RESUMEN
Drug-induced pseudoporphyria is commonly linked to nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen, oxaprozin, ketoprofen, and ibuprofen. The NSAID meloxicam is not a commonly reported inciting agent. We report a case of meloxicam-induced pseudoporphyria in a 55-year-old woman with a past medical history of hypertension, hyperlipidemia, gastroesophageal reflux disease, and osteoarthritis. She presented to the clinic with tense and denuded bullae on her dorsal feet, which was diagnosed as pseudoporphyria after further workup. Upon evaluating the patient's medication history, meloxicam was identified as the most likely inciting agent. The patient's condition resolved with the discontinuation of this medication. Our findings can help dermatologists effectively diagnose and treat meloxicam-induced pseudoporphyria in patients with similar cases.
Asunto(s)
Antiinflamatorios no Esteroideos , Meloxicam , Humanos , Meloxicam/efectos adversos , Femenino , Persona de Mediana Edad , Antiinflamatorios no Esteroideos/efectos adversos , Tiazoles/efectos adversos , Porfirias/inducido químicamente , Dermatosis del Pie/inducido químicamente , Dermatosis del Pie/patología , Tiazinas/efectos adversosRESUMEN
Progressive articular surface degradation during arthritis causes ongoing pain and hyperalgesia that lead to the development of functional disability. TRPA1 channel significantly contributes to the activation of sensory neurons that initiate neurogenic inflammation and mediates pain signal transduction to the central nervous system. Peptide Ms 9a-1 from the sea anemone Metridium senile is a positive allosteric modulator of TRPA1 and shows significant anti-inflammatory and analgesic activity in different models of pain. We used a model of monosodium iodoacetate (MIA)-induced osteoarthritis to evaluate the anti-inflammatory properties of Ms 9a-1 in comparison with APHC3 (a polypeptide modulator of TRPV1 channel) and non-steroidal anti-inflammatory drugs (NSAIDs) such as meloxicam and ibuprofen. Administration of Ms 9a-1 (0.1 mg/kg, subcutaneously) significantly reversed joint swelling, disability, thermal and mechanical hypersensitivity, and grip strength impairment. The effect of Ms 9a-1 was equal to or better than that of reference drugs. Post-treatment histological analysis revealed that long-term administration of Ms9a-1 could reduce inflammatory changes in joints and prevent the progression of cartilage and bone destruction at the same level as meloxicam. Peptide Ms 9a-1 showed significant analgesic and anti-inflammatory effects in the model of MIA-induced OA, and therefore positive allosteric modulators could be considered for the alleviation of OA symptoms.
Asunto(s)
Osteoartritis , Anémonas de Mar , Animales , Meloxicam/efectos adversos , Modelos Animales de Enfermedad , Osteoartritis/tratamiento farmacológico , Osteoartritis/patología , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Dolor , Antiinflamatorios/efectos adversos , Analgésicos/farmacología , Analgésicos/uso terapéutico , Péptidos/uso terapéutico , Ácido Yodoacético/toxicidadRESUMEN
BACKGROUND: Hypersensitivity reactions to nonsteroidal anti-inflammatory drugs (NSAIDs) are common. These patients require an effective and safe analgesic alternative. OBJECTIVE: The aim of the study was to demonstrate the safety of meloxicam and etoricoxib administered by open oral challenge in 2 equal steps in patients with NSAID hypersensitivity. METHODS: A cross-sectional, descriptive study of patients with a diagnosis of NSAID hypersensitivity who underwent an oral drug provocation test (DPT) with meloxicam or etoricoxib between January 2011 and August 2017 was conducted. The analysis was performed from a database in BD Clinic. RESULTS: Two hundred and twenty-eight oral provocations were performed with an alternative NSAID (203 with meloxicam and 25 with etoricoxib) in 217 patients with hypersensitivity to NSAIDs. The median age was 38 years. Ninety-eight percent of meloxicam and 100% of etoricoxib DPTs were performed in 2 steps (without previous placebo), and 52% and 64% of meloxicam and etoricoxib DPTs, respectively, were performed with 50% of the therapeutic dose in each step. Tolerance to meloxicam was demonstrated in 192 patients (94.5%) and in 100% of patients receiving etoricoxib. CONCLUSIONS: Open oral provocation with meloxicam and etoricoxib carried out in 2 steps without placebo seems to be safe and implies less costs and less time expenditure. Also, it could be performed with 2 equal doses.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Inhibidores de la Ciclooxigenasa 2/administración & dosificación , Hipersensibilidad a las Drogas/etiología , Sustitución de Medicamentos , Etoricoxib/administración & dosificación , Meloxicam/administración & dosificación , Pruebas de Provocación Bronquial , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Quimioterapia Combinada , Etoricoxib/efectos adversos , Humanos , Meloxicam/efectos adversosRESUMEN
