Adjunctive lacosamide treatment for adult focal-onset epilepsy: focus on comorbid intellectual/developmental disorders and differing responses (original) (raw)
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Epilepsia Open, 2021
The primary objective of this trial (SP1042; NCT02582866) was to assess long‐term safety and tolerability of lacosamide monotherapy (200‐600 mg/day) in adults with focal (partial‐onset) seizures or generalized tonic‐clonic seizures (without clear focal origin). This Phase III, long‐term, open‐label, multicenter, follow‐up trial enrolled patients with epilepsy who were taking lacosamide in, and completed, the previous double‐blind trial (SP0994; NCT01465997). Primary safety outcomes were treatment‐emergent adverse events (TEAEs), discontinuations due to TEAEs, and serious TEAEs. One hundred and six patients were enrolled and received lacosamide: 84 (79.2%) completed the trial and 22 (20.8%) discontinued. The median duration of exposure was 854.0 days, with a median modal dose of 200 mg/day. Ninety‐six (90.6%), 64 (60.4%), and 44 (41.5%) patients had ≥12, ≥24, and ≥36 months of lacosamide exposure, respectively. At least one TEAE was reported by 61 (57.5%) patients. The most common (≥...
Epilepsy & Behavior, 2009
We report our 6 months of experience with adjunctive lacosamide in 25 patients with pharmacoresistant focal epilepsy. Baseline characteristics of our patients were similar to those of the populations in the three clinical trials that evaluated lacosamide for refractory focal epilepsy. One patient experienced sustained seizure freedom for 5 months; two more patients had nonsustained periods of seizure freedom of 1 and 4 months. A total of eight patients (32%) reported a greater than 50% reduction in seizure frequency. Thirteen patients (52%) reported side effects during the titration, mostly dizziness, fatigue, nausea, and gait instability. In five patients (20%), these disappeared during the maintenance phase and/or with dose reduction. Two patients lost more than 10% of their body weight. Otherwise, in terms of efficacy and adverse effects, our data mirror the profile of lacosamide described in the three clinical trials. Substantial weight loss may occur in individual patients.
Pediatric Neurology, 2014
BACKGROUND: A unicentre, prospective study was performed to investigate the efficacy of lacosamide as adjunctive therapy in children with refractory partial epilepsy. METHODS: The study was performed at a tertiary care hospital over a period of 30 months between November 2011 and May 2014. Seventy-nine children with refractory partial epilepsy (age 5-15 years) who had failed two or more antiepileptic drugs and in whom lacosamide was used as an add-on drug were enrolled. Lacosamide tablets were administered orally, at a dose of 25 mg for 1 week followed by 50 mg twice daily for the remaining period. Efficacy and tolerability evaluation was performed at every visit of titration, maintenance period (3 months), and two follow-up visits at monthly interval. Electrocardiogram and liver function tests were performed before enrollment and at the end of 3 months of lacosamide therapy. Patient's caregiver or investigator observed adverse events were recorded in a predesigned pro forma. RESULTS: A total of 79 patients with uncontrolled partial epilepsy screened from 531 epileptic children were enrolled, after they satisfied the inclusion and exclusion criteria. The mean age of children enrolled was 8.8 AE 3.1 years (range 5-15 years); 53 children (67.0%) were boys. Mean weight of the patients was 24.2 AE 9.8 kg. The mean age at the onset of seizures was 6.4 AE 3.5 years. The mean dose of lacosamide administered was 4.1 mg/kg. Three patients (3.8%) dropped out of the study, because of vomiting, aggressive behavior, and poor response, respectively. Of 76 patients (96.2%) entering the maintenance period, 35 patients (44.3%) were seizure free, 32 patients (40.6%) indicated !50% reduction in seizure frequency, 3 patients (3.8%) indicated 25-49% seizure reduction, and 9 patients (11.4%) either had no change in seizure frequency or experience increase in seizure frequency. CONCLUSION: Lacosamide is an effective add-on antiepileptic drug for children with refractory partial epilepsy and is well tolerated.
