Lacosamide (Vimpat®)
Class:
Anticonvulsant
Regulatory Status: Schedule V
Generic Availability:
No
Pharmacology:
Lacosamide is an amino acid in which precise antiepileptic mechanism is unknown. It
appears to offer dual mode of action by controlling neuronal hyperexcitability via
selective sodium channel slow inactivation, and binding to collapsin response mediator
protein-2 (CRMP-2) which is part of the signal transduction cascade of neurotropic
factors.
Pharmacokinetics:
Absorption:
Bioavailability: (oral tablets) 100%; Effect of Food: None
Distribution:
Vd= 0.6 L/kg; Protein binding <15%
Metabolism:
Hepatic; Demethylation to O-desmethyl-lacosamide (inactive)
Excretion:
Fecal: <0.5%; Renal: 95%; Dialyzable: yes (hemodialysis), 50%
removed; Elimination Half-Life: Adults: 13 hr
Indications:
FDA-Indications: Partial-Onset Seizure, adjunct
Dosing/Administration:
Adults:
Partial Seizures: Adjunct:
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PO: Initial, 50 mg PO BID; increase weekly by 100 mg/day given in 2 divided doses;
Maintenance: 200-400 mg/day; With or without food
IV: initial, 50 mg IV BID; increase weekly by 100 mg/day given in 2 divided doses
Maintenance: 200 to 400 mg/day; infuse over 30 to 60 minutes
Dose Adjustment:
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Renal Impairment: Mild-moderate, no adjustment necessary
Severe Renal Impairment: CrCl < 30 mL/min or ESRD, Maximum Dose: 300 mg/day
Liver Disease: Mild-moderate, Maximum Dose: 300 mg/day
Liver Disease: Severe, use not recommended
Hemodialysis: 50% dosage supplementation following a 4-hour dialysis treatment
Contraindications: Specific contraindications have not been determined
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Warning/Precautions:
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Behavioral or mood changes; may be precursor to suicidal behavior; monitoring
recommended
Depression, new onset or worsening of preexisting condition; may be precursor to
suicidal behavior; monitoring recommended
Suicidal ideation and behavior have been reported; monitoring recommended
Severe hepatic impairment, preexisting; use not recommended
PR interval prolongation; has been reported; monitoring recommended especially in
patients with preexisting cardiac conduction problems or severe cardiac disease (eg,
myocardial ischemia, heart failure)
Cardiovascular disease, preexisting; increased risk of atrial fibrillation or flutter
Diabetic neuropathy, preexisting; risk of atrial fibrillation or flutter and syncope or loss of
consciousness
Engagement in tasks requiring mental alertness or motor coordination; dizziness and
ataxia has been reported
Multi-organ hypersensitivity reactions; reported with anticonvulsants; discontinue therapy
if suspected
Rapid withdrawal of therapy; risk of increased seizure frequency
Pregnancy Category: C
Drug Interactions: Major: Ketorolac and Naproxen
Adverse Effects:
Nausea
Vomiting
Diarrhea
Ataxia
Dizziness
Headache
Diplopia
Nystagmus
Fatigue
Pruritus
Atrial Fibrillation & Fluttering
First Degree Atrioventricular Block
Syncope (dose related)
Tremor
Asthenia
Depression
Memory Impairment
Suicidal behavior
7%-17%
6%-16%
3-5%
4%-15%
16%-53%
11%-14%
6%-16%
5%
7-15%
2-3%
0.5%
0.4-0.5%
1.2%
4-12%
2-4%
2%
2-6%
Administration:
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IV: May be administered without further dilution or may be mixed with NS, D5W, or LR
solution; Infuse over 30-60 minutes
PO: take with or without food
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Monitor:
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Seizure control is evidence of therapeutic effect
Changes in mood or behavior, emergence or worsening of depression, or suicidal
thoughts or behavior
Dizziness or ataxia; may impair patient's ability to participate in tasks requiring mental
alertness or motor coordination
ECG prior to starting and after reaching steady-state for patients with known conduction
problems, concomitant PR interval-prolonging drugs, or severe cardiac disease due to
lacosamide dose-dependent prolongation of the PR interval
Hepatic impairment, mild to moderate; monitor closely especially during dose titration
Multi-organ hypersensitivity reactions (eg, hepatitis, nephritis, myocarditis, eosinophilia,
or lymphadenopathy); discontinue therapy if suspected
Palpitations, rapid pulse, shortness of breath; may indicate atrial fibrillation and flutter;
especially in patients with diabetic neuropathy
Renal impairment; monitor closely especially during dose titration
Therapy discontinuation period; increase risk of seizures; tapering dose is recommended
(min 1 week)
Cost:
Vimpat® (Lacosamide)
Dosage strength
Oral Solu: 10mg/mL
IV Solu: 10mg/mL
Tab: 50 mg
Tab:100 mg
Tab:150 mg
Tab:200 mg
AWP
$362.70
$420.00
$307.03
$480.00
$508.36
$508.52
Product Identification:
Injection solution: Vimpat®: 10mg/mL (20mL)
Tablet: Vimpat®: 50mg, 100mg, 150mg, 200mg
Efficacy:
According to a randomized, double-blinded, placebo-controlled, multi-centered trial by
Ben-Menachem et al, lacosamide was compared to placebo for the treatment of partialonset seizures. The goal of the study was to evaluate the efficacy and safety of
