Strzelczyk A, Zöllner JP, Willems LM, Jost J, Paule E,
Schubert-Bast S, Rosenow F, Bauer S. Lacosamide in status epilepticus:
Systematic review of current evidence. Epilepsia. 2017 Mar 11. doi:
10.1111/epi.13716. [Epub ahead of print]
Abstract
OBJECTIVE:
The intravenous formulation of lacosamide (LCM) and its good
overall tolerability and safety favor the use in status epilepticus (SE). The
aim of this systematic review was to identify and evaluate studies reporting on
the use of LCM in SE.
METHODS:
We performed a systematic literature search of electronic
databases using a combined search strategy from 2008 until October 2016. Using
a standardized assessment form, information on the study design, methodologic
framework, data sources, efficacy, and adverse events attributed to LCM were
extracted from each publication and systematically reported.
RESULTS:
In total, 522 SE episodes (51.7% female) in 486 adults and
36 children and adolescents were evaluated with an overall LCM efficacy of 57%.
Efficacy was comparable between use in nonconvulsive (57%; 82/145) and
generalized-convulsive (61%; 30/49; p = 0.68) SE, whereas overall success rate
was better in focal motor SE (92%; 34/39, p = 0.013; p < 0.001). The
efficacy with later positioning of LCM decreased from 100% to 20%. The main
adverse events during treatment of SE are dizziness, abnormal vision, diplopia,
and ataxia. Overall, lacosamide is well tolerated and has no clinically
relevant drug-drug interactions.
SIGNIFICANCE:
The available data regarding the use of LCM in SE are
promising, with a success rate of 57%. The strength of LCM is the lack of
interaction potential and the option for intravenous use in emergency
situations requiring rapid uptitration.
Misra UK, Dubey D, Kalita J. A randomized controlled trial
of lacosamide versus sodium valproate in status epilepticus. Epilepsia.
2017 Feb 18. doi:10.1111/epi.13706. [Epub ahead of print]
Abstract
OBJECTIVE:
To compare the efficacy and safety of lacosamide (LCM) and
sodium valproate (SVA) in lorazepam (LOR)-resistant status epilepticus (SE).
METHODS:
Patients with LOR-resistant SE were randomized to
intravenous LCM 400 mg at a rate of 60 mg/kg/min or SVA 30 mg/kg at a rate of
100 mg/min. The SE severity score (STESS), duration of SE and its etiology, and
magnetic resonance imaging (MRI) findings were noted. Primary outcome was
seizure cessation for 1 h, and secondary outcomes were 24 h seizure remission,
in hospital death and severe adverse events (SAEs).
RESULTS:
Sixty-six patients were included, and their median age was
40 (range 18-90) years. Thirty-three patients each received LCM and SVA. Their
demographic, clinical, STESS, etiology, and MRI findings were not significantly
different. One hour seizure remission was not significantly different between
LCM and SVA groups (66.7% vs. 69.7%; p = 0.79). Twenty-four hour seizure
freedom was higher in SVA (20, 66.6%) compared with LCM group (15, 45.5%), but
this difference was not statistically significant. Death (10 vs. 12) and
composite side effects (4 vs. 6) were also not significantly different in LCM
and SVA groups. LCM was associated with hypotension and bradycardia (one
patient), and SVA with liver dysfunction (six patients).
SIGNIFICANCE:
In LOR-resistant SE patients, both LCM and SVA have
comparable efficacy and safety. SVA resulted in slightly better 24 h seizure
remission.