2014
Background: A unicentre, prospective study was carried out to investigate the efficacy of lacosamide as adjunctive therapy in children with refractory partial epilepsy. Methods: The study was carried out at tertiary care hospital over a period of 30 months between November 2011 and May 2014. Seventy nine children with refractory partial epilepsy (age: 5-15 years) who had failed ≥ 2 antiepileptic drugs and in whom lacosamide was used as add-on drug were enrolled. Lacosamide tablets were given orally, at a dose of 25mg for one week followed by 50mg twice daily for the remaining period. Efficacy and tolerability evaluation was performed at every visit of titration, maintenance period (3 months) and at 2 follow-up visits at monthly interval. Electrocardiogram (ECG) and liver function tests were done before enrollment and at the end of 3 months of lacosamide therapy. Patient's caregiver or investigator observed adverse events were recorded in a predesigned proforma. Results: A total of 79 patients with uncontrolled partial epilepsy screened from 531 epileptic children were enrolled, after they satisfied the inclusion and exclusion criteria. The mean age of children enrolled was 8.84±3.09 years (range: 5-15 years); 53 (67%) children were males. Mean weight of the subjects was 24.22±9.84 kg. The mean age at the onset of seizures was 6.43±3.49 years. The mean dose of lacosamide given was 4.1mg/kg. Three patients (3.79%) dropped out of the study, because of vomiting, aggressive behavior and poor response respectively. Out of 76 (96.20%) patients entering the maintenance period, 35 (44.3%) patients were seizure free, 32 (40.6%) patients showed ≥ 50 reduction in seizure frequency, 3 (3.8%) showed 25-49% seizure reduction and 9 (11.4%) patients either had no change in seizure frequency or experience increase in seizure frequency. Conclusion: Lacosamide is an effective add-on antiepileptic drug for children with refractory partial epilepsy and is well tolerated.
Clinical experience with using lacosamide for the treatment of epilepsy in a tertiary centre
Acta Neurologica Scandinavica, 2013
Objective-Lacosamide is approved for the adjunctive treatment of partial-onset seizures in adults. Phase II/III clinical trials suggest that it is a safe, effective and well-tolerated medication. However, there is little post-marketing information available about this medication. Methods-We report our clinical experience from a tertiary referral epilepsy centre, which has been using lacosamide for the past 18 months, with 128 patients treated during this time. Results-Fiftythree patients (41%) achieved at least a 50% reduction in seizure frequency, with 14 patients (11%) achieving seizure freedom for a mean time of 35 weeks. This 50% responder rate matches, and the seizure free rate outperforms that seen in previous pooled trials. The efficacy of lacosamide did not vary with concurrent sodium channel blocking agent (SCB) use, and a statistically significant dosedependent response was not shown, which is in contrast to previous trials. Treatment emergent adverse effects (TEAEs) were noted in 52 patients (41%), with 24 patients (19%) discontinuing the medication. TEAEs were more frequent in patients on concurrent SCBs, affecting 51% vs. 28% of patients not on other SCBs. This increased risk of TEAEs from concurrent SCB use was of statistical significance (P = 0.01). The most frequently noted TEAEs from lacosamide were dizziness, sedation and diplopia, which all appeared to be doserelated. Conclusion-This post-marketing analysis suggests that lacosamide in clinical practice at least mirrors, and possibly outperforms the results seen in previous phase II/III trials.
Journal of Dr. Behcet Uz Children s Hospital, 2021
Objective: Treatment of childhood refractory epilepsy is a challenge for clinicians. Lacosamide is a new generation antiepileptic drug which is being used for focal onset seizures of adults and children. Efficacy and safety of the drug for adults have been demonstrated in various studies. The aim of this retrospective cross-sectional study is to evaluate the efficacy and safety of lacosamide in childhood refractory focal seizures in our clinic. Methods: We examined the medical records of 14 patients treated with lacosamide in our clinic between January 2016 and January 2020 in terms of demographic, etiological, neuroimaging findings, responses to treatment, adverse effects and drug-drug interactions. We evaluated the patients as responders to treatment whose seizure frequency decreased ≥%50 after 6 months of lacosamide treatment. Results: In 12 patiens (%85.7) seizure frequency decreased ≥%50 (p<0.001) while 5 of them (%35.7) was seizure free. Despite to the long term treatment o...
