Use Of Lacosamide Research Articles

Observational study of intravenous lacosamide in patients with convulsive versus non-convulsive status epilepticus.

Status epilepticus (SE) is an important emergency situation associated with high morbidity and mortality. The goal of pharmacological therapy-rapid seizure termination-is only achieved in just over half of patients with first-line anti-epileptic drug (AED) therapy and many patients require second and higher lines of AEDs to achieve seizure termination; therefore, there is a clear need for more effective treatment options. Lacosamide is a relatively new AED and the intravenous formulation has shown promise for treatment of SE. The aim of the current study was to compare electroencephalographic (EEG) response and seizure termination with intravenous lacosamide (±other AEDs) in patients with convulsive versus non-convulsive SE, in a Spanish intensive care setting. In this prospective, observational study, patients with convulsive or non-convulsive SE who received intravenous lacosamide 400 mg/day for 8 days were compared in terms of EEG response and seizure termination. Adverse events were not specifically assessed. Fifty-three patients (69.8 % male; mean age 55.2 years) were treated with lacosamide (mean dose 390.6 mg) as first- (20.8 %), second- (34 %), third (22.6 %) or fourth-line (22.6 %) treatment for convulsive (n = 23, 43.4 %) or non-convulsive (n = 30, 56.6 %) SE. The majority of patients (73.6 %) had a comorbid condition, predominantly hypertension (35.8 %), and most (79.2 %) received at least one concomitant AED, including midazolam (54.7 %), valproic acid (52.8 %), and levetiracetam (30.2 %). Patient characteristics and treatment received did not differ significantly between the convulsive and non-convulsive SE groups. EEG recordings following lacosamide treatment demonstrated the elimination of paroxysmal activity (disappearance and/or attenuation of epileptiform activity in >60 % of recording time) in 56.6 % of patients; 69.6 % of convulsive and 46.7 % of non-convulsive SE groups. Among all patients, 90.6 % showed some EEG improvement (disappearance of epileptiform activity in <30 % total recording time or disappearance and/or attenuation of epileptiform activity in 30-60 % total recording time); and there was no significant between-group difference for achievement of seizure termination (90.0 vs. 91.3 % for non-convulsive vs. convulsive SE). Intravenous lacosamide (±other AEDs) was similarly effective in patients with convulsive or non-convulsive SE. Further investigation into the use of lacosamide in the treatment of SE is warranted.

A case report of exacerbation of myoclonus in idiopathic generalized epilepsy from use of lacosamide (P7.038)

A case report of exacerbation of myoclonus in idiopathic generalized epilepsy from use of lacosamide (P7.038)

Lacosamide use in the treatment of refractory epilepsy in tuberous sclerosis complex

Lacosamide (LCS) was approved by the United States Food and Drug Administration (FDA) in 2008 as adjunctive therapy to other anti-epileptic drugs (AEDs) to treat focal-onset seizures, with or without secondary generalization. Its role in the treatment of epilepsy in individuals with tuberous sclerosis complex (TSC) has yet to be determined. This study evaluates LCS treatment of focal-onset refractory epilepsy in patients with TSC. From November 2009 to June 2014, 46 TSC patients followed by a single neurologist were treated with LCS. Forty-eight percent were responders (seizure reduction ≥50%). No significant differences between responders and non-responders in demographic characteristics were found. LCS appears to be an effective and safe treatment of refractory focal onset seizures in TSC. Determining the long-term tolerability and efficacy of LCS in TSC patients requires additional clinical experience.

