administration of nonsteroidal anti-inflammatory analgesics (NSAIDs) for the control of postsurgical pain in dogs and cats is common given the anti-inflammatory, analgesic, and antipyretic effects of these drugs. This study compared the serum biochemical changes and postoperative analgesic effects of paracetamol, meloxicam, and carprofen in bitches submitted to an ovariohysterectomy using the Dynamic Interactive Visual Analog Scale (DIVAS) and Pain Scale of the University of Melbourne (UMPS) scoring systems.
METHODS
Thirty bitches of different breeds underwent elective ovariohysterectomies and were randomly assigned to one of three treatment groups: a paracetamol group [15 mg kg-1 intravenous (IV)], a carprofen group (4 mg kg-1 IV), and a meloxicam group (0.2 mg kg-1 IV). All treatments were administered 30 minutes prior to surgery. Paracetamol was administered every 8 hours postoperatively for 48 hours total, while carprofen and meloxicam were intravenously administered every 24 hours. An evaluation of post-surgical pain was done with the DIVAS and the UMPS. The first post-surgical pain measurement was performed 1 hour after surgery and then 2, 4, 6, 8, 12, 16, 20, 24, 36, and 48 hours after surgery.
RESULTS
All groups exhibited a gradual reduction in pain throughout the postoperative period in both scales; however, neither scale significantly differed between the three treatment groups (P > 0.05) during the 48 postoperative hours.
CONCLUSIONS
Paracetamol was as effective as meloxicam and carprofen for post-surgical analgesia in bitches subjected to elective ovariohysterectomy. The present study demonstrates that paracetamol may be considered a tool for the effective treatment of acute perioperative pain in dogs. Furthermore, this drug led to no adverse reactions or changes in the parameters assessed in the present study, indicating its safety.
Topics: Acetaminophen; Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Cardiorespiratory Fitness; Dogs; Female; Hysterectomy; Kidney Function Tests; Liver Function Tests; Meloxicam; Ovariectomy; Pain, Postoperative
PubMed: 32059002
DOI: 10.1371/journal.pone.0223697 -
Journal of the American Association For... May 2022Several analgesics are suggested for pain management in mice. Nonsteroidal antiinflammatories (NSAIDs), such as meloxicam can be administered for the treatment of...
Several analgesics are suggested for pain management in mice. Nonsteroidal antiinflammatories (NSAIDs), such as meloxicam can be administered for the treatment of inflammation and acute pain; however, several side effects can occur which include gastrointestinal ulceration and renal and hepatic toxicity. We previously performed a pilot study to test the antinociceptive activity of meloxicam in mice, but we observed behavioral changes in unoperated control mice. These observations spurred further investigation. One hypothesis for the result was potential differences in formulation between commercial brands of meloxicam. Thus, this current study aimed to evaluate the effects of 3 different commercial brands of meloxicam (20 mg/kg) in the general activity of mice using the open field test. Our results showed that meloxicam had several effects on mouse behavior and caused the formation of skin lesions at the injection site, depending on the brand of the drug. The most significant adverse effect observed was decreased exploratory activity. Grooming frequency was reduced in all groups. These adverse effects might be related to the quality of the drugs because meloxicam formulations can contain crystal polymorphisms that affect drug quality and efficacy. This study points out the importance of drug quality variation that can affect the outcome of behavioral studies in mice.
Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Mice; Open Field Test; Pilot Projects; Thiazines
PubMed: 35101160
DOI: 10.30802/AALAS-JAALAS-21-000046 -
Molecules (Basel, Switzerland) Mar 2021Recently, the design of new biological metal-ligand complexes has gained a special interest all over the world. In this research, new series of mixed ligand complexes...
Recently, the design of new biological metal-ligand complexes has gained a special interest all over the world. In this research, new series of mixed ligand complexes from meloxicam (Hmel) and glycine (Gly) were synthesized. Structures of the compounds were investigated employing elemental analyses, infrared, electronic absorption, H NMR, thermal analyses, effective magnetic moment and conductivity. The estimated molar conductivity of the compounds in 1 × 10 M DMF solution indicates the non-electrolyte existence of the examined complexes. Additionally, the effective magnetic moment values refer to the complexes found as octahedral molecular geometry. The data of the infrared spectra showed the chelation of Hmel and Gly with metal ions from amide oxygen and nitrogen of the thyizol groups of Hmel and through nitrogen of the amide group and oxygen of the carboxylic group for Gly. Thermal analyses indicated that the new complexes have good thermal stability and initially lose hydration water molecules followed by coordinated water molecules, Gly and Hmel. The kinetic parameters were calculated graphically using Coats-Redfern and Horowitz-Metzeger methods at = 1 and ≠ 1. The density functional theory (DFT) calculations were performed at B3LYP levels. The optimized geometry of the ligand and its complexes were obtained based on the optimized structures. The data indicated that the complexes are soft with η value in the range 0.114 to 0.086, while η = 0.140 for free Hmel. The new prepared complexes were investigated as antibacterial and antifungal agents against some phyto- and human pathogens and the minimum inhibitory concentration (MIC) data showed that complex () has the lowest MIC for and (10.8 µg/mL).
