Extensión de tiempo QT
Efectos adversos de las drogas
|Aumento de la creatinina sérica|
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 dronedaron. 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 dronedaron. La exposición a dronedaron 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 dronedaron tiene una baja biodisponibilidad oral [ F ] del 13%, por lo que el nivel plasmático máximo [Cmax] tiende a cambiar fuertemente con una interacción. La vida media terminal [ t12 ] es de 16 horas y se alcanzan niveles plasmáticos constantes [ Css ] después de aproximadamente 64 horas. La unión a proteínas [ Pb ] es muy fuerte al 98.1% y el volumen de distribución [ Vd ] es muy grande a 1400 litros. 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 dronedaron aumentan la actividad serotoninérgica.
|Kiesel & Durán b||0||Ø||Ø|
Clasificación: Según nuestros hallazgos, ni la abirateron ni la dronedaron aumentan la actividad anticolinérgica.
Extensión de tiempo QT
Clasificación: En combinación, la abirateron y la dronedaron pueden desencadenar potencialmente arritmias ventriculares del tipo torsades de pointes.
Efectos secundarios generales
|Efectos secundarios||∑ frecuencia||abi||dro|
|Aumento de la creatinina sérica||51.0 %||n.a.||51.0|
|Edema periférico||20.0 %||20.0||n.a.|
|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.|
Náusea (5%): dronedaron
Dolor abdominal (4%): dronedaron
Dispepsia (2%): dronedaron
Vómitos (2%): dronedaron
Fibrilación auricular (2.6%): abirateron
Angina de pecho (1.6%): abirateron
Insuficiencia cardiaca: dronedaron
Reacciones alérgicas de la piel: dronedaron
Insuficiencia hepática: dronedaron
Insuficiencia renal: dronedaron
Enfermedad pulmonar intersticial: dronedaron
Con base en sus
Referencias de literatura
Abstract: BACKGROUND: Amiodarone is an effective antiarrhythmic drug rarely associated with torsade de pointes arrhythmias (TdP). The noniodinated compound dronedarone could resemble amiodarone and be devoid of the adverse effects. In the dog with chronic complete atrioventricular (AV) block (CAVB) and acquired long-QT syndrome, the electrophysiological and proarrhythmic properties of the drugs were compared after 4 weeks of oral treatment. METHODS AND RESULTS: Amiodarone (n=7, 40 mg. kg(-1). d(-1)) and dronedarone (n=8, 20 mg/kg BID) were started at 6 weeks of CAVB (baseline). Six dogs served as controls. Surface ECGs and endocardially placed monophasic action potential catheters in the left (LV) and right (RV) ventricles were recorded to assess QTc time, action potential duration (APD), interventricular dispersion (DeltaAPD=LV APD minus RV APD), early afterdepolarizations (EADs), ectopic beats, and TdP. Both amiodarone (+21%) and dronedarone (+31%) increased QTc time. Amiodarone showed no increase in DeltaAPD in 4 of 7 dogs, whereas dronedarone augmented DeltaAPD in 7 of 8 animals. After dronedarone, TdP occurred in 4 of 8 dogs with the highest DeltaAPD (105+/-20 ms). TdP was never seen with amiodarone, not even in the dogs that had DeltaAPD values comparable to those with dronedarone. Furthermore, a difference existed in EADs and ectopic activity incidence (dronedarone 3 of 8; amiodarone 0 of 7), which was also seen during an epinephrine challenge. CONCLUSIONS: In the CAVB dog model, both amiodarone and dronedarone prolong QT time (class III effect). The absence of TdP with amiodarone seems to be related to homogeneous APD lengthening in the majority of dogs and the lack of EADs and/or ventricular ectopic beats in all.
Abstract: Dronedarone, a non-iodinated benzofuran derivative, was developed as a potentially less toxic alternative to amiodarone. This study describes Holter data of dronedarone in humans. Five groups of healthy subjects were given 1 of 5 oral doses of dronedarone in a twice-daily regimen or placebo. Holter recordings of circadian rhythmicity of RR and QT intervals were evaluated. Dronedarone prolonged RR and QT intervals as a function of dose, without effect on circadian patterns. The relative prolongation of QT, QTc, and RR by dronedarone was significant. The QTc interval did not exhibit a clearly recognizable circadian pattern, suggesting that the circadian pattern of the QT interval was mostly a reflection of circadian changes in the RR interval in the study population. Dronedarone resembled amiodarone in class III and sympatholytic effects, indicating its potential as a unique antiarrhythmic compound seemingly devoid of the side effects mediated by iodine in amiodarone.
Abstract: Class III drugs prolong the QT interval by blocking mainly the delayed rectifier rapid potassium outward current (IKr), with little effect on depolarization. This K(+) channel in encoded by the human ether-a-go-go-related gene (hERG). Inhibition of hERG potassium currents by class III antiarrhythmic drugs causes lengthening of cardiac action potential, which produces a beneficial antiarrhythmic effect. Excessive prolongation of the action potential may lead to acquired long QT syndrome, which is associated with a risk of "torsade de pointes". Class III agents can block all types of potassium channels: IKs, IKr, IKur and IK1. The main representing class III agent is amiodarone. It is the gold standard in the prevention of recurrence of atrial fibrillation. Although it is highly effective in treating many arrhythmias, large number of adverse effects limits its clinical use. Dronedarone is a synthetic amiodarone analogue, iodine-free compound, with fewer adverse effects, and shares amiodarone's multichannel blocking effects, inhibiting transmembrane Na+, IKs, IKur, IK1, and slow Ca(++)L-type calcium currents. The main new generation class III drugs are: dofetilide, dronedarone, azimilide, and ibutilide. Oral dofetilide did not increase mortality in patients with a recent myocardial infarction or congestive heart failure. It is an alternative for the pharmacological conversion of atrial fibrillation and flutter. Azimilide blocks both rapid and slow potassium channels components. Azimilide is not a methanesulfonanilide compound. Trecitilide, tedisamil, ersentilide, ambasilide, chromanol and sematilide are class III miscellaneous agents. Old mixed agents are sotalol and bretylium. The present article reviews the main trials accomplished with these drugs.
Abstract: Amiodarone is an effective treatment for atrial and ventricular arrhythmias, but its use is limited by a toxic adverse-effect profile. Although dronedarone has been touted as an antiarrhythmic agent devoid of both solid organ toxicity and proarrhythmic properties, its potential for prolonging ventricular repolarization may augment triggered ectopy. We describe a 66-year-old man who began dronedarone 400 mg twice/day for new-onset paroxysmal atrial fibrillation; he had no left ventricular dysfunction or clinical heart failure. Three months after starting the drug, he complained of malaise, fatigue, and rare palpitations. Twenty four-hour Holter monitoring revealed increased premature ventricular complexes, and the rate-corrected QT (QTc) interval was prolonged (range 525-760 msec). Dronedarone was discontinued and the patient's symptoms gradually resolved over the next 3 weeks. Holter monitoring revealed a marked reduction in ventricular ectopy burden, and the QTc interval decreased to his baseline values. Even in the absence of documented symptomatic torsade de pointes, this case suggests that caution should be exercised when prescribing dronedarone and that serial QTc interval monitoring may be appropriate. In addition, clinicians should have a low threshold to perform Holter monitoring if symptoms develop during dronedarone therapy.
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: 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.