Add-on lacosamide: A retrospective study on the relationship between serum concentration, dosage, and adverse events

Hillenbrand, Barbara; Wisniewski, Ilona; Jürges, Uta; Steinhoff, Bernhard J.

doi:10.1016/j.yebeh.2011.08.032

Cited by 21 publications

(22 citation statements)

References 19 publications

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“…In a double‐blind trial with >200 patients the responder after 3 months (38.3%) of 400 mg orally administered LCM (Chung et al., 2010) was comparable with the results of our study (42.8%), supporting an overall clinical utility of de novo intravenous LCM application beyond acute efficacy and tolerability. AEs seemed to be more frequent in patients with a combination of LCM and classical sodium channel blockers (in our cases predominantly LTG) as shown in previous studies (Hillenbrand et al., 2011). Eleven (64.7%) of the 17 patients had sodium blockers as part of their comedication.…”

Section: Discussionsupporting

confidence: 87%

Rapid loading of intravenous lacosamide: Efficacy and practicability during presurgical video‐EEG monitoring

Stefan

Matzen

et al. 2012

Epilepsia

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SUMMARYPurpose: This study investigates immediate efficacy and safety of intravenous application of de novo lacosamide (LCM) as add-on therapy in patients with pharmacoresistant focal epilepsy. Methods: During presurgical video-electroencephalography (EEG) monitoring, 17 adult inpatients received LCM infusion (200 mg every 12 h for 2-3 days) followed by oral formulation with the same regimen. Before and after intravenous application of LCM, seizures and interictal epileptiform discharges (IEDs) recorded with continuous video-EEG monitoring were analyzed, and an assessment of adverse events (AEs) was performed daily. To evaluate the midterm tolerability and efficacy, follow-up visits were conducted 1 and 3 months after discharge from hospital.Key Findings: In the acute phase, intravenous initiation of LCM was well tolerated with few mild or moderate AEs (3 of 17, 17.6%). A significant reduction of seizure frequency in the treatment phase as compared to mean seizure frequency in the 2-day baseline phase was achieved (p < 0.05 for the first treatment day, and p < 0.005 for the second treatment day). On the first treatment day, 61.5% of the patients were seizure free, and 84.6% on the second treatment day. IED reduction after intravenous application of LCM was not significant. After 1 month, the 50% responder rate was 46.6% and after the 3-month period, 42.8%. Significance: Our data suggest that rapid intravenous initiation of de novo LCM is safe and may protect against seizures in a rapid and midterm time window.

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Section: Discussionsupporting

confidence: 87%

Rapid loading of intravenous lacosamide: Efficacy and practicability during presurgical video‐EEG monitoring

Stefan

Matzen

et al. 2012

Epilepsia

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“…Adverse effects were reported in 45% in those with ID and in 57% in those without ID. Such a tolerability profile is similar to another clinical study . There was a significant increased risk of withdrawal of LCM among those who used other sodium channel‐blocking AEDs.…”

Section: Discussionsupporting

confidence: 92%

“…Our findings indicate that serum concentrations of LCM below 10 µmol/L (ie, the lower limit of the reference range) result in poor efficacy. Some of these patients with low concentrations seemed to have relevant therapeutic daily dosages above 200 mg, which underlines the importance of using TDM when experiencing lack of efficacy . Concomitantly used AEDs contributed only moderately to variability between patients.…”

Section: Discussionmentioning

confidence: 96%

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Clinical experience combined with therapeutic drug monitoring of lacosamide

et al. 2020

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Objective Lacosamide (LCM) is an antiepileptic drug (AED) with insufficient clinical experience in patients with intellectual disability (ID). They often have more severe epilepsy with comorbidities. The objective was to evaluate the efficacy and tolerability of lacosamide (LCM) in patients with refractory epilepsy with and without ID in a real‐life setting, taking drug monitoring (TDM) data into account therapeutic. Methods Retrospectively, we identified 344 patients using LCM from the TDM service covering the majority of the country, at the National Center for Epilepsy in Norway (2013‐2018). Clinical and TDM data were available for 132 patients. Results Forty‐four of the 132 patients (33%) had ID. The retention rate was significantly higher in the ID vs the non‐ID group after 1 year (84% vs 68%, P < .05). By combining clinical and TDM data, we demonstrated that 37/38 responding patients had serum concentrations above the lower limit of the reference range (>10 µmol/L), and 16/17 with lower concentrations were non‐responders. Mean serum concentration/dose ratios were similar in both groups, 0.06 and 0.07 µmol/L/mg. There were no significant differences regarding efficacy and tolerability. The risk of LCM withdrawal was significantly higher when LCM was added to sodium channel blockers, even if the latter was discontinued. Significance Lacosamide was generally well tolerated in patients with drug‐resistant epilepsy, where one third had ID, and in these patients the retention rate was higher. The combination of clinical and TDM data could possibly facilitate LCM therapy in these vulnerable patients.

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“…Others have published small case series and retrospective studies also identifying potential differences in tolerability with lacosamide based on the mechanism of action of concomitant AEDs, though variation in how treatment groups were defined based on the mechanism of action complicates the ability to compare findings . Regardless, without properly controlled, prospective studies to directly address the potential for differential outcome with lacosamide in combination with individual AEDs, it is not possible to make definitive comparative statements on treatment combinations with lacosamide.…”

Section: Safety and Tolerability Of Lacosamidementioning

confidence: 99%

Development of lacosamide for the treatment of partial‐onset seizures

Doty

Hébert

Mathy

et al. 2013

Annals of the New York Academy of Sciences

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Lacosamide is an antiepileptic drug (AED) available in multiple formulations that was first approved in 2008 as adjunctive therapy for partial-onset seizures (POS) in adults. Unlike traditional sodium channel blockers affecting fast inactivation, lacosamide selectively enhances sodium channel slow inactivation. This mechanism of action results in stabilization of hyperexcitable neuronal membranes, inhibition of neuronal firing, and reduction in long-term channel availability without affecting physiological function. Lacosamide has a well-characterized and favorable pharmacokinetic profile, including a fast absorption rate, minimal or no interaction with cytochrome P-450 izoenzymes, and a low potential for drug–drug interactions. Lacosamide clinical development included three placebo-controlled, double-blind, randomized trials conducted in more than 1300 patients, each demonstrating safety and efficacy of lacosamide compared to placebo as adjunctive therapy for adults with POS. The clinical use of lacosamide may broaden, pending results of trials evaluating its use as monotherapy for POS in adults, as treatment for epilepsy in pediatric subjects, and as adjunctive treatment for uncontrolled primary generalized tonic–clonic seizures in those with idiopathic generalized epilepsy.

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Add-on lacosamide: A retrospective study on the relationship between serum concentration, dosage, and adverse events

Cited by 21 publications

References 19 publications

Rapid loading of intravenous lacosamide: Efficacy and practicability during presurgical video‐EEG monitoring

Rapid loading of intravenous lacosamide: Efficacy and practicability during presurgical video‐EEG monitoring

Clinical experience combined with therapeutic drug monitoring of lacosamide

Development of lacosamide for the treatment of partial‐onset seizures

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