lacosamide and Heart-Arrest

Topics: Anticonvulsants; Epilepsy; Heart Arrest; Humans; Lacosamide; Seizures

Lacosamide is an antiepileptic drug with US Food and Drug Administration approval for the treatment of partial-onset seizures in patients older than one month. Lacosamide works by selective enhancement of proteins that induce preferential slow promotion of sodium channels to the hyperpolarized inactive state. Lacosamide is generally well-tolerated; however, clinical and nonclinical studies have linked its use with cardiac side effects including PR prolongation and atrioventricular (AV) block.. We present the case of a three-week-old female neonatal patient born at 25 weeks' gestation who developed second-degree AV heart block and cardiac arrest after initiating lacosamide therapy. The patient was being treated for neonatal seizure complicated by intraventricular hemorrhage (grade II) and electrolyte disturbances with phenobarbital, levetiracetam, and phenytoin. Before addition of lacosamide therapy, the patient had an unremarkable electrocardiogram and no known cardiac risk factors for lacosamide. After medication discontinuation, the patient experienced no reoccurring episodes or other cardiac events.. Use of lacosamide for neonatal populations is currently under evaluation. This is the first report of adverse cardiac event (AV block) in the setting of neonatal lacosamide use. Risk of future adverse cardiac events should be evaluated when determining the safety and efficacy of lacosamide in the neonatal population.

Topics: Anticonvulsants; Atrioventricular Block; Female; Heart Arrest; Humans; Infant, Newborn; Infant, Newborn, Diseases; Lacosamide; United States

Lacosamide is an antiepileptic drug whose exact mechanism of action remains unknown. It acts by increasing the slow inactivation of the voltage-dependent sodium channels of the cell membranes. It is indicated in the treatment of focal seizures with or without secondary generalisation and is occasionally used as adjunct treatment in neuropathic pain. Although the most frequent side effects are mild (dizziness, diplopia, blurred vision, headache, tremor, etc.), others such as supraventricular tachyarrhythmias, changes in repolarisation, atrioventricular blocks and even cardiac arrest or sudden death have been reported.. A 74-year-old male, diagnosed with classic trigeminal neuralgia treated with 200 mg/12 h of carbamazepine, who visited due to a worsening of the pain in the trigeminal V1-V2 region. On the sixth day after admission, after adjusting the carbamazepine treatment to a descending regime, 400 mg/24 h of eslicarbazepine and 100 mg/12 h of intravenous lacosamide, he presented a complete atrioventricular block with extreme bradycardia that required the placement of a pacemaker.. Voltage-dependent sodium channel blockade mainly affects non-sinusal cardiac tissue. An alteration in the atrioventricular or infrahisian node is more consistent with its mechanism of action. Other cases of atrioventricular block in this kind of polytherapy have been reported. Precaution is advised in the concomitant use of antiepileptic drugs, above all among those that prolong the PR interval, and they should be contraindicated in patients with a history of atrioventricular block, ischaemic heart disease or heart failure. Before starting, a baseline electrocardiogram and regular electrocardiographic monitoring are advised during the first few weeks.. Lacosamida asociada a bloqueo de alto grado en un paciente con neuralgia del trigemino.. Introduccion. La lacosamida es un farmaco antiepileptico cuyo mecanismo de accion exacto se desconoce. Actua aumentando la inactivacion lenta de los canales de sodio dependientes del voltaje de las membranas celulares. Indicado en el tratamiento de crisis focales con o sin generalizacion secundaria, ocasionalmente se emplea como tratamiento coadyuvante en el dolor neuropatico. Aunque los efectos adversos mas frecuentes son leves (mareo, diplopia, vision borrosa, cefalea, temblor…), se han descrito taquiarritmias supraventriculares, cambios en la repolarizacion, bloqueos auriculoventriculares e incluso parada cardiaca o muerte subita. Caso clinico. Varon de 74 años, diagnosticado de neuralgia del trigemino clasica en tratamiento con 200 mg/12 h de carbamacepina, que acude por reagudizacion del dolor en el territorio trigeminal V1-V2. El sexto dia de ingreso, tras ajustar el tratamiento con carbamacepina en pauta descendente, 400 mg/24 h de eslicarbacepina y 100 mg/12 h de lacosamida intravenosa, presenta bloqueo auriculoventricular completo con bradicardia extrema que precisa la implantacion de un marcapasos definitivo. Conclusiones. El bloqueo de canales de sodio dependientes del voltaje afecta predominantemente al tejido cardiaco no sinusal. Una alteracion en el nodo auriculoventricular o infrahisiano es mas congruente con su mecanismo de accion. Existen mas casos comunicados de bloqueo auriculoventricular en este tipo de politerapia. Se recomienda precaucion en el uso concomitante de farmacos antiepilepticos, sobre todo entre los que prolonguen el intervalo PR, asi como su contraindicacion en pacientes con antecedentes de bloqueo auriculoventricular, cardiopatia isquemica o insuficiencia cardiaca. Antes de su inicio, se aconseja realizar un electrocardiograma basal y monitorizacion electrocardiografica regular durante las primeras semanas.

