Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures

Rudd, G. David; Haverkamp, Wilhelm; Mason, Jay W.; Wenger, T.; Jay, Gene T.; Hébert, David; Doty, Pamela; Horstmann, Rolf D.

doi:10.1111/ane.12414

Cited by 38 publications

(24 citation statements)

References 28 publications

(30 reference statements)

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“…The safety of lacosamide is further supported by a comprehensive analysis of the cardiac safety data pooled from 1304 patients who took part in the registration trials for lacosamide in the treatment of POS. This analysis showed no specific cardiac risks, aside from the small, dose-related increase in PR interval, with no evident symptomatic consequence [19]. Furthermore, a positively controlled QTc trial in healthy volunteers showed no detrimental effect associated with lacosamide use at approved dosages [20].…”

Section: Discussionmentioning

confidence: 75%

“…Cardiac conduction side effects are associated with the use of several AEDs, particularly those that block sodium channels [14][15][16][17]. A small dose-related increase in the PR interval has been observed in trials of oral and intravenous lacosamide, with no significant change in blood pressure or QTc interval [11][12][13][18][19][20]. There have also been some published reports of cardiac AEs in patients receiving lacosamide [9,18,[21][22][23][24][25][26][27][28].…”

Section: Introductionmentioning

confidence: 99%

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A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures

Steinhoff

Eckhardt

Doty

et al. 2016

Epilepsy & Behavior

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This noninterventional, observational, postauthorization safety study (SP0942, NCT00771927) evaluated the incidence of predefined cardiovascular- (CV) and psychiatric-related treatment-emergent adverse events (TEAEs), in patients with epilepsy and uncontrolled partial-onset seizures, when initiating adjunctive therapy with lacosamide or another approved antiepileptic drug (AED) according to standard medical practice. Active recording of predefined TEAEs of interest took place at three-monthly recommended visits for up to 12months. Of 1004 patients who received at least one dose of adjunctive AEDs, 511 initially added lacosamide therapy, 493 added another AED, 69 were ≥65years of age, and 72 took concomitant antiarrhythmic drugs. Patients in the lacosamide cohort had a higher median frequency of partial-onset seizures (6.0 versus 3.5 per 28days) despite taking more concomitant AEDs (84.9% versus 66.9% took ≥2) at baseline. Patients who added lacosamide took a modal dose of 200mg/day over the treatment period (n=501), and 50.1% (256/511) completed 12months of treatment. Fifty-one point nine percent (256/493) of patients who added another AED completed the study, with the most commonly added AED being levetiracetam (28.4%). Four patients (0.8%) in each cohort, all <65years of age, reported predefined CV-related TEAEs. None were considered serious or led to discontinuation. One event each of sinus bradycardia (lacosamide), atrioventricular block first degree (lacosamide), and syncope (other AED) were judged to be treatment-related. Another patient in the other AED cohort reported bradycardia while taking concomitant antiarrhythmic drugs. Predefined psychiatric-related TEAEs were reported by 21 patients (4.1%) in the lacosamide cohort and 27 patients (5.5%) in the other AED cohort. Depression was the most common to be treatment-related (7/11 and 12/18 of patients reporting treatment-related psychiatric TEAEs, respectively). Serious psychiatric-related TEAEs were reported by four patients who added lacosamide (two cases of depression, two of suicide attempt) and one who added another AED (depression). Seven deaths occurred, all of which were considered unrelated/unlikely related to study medication. This thorough evaluation revealed a low incidence of predefined CV- and psychiatric-related TEAEs in patients taking adjunctive AED therapy according to standard medical practice. No specific safety concerns related to adjunctive lacosamide therapy were noted.

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Section: Discussionmentioning

confidence: 75%

Section: Introductionmentioning

confidence: 99%

A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures

Steinhoff

Eckhardt

Doty

et al. 2016

Epilepsy & Behavior

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“…A total of three cardiac TEAEs were reported during lacosamide treatment in patients with CVEE. Analyses of pooled cardiac safety data from three randomized, placebo‐controlled trials of adjunctive lacosamide in patients with focal seizures showed no clear cardiac effects at the maximum recommended dose (400 mg/day) other than a small dose‐related increase in PR interval . Lacosamide should be used with caution in patients with underlying proarrhythmic conditions (known cardiac conduction problems, severe cardiac disease, and cardiac sodium channelopathies), as well as in patients taking concomitant medications that affect cardiac conduction or prolong the PR interval…”

Section: Discussionmentioning

confidence: 99%

Lacosamide in patients with epilepsy of cerebrovascular etiology

et al. 2020

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Objectives:To assess tolerability and efficacy of lacosamide in adults with cerebrovascular epilepsy etiology (CVEE). Materials and methods:Exploratory post hoc analyses of a double-blind, initial monotherapy trial of lacosamide vs carbamazepine-controlled release (carbamazepine-CR) (SP0993; NCT01243177); a double-blind conversion to lacosamide monotherapy trial (SP0902; NCT00520741); and an observational study of adjunctive lacosamide added to one antiepileptic drug (SP0973 VITOBA; NCT01098162). Patients with CVEE were identified based on epilepsy etiology recorded at baseline. Results: In the initial monotherapy trial, 61 patients had CVEE (lacosamide: 27; carbamazepine-CR: 34). 20 (74.1%) patients on lacosamide (27 [79.4%] on carbamazepine-CR) reported treatment-emergent adverse events (TEAEs), most commonly (≥10%) headache, dizziness, and fatigue (carbamazepine-CR: headache, dizziness). A numerically higher proportion of patients on lacosamide than carbamazepine-CR completed 6 months (22 [81.5%]; 20 [58.8%]) and 12 months (18 [66.7%]; 17 [50.0%]) treatment without seizure at last evaluated dose. In the conversion to monotherapy trial, 26/30 (86.7%) patients with CVEE reported TEAEs, most commonly (≥4 patients) dizziness, convulsion, fatigue, headache, somnolence, and cognitive disorder. During lacosamide monotherapy, 17 (56.7%) patients were 50% responders and six (20.0%) were seizure-free. In the observational study, 36/83 (43.4%) patients with CVEE reported TEAEs, most commonly (≥5%) fatigue and dizziness. Effectiveness was assessed for 75 patients. During the last 3 months, 60 (80%) were 50% responders and 42 (56.0%)were seizure-free. Conclusions:These exploratory post hoc analyses suggested lacosamide was generally well tolerated and effective in patients with CVEE, with data from the initial monotherapy trial suggesting numerically better efficacy than carbamazepine-CR. K E Y W O R D Santiepileptic drugs, elderly, epilepsy, lacosamide, seizures, stroke

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“…Cardiac safety issues were analyzed in a pooled analysis that showed a dose‐dependent prolongation of PR interval from baseline to the end‐of‐maintenance from 1.4 msec (LCM 200 mg/day), 4.4 msec (LCM 400 mg/day), to 6.6 msec (LCM 600 mg/day). The frequency of first‐degree AV block differed between 1.1% and 4.9% on LCM compared to placebo with 2.4–3.2%.…”

Section: Special Considerations In Populations With Renal Hepatic Omentioning

confidence: 99%

Lacosamide in status epilepticus: Systematic review of current evidence

et al. 2017

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Lacosamide cardiac safety: clinical trials in patients with partial-onset seizures

Cited by 38 publications

References 28 publications

A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures

A long-term noninterventional safety study of adjunctive lacosamide therapy in patients with epilepsy and uncontrolled partial-onset seizures

Lacosamide in patients with epilepsy of cerebrovascular etiology

Lacosamide in status epilepticus: Systematic review of current evidence

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