P18.08 * A MULTICENTRIC, OBSERVATIONAL, NON INTERVENTIONAL STUDY OF EFFICACY AND SAFETY OF LACOSAMIDE FOR THE TREATMENT OF EPILEPTIC SEIZURES IN PATIENTS WITH BRAIN TUMORS

INTRODUCTION: Epileptic seizures are common in oncologic patients. Seizures could be the initial symptom of a brain tumor in 20-40% of the cases and 40% of the patients with brain tumors will have a seizure throught the diseqse. Management of these complications is crucial in the treatment of brain tumors. The ideal antiepileptic drug (AED) would be that one which could ensure a high and proved efficacy, wide security, low interactions, easy and quick to titrate and available in i.v. formulation. Until today there is a scarce number of publications on the use of lacosamide (LCM) in patients with btain tumors, although there is some experience in routine clinical practice that has previously shown a very promising profile of efficacy and safety. This study tries to compile some of these experiences in Spain. OBJECTIVES: To evaluate the efficacy of LCM in the management of seizures in patients with brain tumors. Secondary objectives were the evaluation of safety and tolerability of LCM . DESIGN: Multicentric, observational, non-interventional retrospective study. Patients who suffered at least 1 convulsive episode and at least treated with 1 dose of LCM were recruited. RESULTS: 37 patients with brain tumor suffering seizures were recruited in 6 centers all over the country, and 24 of them (64.9%) could be followed-up until the end of the study (after 6 months). Of these 37 patients, 26 (70%) were male, the age was 54.14 ± 14 years. 28 patients had one lesion and 9 had several lesions, 7 of them were metastatic. The average of total number of seizures from the onset of LCM treatment to the last visit performed shows a statistically significant change from the initiation of LCM treatment, showing a reduction of -16.8 ± 41'7 seizures. (p <000.1) The reason for withdrawing from the study was death by cancer in 7 of all the 37 initially included (53.85%), being a lack of LCM efficacy in 2 patients. A total of 12 more patients needed a LCM modification of treatment, 9 due to lack of efficacy, 3 due to adverse events. CONCLUSIONS: In a retrospective, non-interventional study with brain tumor patients, LCM has shown to be effective and safe in the management of seizures in neurooncological patients.

Factors influencing response to intravenous lacosamide in emergency situations: LACO-IV study

Status epilepticus (SE) and acute repetitive seizures (ARSs) frequently result in emergency visits. Wide variations in response are seen with standard antiepileptic drugs (AEDs). Oral and intravenous (IV) formulations of lacosamide are approved as adjunctive therapy in the treatment of partial-onset seizures in adults and adolescents. The aim of the retrospective multicenter observational study (LACO-IV) was to analyze data from a large cohort of patients with SE or ARSs of varying severity and etiology, who received IV lacosamide in the emergency setting. Patient clinical data were entered into a database; lacosamide use and efficacy and tolerability variables were analyzed. In SE, IV lacosamide tended to be used mainly in nonconvulsive status epilepticus as second- or third-line treatment. The proportion of patients with no seizures when IV lacosamide was the last drug administered was 76.5% (70.9% SE and 83.7% ARSs). The rate of seizure cessation ≤24h after IV lacosamide administration was 57.1% (49.1% SE and 67.4% ARSs). Of the factors analyzed, a shorter latency from seizure onset to IV lacosamide infusion influenced treatment response significantly. A nonsignificant tendency towards a higher response was seen with lacosamide dose >200mg versus ≤200mg. Analysis of response according to mechanism of action showed no significant differences in response to IV lacosamide in patients receiving prior sodium channel blocker (SCB) or non-SCB AEDs in the overall or SE population; however, in ARSs, a tendency towards a higher response was observed in those receiving non-SCB AEDs. The frequency and nature of adverse events observed were in line with those reported in other studies (somnolence being the most frequent). In the absence of randomized prospective controlled studies of IV lacosamide, our observations suggest that IV lacosamide may be a potential alternative for treatment of SE/ARSs when seizures fail to improve with standard AEDs or when AEDs are contraindicated or not recommended.

