Prolongación del tiempo QT
Eventos adversos de medicamentos
|Dolor de cabeza|
Variantes ✨Para la evaluación computacionalmente intensiva de las variantes, elija la suscripción estándar paga.
Explicaciones de las sustancias para pacientes.
No existen advertencias adicionales para la combinación de metoclopramida y lorcaserin. Consulte también la información especializada pertinente.
Los cambios informados en la exposición corresponden a los cambios en la curva de concentración plasmática-tiempo [ AUC ]. No detectamos ningún cambio en la exposición a la metoclopramida. Actualmente no podemos estimar la influencia de la lorcaserin. No detectamos ningún cambio en la exposición a la lorcaserin. Actualmente no podemos estimar la influencia de la metoclopramida.
Los parámetros farmacocinéticos de la población media se utilizan como punto de partida para calcular los cambios individuales en la exposición debidos a las interacciones.
La metoclopramida tiene una biodisponibilidad oral media [ F ] del 100 %, por lo que los niveles plasmáticos máximos [Cmax] tienden a cambiar con una interacción. La vida media terminal [ t12 ] es relativamente corta a las 5.5 horas y los niveles plasmáticos constantes [ Css ] se alcanzan rápidamente. La unión a proteínas [ Pb ] es muy débil al 100 % y el volumen de distribución [ Vd ] es muy grande a 238 litros, Dado que la sustancia tiene una tasa de extracción hepática baja de 0,9, el desplazamiento de la unión a proteínas [Pb] en el contexto de una interacción puede conducir a una mayor exposición. El metabolismo tiene lugar principalmente a través de CYP2D6 y el transporte activo tiene lugar en parte a través de OATP1A2 y PGP.
Se desconoce la biodisponibilidad de la lorcaserin. La vida media terminal [ t12 ] es de 11 horas y se alcanzan niveles plasmáticos constantes [ Css ] después de aproximadamente 44 horas. La unión a proteínas [ Pb ] es relativamente débil al 100 %. El metabolismo tiene lugar a través de CYP1A2, CYP2B6, CYP2C19, CYP2D6 y CYP3A4, entre otros.
|Efectos serotoninérgicos a||3||+||++|
Recomendación: El riesgo de un síndrome serotoninérgico aumenta, pero sin una respuesta exacta a las preguntas sobre los síntomas cognitivos, vegetativos y neuromusculares no podemos hacer recomendaciones de acción.
Clasificación: La metoclopramida tiene un efecto leve sobre el sistema serotoninérgico. La lorcaserin modula el sistema serotoninérgico en un grado moderado.
|Kiesel & Durán b||0||Ø||Ø|
Clasificación: Según nuestro conocimiento, ni la metoclopramida ni la lorcaserin aumentan la actividad anticolinérgica.
Prolongación del tiempo QT
Recomendación: Asegúrese de minimizar los factores de riesgo que puedan influir. Deben compensarse los desequilibrios electrolíticos, como los niveles bajos de calcio, potasio y magnesio. Debe utilizarse la dosis mínima eficaz de metoclopramida.
Clasificación: La metoclopramida puede prolongar potencialmente el tiempo QT y, si existen factores de riesgo, pueden producirse arritmias del tipo torsades de pointes. No conocemos ningún potencial de prolongación del intervalo QT de la lorcaserin.
Efectos adversos generales
|Efectos secundarios||∑ frecuencia||met||lor|
|Dolor de cabeza||19.6 %||4.7||15.7|
|Sentido del gusto alterado||1.0 %||+||n.a.|
|Edema periférico||1.0 %||+||n.a.|
Síndrome neuroléptico maligno: metoclopramida
Discinesia tardía: metoclopramida
Con base en sus respuestas e información científica, evaluamos el riesgo individual de efectos secundarios adversos. Estas recomendaciones están destinadas a asesorar a los profesionales y no sustituyen la consulta con un médico. En la versión de prueba restringida (alfa), el riesgo de todas las sustancias aún no se ha evaluado de manera concluyente.