BACKGROUND: Infiltration of the surgical site with local anesthetics combined with nonsteroidal anti-inflammatory drugs may play an important role in improving perioperative pain control. This prospective, randomized, blinded, controlled clinical trial aimed to evaluate intraoperative isoflurane requirements, postoperative analgesia, and adverse events of infiltration of the surgical site with ropivacaine alone and combined with meloxicam in cats undergoing ovariohysterectomy. Forty-five cats premedicated with acepromazine/meperidine and anesthetized with propofol/isoflurane were randomly distributed into three treatments (n = 15 per group): physiological saline (group S), ropivacaine alone (1 mg/kg, group R) or combined with meloxicam (0.2 mg/kg, group RM) infiltrated at the surgical site (incision line, ovarian pedicles and uterus). End-tidal isoflurane concentration (FE'ISO), recorded at specific time points during surgery, was adjusted to inhibit autonomic responses to surgical stimulation. Pain was assessed using an Interactive Visual Analog Scale (IVAS), UNESP-Botucatu Multidimensional Composite Pain Scale (MCPS), and mechanical nociceptive thresholds (MNT) up to 24 h post-extubation. Rescue analgesia was provided with intramuscular morphine (0.1 mg/kg) when MCPS was ≥6. RESULTS: Area under the curve (AUC) of FE'ISO was significantly lower (P < 0.0001) in the RM (17.8 ± 3.1) compared to S (23.1 ± 2.2) and R groups (22.8 ± 1.1). Hypertension (systolic arterial pressure > 160 mmHg) coinciding with surgical manipulation was observed only in cats treated with S and R (4/15 cats, P = 0.08). The number of cats receiving rescue analgesia (4 cats in the S group and 1 cat in the R and RM groups) did not differ among groups (P = 0.17). The AUC of IVAS, MCPS and MNT did not differ among groups (P = 0.56, 0.64, and 0.18, respectively). Significantly lower IVAS pain scores were recorded at 1 h in the RM compared to the R and S groups (P = 0.021-0.018). There were no significant adverse effects during the study period. CONCLUSIONS: Local infiltration with RM decreased intraoperative isoflurane requirements and resulted in some evidence of improved analgesia during the early postoperative period. Neither R nor RM infiltration appeared to result in long term analgesia in cats undergoing ovariohysterectomy.
Asunto(s)
Gatos/cirugía , Histerectomía/veterinaria , Meloxicam/farmacología , Ovariectomía/veterinaria , Dolor Postoperatorio/veterinaria , Ropivacaína/farmacología , Anestésicos Locales/administración & dosificación , Anestésicos Locales/efectos adversos , Anestésicos Locales/farmacología , Animales , Femenino , Meloxicam/administración & dosificación , Meloxicam/efectos adversos , Dolor Postoperatorio/prevención & control , Atención Perioperativa , Ropivacaína/administración & dosificación , Ropivacaína/efectos adversosRESUMEN
Repeated administration of meloxicam to cats is often limited by the potential damage to multiple organ systems. Identifying molecules that predict the adverse effects of meloxicam would help to monitor and individualize its administration, maximizing meloxicam's beneficial effects. The objectives of this study were to (a) determine if the repeated administration of meloxicam to cats alters the plasma metabolome and (b) identify plasma metabolites that may serve to monitor during the administration of meloxicam in cats. Purpose bred young adult cats (n = 12) were treated with meloxicam at 0.3 mg/kg or saline subcutaneously once daily for up to 17 days. An untargeted metabolomics approach was applied to plasma samples collected prior to and at designated time points after meloxicam or saline administration. To refine the discovery of biomarkers, the machine-learning algorithms, partial least squares discriminant analysis (PLS-DA) and random forest (RF), were trained and validated using a separate unrelated group of meloxicam- and saline-treated cats (n = 8). A total of 74 metabolites were included in the statistical analysis. Metabolomic analysis shows that the repeated administration of meloxicam alters multiple substances in plasma, including nonvolatile organic acids, aromatic amino acids, monosaccharides, and inorganic compounds as early as four days following administration of meloxicam. Seventeen plasma molecules were able to distinguish meloxicam-treated from saline-treated cats. The metabolomic changes discovered in this study may help to unveil unknown mechanisms of NSAID-induced side effects. In addition, some metabolites could be valuable for individualizing the administration of meloxicam to cats to mitigate adverse effects.
