The efficacy of lacosamide as monotherapy and adjunctive therapy in focal epilepsy and its use in status epilepticus: clinical trial evidence and experience

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.

Lacosamide in status epilepticus: Systematic review of current evidence

“…Serious adverse events were rare and comprised seizures, dizziness, nausea, vomiting, nystagmus, and psychiatric disorders. Adverse events reported in postmarketing studies were similar to those reported in the RCTs . Tolerability seemed lower when LCM was combined with other sodium‐channel blockers, such as carbamazepine, oxcarbazepine, lamotrigine, and phenytoin …”

“…We examined the reference lists of all identified studies for additional studies. Furthermore, review articles on LCM were available …”

“…Furthermore, review articles on LCM were available. 25,26 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. All publications were cross-checked to detect double-reporting of cases.…”

“…Adverse events reported in postmarketing studies were similar to those reported in the RCTs. 26 Tolerability seemed lower when LCM was combined with other sodium-channel blockers, such as carbamazepine, oxcarbazepine, lamotrigine, and phenytoin. 75 Because LCM acts on voltage-gated sodium channels, treatment-induced atrioventricular (AV) block is a possible concern, especially in cases of a rapid intravenous LCM application.…”

Antiepileptic Drugs and Liver Disease

“…71 For focal-onset seizures, levetiracetam is an ideal choice, but virtually any first-or second-line therapy can be considered, including sodium channel blockers such as lacosamide, oxcarbazepine, and eslicarbazepine. 72,73 Hepatotoxicity caused by AEDs There are more than 900 drugs, toxins, and herbs that are known to be hepatotoxic. 74 A drug's hepatotoxicity may not become apparent until after a large number of patients have taken it, so the risk of hepatotoxicity is usually discovered in the postmarketing phase.…”