Abstract: No Abstract available
Abstract: 1 A rapid and sensitive method, based on liquid chromatography, has been developed for determination of metoclopramide concentrations in plasma and urine samples. Concentrations down to 15 nmol/1 (5 ng/ml) of plasma and 100 nmol/1 (30 ng/ml) of urine could be determined with a relative standard deviation of less than or equal to 10%. The method was used to study disposition of metoclopramide in healthy volunteers following single doses intravenously and orally as aqueous solution and a slow release tablet. 2 The initial distribution after intravenous administration was very rapid. The elimination half-life postdistribution was 4.9 h. The apparent volume of distribution, Vd, was 3.0 1/kg body weight. On average 19% was excreted unchanged after intravenous administration of 5 and 10 mg (15 and 30 mumol) of drug. The rate of absorption of metoclopramide was delayed after administration of a slow release tablet and the maximum plasma concentration was about 50% lower than after a solution. The extent of bioavailability was the same following the two different formulations suggesting a first-pass elimination of 25-40%.
Abstract: No Abstract available
Abstract: No Abstract available
Abstract: Metoclopramide is rapidly and well absorbed from the gastrointestinal tract, and in man undergoes variable first-pass metabolism (oral bioavailability 32 to 100%). In man, N-4 sulphate conjugation is an important pathway of metabolism and after oral administration the ratio of free to conjugated metoclopramide in urine correlates with the plasma AUC. The elimination half-life of metoclopramide is dose-dependent after both intravenous and oral administration of single doses between 5 and 20mg. Metabolic profiles in animal species studied are very different from man. The clearance of metoclopramide is reduced in patients with renal failure to approximately 50% of normals and the terminal half-life is prolonged; this is despite the fact that renal clearance of free drug accounts for only 20% of the administered dose in normals. Preliminary studies after 'high dose' metoclopramide demonstrate accumulation to high plasma concentrations with linear kinetics, suggesting that current high dose regimens are unnecessarily cumbersome.
Abstract: Metoclopramide hydrochloride is increasingly used as an antiemetic agent. Clinical and experimental studies have demonstrated dopamine antagonism, and extrapyramidal side effects have been reported in patients given the drug for gastrointestinal disorders. Multifocal myoclonic jerking developed in our patient after he received metoclopramide therapy for gastroparesis due to renal failure. He had had no previous neurologic symptoms, and no evidence of CNS abnormality was found; the myoclonic jerking subsided when metoclopramide therapy was discontinued. Multifocal myoclonus must be differentiated from seizure activity in patients with renal failure and other metabolic encephalopathies. Metoclopramide clearance is reduced in renal failure, and myoclonus or other neurologic complications may be precipitated in such patients by usual doses of this drug.
Abstract: No Abstract available
Abstract: The pharmacokinetics of 4-amino-5-chloro-N-(2-diethylaminoethyl)-2-methoxybenzamide (metoclopramide, Paspertin) after a single dose of the drug in five different dosage forms: ampoules, tablets, drops, dragées and suppositories, were studied. The clinical investigations were carried out on 10 healthy subjects under carefully controlled conditions. The analysis of metoclopramide in plasma was carried out using reverse-phase high-pressure liquid chromatography. Bioavailabilities between 76 and 79% were determined for the oral application forms and 53% for the rectal application form. Significant differences between maximum plasma levels were found for different individuals. The initial distribution of the drug is very rapid, and the elimination half-lives are comparable for all formulations and ranged from 3.9 and 5.3 h. The apparent volume of distribution is 3.1 l/kg body weight and the total body clearance is 38.4 l/h.
