Extensión de tiempo QT
Efectos adversos de las drogas
Variantes ✨Para la evaluación computacionalmente intensiva de las variantes, elija la suscripción estándar paga.
Áreas de aplicación
Explicaciones para pacientes
No tenemos advertencias adicionales para la combinación de abirateron y claritromicina. Consulte también la información especializada pertinente.
Los cambios en la exposición mencionados se refieren a cambios en la curva de concentración plasmática-tiempo [AUC]. No detectamos ningún cambio en la exposición a abirateron. Actualmente no podemos estimar la influencia de la claritromicina. La exposición a claritromicina aumenta al 102%, cuando se combina con abirateron (102%).
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 abirateron tiene una biodisponibilidad oral media [ F ] del 50%, por lo que los niveles plasmáticos máximos [Cmax] tienden a cambiar con una interacción. La vida media terminal [ t12 ] es de 18 horas y se alcanzan niveles plasmáticos constantes [ Css ] después de aproximadamente 72 horas. La unión a proteínas [ Pb ] es muy fuerte al 99.8% y el volumen de distribución [ Vd ] es muy grande a 2815 litros, El metabolismo tiene lugar principalmente a través de CYP3A4..
La claritromicina tiene una biodisponibilidad oral media [ F ] del 53%, por lo que los niveles plasmáticos máximos [Cmax] tienden a cambiar con una interacción. La vida media terminal [ t12 ] es bastante corta a las 4.6 horas y se alcanzan rápidamente niveles plasmáticos constantes [ Css ]. La unión a proteínas [ Pb ] es bastante débil al 70% y el volumen de distribución [ Vd ] es muy grande a 176 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 aumentar la exposición. Aproximadamente el 27.5% de la dosis administrada se excreta inalterada a través de los riñones y esta proporción rara vez se modifica por las interacciones. El metabolismo tiene lugar principalmente a través de CYP3A4. y el transporte activo tiene lugar en particular a través de PGP.
|Efectos serotoninérgicos a||0||Ø||Ø|
Clasificación: Según nuestro conocimiento, ni la abirateron ni la claritromicina aumentan la actividad serotoninérgica.
|Kiesel & Durán b||0||Ø||Ø|
Clasificación: Según nuestros hallazgos, ni la abirateron ni la claritromicina aumentan la actividad anticolinérgica.
Extensión de tiempo QT
Clasificación: En combinación, la abirateron y la claritromicina pueden desencadenar potencialmente arritmias ventriculares del tipo torsades de pointes.
Efectos secundarios generales
|Efectos secundarios||∑ frecuencia||abi||cla|
|Edema periférico||20.0 %||20.0||n.a.|
|Trastorno del gusto||13.5 %||n.a.||13.5|
|ALT elevado||13.0 %||13.0||n.a.|
|AST elevado||13.0 %||13.0||n.a.|
|Infección del tracto urinario||10.0 %||10.0||n.a.|
Dolor de cabeza (9%): claritromicina
Sepsis (5.5%): abirateron
Reacción anafiláctica: claritromicina
Dolor abdominal (4.5%): claritromicina
Dispepsia (4%): claritromicina
Diarrea por clostridium difficile: claritromicina
Fibrilación auricular (2.6%): abirateron
Angina de pecho (1.6%): abirateron
Síndrome de Stevens-Johnson: claritromicina
Necrolisis epidérmica toxica: claritromicina
Hepatitis colestásica: claritromicina
Con base en sus
Referencias de literatura
Abstract: Erythromycin, clarithromycin, and azithromycin are clinically effective for the treatment of common respiratory and skin/skin-structure infections. Erythromycin and azithromycin are also effective for treatment of nongonococcal urethritis and cervicitis due to Chlamydia trachomatis. Compared with erythromycin, clarithromycin and azithromycin offer improved tolerability. Clarithromycin, however, is more similar to erythromycin in pharmacokinetic measures such as half-life, tissue distribution, and drug interactions. Misunderstandings about differences among the macrolides (erythromycin and clarithromycin) and the azalide (azithromycin) in terms of pharmacokinetics and pharmacodynamics, spectrum of activity, safety, and cost are common. The uptake and release of these compounds by white blood cells and fibroblasts account for differences in tissue half-life, volume of distribution, intracellular:extracellular ratio, and in vivo potency. Although microbiologic studies reveal that gram-positive pathogens are equally susceptible to these agents, significantly more isolates of Haemophilus influenzae are susceptible to azithromycin than to erythromycin or clarithromycin. Concentrations achieved at the infection site and duration above the minimum inhibitory concentration are as important as in vitro activity in determining in vivo activity against bacterial pathogens. Analysis of safety data indicates differences among these agents in drug interactions and use in pregnancy. Analysis of safety data reveals pharmacokinetic drug interactions for erythromycin and clarithromycin with theophylline, terfenadine, and carbamazepine that are not found with azithromycin. Both erythromycin and azithromycin are pregnancy category B drugs; clarithromycin is a category C drug. The numerous differences in pharmacokinetics, microbiology, safety, and costs among erythromycin, clarithromycin, and azithromycin can be used in the judicious selection of treatment for indicated infections.