Asunto(s)
Antiinflamatorios no Esteroideos/metabolismo , Gatos/metabolismo , Meloxicam/metabolismo , Metabolómica , Algoritmos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/sangre , Biomarcadores , Gatos/sangre , Análisis Discriminante , Femenino , Meloxicam/administración & dosificación , Meloxicam/efectos adversos , Meloxicam/sangreRESUMEN
OBJECTIVE: To compare the effects of meloxicam or carprofen on glomerular filtration rate (GFR), and to evaluate the effect of meloxicam on urinary N-acetyl-ß-D-glucosaminidase (NAG) activity, of cats after dental surgery. STUDY DESIGN: Randomized, blinded, controlled trial. ANIMALS: A total of 24 mixed breed cats. METHODS: Cats were randomly assigned to one of three groups (n = 8 per group): meloxicam (0.2 mg kg-1); carprofen (4 mg kg-1); or saline (2 mL). Acepromazine (0.04 mg kg-1) and buprenorphine (0.02 mg kg-1) were administered intramuscularly as preanaesthetic medication. Test drugs were injected subcutaneously at the time of preanaesthetic medication. Anaesthesia was induced with intravenous propofol and maintained with isoflurane in oxygen. Mean arterial blood pressure (MAP), respiratory rate (fR), heart rate (HR) and haemoglobin oxygen saturation values (SpO2) were recorded. All cats underwent ultrasonic dental scaling with polishing. Teeth extraction involved mucosal flap creation, removal of alveolar bone and flap closure. Plasma iohexol clearance (ICL), a measure of GFR, was estimated before and 24 hours after anaesthesia induction in all cats. Urinary NAG index was estimated in saline and meloxicam groups at the same time points as GFR. Between-group and -time point differences in GFR and NAG index were compared using mixed model analyses. Data are presented as mean ± standard deviation (p < 0.05). RESULTS: There was no significant difference in plasma ICL rate (range: from 1.22 ± 0.05 to 1.27 ± 0.04 mL kg minute-1) between groups or between time points. Urinary NAG index (range: from 1.0 ± 0.19 to 1.36 ± 0.29 Units gram-1) was not significantly different between meloxicam and saline groups. MAP, HR, fR and SpO2 did not differ significantly between groups. CONCLUSIONS AND CLINICAL RELEVANCE: Meloxicam and carprofen appeared to produce nonsignificant effects on GFR, and meloxicam did not affect the urinary NAG activity, of cats after dental surgery.
