Abstracts

Rationale: Lacosamide (LCM) is a novel anti-epileptic drug that enhances slow inactivation of voltage-gated sodium channels. In clinical trials in diabetic peripheral neuropathy, LCM was associated with cardiac conduction defects (AV block) in 0.5% and atrial fibrillation in 0.5%. In clinical trials in epilepsy, conduction defects (AV block) occurred in 0.4%; atrial fibrillation has not been reported. We report two cases of serious cardiac arrhythmias possibly associated with LCM treatment for partial seizures. Methods: Case Series: Two patients at the UCLA Seizure Disorders Center who sustained severe cardiac arrhythmias (acute atrial fibrillation and acute sustained ventricular tachycardia) during LCM treatment were identified. Hospital and clinic records, cardiology consultations, electrocardiograms (ECG) and electrophysiological studies were evaluated. Results: Case I. A 37 year-old female with intractable partial seizures and no cardiac risk factors was initiated on LCM as adjunctive therapy. While on LCM 600 mg/day and Lamotrigine 300 mg/day, the patient experienced sudden onset of rapid heartbeat, palpitations, and lightheadedness. Upon hospitalization, an ECG detected atrial flutter/atrial fibrillation with a rapid rate of 136 bpm. Warfarin and a calcium channel blocker were initiated. Her dosage of LCM was reduced to 400 mg/day, but on reevaluation three weeks later, atrial fibrillation persisted. A decision was made to taper and discontinue LCM by 100 mg/week. An ECG one week after cessation of LCM showed complete resolution of atrial fibrillation/flutter. Atrial fibrillation has not recurred in the six months since discontinuation. Case II. A 49 year-old male with severe intractable frontal lobe seizures was initiated on LCM 400 mg/day as adjunctive therapy in addition to preexisting Carbamazepine, Lamotrigine, Clonazepam, and Valproate. The patient had no prior history of cardiac arrhythmias, but had well controlled hypertension and hypercholesterolemia, treated with atorvastatin, valsartan, and triamterene. A cardiac stress test prior to the addition of LCM demonstrated no abnormalities. While undergoing a repeat cardiac stress test, he experienced sustained ventricular tachycardia, which required acute stabilization and hospitalization. LCM was tapered by 100 mg/day until discontinued. Repeat electrophysiological study 24 hours after discontinuation of LCM was normal. An ECG loop monitor was implanted. There has been no recurrence of the arrhythmia at four months following discontinuation of LCM. Conclusions: Adjunctive treatment with LCM in two patients with intractable partial seizures was associated with severe cardiac arrhythmias. The onset of the arrhythmias while on LCM, followed by resolution after discontinuation of LCM, provides evidence of a possible link to LCM. Given evidence of arrhythmias in clinical trials in diabetes, and the possible association of LCM with arrhythmias in our patients, physicians should be alert to the potential for cardiac arrhythmias in patients with epilepsy treated with Lacosamide.