Update On the Use of Lacosamide in the Treatment of Partial-Onset Seizures

ABSTRAT: Lacosamide has a novel mechanism of action, namely selective enhancement of slow inactivation of voltage-gated sodium channels. Trial data and clinical experience indicate that it is effective in the treatment of partial-onset seizures, and that it is well tolerated. Pivotal early clinical trials demonstrated median percent reductions in seizure frequency ranging from 26 to 35.3% in the 200 mg/day, from 36.4 to 39% in the 400 mg/day, and from 37.8 to 40% in the 600 mg/day treatment groups. Dose-related adverse events were similar in the early clinical trials, and were mainly CNS complaints including dizziness, nausea, vomiting, fatigue, ataxia, abnormal vision, diplopia and nystagmus. Because of the dose-dependent adverse events and lack of additional efficacy at the 600 mg/day daily dose, lacosamide has been approved as an adjunctive treatment at recommended daily doses of 200–400 mg/day.

Lacosamide: A Review of Its Use as Adjunctive Therapy in the Management of Partial-Onset Seizures

Lacosamide (Vimpat(®)) is a functionalized amino acid available orally (as a syrup or tablet) and as an intravenous infusion. It is believed to exert its antiepileptic effect by selectively enhancing the slow inactivation of voltage-gated sodium channels. Lacosamide is approved in several countries worldwide as an adjunctive therapy for the treatment of partial-onset seizures; however, prescribing regulations differ between countries. This article reviews the use of lacosamide as indicated in adults and adolescents (aged 16-18 years) in the EU, where it is approved in this patient population as an adjunctive therapy to other AEDs in the treatment of partial-onset seizures, with or without secondary generalization. In three randomized, double-blind, placebo-controlled, multicentre studies in adults and adolescents (aged 16-18 years) with partial-onset seizures, adjunctive therapy with oral lacosamide (administered for an initial titration period followed by 12 weeks' maintenance therapy) generally reduced the frequency of seizures to a significantly greater extent than placebo, with antiepileptic efficacy sustained following longer-term treatment (up to 8 years) in this patient population. Oral and intravenous lacosamide were generally well tolerated in clinical studies, with the majority of adverse events being mild or moderate in severity. Very common adverse reactions following adjunctive therapy with oral lacosamide included diplopia, dizziness, headache and nausea; the tolerability profile of intravenous lacosamide appeared consistent with that of oral lacosamide, although intravenous administration was associated with local adverse events, such as injection site discomfort or pain, irritation and erythema. Thus, oral and intravenous lacosamide as an adjunctive therapy to other AEDs provides a useful option in the treatment of patients with partial-onset seizures.

Development of lacosamide for the treatment of partial-onset seizures.

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.

Lacosamide Use in Institutionalized Mentally Retarded and Refractory Epileptic Patients (P01.041)

Lacosamide Use in Institutionalized Mentally Retarded and Refractory Epileptic Patients (P01.041)

Sinus node dysfunction: An adverse effect of lacosamide

Lacosamide, a recently introduced antiepileptic drug, acts by enhancing the slow inactivation of voltage-dependent sodium channels. Cardiac conduction disturbances, namely atrial fibrillation and atrioventricular block, have been reported in patients with epilepsy. We report a patient with drug-resistant focal epilepsy who developed asymptomatic sinus node dysfunction following lacosamide use, which resolved on stopping lacosamide. This is the first report of sinus node dysfunction associated with lacosamide therapy.

Profile of lacosamide and its role in the long-term treatment of epilepsy: a perspective from the updated NICE guideline