Asunto(s)
Acetilglucosaminidasa/orina , Carbazoles/farmacología , Enfermedades de los Gatos/cirugía , Tasa de Filtración Glomerular/veterinaria , Meloxicam/farmacología , Enfermedades Dentales/veterinaria , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/farmacología , Carbazoles/administración & dosificación , Carbazoles/efectos adversos , Gatos , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Masculino , Meloxicam/administración & dosificación , Meloxicam/efectos adversos , Enfermedades Dentales/cirugíaRESUMEN
BACKGROUND: Non-steroidal anti-inflammatory drugs constitute a main cause of fixed drug eruption (FDE). A few cases of piroxicam-induced FDE have been reported; however, the cross-reactivity among oxicams has rarely been evaluated. OBJECTIVES: To describe a series of patients with piroxicam-induced FDE, mostly confirmed by a positive patch test reaction, in whom cross-reactivity to meloxicam was assessed. METHODS: We included all cases of piroxicam-induced FDE diagnosed in the department of pharmacovigilance of Monastir. Patch tests for piroxicam and meloxicam were performed in the involved skin according to the European Network on Drug Allergy recommendations. Oral provocation tests (OPTs) were performed for patients with negative skin test results. RESULTS: Seven patients were included in this study. FDE was multiple for five patients and solitary for two. Bullous eruption was noticed in two cases. Lesional patch tests for piroxicam gave positive results in six patients. To assess cross-reactivity with meloxicam, this was patch tested. The test gave a positive result in only one patient. OPTs with meloxicam gave positive results in two patients with negative patch test results. CONCLUSION: Meloxicam is not a safe alternative for the treatment of piroxicam-induced FDE, and OPTs can be used to confirm tolerance before this drug is prescribed as a safer alternative.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Erupciones por Medicamentos/etiología , Meloxicam/efectos adversos , Piroxicam/efectos adversos , Adulto , Reacciones Cruzadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas del Parche , Estudios RetrospectivosRESUMEN
Repeated administration of meloxicam can cause kidney damage in cats by mechanisms that remain unclear. Metabolomics and lipidomics are powerful, noninvasive approaches used to investigate tissue response to drug exposure. Thus, the objective of this study was to assess the effects of meloxicam on the feline kidney using untargeted metabolomics and lipidomics approaches. Female young-adult purpose-breed cats were allocated into the control (n = 4) and meloxicam (n = 4) groups. Cats in the control and meloxicam groups were treated daily with saline and meloxicam at 0.3 mg/kg subcutaneously for 17 days, respectively. Renal cortices and medullas were collected at the end of the treatment period. Random forest and metabolic pathway analyses were used to identify metabolites that discriminate meloxicam-treated from saline-treated cats and to identify disturbed metabolic pathways in renal tissue. Our results revealed that the repeated administration of meloxicam to cats altered the kidney metabolome and lipidome and suggest that at least 40 metabolic pathways were altered in the renal cortex and medulla. These metabolic pathways included lipid, amino acid, carbohydrate, nucleotide and energy metabolisms, and metabolism of cofactors and vitamins. This is the first study using a pharmacometabonomics approach for studying the molecular effects of meloxicam on feline kidneys.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades de los Gatos/inducido químicamente , Corteza Renal/efectos de los fármacos , Médula Renal/efectos de los fármacos , Meloxicam/efectos adversos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Enfermedades de los Gatos/patología , Gatos , Esquema de Medicación , Femenino , Metabolismo de los Lípidos , Meloxicam/administración & dosificación , MetabolómicaAsunto(s)
Lesión Renal Aguda , Meloxicam , Tiazinas , Tiazoles , Meloxicam/efectos adversos , Meloxicam/administración & dosificación , Meloxicam/uso terapéutico , Animales , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/veterinaria , Tiazoles/efectos adversos , Tiazoles/administración & dosificación , Tiazinas/efectos adversos , Tiazinas/administración & dosificación , Inyecciones Subcutáneas/veterinaria , Inyecciones Subcutáneas/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/administración & dosificaciónAsunto(s)
Lesión Renal Aguda , Meloxicam , Animales , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/veterinaria , Antiinflamatorios no Esteroideos/efectos adversos , Antiinflamatorios no Esteroideos/administración & dosificación , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológico , Inyecciones Subcutáneas/veterinaria , Inyecciones Subcutáneas/efectos adversos , Meloxicam/efectos adversos , Meloxicam/administración & dosificación , Meloxicam/uso terapéutico , Tiazinas/efectos adversos , Tiazinas/administración & dosificación , Tiazoles/efectos adversos , Tiazoles/administración & dosificación , GatosRESUMEN
This study aimed to compare the efficacy and safety of very early preemptive meloxicam, early preemptive meloxicam, and postoperative meloxicam administration for postoperative pain relief in patients undergoing arthroscopic knee surgery (AKS). Three hundred and six patients about to receive AKS were consecutively enrolled in this randomized, controlled study and randomly allocated into three groups: very early analgesia (VEA) group, early analgesia (EA) group, and postoperative analgesia (PA) group. Pain visual analog scale (VAS) score at rest and at flexion, patient global assessment (PGA) score, consumption of rescue pethidine, and adverse events (AEs) were assessed. Pain VAS score and severity at rest/flexion were all decreased in the VEA group compared with EA group and PA group at 4 h post-operation and were also reduced in the VEA and EA groups compared with the PA group at 8 h and 12 h post-operation. PGA score was lower in the VEA group compared with the EA group and PA group at 4 h post-operation, and was attenuated in the VEA group and the EA group compared with the PA group at 8 h, 12 h, and 24 h post-operation as well. Consumption of rescue pethidine was less in the VEA group than that in the PA group. In addition, no difference in the incidence of AEs was found among the VEA, EA, and PA groups. In conclusion, preemptive meloxicam is more effective in postoperative pain control and equally tolerated compared with postoperative meloxicam in patients receiving AKS.