Abstract: The pharmacokinetics of metoclopramide have been studied after intravenous and oral dosing (10 mg) to 6 patients with chronic renal failure. The mean terminal half-life was 13.9 h after intravenous and 14.8 h after oral administration. Total body clearance after i.v. dosing was 16.7 l/h. Oral bioavailability was 71.8%. In comparison to previous studies on normal subjects these results indicate that clearance of metoclopramide in renal failure is approximately 30% of normals. This difference is not accounted for by the change in renal clearance and suggests impaired metabolism or an alteration in enterohepatic circulation of metoclopramide in renal failure.
Abstract: The time courses of plasma metoclopramide concentrations were followed in six subjects after oral and intravenous single dose administration. Plasma concentration-time data following i. v. administration in each subject were found to fit a two compartment model with a mean terminal half-life of 4.55 h +/- 0.80 h and a mean distribution half-time of 0.35 h +/- 0.09 h. Volumes of distribution were high (3.43 +/- 1.181 . kg-1), and clearances (0.53 +/- 0.191 . kg-1 h-1) approached liver plasma flow. This suggests that metoclopramide occurs at higher concentrations in tissues than in plasma, and that its clearance is probably limited by liver blood flow rather than liver metabolic capacity. The postabsorption decline in metoclopramide plasma levels after oral administration was also biexponential in each subject. The terminal half-life was 5.17 h +/- 0.98 h. Mean volume of distribution and mean clearance were similar to intravenous values (after adjustment for bioavailability). Oral absorption was rapid with peak plasma concentrations being reached at a mean time of 0.93 h. A mean bioavailability of 0.77 was calculated for the six subjects, and it was postulated that this incomplete availability is due to a first-pass effect. The inter-individual variation in the degree of "first-pass' was considerable (0.47--1.14).
Abstract: OBJECTIVE: To report 2 cases of serotonin syndrome with serious extrapyramidal movement disorders occurring when metoclopramide was coadministered with sertraline or venlafaxine. CASE SUMMARY: A 72-year-old white woman was treated with sertraline for depression for 18 months and was then admitted to the hospital with a fractured tibia. She was administered metoclopramide because of nausea and, within 2 hours, developed agitation, dysarthria, diaphoresis, and a movement disorder. These symptoms recurred following 2 subsequent administrations of metoclopramide. Treatment with diazepam led to resolution of symptoms within 6 hours, and there was no recurrence at 6 weeks' follow-up. A 32-year-old white woman with major depression was treated with venlafaxine for 3 years. She was admitted following a fall and, after being given metoclopramide, developed movement disorder and a period of unresponsiveness. After a second dose of metoclopramide, these symptoms recurred and were associated with confusion, agitation, fever, diaphoresis, tachypnea, tachycardia, and hypertension. She improved with administration of diazepam, but needed repetition of this treatment over the next 16 hours. Symptoms resolved within 2 days, and she continued venlafaxine with no further adverse effects. DISCUSSION: Both cases met Stembach's criteria for serotonin syndrome and had serious extrapyramidal movement disorders. The possible pathophysiologic mechanisms for the adverse reactions include a single-drug effect, a pharmacodynamic interaction, and a pharmacokinetic interaction. We believe that a pharmacodynamic interaction is most likely. CONCLUSIONS: Clinicians should be aware of a risk of serotonin syndrome with serious extrapyramidal reactions in patients receiving sertraline or venlafaxine when metoclopramide is coadministered even in a single, conventional dose.
Abstract: BACKGROUND: Metoclopramide, a central and peripheral dopamine type 2 receptor antagonist, has been used as an attractive and safer alternative to cisapride. However, cardiac side-effects have also been reported with this drug. AIM: To evaluate the effects of intravenous metoclopramide administration on cardiac repolarization using QT dynamicity, a reliable indicator of arrhythmic side-effects. METHODS: The effect of metoclopramide on cardiac repolarization was evaluated in 10 healthy male volunteers in the supine position. Metoclopramide (10 mg) or placebo was administered intravenously at random in a double-blind, cross-over manner to the participants during continuous electrocardiographic recording in the supine position. The 30-min stationary segments of the recordings before and after drug administration were used to investigate QT dynamicity. RESULTS: Metoclopramide administration, but not placebo, resulted in steeper QT/RR slopes compared with the pre-drug values (metoclopramide: 0.037 +/- 0.004 vs. 0.064 +/- 0.012; P = 0.041; placebo: 0.045 +/- 0.006 vs. 0.050 +/- 0.004; P = 0.563). In a two-way analysis of variance model, metoclopramide administration also increased the QT variance independently (F = 6.225, P = 0.023). CONCLUSIONS: Metoclopramide administration increases the QT/RR slope and QT variance. These findings may partly explain the underlying mechanism of ventricular arrhythmias associated with metoclopramide.