AimThe goal of antiepileptic treatment is to achieve seizure freedom or seizure control. The aim of this paper is to review the evidence for the use of lacosamide for adjunctive treatment of refractory focal seizures with or without secondary generalization, within the scope of the 2012 update of the Clinical Guideline published by the National Institute for Health and Clinical Excellence (NICE).MethodsClinical evidence for the use of lacosamide and other antiepileptic drugs (AEDs) was systematically reviewed, evaluated, and presented to the Guideline Development Group. Only randomized clinical trials were included. Outcomes of clinical efficacy (seizure freedom, 50% reduction in seizure frequency, time to first seizure, time to 12-month remission, treatment withdrawal, and time to treatment withdrawal), experience of adverse events, and cognitive and quality of life outcomes were reviewed. A decision model was built to weigh the clinical benefits of each adjunctive AED, measured by seizure control and seizure reduction, compared with the harm from adverse events, as measured by withdrawals from treatment due to adverse events.ResultsLacosamide was included as part of the recommended AEDS to be used in tertiary epilepsy centers. The evidence review showed that more participants who received lacosamide as an adjunctive treatment had at least a 50% reduction in seizure frequency compared with those taking placebo. However, more participants on lacosamide were found to experience adverse events and withdrawal from treatment compared with those on placebo. The cost-effectiveness analysis showed that compared with placebo, the benefits gained from adjunctive lacosamide were modest and uncertain, whereas the costs were significantly high. Compared with other AEDs licensed for adjunctive therapy in focal seizures, lacosamide was associated with fewer quality-adjusted life years and higher costs. Therefore, the Guideline Development Group noted that the balance of benefit and harm needs to be carefully monitored in all patients.

Use of Lacosamide in Children with Refractory Epilepsy

Lacosamide was approved by the US Food and Drug Administration in 2008 for adjunctive therapy for focal onset seizures in patients 17 years of age and older. The efficacy of this agent in adults has led clinicians to consider lacosamide for children with refractory seizures. The MEDLINE database (1950-June 2012) was searched for abstracts containing lacosamide as the key term. Additional references were obtained from the manufacturer and the bibliographies of the articles reviewed. All available English-language case reports and clinical trials were included in the evaluation. Several case series studies have been published which support the use of lacosamide in children with refractory seizures. In the papers published to date, 30% to 50% of children experienced at least a 50% reduction in seizure frequency, similar to results obtained in clinical trials in adults. Children with focal onset seizures were most likely to benefit from treatment, while results in children with generalized seizures or multiple seizure types were mixed. Adverse effects in children were similar to those seen in adults, with dizziness, headache, and nausea occurring most frequently. Lack of efficacy has been the most common cause of discontinuation. Lacosamide appears to be a useful adjunct therapy in children with refractory seizures. Clinical trials are under way that may provide more definitive information on the efficacy and safety of lacosamide in children and allow clinicians to determine the appropriate place of this antiseizure drug in pediatric epilepsy management.

Ventricular tachycardia associated with lacosamide co-medication in drug-resistant epilepsy.

We report a case of sustained ventricular tachycardia following the initiation of lacosamide as adjunctive epilepsy treatment. A 49-year-old male with intractable frontal lobe seizures experienced severe ventricular tachycardia following the addition of 400 mg lacosamide to his existing regimen of carbamazepine, lamotrigine, clonazepam, and valproate. The tachycardia occurred during a cardiac stress test; stress tests prior to initiation of lacosamide were normal. Conduction defects, including QRS prolongation, persisted during hospitalization until lacosamide was discontinued. The patient had no prior history of cardiac arrhythmia but did possess cardiac risk factors, including hypertension, hypercholesterolemia, and low heart rate variability. This case represents one part of a growing body of literature suggesting a link between arrhythmia and use of lacosamide, which enhances slow inactivation of sodium channels in both the brain and the heart. We believe further study may be necessary to assess the safety of lacosamide in epilepsy patients with cardiac risk factors.

Erfahrungen mit Levetiracetam in der Behandlung des Status epilepticus

Non-convulsive status epilepticus and epilepsia partialis continua are common epileptic conditions for which straightforward recommendations based on controlled randomised trials for treatment of therapy refractory courses are lacking. Therefore in these conditions sometimes antiepileptic drugs that are not approved by governmental authorities for the treatment of status epilepticus (SE) are used. Here we review all case reports and case series concerning the treatment of SE with levetiracetam (LEV), that had been listed in pub-med up to December 12th 2011. Additionally we analysed abstracts and papers in peer reviewed journals, that were listed in the references of the primarily reviewed papers. Furthermore we looked for LEV treatments in papers on the use of lacosamide (LCM) in SE. LEV was given in dosages ranging from 500 mg to 9000 mg per day. Side effects were especially sedation and irritability. Estimated on the basis of the case series the overall success-rate of LEV in terminating status epilepticus may be set in a range between 53.7% and 58.1%. Therefore LEV may be a useful alternative for the treatment of SE when the approved drugs are contraindicated or when these drugs have been taken without success.