Asunto(s)
Antiinflamatorios no Esteroideos/uso terapéutico , Artroscopía/métodos , Articulación de la Rodilla/cirugía , Meloxicam/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Meloxicam/administración & dosificación , Meloxicam/efectos adversos , Meperidina/uso terapéutico , Dimensión del DolorRESUMEN
Drug induced linear IgA bullous dermatosis (LABD) is a rare blistering disease that has been shown to be associated with the use of various medications. Although rarely seen together, some of the medications associated with LABD can lead to the syndrome drug reaction with eosinophilia and systemic symptoms (DRESS), which presents with fever, cutaneous eruption, and multi-organ involvement. We present a patient who developed fever and a generalized vesiculobullous eruption after recently starting amlodipine and meloxicam. Initial laboratory tests demonstrated elevated liver function tests, leukocystosis, and eosinophilia. Histopathologic examination of the punch biopsy revealed a bulla with sub-epidermal split and numerous neutrophils. Direct immunofluorescence demonstrated broad deposition of IgA along the dermal-epidermal junction. These findings were consistent with an overlap between LABD and DRESS. Drug induced LABD and DRESS are independently both rare diseases. It is even more uncommon to see the two concurrently in the same patient. In this patient, these two conditions were thought to be triggered by either amlodipine or meloxicam. Given the high mortality rate associated with DRESS, it is important to recognize the presentation and initiate the appropriate treatment plan as soon as possible.
Asunto(s)
Amlodipino/efectos adversos , Antiinflamatorios no Esteroideos/efectos adversos , Antihipertensivos/efectos adversos , Síndrome de Hipersensibilidad a Medicamentos/etiología , Dermatosis Bullosa IgA Lineal/inducido químicamente , Meloxicam/efectos adversos , Amlodipino/uso terapéutico , Antiinflamatorios no Esteroideos/uso terapéutico , Antihipertensivos/uso terapéutico , Artralgia/tratamiento farmacológico , Femenino , Humanos , Hipertensión/tratamiento farmacológico , Meloxicam/uso terapéutico , Persona de Mediana Edad , Osteoartritis/complicacionesRESUMEN
Meloxicam is a nonsteroidal anti-inflammatory drug with preferential cyclooxygenase-2 inhibitory activity. It is frequently used in veterinary medicine, including in fish species. The efficacy and safety of meloxicam, however, has not yet been reported in adult fish. The purpose of this study was to evaluate the acute toxicity of a single intramuscular injection of meloxicam in goldfish ( Carassius auratus auratus). Following 3 wk of acclimation, 32 goldfish were randomly assigned to two groups of 16 individuals. Fish from the treatment group received a single intramuscular injection of 5 mg/kg meloxicam, while the fish from the control group received a single intramuscular injection of a 0.9% sodium chloride solution using a similar volume (1 ml/kg). No external lesions, mortality, or modifications in behavior or position in the water column were noted during the following 72 hr. Three days after the initial injection, all fish were euthanized by immersion in a solution of tricaine methanesulfonate. Complete postmortem and histologic evaluations were performed for each fish. Hemorrhage and muscular necrosis were observed at the site of injection in fish from both groups. Multiple granulomas of undetermined etiology were detected in numerous organs from fish of both groups. No statistically significant differences were detected in regard to the lesions observed in these two groups. This study demonstrates that a single intramuscular injection of meloxicam at a dosage of 5 mg/kg does not cause acute toxicity in goldfish.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Carpa Dorada , Meloxicam/efectos adversos , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Relación Dosis-Respuesta a Droga , Femenino , Inyecciones Intramusculares , Masculino , Meloxicam/administración & dosificación , Distribución AleatoriaRESUMEN