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Coordination Complexes; Escherichia coli; Ions; Kinetics; Ligands; Magnetic Resonance Spectroscopy; Meloxicam; Metals; Microbial Sensitivity Tests; Molecular Structure; Schiff Bases; Spectrophotometry, Infrared; Thermodynamics
PubMed: 33803210
DOI: 10.3390/molecules26051480 -
Journal of Feline Medicine and Surgery Dec 2022Non-steroidal anti-inflammatory drugs (NSAIDs) are infrequently utilized in cats due to concern for renal compromise; however, recent studies demonstrate tolerability of...
OBJECTIVES
Non-steroidal anti-inflammatory drugs (NSAIDs) are infrequently utilized in cats due to concern for renal compromise; however, recent studies demonstrate tolerability of low dose meloxicam. Toceranib phosphate is used to treat several feline cancers and is well tolerated. This study aimed to determine the tolerability and adverse event profile of combined toceranib and low dose meloxicam in cancer-bearing cats. Secondary goals involved assessing anticancer tumor efficacy and impact upon quality of life and analgesia.
METHODS
Cats with any cancer not involving the kidneys were eligible. The study adopted a conventional 3 + 3 dose escalation design. Toceranib was administered every other day at a standard dose with meloxicam administered in an escalating fashion in subsequent cohorts, at a starting dose of 0.01 mg/kg on opposite days to toceranib, up to a maximum of 0.02 mg/kg daily, based upon previous safety studies. Laboratory work, blood pressure, tumor measurements, pain score and client-completed quality-of-life surveys were recorded every 2-4 weeks during the 12-week study period.
RESULTS
Twenty-one cats were enrolled. When combined with toceranib, a meloxicam dose of 0.02 mg/kg q24h was safe and well tolerated, with no cats being withdrawn due to adverse events from the drug combination. The majority of cats demonstrated clinical benefit with stable to mildly improved tumor measurements, quality of life and pain scores.
CONCLUSIONS AND RELEVANCE
Low dose meloxicam combined with toceranib is safe and well tolerated in cancer-bearing cats. Continued patient recruitment and data collection are needed to determine the maximum tolerated dose of meloxicam. The results of our study will guide further phase II/III trials.
Topics: Animals; Cats; Cat Diseases; Meloxicam; Neoplasms; Pain; Quality of Life
PubMed: 34923878
DOI: 10.1177/1098612X211067023 -
BMC Veterinary Research Sep 2020The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine...
BACKGROUND
The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify residues.
RESULTS
Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001-0.0012 µg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 µg/g). Meloxicam was detected in a single liver sample (0.0054 µg/g) at 72 h but was below the EU MRL (0.065 µg/g).
CONCLUSIONS
These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Clonixin; Half-Life; Injections, Intramuscular; Kidney; Liver; Male; Meloxicam; Sus scrofa
PubMed: 32938437
DOI: 10.1186/s12917-020-02556-4 -
Clinical Pharmacology in Drug... Oct 2020Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of... (Comparative Study)
Comparative Study
Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective treatments for pain but may induce bleeding events due to platelet dysfunction associated with inhibition of cyclooxygenase (COX)-1 impairing thromboxane production. An intravenous nanocrystal formulation of meloxicam, a COX-2 preferential nonsteroidal anti-inflammatory drug, is under development for the treatment of moderate to severe pain. This single-center ex vivo study evaluated the effect of meloxicam intravenous and ketorolac on platelet function in whole blood samples from healthy volunteers. Each whole blood sample was aliquoted to allow analysis using a platelet function analyzer under negative control (untreated), positive control (2 therapeutic ketorolac concentrations), and meloxicam intravenous (1 therapeutic, 3 supratherapeutic concentrations) using both collagen with epinephrine and collagen with adenosine diphosphate reagent cartridges. The platelet function analyzer determines closure time by simulating platelet adhesion and aggregation following vascular injury. The final analysis set included data from 8 subjects. The collagen with adenosine diphosphate analysis (sensitive to thrombocytopathies) showed no significant differences in closure time for meloxicam- or ketorolac-treated samples and untreated control. The collagen with epinephrine analysis (sensitive to aspirin-induced platelet abnormalities) produced no significant difference in closure time between any meloxicam concentration and untreated control. Ketorolac was associated with significantly longer closure times vs untreated control at both the 2.5- and 5-µg/mL concentrations (P = .003 and .0257, respectively) and vs meloxicam at several concentrations. Similar results were observed when all analyzed samples were included. Meloxicam intravenous had no significant effect on closure times at therapeutic or supratherapeutic concentrations in this ex vivo study.