Lacosamide for the Treatment of Refractory Status Epilepticus

To evaluate current evidence for the use of lacosamide in the treatment of refractory status epilepticus. Literature was accessed via PubMed (through July 2011) using the terms lacosamide and status epilepticus. All reports on the use of lacosamide in patients with status epilepticus were included for evaluation. Reviews and animal data were excluded. Treatment of status epilepticus is challenging, and most patients fail to respond to initial treatment. Recently, several reports have been published on the use of lacosamide for status epilepticus. Eleven reports (5 case reports and 6 case series) were identified. Lacosamide was credited with successful termination of status epilepticus in a majority of these reports. However, the data are weakened by the heterogeneity of the reports, their descriptive nature, and the common divergence from current recommendations for the treatment of status epilepticus. While lacosamide has been reported as an effective treatment for refractory status epilepticus, there is insufficient evidence for its routine use. For cases in which the risks associated with anesthetizing drugs are believed to outweigh the benefits, such as in complex partial status epilepticus, lacosamide may be a reasonable option after more established drug therapies fail.

Experience With Lacosamide in a Series of Children With Drug-Resistant Focal Epilepsy

We report our pediatric experience with lacosamide, a new antiepileptic drug, approved by the US Food and Drug Administration as adjunctive therapy in focal epilepsy in patients more than 17 years old. We retrospectively reviewed charts for lacosamide use and seizure frequency outcome in patients with focal epilepsy (Wilcoxon signed rank test). Sixteen patients (7 boys) were identified (median dose 275 mg daily, 4.7 mg/kg daily; mean age 14.9 years, range 8-21 years). Patients were receiving a median of 2 antiepileptic drugs (interquartile range [IQR] 1.7-3) in addition to having undergone previous epilepsy surgery (n=3), vagus nerve stimulation (n=9), and ketogenic diet (n=3). Causes included structural (encephalomalacia and diffuse encephalitis, 1 each; stroke in 2) and genetic abnormalities (Aarskog and Rett syndromes, 1 each) or cause not known (n=10). Median seizure frequency at baseline was 57 per month (IQR 7-75), and after a median follow-up of 4 months (range 1-13 months) of receiving lacosamide, it was 12.5 per month (IQR 3-75), (P<0.01). Six patients (37.5%; 3 seizure free) were classified as having disease that responded to therapy (≥50% reduction seizure frequency) and 10 as having disease that did not respond to therapy (<50% in 3; increase in 1; unchanged in 6). Adverse events (tics, behavioral disturbance, seizure worsening, and depression with suicidal ideation in 1 patient each) prompted lacosamide discontinuation in 4/16 (25%). This retrospective study of 16 children with drug-resistant focal epilepsy demonstrated good response to adjunctive lacosamide therapy (median seizure reduction of 39.6%; 37.5% with ≥50% seizure reduction) without severe adverse events.