Abstract: No Abstract available
Abstract: Lorcaserin, a selective serotonin 5-hydroxytryptamine 2C receptor agonist, is being developed for weight management. The oxidative metabolism of lorcaserin, mediated by recombinant human cytochrome P450 (P450) and flavin-containing monooxygenase (FMO) enzymes, was examined in vitro to identify the enzymes involved in the generation of its primary oxidative metabolites, N-hydroxylorcaserin, 7-hydroxylorcaserin, 5-hydroxylorcaserin, and 1-hydroxylorcaserin. Human CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, CYP3A4, and FMO1 are major enzymes involved in N-hydroxylorcaserin; CYP2D6 and CYP3A4 are enzymes involved in 7-hydroxylorcaserin; CYP1A1, CYP1A2, CYP2D6, and CYP3A4 are enzymes involved in 5-hydroxylorcaserin; and CYP3A4 is an enzyme involved in 1-hydroxylorcaserin formation. In 16 individual human liver microsomal preparations (HLM), formation of N-hydroxylorcaserin was correlated with CYP2B6, 7-hydroxylorcaserin was correlated with CYP2D6, 5-hydroxylorcaserin was correlated with CYP1A2 and CYP3A4, and 1-hydroxylorcaserin was correlated with CYP3A4 activity at 10.0 μM lorcaserin. No correlation was observed for N-hydroxylorcaserin with any P450 marker substrate activity at 1.0 μM lorcaserin. N-Hydroxylorcaserin formation was not inhibited by CYP1A2, CYP2A6, CYP2B6, CYP2C19, CYP2D6, and CYP3A4 inhibitors at the highest concentration tested. Furafylline, quinidine, and ketoconazole, selective inhibitors of CYP1A2, CYP2D6, and CYP3A4, respectively, inhibited 5-hydroxylorcaserin (IC(50) = 1.914 μM), 7-hydroxylorcaserin (IC(50) = 0.213 μM), and 1-hydroxylorcaserin formation (IC(50) = 0.281 μM), respectively. N-Hydroxylorcaserin showed low and high K(m) components in HLM and 7-hydroxylorcaserin showed lower K(m) than 5-hydroxylorcaserin and 1-hydroxylorcaserin in HLM. The highest intrinsic clearance was observed for N-hydroxylorcaserin, followed by 7-hydroxylorcaserin, 5-hydroxylorcaserin, and 1-hydroxylorcaserin in HLM. Multiple human P450 and FMO enzymes catalyze the formation of four primary oxidative metabolites of lorcaserin, suggesting that lorcaserin has a low probability of drug-drug interactions by concomitant medications.
Abstract: A 40-year-old woman with bipolar disorder who was taking mirtazapine presented with mydriasis, abnormal diaphoresis, myoclonus and muscle rigidity after taking metocloplamide. Her medical history, which included the use of serotonergic agents, and the presence of symptoms including myoclonus and muscle rigidity were consistent with a diagnosis of serotonin syndrome (SS) according to the Hunter criteria. The symptoms diminished following three days of treatment with oral lorazepam and cyproheptadine and a reduced dose of mirtazapine. Metoclopramide is frequently used to various gastric symptom. Metoclopramide is not widely known to induce SS. This potentially fatal condition should be avoided by exercising care in the use of drugs that have the potential to cause drug-drug interactions.