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JACC. Clinical Electrophysiology Apr 2020This study assessed the safety and efficacy of novel and standardized protocols for the use of intravenous (IV) sotalol in pediatric patients.
OBJECTIVES
This study assessed the safety and efficacy of novel and standardized protocols for the use of intravenous (IV) sotalol in pediatric patients.
BACKGROUND
Acute arrhythmia treatments in children remain limited. IV sotalol is a new option but pediatric experience is limited. There is no standardized protocol for rapid infusion during acute arrhythmias. This study assessed a single center's initial experience with IV sotalol in young patients, describing a protocol for rapid infusion for acute treatment, and reviewed the safety and efficacy of maintenance dosing.
METHODS
This is a retrospective study of all patients who received IV sotalol at Rady Children's Hospital. Demographics, arrhythmia, hemodynamics, and effects of IV sotalol were assessed.
RESULTS
Thirty-seven patients received IV sotalol from December 2015 to December 2018. Group 1 (n = 26) received sotalol for acute therapy and group 2 (n = 11) received a maintenance dose of sotalol after successful cardioversion with alternate therapies. The groups had similar demographics. Group 1 included patients with atrial flutter (n = 16), patients with supraventricular tachycardia (SVT) (n = 9), and patients with atrial ectopic tachycardia (AET) (n = 1). All 9 patients with SVT (100%) converted to sinus rhythm after failure to convert using adenosine. Median administration time was 15 min, the median dose was 30 mg/m, and mean time to cardioversion was 14 min. Group 2 median infusion time was 120 min, the median dose was 54 mg/m/day, and all patients maintained sinus rhythm. No patients required cessation for adverse effects previously described for IV sotalol.
CONCLUSIONS
IV sotalol was safe and effective for acute and maintenance therapy in young patients. In acute patients, 30 mg/m over 15 min converted most patients. IV sotalol adds a valuable option to IV therapies in the young.
Topics: Anti-Arrhythmia Agents; Atrial Flutter; Child; Humans; Retrospective Studies; Sotalol; Tachycardia, Supraventricular
PubMed: 32327076
DOI: 10.1016/j.jacep.2019.11.019 -
JACC. Clinical Electrophysiology Apr 2023Inpatient initiation of sotalol is recommended owing to its proarrhythmic effects.
BACKGROUND
Inpatient initiation of sotalol is recommended owing to its proarrhythmic effects.
OBJECTIVES
The DASH-AF (Feasibility and Safety of Intravenous Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy in Adult Patients With Atrial Fibrillation) trial evaluates the safety and feasibility of intravenous (IV) sotalol, achieving a steady state with maximum QTc prolongation within 6 hours instead of the traditional 5-dose inpatient oral (PO) titration.
METHODS
DASH-AF is a prospective, nonrandomized, multicenter, open-label trial consisting of patients who underwent IV sotalol loading dose to initiate rapid oral therapy for atrial arrhythmias. IV dose was calculated based on the target oral dose as indicated by baseline QTc and renal function. Patients' QTc (in sinus) was measured via electrocardiography at 15-minute intervals and after IV loading completion. Patients were discharged 4 hours after first oral dose. All patients were monitored via mobile cardiac outpatient telemetry for 72 hours. The control group was composed of patients admitted for the traditional 5 PO doses. Safety outcomes were assessed in both groups.
RESULTS
A total of 120 patients from 3 centers were enrolled from 2021 to 2022 in the IV loading group (compared with type of AF- and renal function-matched patients in the conventional PO loading cohort). This study demonstrated no significant change in ΔQTc in both groups, with a significantly lower number of patients requiring dose adjustment in the IV arm compared with the PO arm (4.1% vs 16.6%; P = 0.003). This led to potential cost savings of up to $3,500.68 per admission.
CONCLUSIONS
The DASH-AF trial shows that rapid IV sotalol loading in atrial fibrillation/flutter patients for rhythm control is feasible and safe compared with conventional oral loading with significant cost reduction. (Feasibility and Safety of Intravenous Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy in Adult Patients With Atrial Fibrillation [DASH-AF]; NCT04473807).