Topics: Adenosine Diphosphate; Administration, Intravenous; Adult; Anti-Inflammatory Agents, Non-Steroidal; Blood Specimen Collection; Collagen; Cyclooxygenase Inhibitors; Drug Compounding; Epinephrine; Female; Healthy Volunteers; Hemorrhage; Humans; Ketorolac; Male; Meloxicam; Nanoparticles; Pain; Platelet Aggregation; Platelet Function Tests; Reagent Kits, Diagnostic
PubMed: 31961516
DOI: 10.1002/cpdd.772 -
Journal of the American Association For... Jan 2022The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg...
The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg once daily and carprofen at 5-10 mg/kg twice daily may not be adequate to provide analgesia in mice. Several studies have suggested that doses up to 20 mg/kg of meloxicam and carprofen are needed to provide analgesic efficacy. This study investigated the clinical safety of these higher doses of meloxicam and carprofen by evaluating their potential for renal and gastrointestinal toxicity. Female CD-1 mice were given 20 mg/kg of either meloxicam, carprofen, or an equivalent volume of saline subcutaneously once daily for 3 or 7 d. On day 4, mice treated for 3 d were euthanized, and on days 8 and 15, mice treated for 7 d were euthanized. Blood was collected by cardiocentesis for serum chemistry analysis. Feces was collected from the colon for fecal occult blood testing, and tissues were collected for histopathology. No clinically significant changes in serum chemistry profiles were found in the drug-treated mice at any time point as compared with the saline controls. Fecal occult blood and histologic evidence of gastritis was associated with meloxicam administration in mice evaluated at days 4 and 8. By day 15, there was no association with meloxicam treatment and the presence of fecal occult blood or gastritis. There was no association between fecal occult blood and gastritis in the carprofen or saline-treated mice regardless of the treatment durations. These findings suggest that 20 mg/kg of meloxicam in mice causes gastric toxicity when given for 3 or 7 d and should be used cautiously; however, carprofen at 20 mg/kg appears to have minimal toxic effects with regard to the parameters measured.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Female; Meloxicam; Mice; Thiazines; Thiazoles
PubMed: 34920791
DOI: 10.30802/AALAS-JAALAS-21-000071 -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2021The influence of different chromatographic conditions and the process of spot visualization on determining the limit of detection as well as quantification (LOD and LOQ)...
The influence of different chromatographic conditions and the process of spot visualization on determining the limit of detection as well as quantification (LOD and LOQ) of meloxicam by TLC-densitometric technique was estimated. Of all chromatographic conditions tested, the lowest limiting values, thus the best sensitivity, in the NP-TLC system was achieved on silica gel 60F254 and neutral aluminum oxide plates developed with the mobile phase consisting of ethyl acetate/toluene/n-butylamine (2:2:1, V/V/V). In the case of the RP-TLC method, a mixture of methanol/water (8:2, V/V) enabled densitometric detection of meloxicam at the lowest concentration level on RP-8F254 and RP-18F254 plates. Additionally, the smallest LOD value of meloxicam ensured crystalline violet and gentian violet as visualization agents on silica gel 60F254 and neutral aluminum oxide 150F254 plates, resp. Comparison of the densitometrically obtained spectra of meloxicam drug and its standard after the use of appropriate visualization agents could be a good and cheap alternative tool for the identification of meloxicam as an active pharmaceutical ingredient.
Topics: Chromatography, Thin Layer; Cost-Benefit Analysis; Densitometry; Indicators and Reagents; Limit of Detection; Meloxicam; Reference Standards; Reproducibility of Results
PubMed: 32697743
DOI: 10.2478/acph-2021-0006