BACKGROUND AND PURPOSE: Non-steroidal anti-inflammatory drugs (NSAIDs) are the most widely prescribed drugs in the world due to their analgesic, antipyretic and anti-inflammatory effects. However, NSAIDs inhibit prostanoid synthesis, interfering with their pro-inflammatory and anti-inflammatory functions and potentially prolonging acute inflammation. EXPERIMENTAL APPROACH: We used high-content immunohistochemistry to define the impact of meloxicam treatment on spatially separated pro-inflammatory and anti-inflammatory processes during innate inflammation in mice induced by zymosan. This allowed us to determine the effect of meloxicam treatment on the organization of pro-inflammatory and anti-inflammatory microenvironments, thereby identifying relevant changes in immune cell localization, recruitment and activation. KEY RESULTS: Meloxicam treatment reduced zymosan-induced thermal hypersensitivity at early time points but delayed its resolution. High-content immunohistochemistry revealed that the pro-inflammatory area was smaller after treatment, diminishing neutrophil recruitment, M1-like macrophage polarization, and especially phagocytosis by neutrophils and macrophages. The polarization of macrophages towards the M2-like anti-inflammatory phenotype was unaffected, and the number of anti-inflammatory eosinophils actually increased. CONCLUSION AND IMPLICATIONS: High-content immunohistochemistry was able to identify relevant meloxicam-mediated effects on inflammatory processes based on alterations in the regional structure of inflammation sites. Meloxicam delayed the clearance of pathogens by inhibiting pro-inflammatory processes, causing prolonged inflammation. Our data suggest that the prescription of NSAIDs as a treatment during an acute pathogen-driven inflammation should be reconsidered in patients with compromised immune systems.
Asunto(s)
Prostaglandinas , Tiazinas , Humanos , Ratones , Animales , Meloxicam/efectos adversos , Zimosan , Tiazoles/farmacología , Tiazoles/uso terapéutico , Tiazinas/farmacología , Tiazinas/uso terapéutico , Antiinflamatorios no Esteroideos/efectos adversos , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Antiinflamatorios/efectos adversosRESUMEN
Meloxicam is an enolate nonsteroidal anti-inflammatory agent. This trial investigated the pharmacokinetics, safety, and bioequivalence of single oral doses of Aomei meloxicam (15 mg) and Mobic meloxicam (15 mg) in healthy volunteers under fasting and fed conditions. A single-site, single-dose, randomized, open, 2-period, 2-sequence, crossover bioequivalence study was performed: 24 healthy volunteers were enrolled in each of the fasting and fed arms. Each HV was randomly assigned to receive the Aomei drug (test) in one period and the Mobic drug (reference) in the other period. The concentration of meloxicam in plasma was detected using liquid chromatography-tandem mass spectrometry. The primary pharmacokinetic parameters were calculated using a noncompartmental model. In the fasting arm, the 90% confidence interval of the geometric mean ratios of maximum plasma concentration, area under the concentration-time curve from time 0 to the last measurable plasma concentration, and area under the concentration-time curve from time 0 to infinity between the test and reference products were 99.5% to 111.7%, 101.2% to 106.8%, and 101.8% to 108.3%, respectively. In the fed arm, the 3 parameters were 94.1% to 102.4%, 97.6% to 103.0%, and 97.5% to 103.7%, respectively. These parameters were in the range of 80% to 125%, and the 2 products were considered bioequivalent in both the fasting and fed states and were well tolerated. The severity of all adverse events was mild. Aomei meloxicam tablets and Mobic meloxicam tablets were bioequivalent in healthy Chinese volunteers.