Topics: Humans; Adult; Sotalol; Atrial Fibrillation; Anti-Arrhythmia Agents; Prospective Studies; Feasibility Studies
PubMed: 37014289
DOI: 10.1016/j.jacep.2022.11.026 -
Children (Basel, Switzerland) May 2023Antiarrhythmic drugs represent a mainstay of pediatric arrhythmia treatment. However, official guidelines and consensus documents on this topic remain scarce. There are... (Review)
Review
Antiarrhythmic drugs represent a mainstay of pediatric arrhythmia treatment. However, official guidelines and consensus documents on this topic remain scarce. There are rather uniform recommendations for some medications (including adenosine, amiodarone, and esmolol), while there are only very broad dosage recommendations for others (such as sotalol or digoxin). To prevent potential uncertainties and even mistakes with regard to dosing, we summarized the published dosage recommendations for antiarrhythmic drugs in children. Because of the wide variations in availability, regulatory approval, and experience, we encourage centers to develop their own specific protocols for pediatric antiarrhythmic drug therapy.
PubMed: 37238395
DOI: 10.3390/children10050847 -
Clinical Pharmacology and Therapeutics Mar 2001This pharmacokinetic-pharmacodynamic study was designed to define the steady-state relationship between pharmacologic response and dose or concentration of sotalol in... (Clinical Trial)
Clinical Trial
OBJECTIVE
This pharmacokinetic-pharmacodynamic study was designed to define the steady-state relationship between pharmacologic response and dose or concentration of sotalol in children with cardiac arrhythmias, with an emphasis on neonates and infants.
METHODS
The treatment consisted of an upward titration with unit doses of 10, 30, and 70 mg of sotalol per square meter of body surface area. The patients received 3 doses at each dose level. The dosing interval was 8 hours. The Class III and beta-blocking activities of sotalol were derived from the QT and R-R intervals, respectively, of the surface electrocardiogram, which was recorded at 6 scheduled times before and after the third, sixth, and ninth doses. During these three dose intervals, 4 scheduled blood samples were also collected. Drug concentrations were measured with a validated nonstereoselective liquid chromatographic tandem mass spectrometric detection assay. Pharmacokinetic and pharmacodynamic parameters were obtained with standard methods.
RESULTS
Twenty-one centers enrolled 25 patients in the study: 7 were neonates, 9 were infants, and 11 were children between the ages of 2 years and 12 years. The area under the drug concentration-time curve increased proportionately with dose. The apparent oral clearance of sotalol was linearly correlated with body surface area and creatinine clearance. The smallest children (body surface area <0.33 m2) displayed greater drug exposure than the larger children. The increase of QTc and R-R intervals was dose dependent. At the 70-mg/m(2) dose level, the mean (+/- standard deviation) maximum increase for the QTc interval was 14% +/- 7% and the average Class III effect during a dose interval was 7% +/- 5%. At the same dose level, the mean maximum increase of the R-R interval was 25% +/- 15% and the average beta-blocking effect during a dose interval was 12% +/- 13%. The effects tended to be larger in the smallest children. The Class III response and the plasma concentrations of sotalol were linearly related. The treatment was well tolerated.
CONCLUSIONS
The steady-state pharmacokinetics of sotalol were dose proportionate. Pharmacologically important beta-blocking effects were observed at the 30-mg/m2 and 70-mg/m2 dose levels. Important Class III effects were seen at the 70-mg/m2 dose level. The Class III effect was linearly related to the drug concentration.
Topics: Anti-Arrhythmia Agents; Area Under Curve; Child; Child, Preschool; Dose-Response Relationship, Drug; Electrocardiography; Female; Humans; Infant; Infant, Newborn; Male; Metabolic Clearance Rate; Sotalol; Tachycardia, Supraventricular; Tachycardia, Ventricular
PubMed: 11240979
DOI: 10.1067/mcp.2001.113795 -
Pharmaceuticals (Basel, Switzerland) Jul 2023We focused on the first demonstration that antiarrhythmics, particularly class II and class III antiarrhythmic and beta-blocker sotalol can induce severe...