lacosamide 200 mg/day, 400 mg/day, and 600 mg/day when added to 1 to 2 antiepileptic drugs (AEDs) in adult patients with uncontrolled partial onset seizures, and
assess plasma concentrations of concomitant AEDs to determine any potential for drug
interactions. Of the 418 patients who were randomized and received trial medications in
a 1:1:1:1 ratio; 312 completed the trial. The results of the study showed a statistically
significant median percent reduction in seizure frequency over placebo that was
observed in the lacosamide 400mg/day (28.4%; p=0.0023) and 600mg/day (21.3%;
p=0.0084) treatment groups. Statistically significant differences in the percentage of
seizure-free days over placebo were observed in the lacosamide 400mg/day and
600mg/day groups. Patients in the lacosamide 400 mg/day group experienced more
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improvement in quality of life than patients in the other treatment groups, as assessed by
median changes in Quality of Life in Epilepsy (QOLIE-31) questionnaire overall score
from baseline. The number of patients reporting the treatment-emergent adverse events
(TEAE) was highest in those randomized to the 600mg/day treatment group. The most
commonly reported TEAEs were in the CNS and GI system (dizziness, headache,
nausea, fatigue, ataxia, vision abnormalities, vomiting, diplopia, somnolence, and
nystagmus). The conclusion of the study was that twice daily dosing of lacosamide
produced statistically significant reductions in seizure frequency at doses of 400 and 600
mg/day in patients with uncontrolled partial-onset seizures; however, the 400mg/day
dose of lacosamide was better tolerated than the 600mg/day dose.
Another study, prepared by Halász et al, compared the efficacy and safety of lacosamide
200 and 400 mg/day when added to 1 to 3 concomitant AEDs in patients with
uncontrolled partial-onset seizures. In this multicenter, double-blind, placebo-controlled
randomized trial, patients were randomized in a 1:1:1 ratio to one of 3 treatment arms:
placebo, lacosamide 200 mg/day, or lacosamide 400 mg/day. The results of the study
showed a statistically significant median percent reduction in seizure frequency per 28
days from baseline to the maintenance period for both the lacosamide 200mg/day group
(14.4%; p=0.02) and the 400mg/day group (15%; p=0.03). The 50% response rate for
lacosamide 400mg/day (40.5%) was statistically significant (p=0.01) over placebo
(25.8%). A statistically significant increase of 5% in the percentage of seizure-free days
over placebo during the maintenance period was observed for lacosamide 400mg/day
(p=0.01). The incidence of TEAEs was generally low and most events were considered
mild or moderate in intensity. The most commonly reported TEAEs were associated
with the CNS and the GI systems. Adverse events that appeared to be dose related
included dizziness, nausea, and vomiting. The conclusion of the study confirmed and
extended those from the previous randomized, placebo-controlled trial (Ben-Menachem
et al., 2007), confirming the efficacy of lacosamide 200mg/day or 400mg/day, as
adjunctive treatment for uncontrolled partial-onset seizures.
Overall the two studies showed the efficacy of lacosamide, as adjunctive treatment for
partial-onset seizures in patients with epilepsy has shown to be well tolerated with twicedaily dosing.
Conclusion:
Lacosamide fits the properties of an ideal antiepileptic drug. Lacosamide has high oral
efficacy, (BA=100%); good tolerability, twice daily dosing, minimal drug-drug
interactions, reduces the frequency of seizures and achieves a seizure-free state with
minimal side effects and no seizure aggravation or teratogenicity.
Adjunctive lacosamide may be an advantageous option for the treatment of partial-onset
seizures in patients with epilepsy. Based on the clinical studies, the goal maintenance
dose that produced a statistically significant reduction in seizure frequency and achieved
a significantly higher 50% response rate compared to placebo was 400mg/day twice
daily dosed.
Recommendations:
Add to formulary.
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Reference:
1. Ben-Mechachem E, Biton V, Dalius J, et al. Efficacy and Safety of Oral Lacosamide as
Adjunctive Therapy in Adults with Partial-Onset Seizures. Epilepsia, 48(7):1308–1317,
2007. http://www.ncbi.nlm.nih.gov/pubmed/17635557?dopt=AbstractPlus
2. Halász P, Kälviäinen R, Mazurkiewicz-Beldzińska M, Rosenow F, Doty P, Hebert D, Sullivan
T. Adjunctive lacosamide for partial-onset seizures: Efficacy and safety results from a
randomized controlled trial. Epilepsia, 50(3):443–453, 2009.
http://www.ncbi.nlm.nih.gov/pubmed/19183227?dopt=AbstractPlus
3. Statref! Website.
http://online.statref.com/TOC/TOC.aspx?SessionId=139154CNQHYIINQU/ Accessed
November 1, 2010.
4. Micromedex website. http://www.thomsonhc.com/ Accessed June 27, 2011.
5. Lexicomp website. http://www.online.lexi.com/ Accessed November 1, 2010.
6. Morris & Dickson Company, LLC website. http://mdwebportal.net/mdwp. Accessed June
27, 2011
Prepared by:
Celest Pedraza PharmD Candidate
University of the Incarnate Word Feik School of Pharmacy
November 2010
Reviewed by:
Ann L. Richards, Pharm.D., BCPP
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