Verrotti A, Ambrosi M, Pavone P, Striano P. Pediatric status
epilepticus: improved management with new drug therapies? Expert Opin
Pharmacother. 2017 May 19:1-10. doi:10.1080/14656566.2017.1323873. [Epub ahead of
print]
Abstract
INTRODUCTION:
Status Epilepticus (SE) is the most common neurological
emergency of childhood. It requires prompt administration of appropriately
selected anti-seizure medications. Areas covered: Following a distinction
between estabilished and emergent drugs, we present pharmacological treatment
options and their clinical utility in children, with a short mention on
alternatives to drug treatment. We also propose an algorithm for the management
of pediatric SE. For this review a Pubmed, Medline and Embase search was
performed. Expert opinion: In early SE in children, in the prehospital setting,
rectal diazepam or buccal midazolam are efficacious drugs; whereas in the
hospital setting, intravenous lorazepam or diazepam are indicated. As regard
estabilished stage of SE, in addition to the 'classic' compounds, such as
phenytoin and phenobarbital, other drugs such as valproic acid, levetiracetam
and lacosamide have been demonstrated efficacious. Treatment recommendations of
refractory SE depend on retrospective case series and uncontrolled studies. We
reported experiences about the use of midazolam, propofol, ketamine and
lidocaine. They could be a valid option, but further prospective studies are
necessary. Over the last few decades, important advances in basic mechanisms
underlying refractory SE have been achieved, but few data are available
regarding management of these stages.
Bauer S, Willems LM, Paule E, Petschow C, Zöllner JP,
Rosenow F, Strzelczyk A.The efficacy of lacosamide as monotherapy and adjunctive
therapy in focal epilepsy and its use in status epilepticus: clinical trial
evidence and experience. Ther Adv Neurol Disord. 2017 Feb;10(2):103-126.
Abstract
Lacosamide (LCM) is approved for anticonvulsive treatment in
focal epilepsy and exhibits its function through the slow inactivation of
voltage-gated sodium channels (VGSCs). LCM shows comparable efficacy with other
antiepileptic drugs (AEDs) licensed in the last decade: in three randomized
placebo-controlled trials, significant median seizure reduction rates of 35.2%
for 200 mg/day, 36.4-39% for 400 mg/day and 37.8-40% for 600 mg/day were
reported. Likewise, 50% responder rates were 38.3-41.1% for 400 mg/day and
38.1-41.2% for 600 mg/day. Similar rates were reported in post-marketing
studies. The main adverse events (AEs) are dizziness, abnormal vision, diplopia
and ataxia. Overall, LCM is well tolerated and has no clinically-relevant
drug-drug interactions. Due to the drug's intravenous availability, its use in
status epilepticus (SE) is increasing, and the available data are promising.
Matthieu Perrenoud, Pascal André, Vincent Alvarez, Christine
Stähli, Laurent A. Decosterd, Andrea O. Rossetti, Jan Novy. Intravenous lacosamide in status epilepticus:
Correlation between loading dose, serum levels, and clinical response. Epilepsy research. [Epub ahead of print]
Abstract
Introduction
Intravenous lacosamide (LCM) is increasingly used in the
treatment of status epilepticus (SE), but optimal loading dose and target serum
levels are unclear. We analysed the correlation between LCM serum levels after
intravenous loading dose and clinical response.
Materials and methods
Retrospective study in two centres from December 2014 to May
2016 including consecutive SE patients treated with LCM, in which trough serum
levels after intravenous loading dose were available. Trough levels were
correlated with the loading dose and the clinical response, defined as LCM
introduction terminating SE without the need of further treatment. Correlations
were adjusted for other SE characteristics.
Results
Among 40 patients, 16 (40%) responded to LCM. LCM serum
concentrations within the reference interval (10–20 mg/l) were associated with
loading doses of >9 mg/kg (p = 0.003; χ2). However, we observed no
difference between LCM serum levels in responders (median 10.4 mg/l) versus
non-responders (median 9.5 mg/l; p = 0.36; U-test), even after adjusting for
other predictors of clinical outcome (SE severity, aetiology, and number of
previous treatment).
Discussion
High intravenous LCM loading doses ( > 9 mg/kg) were
associated with serum levels within the reference interval, there was however
no correlation with the clinical response. Prospective studies are needed to
evaluate the benefit of increasing the LCM loading dose in SE.
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