QT time prolongation
Adverse drug events
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Explanations of the substances for patients
We have no additional warnings for the combination of abarelix and sotalol. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We do not expect any change in exposure for abarelix, when combined with sotalol (100%). We do not expect any change in exposure for sotalol, when combined with abarelix (100%).
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
The bioavailability of abarelix is unknown. The terminal half-life [ t12 ] is rather long at 316.8 hours and constant plasma levels [ Css ] are only reached after more than 1267.2 hours. The protein binding [ Pb ] is 97.5% strong. The metabolism via cytochromes is currently still being worked on.
Sotalol has a high oral bioavailability [ F ] of 95%, which is why the maximum plasma level [Cmax] tends to change little during an interaction. The terminal half-life [ t12 ] is 12 hours and constant plasma levels [ Css ] are reached after approximately 48 hours. The therapeutic window is narrow and the safety margin is therefore small. Even small changes in exposure can increase the risk of toxicity. Protein binding [ Pb ] is not known. The metabolism does not take place via the common cytochromes and the active transport takes place in particular via OATP1A2.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor sotalol increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor sotalol increase anticholinergic activity.
QT time prolongation
Rating: In combination, abarelix and sotalol can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||sot|
|Chest pain||16.0 %||n.a.||16.0|
|Heart failure||2.3 %||n.a.||2.3|
|Cerebrovascular accident||1.0 %||n.a.||+|
|Atrioventricular block||0.0 %||n.a.||0.01|
Based on your answers and scientific information, we assess the individual risk of undesirable side effects. These recommendations are intended to advise professionals and are not a substitute for consultation with a doctor. In the restricted test version (alpha), the risk of all substances has not yet been conclusively assessed.
Abstract: INTRODUCTION: Torsade de Pointes (Tdp) is a form of polymorphic ventricular tachycardia in the setting of prolonged QT interval. Any drug that prolongs repolarisation, and hence QT interval, may cause Tdp. Predisposing factors of drug-induced Tdp include female sex, bradyarrhythmia and hypokalaemia. METHODS: We retrospectively analysed the case notes of 13 patients with drug-induced LQTS from 1991 to 2000 from National Heart Centre and Changi General Hospital. RESULTS: Causative drugs in the series were amiodarone (seven patients, 54%), sotalol (two patients), quinidine (one patient), phenothiazine (two patients) and astemizole (one patient). There were eight females and all were Chinese. The mean age was 72 +/- nine years. The patients commonly present with syncope (38%) and cardiac arrest (38%). The mean corrected QTC interval was 545 ms. The most common precipitating factor was hypokalaemia (31%). Nine patients require cardiopulmonary resuscitation and two patients (15%) died. Nine patients (69%) had underlying structural heart disease such as ischaemic heart disease, valvular heart disease and hypertensive heart disease. The left ventricular ejection fraction was normal in six patients. The onset of Tdp ranged from Day 2 to Day 5 in the seven patient with amiodarone-induced LQTS. These were inpatients who were given intravenous loading doses of amiodarone. Both patients with sotalol-induced LQTS were females on sotalol 80 mg and 240 mg per day with Tdp occurring on Day 2 and 10 months respectively. CONCLUSION: Tdp is a potentially life-threatening arrhythmia. The list of torsadogenic drugs is ever expanding. Physicians need to know the drugs which can lead to Tdp. Careful assessment of risk-benefit ratio is important before prescribing such drugs. Amiodarone-induced Tdp is not uncommon in our local population. Initiation of a class III agent, especially amiodarone, should be done judiciously, with monitoring of the QT interval and avoidance of hypokalaemia.
Abstract: Many drugs, including sotalol, have been implicated in prolonging QT interval and triggering torsades de pointes, a potentially fatal ventricular arrhythmia, especially during chronic therapy or in case of acute high dose toxicity. We report here a case with a severely prolonged QT interval and torsades de pointes after an initial intake of low dose sotalol (80 mg), indicating a probable inherent individual oversensitivity to sotalol.
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.