Abstract: To investigate whether grapefruit juice inhibits the metabolism of clarithromycin, 12 healthy subjects were given water or grapefruit juice before and after a clarithromycin dose of 500 mg in a randomized crossover study. Administration of grapefruit juice increased the time to peak concentration of both clarithromycin (82 +/- 35 versus 148 +/- 83 min; P = 0.02) and 14-hydroxyclarithromycin (84 +/- 38 min versus 173 +/- 85; P = 0.01) but did not affect other pharmacokinetic parameters.
Abstract: No Abstract available
Abstract: Clarithromycin is a macrolide antibacterial that differs in chemical structure from erythromycin by the methylation of the hydroxyl group at position 6 on the lactone ring. The pharmacokinetic advantages that clarithromycin has over erythromycin include increased oral bioavailability (52 to 55%), increased plasma concentrations (mean maximum concentrations ranged from 1.01 to 1.52 mg/L and 2.41 to 2.85 mg/L after multiple 250 and 500 mg doses, respectively), and a longer elimination half-life (3.3 to 4.9 hours) to allow twice daily administration. In addition, clarithromycin has extensive diffusion into saliva, sputum, lung tissue, epithelial lining fluid, alveolar macrophages, neutrophils, tonsils, nasal mucosa and middle ear fluid. Clarithromycin is primarily metabolised by cytochrome P450 (CYP) 3A isozymes and has an active metabolite, 14-hydroxyclarithromycin. The reported mean values of total body clearance and renal clearance in adults have ranged from 29.2 to 58.1 L/h and 6.7 to 12.8 L/h, respectively. In patients with severe renal impairment, increased plasma concentrations and a prolonged elimination half-life for clarithromycin and its metabolite have been reported. A dosage adjustment for clarithromycin should be considered in patients with a creatinine clearance < 1.8 L/h. The recommended goal for dosage regimens of clarithromycin is to ensure that the time that unbound drug concentrations in the blood remains above the minimum inhibitory concentration is at least 40 to 60% of the dosage interval. However, the concentrations and in vitro activity of 14-hydroxyclarithromycin must be considered for pathogens such as Haemophilus influenzae. In addition, clarithromycin achieves significantly higher drug concentrations in the epithelial lining fluid and alveolar macrophages, the potential sites of extracellular and intracellular respiratory tract pathogens, respectively. Further studies are needed to determine the importance of these concentrations of clarithromycin at the site of infection. Clarithromycin can increase the steady-state concentrations of drugs that are primarily depend upon CYP3A metabolism (e.g., astemidole, cisapride, pimozide, midazolam and triazolam). This can be clinically important for drugs that have a narrow therapeutic index, such as carbamazepine, cyclosporin, digoxin, theophylline and warfarin. Potent inhibitors of CYP3A (e.g., omeprazole and ritonavir) may also alter the metabolism of clarithromycin and its metabolites. Rifampicin (rifampin) and rifabutin are potent enzyme inducers and several small studies have suggested that these agents may significantly decrease serum clarithromycin concentrations. Overall, the pharmacokinetic and pharmacodynamic studies suggest that fewer serious drug interactions occur with clarithromycin compared with older macrolides such as erythromycin and troleandomycin.
Abstract: Two cases of QT prolongation and torsades de pointes (TdP) are presented. The patients had been taking clarithromycin (400 mg/day) for respiratory disease. Although erythromycin is reportedly associated with TdP, this is the first report of clarithromycin associated with TdP in the absence of other drugs already known to produce QT prolongation.
