-
The Annals of Pharmacotherapy Jan 2023To review data for bupivacaine/meloxicam extended-release (ER) solution for management of postoperative pain and opioid-sparing effects. (Review)
Review
OBJECTIVE
To review data for bupivacaine/meloxicam extended-release (ER) solution for management of postoperative pain and opioid-sparing effects.
DATA SOURCES
Literature search of PubMed (1946 to August 2021) and ProQuest (1946 to August 2021) was performed using the terms: Zynrelef, HTX-011, and "bupivacaine AND meloxicam." Additional information sources include ClinicalTrials.gov, prescribing information, Heron Therapeutics' Clinical and Economic Evidence Dossier, meeting abstracts, and references of identified articles.
STUDY SELECTION AND DATA EXTRACTION
Clinical trials and articles evaluating bupivacaine/meloxicam ER for postoperative pain management.
DATA SYNTHESIS
Bupivacaine is a short-acting local anesthetic. Its efficacy is negatively impacted by the acidic environment of surgical sites. Meloxicam, a nonsteroidal antiinflammatory, reduces inflammation at the surgical site and increases pH propagating bupivacaine movement into the neurons. In Phase 2 and Phase 3 clinical trials, bupivacaine/meloxicam ER was compared with bupivacaine HCl, bupivacaine ER, and meloxicam ER with and without scheduled nonopioid multimodal analgesia (MMA) in bunionectomies, herniorrhaphies, total knee arthroplasty and abdominoplasty. Postoperative pain was well controlled for 72 hours and consistently superior to placebo, with minimal or no opioid use. Wound healing was not impacted and adverse effects were similar to placebo (most commonly nausea, dizziness, constipation, and headaches).
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Bupivacaine/meloxicam ER is a viable, safe, nonopioid local anesthetic for sustained 72-hour postoperative pain management mitigating opioid consumption.
CONCLUSION
Bupivacaine/meloxicam ER is the only dual-acting, extended-release local anesthetic available. It provides effective analgesia in the postoperative setting and successfully reduces or eliminates postoperative opioid consumption.
Topics: Humans; Anesthetics, Local; Analgesics, Opioid; Meloxicam; Bupivacaine; Pain, Postoperative
PubMed: 35536151
DOI: 10.1177/10600280221086639 -
Veterinary Anaesthesia and Analgesia Nov 2023To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg in...
OBJECTIVE
To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg in Pekin ducks.
STUDY DESIGN
Randomized experimental trial.
ANIMALS
A total of 18 clinically healthy male Pekin ducks.
METHODS
Pekin ducks were randomly assigned to three groups of six ducks: IV, IM and oral. Meloxicam (1.0 mg kg) was administered to each Pekin duck. A non-compartmental analysis was used to evaluate pharmacokinetic parameters.
RESULTS
No local or systemic adverse effects were observed in any bird. Meloxicam was detected in the plasma up to 120 hours following IV, IM or oral administration. The elimination half-life of the IV route was slightly shorter than that of the IM and oral routes (p < 0.05). Following IV administration, volume of distribution at steady state and total clearance were 133.17 mL kg and 6.68 mL kg hour, respectively. The mean absorption time was 2.29 hours for IM and 1.13 hours for oral route. There were significant differences between IM and oral administration for the peak plasma concentration (C), time to reach C and bioavailability (p < 0.05).
CONCLUSIONS AND CLINICAL RELEVANCE
Meloxicam showed long elimination half-life and high bioavailability following IM and oral administration. Meloxicam in Pekin ducks provided the effective therapeutic concentration indicated in other species for up to 48 hours. However, there is a need to determine the clinical efficacy of meloxicam in Pekin ducks.
Topics: Male; Animals; Meloxicam; Ducks; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Area Under Curve; Half-Life; Injections, Intravenous; Administration, Oral; Injections, Intramuscular; Administration, Intravenous
PubMed: 37620232
DOI: 10.1016/j.vaa.2023.07.007 -
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 -
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 -
Terapevticheskii Arkhiv 2016Meloxicam is one of the most commonly used representatives of the group of nonsteroidal anti-inflammatory drugs prescribed in our country. It has been used in Russian... (Review)
Review
Meloxicam is one of the most commonly used representatives of the group of nonsteroidal anti-inflammatory drugs prescribed in our country. It has been used in Russian clinical practice for 20 years and established itself as an effective and rather safe analgesic and anti-inflammatory medications. During this period almost 48 million packages of brand-name meloxicam have been sold; millions of people in our country have been successfully treated with this drug. During this period, there have been at least 29 Russian clinical trials of brand-name meloxicam, which covered 3,736 patients. In all the trials, meloxicam has demonstrated a good therapeutic potential (a substantial improvement in more than 75% of patients) and a low incidence of side effects, which averaged 6.4% (30.5% in the control groups). The good tolerability of brand-name meloxicam (Movalis) is confirmed by a total of 120 spontaneous reports of the adverse events due to this drug, which were sent to the Federal Service for Health Supervision in December 2008 to July 2015 (over the last 7 years). This number seems negligible (nearly 30 million packages) if the amount of meloxicam sold over the period is taken into account. Extensive experience in clinical practice with this drug and a wide series of national clinical trials support the good reputation of brand-name meloxicam among Russian physicians and patients. This review briefly gives the data of Russian and main foreign clinical trials of the therapeutic effect and safety of meloxicam.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Meloxicam; Russia; Thiazines; Thiazoles
PubMed: 28635891
DOI: 10.17116/terarkh20168812149-158 -
JAAPA : Official Journal of the... Jan 2016Significant progress on contraception, and in particular emergency contraception, has been made in the past decade. Emergency contraception was first introduced as a... (Review)
Review
Significant progress on contraception, and in particular emergency contraception, has been made in the past decade. Emergency contraception was first introduced as a stand-alone prescription in 1998, and the interaction of politics and medicine meant a tumultuous course to the drug becoming available over the counter. This article reviews how emergency contraception works, the effectiveness of different methods, pros and cons, and the history of emergency contraception.
Topics: Contraception; Contraception, Postcoital; Contraceptives, Oral, Hormonal; Cyclooxygenase Inhibitors; Female; Health Services Accessibility; Humans; Intrauterine Devices; Levonorgestrel; Meloxicam; Mifepristone; Norpregnadienes; Ovulation Inhibition; Pregnancy; Thiazines; Thiazoles
PubMed: 26656383
DOI: 10.1097/01.JAA.0000475459.00348.81 -
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 -
Pain Management Apr 2021HTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine (sodium-channel blocker) and low-dose meloxicam (non-steroidal anti-inflammatory... (Review)
Review
HTX-011 is an extended-release, dual-acting local anesthetic consisting of bupivacaine (sodium-channel blocker) and low-dose meloxicam (non-steroidal anti-inflammatory drug [NSAID]) applied needle-free during surgery. Introducing low-dose meloxicam addresses the limited efficacy of liposomal bupivacaine in acidic inflamed tissues and allows enhanced analgesic effects over three days. It has great promise to be an extremely effective postoperative pain regimen and produce an opioid-free surgical recovery, as it has consistently significantly reduced pain scores and opioid consumption through 72 h. This manuscript provides an updated, concise narrative review of the pharmacology, clinical efficacy, safety and tolerability of this drug and its applications to prevent postoperative pain.
Topics: Analgesics, Opioid; Anesthetics, Local; Bupivacaine; Humans; Meloxicam; Pain, Postoperative
PubMed: 33618542
DOI: 10.2217/pmt-2020-0097 -
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 -
Fundamental & Clinical Pharmacology Jun 2022Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the best therapeutic options to treat pain. Their use in combination with other drugs may broaden their...
Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the best therapeutic options to treat pain. Their use in combination with other drugs may broaden their applicability in analgesia if their ceiling and adverse effects are reduced. The aim of this study was to evaluate the pharmacological interaction of two NSAIDs, paracetamol and meloxicam, with the antipsychotic drug risperidone in mice, in several experimental tests of nociceptive and inflammatory pain. Antinociception was assessed by dose-response curves to paracetamol and meloxicam before and after the i.p. administration of 0.5 mg/kg of risperidone. Results are presented as means ± SEM and differences were calculated by one-way ANOVA followed by Tukey's post-test. Paracetamol and meloxicam produced a dose-related antinociceptive effect with diverse potencies. Risperidone increased the analgesia mediated by paracetamol and meloxicam only in the tonic tests that detected inflammatory pain. This suggests that COX inhibition is only a partial explanation of the increased analgesic potency of paracetamol and meloxicam since the effects of NSAIDs in the CNS are mediated by multiple mechanisms. These results indicate that the combination of risperidone with paracetamol or meloxicam could be a new and effective alternative for the management of inflammatory pain.
Topics: Acetaminophen; Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Mice; Pain; Risperidone
PubMed: 34989439
DOI: 10.1111/fcp.12754