Seizure, 2012
Lacosamide (LCS) is a new adjunctive drug licensed for the treatment of focal seizures with or without secondary generalisation in patients with epilepsy aged 16 years and older. Lacosamide was approved in the member states of the European Union in September 2008 and in the United States in October 2008. Lacosamide has a novel mechanism of action producing selective enhancement of sodium channel slow inactivation. 1 In addition to the treatment of epilepsy, LCS has also been found to be useful in the treatment of pain in diabetic neuropathy. 2 Three randomised, multicentre, double blind, placebo-controlled trials of LCS have shown a major reduction in seizure frequency at three different doses with responder rates ranging from 32.7% to 35% for 200 mg/day, 38.3% to 41.1% for 400 mg/day and 38.1% to 41.2% for 600 mg/day. With placebo the responder rates in those studies ranged from 18.3% to 25.8%. 3-5 Four postmarketing studies have been published, including one from the United Kingdom (UK), showing a high response rate and good tolerability. 6-9 We present the clinical experience with lacosamide
Epilepsy & Behavior, 2011
The results of adjunctive lacosamide treatment in 18 pediatric patients with pharmacoresistant focal epilepsy are reported. All had severe forms of focal epilepsy with or without secondary generalization and were concurrently receiving one to three other antiepileptic drugs. Lacosamide was administered orally, and final dose, after slow titration, ranged between 1.7 and 10 mg/kg. Mean treatment duration was 8 months (range = 3 weeks-17 months). Treatment efficacy was assessed at two time points with a 1-year interval. The reported greater than 50% reduction in seizure frequency was 36% in the initial short-term and 20% in the following long-term assessment. Side effects, mostly somnolence and irritability, were reported by 39% of patients in both evaluations. Our data suggest that lacosamide treatment in pediatric patients is safe at doses up to 10 mg/kg/day without any major side effects, but studies in larger series are needed to validate and extend these findings.
Drugs in R&D, 2012
Background: The safety and effectiveness of lacosamide, an antiepileptic drug (AED) that selectively enhances the slow inactivation of voltage-gated sodium channels without affecting rapid inactivation, has been demonstrated in randomized, double-blind, placebo-controlled trials in adults with focal epileptic seizures. Although lacosamide is approved for use in patients over 16 years of age, limited clinical experience exists for younger patients. Objective: To assess the efficacy and tolerability of lacosamide in children with refractory epilepsy. Design/Methods: The trial was a prospective, open-label, observational, multicenter study. A total of 130 patients aged less than 16 years (range 6 months to 16 years) with refractory epilepsy who had initiated treatment with lacosamide were enrolled at 18 neuropediatric units in hospitals across Spain. Patients with a variety of etiologies were enrolled, including those with partial epilepsies and symptomatic, generalized epilepsy syndromes. Lacosamide (VIMPAT Ò ; UCB Pharma SA, Brussels, Belgium) was primarily administered once every 12 hours as an oral solution or as an oral tablet, with an initial dose of 1-2 mg/kg/day in the majority of cases. The majority of patients were also receiving stable concomitant therapy with ‡1 other AED. Treatment response
Safety of lacosamide in children with refractory partial epilepsy
Saudi Pharmaceutical Journal, 2015
The study was carried out to investigate the safety of lacosamide on children with refractory partial epilepsy. Materials & methods: The study was carried out at a tertiary care hospital after obtaining approval from the institutional ethics committee. Patients aged between 5 and 15 years taking oral lacosamide (LCM) tablets that were given orally as an adjunctive anti-epileptic drug were enrolled for assessing safety, tolerability and its effect on the behavioural life at every visit of titration, during the treatment period (3 months) and at 2 follow up visits that were done at monthly intervals. Adverse events reported by caregiver or by investigator were recorded. Patients/caregivers also completed a 25 items on Connor's behavioural rating clinical scale at every visit. Results: Out of 531 screened patients, 79 patients with refractory partial epilepsy were enrolled after they fulfilled the inclusion and exclusion criteria. Mean age of the children was 8.84 ± 3.09 years (5-15 years), of which 53 were males and 26 females. The mean age at onset of seizures in males was 6.46 ± 3.57 and in females, 6.38 ± 3.39 years. Seventy-six children of 79, completed 3 months of treatment period showed significant (p < 0.001) decrease in the frequency of seizures, significant improvement in behaviour and showed good tolerability. Three (3.79%) patients dropped out of the study due to hyperactive behaviour, vomiting and lack of seizure control respectively. Conclusions: Lacosamide is a well-tolerated newer antiepileptic drug that is effective in refractory partial epilepsy paediatric patients and concurrently improved patient's behaviour.