Friday, July 22, 2016

Lacosamide

McGinnis E, Kessler SK. Lacosamide use in children with epilepsy: Retention
rate and effect of concomitant sodium channel blockers in a large cohort.
Epilepsia. 2016 Jul 19. doi: 10.1111/epi.13466. [Epub ahead of print]

Abstract
OBJECTIVES:
To evaluate the effectiveness of lacosamide (LCM) in pediatric patients, using time to treatment failure as the outcome measure, and to assess the impact of concomitant sodium channel blocker (SCB) use on LCM retention.
METHODS:
This is a retrospective cohort study of patients <21 years old receiving LCM from 2010 to 2015. Kaplan-Meier survival curves were generated for time to LCM failure, defined as discontinuation of LCM or addition of another antiepileptic therapy. The impact of concomitant use of traditional SCB agents (phenytoin, carbamazepine, oxcarbazepine, and/or lamotrigine) and other factors including age, seizure types, fast drug titration, and prior antiepileptic drug history were evaluated using Cox regression.
RESULTS:
The analysis cohort included 223 patients, of whom 116 were taking one or more SCBs, with median follow-up of 7.4 months (1-53 months). For all patients, the probability of remaining on LCM without addition of another therapy was 44.7% at 12 months and 25.6% at 24 months. Concomitant SCB use was an independent predictor of time to LCM failure (hazard ratio [HR] 1.91, 95% confidence interval [CI] 1.38-2.65, p < 0.001).Although treatment emergent adverse effects were reported more often in patients taking SCB (65% vs. 39%, p < 0.001), intolerability was rarely the sole reason cited for LCM discontinuation, and SCB use was strongly associated with LCM failure, even when controlling for presence of treatment emergent adverse effects (adjusted HR 1.99, 95% CI 1.36-2.90, p < 0.001).
SIGNIFICANCE:
This study provides observational evidence for treatment persistence of LCM in children, in a large cohort with long-term follow-up, using time to treatment failure as the outcome measure. Concomitant SCB use was a key factor increasing risk of LCM failure, but not due to treatment-emergent adverse effects alone.


Courtesy of:  http://www.mdlinx.com/neurology/medical-news-article/2016/07/22/antiepileptic-drug-refractory-epilepsy-pediatric-epilepsy/6767182/?category=sub-specialty&page_id=1&subspec_id=317

3 comments:

  1. Poddar K, Sharma R, Ng YT. Intravenous Lacosamide in Pediatric Status
    Epilepticus: An Open-Label Efficacy and Safety Study. Pediatr Neurol. 2016 Apr
    24. pii: S0887-8994(15)30404-5. doi: 10.1016/j.pediatrneurol.2016.03.021. [Epub
    ahead of print]
    Abstract
    INTRODUCTION:
    Lacosamide is an antiepilepsy drug approved by the Food and Drug Administration for patients aged 17 years and older for partial-onset seizures as monotherapy or adjunctive therapy. We reviewed the use of intravenous lacosamide in children aged less than 17 years with status epilepticus.
    METHODS:
    Children who received at least one dose of intravenous lacosamide for status epilepticus at our tertiary care children's hospital from December 2011 to March 2014 were studied. Status epilepticus was defined as continuous seizure activity for longer than 20 minutes or two or more recurrent seizures without regaining baseline level of awareness. Efficacy was defined as seizure freedom or more than 50% reduction of seizures within 24 hours of administering lacosamide.
    RESULTS:
    Nine children with a mean age of 5.7 years (range: three months to 16 years) were included. The mean initial or loading dose was 8.7 mg/kg, with seven of nine patients receiving a dose of 10 mg/kg. The average total amount of intravenous lacosamide administered within the initial 24 hours was 13.8 mg/kg. Lacosamide was found to be efficacious in seven of nine (77.8%) patients. Four patients (44.4%) became seizure free. Two patients continued to have status epilepticus within 24 hours of lacosamide administration. Bradycardia was observed in one patient.
    CONCLUSION:
    In children with status epilepticus, intravenous lacosamide was efficacious in 78% of the patients and 44% become seizure free. In addition, no significant adverse reactions were observed. An appropriate safe, effective initial, or loading dose may be 10 mg/kg.

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  2. Miskin C, Khurana DS, Valencia I, Legido A, Hasbani DM, Carvalho KS. Efficacy and Tolerability of Lacosamide in the Treatment of Children With Refractory Generalized Epilepsy. J Child Neurol. 2016 Jun;31(7):925-8.

    Abstract
    Lacosamide is FDA-approved in patients 17 years or older with partial-onset epilepsy. We evaluated the efficacy and tolerability of lacosamide in children with refractory generalized epilepsy. We retrospectively reviewed records of 21 children with refractory generalized epilepsy treated with lacosamide in our institution from 2009-2013 divided into 2 subgroups- I, Lennox-Gastaut Syndrome, and II, other generalized epilepsies. Efficacy was defined as seizure freedom or ≥50% seizure reduction. Descriptive data analysis including seizure freedom was compared using c(2) analysis. There were eleven females and ten males with a mean age, of 11.9 years. Five patients became seizure free, nine had ≥50% seizure reduction, and seven had no response. Group I: seven had ≥50% improvement, one did not respond. Group II: five became seizure free, two had ≥50% improvement, five had no response. Lacosamide is effective and well tolerated in children with refractory generalized epilepsy particularly patients with Lennox-Gastaut Syndrome.

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  3. Arkilo D, Gustafson M, Ritter FJ. Clinical experience of intravenous
    lacosamide in infants and young children. Eur J Paediatr Neurol. 2016
    Mar;20(2):212-7.

    Abstract
    OBJECTIVE:
    To review our clinical experience with intravenous (iv) lacosamide (LCM) in children less than 12 years old.
    BACKGROUND:
    Use of LCM to treat children with epilepsy has been supported by multiple studies with limited information on iv use in children.
    DESIGNS/METHODS:
    All children given iv LCM were identified from 2009 to 2015. Records were audited for demographics, seizure classification, etiology, EEG, imaging, indication. Baseline seizure frequency was based on parental reporting, continuous video EEG and direct observation.
    RESULTS:
    47 patients were identified with median age 6.5 years, 18 less than 3 years old, including 8 younger than 12 months. LCM was an adjunctive therapy of ≥2 antiepileptic drugs (AEDs). LCM was administered intravenously to treat epilepsia partialis continua (n = 3, dose range 5-10 mg/kg), status epilepticus (n = 11, median dose 7.2 mg/kg, range 4-11 mg/kg), and acute exacerbation of seizure frequency (n = 18, median dose 4.5 mg/kg, range 1-11 mg/kg). Parenteral form was substituted for oral form for 10 children treated with maintenance LCM unable to ingest/tolerate enteral medication and 5 who were given iv LCM to initiate maintenance treatment (median dose 4 mg/kg, range: 2-10 mg/kg). The infusion was effective for 24 out of 37 children (65%) naive to LCM. Sedation (one with ataxia) was noted in 5/36 children (14%), without any other identified adverse events.
    CONCLUSION:
    This is the first published retrospective study of very young critically ill children receiving iv LCM. The acute tolerability at this dosing range represents a positive trend and need confirmation from larger studies.

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