Asunto(s)
Ayuno , Adulto , China , Estudios Cruzados , Humanos , Meloxicam/efectos adversos , Comprimidos , Equivalencia TerapéuticaRESUMEN
OBJECTIVE: To describe the clinical findings and treatment of 4 dogs that developed colonic perforation shortly after meloxicam administration. SERIES SUMMARY: Three cases were treated with meloxicam for variable nonspecific signs including lethargy and pyrexia. Hemorrhagic diarrhea developed following meloxicam administration in 2 cases. Gastrointestinal perforation was suspected on diagnostic imaging leading to exploratory celiotomy in all 3 cases. Partial colectomy was performed in 2 cases and suture repair with serosal patching in 1 followed by broad spectrum antimicrobials. All 3 dogs recovered from surgery well. One dog that had undergone perineal herniorrhaphy and received meloxicam perioperatively collapsed and died 7 days postsurgery. Postmortem examination revealed ulceration and perforation of the ascending colon with resultant generalized septic peritonitis. Histopathologic findings in all cases showed full thickness infiltration of the colonic wall with inflammatory cells along with ulceration and perforation. Thrombosis of vessels underlying the ulcerated areas was also noted. NEW OR UNIQUE INFORMATION PROVIDED: This report suggests that colonic perforation may be a complication of nonsteroidal anti-inflammatory drug use in some cases. To the authors' knowledge, this has not previously been described in dogs. Colonic perforation associated with NSAIDs administration may be more commonly identified in dogs with concurrent morbidities. Caution may be warranted when using NSAIDs in dogs with colonic pathology or possible risk factors to develop such pathology. Prompt diagnosis and treatment is essential for a positive outcome.
Asunto(s)
Enfermedades de los Perros , Perforación Intestinal , Peritonitis , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades de los Perros/diagnóstico , Perros , Perforación Intestinal/inducido químicamente , Perforación Intestinal/complicaciones , Perforación Intestinal/veterinaria , Meloxicam/efectos adversos , Peritonitis/veterinariaRESUMEN
OBJECTIVE: To report which nonsteroidal anti-inflammatory drugs (NSAIDs) were associated with gastric or duodenal perforation (GDP) in dogs presented to a university teaching hospital and to report the frequency of prescription of NSAIDs by the corresponding referring veterinary community during the same time period. DESIGN: Retrospective cohort study of dogs from January 2007 to March 2020. SETTING: Single university teaching hospital. ANIMALS: A total of 30 dogs met inclusion criteria. MEASUREMENTS AND MAIN RESULTS: Four dogs were administered more than 1 NSAID within 7 days of GDP, 3 dogs received a combination of an NSAID and a corticosteroid, and 1 dog received 2 NSAIDs and a corticosteroid. Four dogs received an overdose of an NSAID. One dog received an overdose of 1 NSAID and received an additional NSAID at the labeled dose within 7 days of GDP. Eighteen dogs received only 1 NSAID at the labeled dose. In these 18 dogs, meloxicam was administered in 44.4% (8/18), firocoxib in 27.8% (5/18), deracoxib in 16.7% (3/18), and piroxicam in 11.1% (2/18). One hundred and sixty surveys on NSAID prescribing practice were returned. Carprofen was the most commonly prescribed NSAID (70.6%), followed by meloxicam (10.6%), deracoxib (8.4%), firocoxib (7.8%), aspirin (1.5%), and other (0.9%). CONCLUSIONS: NSAID administration, even at labeled doses, appears to be a precipitating factor for GDP. Despite carprofen being the most frequently prescribed NSAID over the study period, no case of GDP received it as a single therapeutic agent. Further prospective evaluation is needed to verify these findings.
Asunto(s)
Enfermedades de los Perros , Peritonitis , Perros , Animales , Meloxicam/efectos adversos , Estudios Retrospectivos , Enfermedades de los Perros/inducido químicamente , Enfermedades de los Perros/tratamiento farmacológico , Antiinflamatorios no Esteroideos/efectos adversos , Peritonitis/tratamiento farmacológico , Peritonitis/veterinaria , CorticoesteroidesRESUMEN
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).