We focused on the first demonstration that antiarrhythmics, particularly class II and class III antiarrhythmic and beta-blocker sotalol can induce severe occlusion/occlusion-like syndrome in rats. In this syndrome, as in similar syndromes with permanent occlusion of major vessels, peripheral and central, and other similar noxious procedures that severely disable endothelium function, the stable gastric pentadecapeptide BPC 157-collateral pathways activation, was a resolving therapy. After a high dose of sotalol (80 mg/kg intragastrically) in 180 min study, there were cause-consequence lesions in the brain (swelling, intracerebral hemorrhage), congestion in the heart, lung, liver, kidney, and gastrointestinal tract, severe bradycardia, and intracranial (superior sagittal sinus), portal and caval hypertension, and aortal hypotension, and widespread thrombosis, peripherally and centrally. Major vessels failed (congested inferior caval and superior mesenteric vein, collapsed azygos vein). BPC 157 therapy (10 µg, 10 ng/kg given intragastrically at 5 min or 90 min sotalol-time) effectively counteracted sotalol-occlusion/occlusion-like syndrome. In particular, eliminated were heart dilatation, and myocardial congestion affecting coronary veins and arteries, as well as myocardial vessels; eliminated were portal and caval hypertension, lung parenchyma congestion, venous and arterial thrombosis, attenuated aortal hypotension, and centrally, attenuated intracranial (superior sagittal sinus) hypertension, brain lesions and pronounced intracerebral hemorrhage. Further, BPC 157 eliminated and/or markedly attenuated liver, kidney, and gastrointestinal tract congestion and major veins congestion. Therefore, azygos vein activation and direct blood delivery were essential for particular BPC 157 effects. Thus, preventing such and similar events, and responding adequately when that event is at risk, strongly advocates for further BPC 157 therapy.
PubMed: 37513889
DOI: 10.3390/ph16070977 -
Frontiers in Pharmacology 2021The processes by which fear memory is encoded, consolidated, and re-consolidated are extremely complex and appear to require the release of stress hormones, especially...
Sotalol Treatment may Interfere With Retrieval, Expression, and/or Reconsolidation Processes Thus Disrupting Traumatic Memories in a Post-Traumatic Stress Disorder Mice Model.
The processes by which fear memory is encoded, consolidated, and re-consolidated are extremely complex and appear to require the release of stress hormones, especially adrenaline (AD). AD improves contextual fear memory, acting specifically on peripheral β2-adrenoceptors. Propranolol (peripheral and central β-adrenoceptor antagonist) treatment was shown to prevent post-traumatic stress disorder (PTSD) development and reduce its symptoms. However, propranolol has several side effects. Thus, we aimed to evaluate if sotalol (a peripheral β-adrenoceptor antagonist) treatment interferes with retrieval, expression, and/or reconsolidation of traumatic memories in a validated mice model that mimics the signs/symptoms of PTSD, thus intending to decrease them. Female mice were induced with PTSD following an established protocol. Sotalol (2.0 mg/kg) or vehicle were administered on days 2, 7, and 14. The percentage of freezing was calculated, and behavioral tests were carried out. Catecholamines in plasma were quantified by HPLC with electrochemical detection. Quantitative real-time polymerase chain reaction (qPCR) was used to evaluate mRNA expression of NR4A family genes in hippocampus. Following the submission of the animals to the same aversive context on days 2, 7, and 14, sotalol-treated mice exhibited significant less freezing behavior. In the elevated plus-maze test, the time spent and number of entries in the open arms, and total arm entries were increased in sotalol-treated mice. Also, the light-dark transition test revealed higher time spent, number of transitions to the light, and total number of transitions in sotalol-treated mice. Moreover, plasma AD was significantly decreased in sotalol-treated mice. On day 14, sotalol-treated mice exhibited a decrease in mRNA expression of in the hippocampus. In conclusion, in PTSD mice model, sotalol appears to decrease traumatic memories and anxiety-like behavior, probably due to a decrease in peripheral adrenergic activity, which influences traumatic memories. The effects of sotalol upon re-exposure to the traumatic context may be consistent with interference in the retrieval, expression, and/or reconsolidation processes of contextual traumatic memory, resulting in a long-term reduction of PTSD symptoms and signs. The decreased mRNA expression in the hippocampal formation may be crucial for these mice to develop diminished traumatic contextual memories after sotalol therapy in PTSD.
PubMed: 35173611
DOI: 10.3389/fphar.2021.809271 -
Heart Rhythm Nov 2023Use of d,l-sotalol for rhythm control in patients with atrial fibrillation (AF) has raised safety concerns. Previous randomized studies are few and not designed for...
