Safety and Tolerability of Intravenous Push Lacosamide and Levetiracetam

Abstract

Background Lacosamide and levetiracetam are antiseizure medications (ASMs) commonly utilized in the treatment and prevention of seizures. Historically, these agents have been administered as slow IV infusions after further dilution. Recent literature suggests that rapid administration via undiluted IV push may be safe and may increase efficiency of administration. Objective This study aimed to evaluate the safety and tolerability of undiluted IV push lacosamide and levetiracetam over 5 min. Methods This study was conducted as a single-centered, retrospective, observational cohort that analyzed the rapid administration of undiluted lacosamide and levetiracetam. Adult patients admitted from September 1st, 2019, to May 31st, 2020, receiving at least one administration of IV push lacosamide at any dose or levetiracetam at doses ≤ 1500 mg were evaluated. The primary safety outcomes were the incidence of hypotension and bradycardia. Results A total of 86 subjects were evaluated; 36 patients were administered lacosamide, and 50 patients were administered levetiracetam. Hypotension or bradycardia occurred in 6 patients in the lacosamide group (16.6%) and 6 patients in the levetiracetam group (12.0%). There were no reported infusion site reactions. Among the subjects who received lacosamide and had a 12-lead electrocardiogram (EKG), there were no reported incidences of a prolonged PR interval. Conclusions In this safety-analysis cohort, undiluted lacosamide and levetiracetam were not associated with significant adverse events when administered via IV push over 5 min. This seems to be a safe alternative method of administration to intermittent infusion. A larger, prospective cohort is needed to confirm these findings.

Risk assessment of arrhythmias related to three antiseizure medications: a systematic review and single-arm meta-analysis

“…LEV binds to the unique synaptic vesicle protein 2A (SV2A) to decrease the rate of vesicular release, thereby reducing the release of the neurotransmitter GABA ( 51 ). A study on the safety of LCM and LEV reported that LCM was more likely to induce arrhythmias than LEV ( 52 ), which was consistent with our conclusion that LEV was safer than LCM for arrhythmia treatment. LEV was the first choice for adjunctive treatment of refractory epilepsy.…”

Safety Profile of High-Dose Intravenous Push Lacosamide

“…Even with this consideration, adverse effect rates observed in our cohort were comparable to those studies primarily consisting of doses of 200 mg or less. 3,4,13 In patients with an EKG measured, we did not observe a meaningful increase in the PR interval (1 msec from baseline). Notably, in a large study assessing the cardiac effects of LCM, patients who developed prolonged PR intervals were continued on the medication and had no evident symptomatic consequence.…”

“…12 When comparing our adverse event findings to previous literature, we found similar outcomes regarding safety (Table 3). 3,4,13 An important consideration is that patients receiving high-dose IVP LCM were marginally represented in the literature, with doses greater than 200 mg administered in approximately 0.7% to 17.6% of the study populations. Even with this consideration, adverse effect rates observed in our cohort were comparable to those studies primarily consisting of doses of 200 mg or less.…”

Effective Modulation by Lacosamide on Cumulative Inhibition of INa during High-Frequency Stimulation and Recovery of INa Block during Conditioning Pulse Train

“…It is commonly administrated in patients with epilepsy and occasionally in patients with trigeminal neuralgia or other neuropathic pain [ 1 , 5 , 7 , 8 , 9 , 10 , 11 , 12 ]. A growing body of evidence demonstrated the effectiveness and tolerability of LCS in patients with epilepsy [ 13 , 14 , 15 , 16 , 17 , 18 , 19 ]. Earlier reports have shown that this compound can decrease the frequency of interictal spikes as well as high-frequency oscillations in mesial temporal lobe epilepsy or refractory focal epilepsy [ 13 , 20 ].…”