Asunto(s)
Enfermedades Cardiovasculares , Inhibidores de la Ciclooxigenasa 2 , Adulto , Antiinflamatorios no Esteroideos/efectos adversos , Enfermedades Cardiovasculares/inducido químicamente , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/epidemiología , Celecoxib/efectos adversos , Inhibidores de la Ciclooxigenasa 2/efectos adversos , Diclofenaco/efectos adversos , Etodolaco , Etoricoxib/efectos adversos , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Meloxicam/efectos adversos , Factores de RiesgoRESUMEN
The sustained-release formulation of meloxicam (MSR) is a compounded NSAID that may provide pain relief for as long as 72 h after administration. MSR injection-site skin reactions have occurred in several species but have not previously been observed in mice. We investigated the development and progression of localized skin reactions after a single injection of MSR in Crl:CD1(ICR), C57BL/6J, and BALB/cJ mice. Each mouse received a subcutaneous injection of MSR (n = 60), standard-formulation meloxicam (MEL; n = 24) or saline (control; SC; n = 24) and was scored daily according to a 5-point system for erythema and mass characteristics. Mice were euthanized at either 7 or 14 d after injection and underwent postmortem analysis. MSR-treated mice had more erythematous and mass reactions than did MEL and SC mice. Mass lesions developed in 49 MSR mice (82%; 95% CI, 70% to 90%), 5 MEL animals (21%; 95% CI, 7% to 42%), and 1 SC mouse. MSR-treated BALB/cJ developed erythematous lesions less frequently than similarly treated Crl:CD1(ICR) or C57BL/6J. Lesions often were ventrolateral to the injection site. The median times to the appearance of mass and erythematous lesions were 2 d and 3 d, respectively. Histologically, the erythematous and mass reactions correlated with necrotizing to pyogranulomatous injection-site panniculitis. Inflammation severity scores at 7 and 14 d after injection were greater in the MSR-treated group than the other 2 groups. No strain- or sex-associated differences emerged except that inflammation severity scores at day 14 were higher in Crl:CD1(ICR) females than males. The character of the inflammatory response in MSR-treated mice did not differ between 7 and 14 d after injection, indicating that MSR-induced inflammation is slow to resolve. The ventral migration and delayed onset of MSR injection-site reactions could result in their being attributed to another cause or not being identified. Researchers and clinicians should be aware of the potential for slowly resolving injection-site reactions with MSR.
Asunto(s)
Antiinflamatorios no Esteroideos/efectos adversos , Meloxicam/efectos adversos , Enfermedades de los Roedores/inducido químicamente , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Preparaciones de Acción Retardada , Femenino , Inyecciones Subcutáneas , Masculino , Meloxicam/administración & dosificación , Ratones , Ratones Endogámicos , Caracteres SexualesRESUMEN
Prolonged-release (PR; as ascribed in the EU) or extended-release (as ascribed in the USA) bupivacaine/meloxicam (HTX-011; hereafter referred to as bupivacaine/meloxicam PR; Zynrelef®) is a synergistic fixed-dose combination (FDC) of the local anaesthetic bupivacaine and the NSAID meloxicam. It is approved in the EU and the USA to treat postoperative pain. After needle-free application at the surgical site, the novel polymer technology allows simultaneous diffusion of bupivacaine and meloxicam over 72 h. In clinical trials, bupivacaine/meloxicam PR significantly reduced postoperative pain and opioid consumption relative to bupivacaine hydrochloride (HCl) and placebo in patients undergoing bunionectomy, herniorrhaphy or total knee arthroplasty (TKA). When used as the foundation of a scheduled non-opioid multimodal analgesia (MMA) regimen, bupivacaine/meloxicam PR further improved pain control and reduced the need for opioids following surgery. Bupivacaine/meloxicam PR was generally well tolerated, with a lower incidence of opioid-related adverse events than bupivacaine HCl and placebo. Although additional data would be beneficial, current evidence indicates that bupivacaine/meloxicam PR is a promising non-opioid treatment option for the management of postoperative pain.
Poorly managed pain after surgery can lead to decreased quality of life, longer recovery time and a higher risk of complications. Perioperative local anaesthetics are commonly used to manage postoperative pain, but these drugs have a short duration of action. Bupivacaine/meloxicam PR (Zynrelef®) is a long-acting FDC of the local anaesthetic bupivacaine and the NSAID meloxicam approved for the treatment of postoperative pain. Following application without a needle into the surgical site, the active ingredients are simultaneously released for ≈ 3 days. Bupivacaine/meloxicam PR significantly reduced postoperative pain and opioid consumption and increased the proportion of opioid-free patients following bunionectomy, herniorrhaphy and TKA. When used as the foundation of a scheduled non-opioid MMA regimen, bupivacaine/meloxicam PR further reduced pain and the need for opioids. Bupivacaine/meloxicam PR had a similar tolerability profile to those of bupivacaine hydrochloride and placebo, with a lower incidence of opioid-related adverse events. Bupivacaine/meloxicam PR is a promising non-opioid treatment option for managing postoperative pain.