The Use of Lacosamide in Refractory Status Epilepticus

Case reports suggest lacosamide may have a role in status epilepticus (SE). The purpose of this case series is to describe the use of lacosamide in refractory SE (RSE) at our institution. Observational study of all patients admitted to the neurosciences intensive care unit with RSE who received at least one dose of lacosamide from October 2009 to September 2010. Nine patients received lacosamide after failure of at least two other agents. Lacosamide was started a median of 2 days (range: 0-14 days) after the onset of SE. The most frequently used dosing regimen was an initial intravenous dose of 200 mg followed by 200 mg every 12 h. Most patients had received 3 (range: 2-5) AEDs prior to lacosamide. Levetiracetam was used prior to lacosamide in all cases. No patients evaluated responded to lacosamide according to our predefined criteria. One patient developed angioedema after receiving two doses; another patient developed angioedema where timing in relation to the lacosamide was unclear. Care was withdrawn in three of the nine patients for reasons unrelated to lacosamide. Lacosamide was continued at discharge on all surviving patients except in one case of angioedema. This is the largest case series to date describing the use of lacosamide in patients with RSE. Despite the novel mechanism of action, we observed no evidence that lacosamide is effective in RSE; however, our sample size was small. Further study is needed to determine the role of lacosamide in SE, especially early in the treatment course.

Lacosamide and Epilepsy

We will review all available studies on the use of lacosamide in the treatment of partial-onset seizures. The available evidence includes two open-label studies and three randomized controlled trials evaluating the safety and efficacy of oral lacosamide. One open-label study and one randomized controlled trial evaluating the safety and tolerability of intravenous lacosamide was also identified. Lacosamide was found to be efficacious with significant reduction in seizure frequency dosed 400-600 mg daily. Moreover, its adverse drug effects were mild and infrequently reported in the literature. Findings suggest that lacosamide is an effective agent for adjunctive treatment of refractory partial-onset seizures.

Lacosamide for pain

Importance of the field: Neuropathic pain remains a condition that is difficult to treat and with which therapeutic failure is not uncommon. The need for new and effective drugs to treat neuropathic pain remains strong.Areas covered in this review: The available preclinical and clinical data for the pain relieving effect of lacosamide have been examined using the papers published and referenced on Medline between 1990 and present.What the reader will gain: It is hoped that readers will gain an insight into the use of this novel analgesic agent in human clinical pain.Take home message: The data relating to the pain relieving effect of lacosamide are sparse. The majority of the published human data relate to the use of lacosamide for the treatment of painful diabetic neuropathy where the extent of pain relief produced has not been deemed sufficient to warrant an application for a product license for this indication. That said, it is suggested that there remains merit in further investigation of this drug for other neuropathic pain conditions.

Lacosamide: An Adjunctive Agent for Partial-Onset Seizures and Potential Therapy for Neuropathic Pain

To review the pharmacology, pharmacokinetics, efficacy, and safety of lacosamide, a new agent for use as adjunctive treatment in partial-onset seizures and a potential agent for treatment of neuropathic pain. A MEDLINE search (1966-July 2009) was conducted using the key words lacosamide, harkoseride, SPM-927, ADD-234037, epilepsy, anticonvulsant, and neuropathic pain. Bibliographies of all articles retrieved were also reviewed. All studies including humans and published in English with data describing lacosamide for the adjunctive treatment of partial-onset seizures and for treatment of neuropathic pain were reviewed. Lacosamide is a functionalized amino acid molecule that selectively enhances the slow inactivation of voltage-gated sodium channels and interacts with the collapsin-response mediator protein-2. With its bioavailability of approximately 100%, minimal protein binding, and few drug-drug interactions, lacosamide has a favorable pharmacokinetic profile. Recent data suggest that lacosamide may have a role as adjunctive treatment of partial-onset seizures. Open-label studies showed a 14-47% reduction in seizure frequency, while placebo-controlled trials demonstrated a 26-40% reduction in seizure frequency. The 50% responder rates ranged from 32.7% to 41.2% with varying doses of lacosamide. Although lacosamide use is not approved by the Food and Drug Administration for treatment of neuropathic pain, studies demonstrated reductions of 2.01-3.60 in pain scale scores. The most common adverse effects, occurring in greater than 10% of subjects in the clinical trials, include arthralgia, ataxia, blurred vision, diplopia, dizziness, fatigue, headache, injection site pain (only in intravenous studies), nausea, tremor, upper respiratory tract infection, and vomiting. Lacosamide is an effective agent for adjunctive treatment of refractory partial-onset seizures. Its exact role in the treatment of neuropathic pain needs to be determined.