Topics: Aged; Anticonvulsants; Atrioventricular Block; Bradycardia; Carbamazepine; Cardiopulmonary Resuscitation; Combined Modality Therapy; Contraindications, Drug; Dibenzazepines; Drug Substitution; Electrocardiography; Heart Arrest; Humans; Lacosamide; Male; Nerve Block; Nociceptors; Pacemaker, Artificial; Trigeminal Neuralgia; Voltage-Gated Sodium Channel Blockers

Lacosamide treats partial seizures by enhancing slow inactivation of voltage-gated sodium channels. The described cardiac toxicity of lacosamide in the literature to date includes atrioventricular blockade (PR prolongation), atrial flutter, atrial fibrillation, sinus pauses, ventricular tachycardia and a single cardiac arrest. We report a second case of cardiac arrest following an intentional lacosamide overdose.. A 16 year-old female with a seizure disorder was found unresponsive in pulseless ventricular tachycardia after intentionally ingesting 4.5 g (76 mg/kg) lacosamide, 120 mg (2 mg/kg) cyclobenzaprine and an unknown amount of levetiracetam. Exact time of ingestion was unknown. Her initial electrocardiogram (ECG) demonstrated sinus tachycardia at 139 beats per minute, QRS duration 112 ms, and terminal R-wave in lead aVR > 3 mm. Despite treatment with 150 mEq of sodium bicarbonate, she had persistent EKG findings eight hours after presentation. Her serum lacosamide concentration nine hours after presentation was elevated at 22.8 μg/mL, while serum cyclobenzaprine concentration was 16 ng/mL (therapeutic: 10-30 ng/mL), and serum levetiracetam concentration was 22.7 μg/mL (therapeutic: 12-46 μg/mL). On hospital day three, ECG demonstrated resolution of the terminal R-wave with QRS of 78 ms. The patient recovered without physical or neurologic sequelae.. The patient's lacosamide, cyclobenzaprine and levetiracetam overdose was associated with QRS prolongation and terminal right axis deviation--suggesting sodium channel blockade as a likely etiology for her cardiac arrest. Cyclobenzaprine has potential for sodium channel blockade and ventricular dysrhythmias although cardiac toxicity due to cyclobenzaprine alone is rare. The combination of cyclobenzaprine with lacosamide may have resulted in cardiovascular collapse. In conclusion, overdose of lacosamide combined with therapeutic concentrations of sodium channel blocking xenobiotics may cause cardiac conduction delays and cardiac arrest.

Topics: Acetamides; Adolescent; Amitriptyline; Anticonvulsants; Drug Interactions; Drug Overdose; Electrocardiography; Epilepsy; Female; Heart Arrest; Humans; Lacosamide; Levetiracetam; Piracetam; Risk Factors; Sodium Bicarbonate; Sodium Channel Blockers; Sodium Channels; Suicide, Attempted; Tachycardia, Ventricular; Treatment Outcome

Topics: Acetamides; Anticonvulsants; Cardiovascular System; Drug Overdose; Epilepsy; Fatal Outcome; Heart Arrest; Heart Conduction System; Humans; Hypertension; Lacosamide; Male; Middle Aged; Multiple Organ Failure; Suicide