Pharmacology Update
Lacosamide Tablets and Injection (Vimpat®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD. Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente; and Assistant Clinical Professor of Medicine, University of California, San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA. Drs. Chan and Elliott report no financial relationship to this field of study.
A new antiepileptic drug with a novel mechanism of action has been approved for the treatment of partial seizures. Lacosamide is a new chemical entity, which potentially has a dual mechanism of action. It will be marketed by UCB, Inc., as Vimpat®.
Indication
Lacosamide is indicated for adjunctive treatment of partial seizures in patients 17 years of age and older.1
Dosage
The initial dose is 50 mg twice daily (oral or intravenous administration). Depending on response and tolerability, the dose may be increased at weekly intervals by 100 mg (2 divided doses) up to 400 mg daily.1 The injection should be administered at the same daily dose and frequency. The infusion should be over 30-60 minutes. Oral tablets may be taken without regard to meals. No dose adjustment is necessary for patients with mild-to-moderate renal impairment. For patients with impaired hepatic function, titration should be done with caution and the daily dose should not exceed 300 mg in patients with mild or moderate hepatic impairment.
Lacosamide is available as 50 mg, 100 mg, 150 mg, and 200 mg tablets, and a single-use vial (200 mg/20 mL).
Potential Advantages
Lacosamide has been shown to improve seizure control in patients with uncontrolled partial-onset seizures taking up to 3 antiepileptic drugs.1-3 The drug has high oral bioavailability and its pharmacokinetics have low intrapatient and interpatient variability. Lacosamide does not appear to have any significant drug-drug interaction with common antiepileptic drugs.1,2
Potential Disadvantages
As with other antiepileptics, there is potential for increased risk of suicidal thoughts or behavior. Patients should be monitored for signs of worsening depression, suicidal ideation, and/or other mood or behavior changes.1 Albeit rare (0.4%-0.5%), lacosamide may prolong PR interval and predispose patients to atrial arrhythmias. Common adverse events for the 400 mg daily dose include dizziness (30%), headache (14%), nausea (11%), and diplopia (10%). Ataxia (7%) and syncope (1.2%) have also been reported. Safety and effectiveness have not been established in patients younger than 17 years of age.
Comments
Lacosamide is an antiepileptic that is chemically and mechanistically different from currently marketed agents. Its proposed mechanism of action is selective enhancement of the slow inactivation of voltage-gated sodium channels and binding to collapsin response protein-2 (CRMP-2), a phosphoprotein mainly expressed in the nervous system.1 These actions may result in controlling neuronal hyperexcitability and neuroprotective effects.2 The efficacy of lacosamide was established in three 12-week, randomized, placebo-controlled studies (n = 1294).1,2 Study participants had partial-onset seizures with or without generalization and were not adequately controlled with up to 3 concomitant antiepileptics. They had an average of 4 or more seizures per 28 days and no seizure-free period greater than 21 days. Across these studies, subjects were randomized to 200 mg, 400 mg, and 600 mg daily or placebo. These studies included 3 phases: 8-week baseline phase, 6-week titration phase, and a 12-week maintenance phase. The primary endpoints were reduction in the seizure frequency per 28 days and percent of subjects with at least a 50% reduction in frequency from baseline to maintenance phase (50% responder rates). Median reduction in seizure episodes ranged from 26%-35% for 200 mg, 39%-37% for 400 mg, and 10%-21% for placebo. The 600 mg dose showed essentially the same efficacy as the 400 mg, but with a higher frequency of adverse events. Forty percent (40%) of patients had a 50% or greater reduction in seizure frequency at 400 mg daily compared to 23% for placebo. Discontinuation rates were 5%, 11%, 19%, and 30% for placebo, 200 mg, 400 mg, and 600 mg, respectively.2 Dizziness is the most common adverse event resulting in discontinuation. Lacosamide has also shown antinociceptive activity and is being studied for the treatment of diabetic neuropathic pain.4
Clinical Implications
The new antiepileptic lacosamide provides an alternative to patients with partial-onset seizures who are not adequately controlled on multiple antiepileptics.
References
1. Vimpat Prescribing Information. Smyrna, GA: UCB, Inc.; October 2008.
2. Doty P, et al. Lacosamide. Neurotherapeutics 2007;4: 145-148.
3. Ben-Menachem E, et al. Efficacy and safety of oral lacosamide as adjunctive therapy in adults with partial-onset seizures. Epilepsia 2007;48:1308-1317.
4. Biton V. Lacosamide for the treatment of diabetic neuropathic pain. Expert Rev Neurother 2008;8:1649-1660.
A new antiepileptic drug with a novel mechanism of action has been approved for the treatment of partial seizures.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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