Lacosamide (Vimpat®)

Enhances slow inactivation of voltage-gated sodium channels, affecting only neurons that are depolarized or active over a prolonged period (as in a seizure).

Partial onset seizures. Painful diabetic neuropathy.

There was no difference between lacosamide and phenytoin in the prevention of early posttraumatic epilepsy in patients following TBI. Lacosamide may have a more tolerable side effect profile ¹⁾.

In neuropathic pain due to different causes could be considered an effective and well-tolerated alternative for patients who fail to respond to standard treatments ²⁾.

Long-term anti-seizure drug therapy with zonisamide, sultiam, lacosamide, clobazam, and rufinamide from prepubertal to adulthood causes apoptosis and disruption of folliculogenesis in the ovarian follicles of nonepileptic rats ³⁾.

Brain tumor-related epilepsy

℞ Adult: 200–400 mg. Supplied: mg tabs.

Many pharmacokinetic studies of lacosamide (LCM) have been reported, but no large-scale clinical study has been conducted on genetic polymorphisms that affect the metabolism of LCM. Therefore, we designed a pharmacogenetic study of LCM to explore the effect of genetic polymorphisms on serum LCM concentration. We evaluated the pharmacodynamic characteristics of LCM, including clinical efficacy and toxicity.

Methods: Adult patients with epilepsy who received LCM at Seoul National University Hospital were enrolled. Blood samples were obtained from 115 patients taking LCM for more than 1 month with unchanged doses and were used to analyze the serum LCM concentration, the concentration/dose (C/D) ratio and the single nucleotide polymorphisms (SNPs) of the cytochrome P450 (CYP)2C9 and CYP2C19 genes. In addition, clinical information-including efficacy, toxicity, and concomitant drugs-was collected.

Results: The serum LCM concentration showed a linear correlation with the daily dose (r = .66, p < .001). In genetic analysis, 43 patients (38.7%) were extensive metabolizers (EMs), 51 (45.9%) were intermediate metabolizers (IMs), and 17 (15.3%) were poor metabolizers (PMs). In the group comparison, mean serum concentrations and the C/D ratio showed significant differences between the three groups (p = .01 and p < .001, respectively). The C/D ratios of IM (27.78) and PM (35.6) were 13% and 39% higher than those of EM (25.58), respectively. In the pharmacodynamic subgroup analysis, patients in the ineffective LCM group had significantly lower serum concentrations (6.39 ± 3.25 vs. 8.44 ± 3.68 μg/ml, p = .024), whereas patients with adverse events had higher serum concentrations than those without adverse events (11.03 ± 4.32 vs. 7.4 ± 3.1 μg/ml, p < .001). Based on this, we suggest a reference range for LCM in the Korean population (6-9 μg/ml).

Genetic polymorphisms of the CYP2C19 gene affect the serum LCM concentration. Because efficacy and toxicity are apparently related to serum LCM levels, the genetic phenotype of CYP2C19 should be considered when prescribing LCM for patients with epilepsy ⁴⁾.

Results indicate that adjuvant treatment with radiotherapy and a history of drug allergy correlated with a high incidence of ASD-related skin rashes in patients with glioma who receive LEV and LCM. Patients with these two factors should be carefully checked for skin rashes ⁵⁾.