BACKGROUND
Use of d,l-sotalol for rhythm control in patients with atrial fibrillation (AF) has raised safety concerns. Previous randomized studies are few and not designed for mortality outcome.
OBJECTIVE
The purpose of this study was to compare the incidences of mortality and ventricular arrhythmias in AF patients treated with d,l-sotalol for rhythm control vs matched control patients treated with cardioselective beta-blockers.
METHODS
This population-based cohort study included AF patients from the Swedish National Patient Registry (2006-2017) who underwent rhythm control after a second cardioversion. Incidence rates (IRs) and adjusted hazard ratios (aHRs) for mortality and a composite endpoint of cardiac arrest/death and ventricular arrhythmias were calculated for the overall cohort and a 1:1 propensity score matched cohort of d,l-sotalol vs beta-blocker treatment.
RESULTS
Among patient treated with d,l-sotalol (n = 4987) and beta-blocker (n = 27,078) (mean follow-up 458 days), all-cause mortality was lower in patients treated with d,l-sotalol: IR 1.21; 95% confidence interval 0.95-1.52 vs 2.42 (2.26-2.60) deaths per 100 patient-years; aHR 0.66 (0.52-0.83). The difference in mortality persisted in the propensity score matched comparison (n = 4953 in each group): aHR 0.63 (0.48-0.86). No differences were observed in the composite outcome: IR in propensity cohorts 2.13 (1.78-2.52) vs 2.07 (1.73-2.53) events per 100 years; aHR 1.01 (0.78-1.29).
CONCLUSION
There was no excess mortality with d,l-sotalol compared with cardioselective beta-blockers in patients undergoing rhythm control treatment for AF after a second cardioversion. Our results indicate that the risk associated with d,l-sotalol treatment for AF can be mitigated by careful patient selection and strict adherence to follow-up protocols.
Topics: Humans; Sotalol; Atrial Fibrillation; Anti-Arrhythmia Agents; Cohort Studies; Adrenergic beta-Antagonists
PubMed: 37598987
DOI: 10.1016/j.hrthm.2023.08.019 -
Pharmacological Reports : PR Apr 2021Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the...
BACKGROUND
Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice.
MATERIALS AND METHODS
As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography-mass spectrometry.
RESULTS
Sotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80-100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study.
CONCLUSION
Sotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions.
Topics: Adrenergic beta-Antagonists; Animals; Anticonvulsants; Avoidance Learning; Brain; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Female; Memory, Long-Term; Mice; Seizures; Sotalol; Tissue Distribution
PubMed: 33492655
DOI: 10.1007/s43440-020-00210-2 -
British Medical Journal (Clinical... Dec 1981
Topics: Alcohol Drinking; Drug Interactions; Ethanol; Humans; Propranolol; Sotalol
PubMed: 6799035
DOI: 10.1136/bmj.283.6305.1489 -
Journal of Managed Care Pharmacy : JMCP Oct 2006Amiodarone (Cordarone, Pacerone) is a powerful antiarrhythmic that is effective in converting atrial fibrillation (AF) to sinus rhythm and superior to sotalol in...
Amiodarone (Cordarone, Pacerone) is a powerful antiarrhythmic that is effective in converting atrial fibrillation (AF) to sinus rhythm and superior to sotalol in maintaining sinus rhythm. In 665 patients who were receiving anticoagulants and had persistent AF, Singh et al. found a median time to recurrence of AF of 487 days in the amiodarone group versus 74 days in the sotalol group and 6 days in the placebo group, with improved quality of life and improved exercise performance in the amiodarone group.1 In this study known as the Sotalol Amiodarone Atrial Fibrillation Efficacy Trial (SAFE-T), spontaneous conversion occurred in 72.1% of amiodarone patients, 24.2% for sotalol, and 0.8% for placebo. However, the use of amiodarone in AF is not approved by the U.S. Food and Drug Administration (FDA). The unlabeled (off-label) uses of amiodarone include conversion of atrial fibrillation and maintenance of sinus rhythm, and treatment of supraventricular tachycardia.
Topics: Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Humans; Safety Management; United States
PubMed: 17269848
DOI: 10.18553/jmcp.2006.12.8.687