Abstract: Three open-label, single-dose studies investigated the impact of hepatic or renal impairment on abiraterone acetate pharmacokinetics and safety/tolerability in non-cancer patients. Patients (n = 8 each group) with mild/moderate hepatic impairment or end-stage renal disease (ESRD), and age-, BMI-matched healthy controls received a single oral 1,000 mg abiraterone acetate (tablet dose); while patients (n = 8 each) with severe hepatic impairment and matched healthy controls received 125- and 2,000-mg abiraterone acetate (suspension doses), respectively (systemic exposure of abiraterone acetate suspension is approximately half to that of tablet formulation). Blood was sampled at specified timepoints up to 72 or 96 hours postdose to measure plasma abiraterone concentrations. Abiraterone exposure was comparable between healthy controls and patients with mild hepatic impairment or ESRD, but increased by 4-fold in patients with moderate hepatic impairment. Despite a 16-fold reduction in dose, abiraterone exposure in patients with severe hepatic impairment was about 22% and 44% of the Cmax and AUC∞ of healthy controls, respectively. These results suggest that abiraterone pharmacokinetics were not changed markedly in patients with ESRD or mild hepatic impairment. However, the capacity to eliminate abiraterone was substantially compromised in patients with moderate or severe hepatic impairment. A single-dose administration of abiraterone acetate was well-tolerated.
Abstract: The involvement of intestinal permeability in the oral absorption of clarithromycin (CAM), a macrolide antibiotic, and telithromycin (TEL), a ketolide antibiotic, in the presence of efflux transporters was examined. In order independently to examine the intestinal and hepatic availability, CAM and TEL (10 mg/kg) were administered orally, intraportally and intravenously to rats. The intestinal and hepatic availability was calculated from the area under the plasma concentration-time curve (AUC) after administration of CAM and TEL via different routes. The intestinal availabilities of CAM and TEL were lower than their hepatic availabilities. The intestinal availability after oral administration of CAM and TEL increased by 1.3- and 1.6-fold, respectively, after concomitant oral administration of verapamil as a P-glycoprotein (P-gp) inhibitor. Further, an in vitro transport experiment was performed using Caco-2 cell monolayers as a model of intestinal epithelial cells. The apical-to-basolateral transport of CAM and TEL through the Caco-2 cell monolayers was lower than their basolateral-to-apical transport. Verapamil and bromosulfophthalein as a multidrug resistance-associated proteins (MRPs) inhibitor significantly increased the apical-to-basolateral transport of CAM and TEL. Thus, the results suggest that oral absorption of CAM and TEL is dependent on intestinal permeability that may be limited by P-gp and MRPs on the intestinal epithelial cells.
Abstract: Two novel oral drugs that target androgen signaling have recently become available for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate inhibits the synthesis of the natural ligands of the androgen receptor, whereas enzalutamide directly inhibits the androgen receptor by several mechanisms. Abiraterone acetate and enzalutamide appear to be equally effective for patients with mCRPC pre- and postchemotherapy. Rational decision making for either one of these drugs is therefore potentially driven by individual patient characteristics. In this review, an overview of the pharmacokinetic characteristics is given for both drugs and potential and proven drug-drug interactions are presented. Additionally, the effect of patient-related factors on drug disposition are summarized and the limited data on the exposure-response relationships are described. The most important pharmacological feature of enzalutamide that needs to be recognized is its capacity to induce several key enzymes in drug metabolism. The potency to cause drug-drug interactions needs to be addressed in patients who are treated with multiple drugs simultaneously. Abiraterone has a much smaller drug-drug interaction potential; however, it is poorly absorbed, which is affected by food intake, and a large interpatient variability in drug exposure is observed. Dose reductions of abiraterone or, alternatively, the selection of enzalutamide, should be considered in patients with hepatic dysfunction. Understanding the pharmacological characteristics and challenges of both drugs could facilitate decision making for either one of the drugs.
Abstract: We present a case of a 77 year-old gentleman with previous coronary artery bypass grafting, admitted to hospital with recurrent torsades de pointes (TdP) due to abiraterone-induced hypokalaemia and prolonged QTc. The patient was on abiraterone and prednisone for metastatic prostate cancer. He required multiple defibrillations for recurrent TdP. Abiraterone is a relatively novel drug used in metastatic prostate cancer and we discuss this potential adverse effect and its management in this unusual presentation.
Abstract: Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers.