====== Lacosamide (Vimpat®) ====== ===== Drug info ===== Enhances slow inactivation of [[voltage-gated sodium channels]], affecting only [[neuron]]s that are depolarized or active over a prolonged period (as in a [[seizure]]). ===== Indications ===== 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 ((Kwon SJ, Barletta JF, Hall ST, Mangram AJ, Dzandu JK, Abdulhamid M, Zach V. Lacosamide versus phenytoin for the prevention of early post traumatic seizures. J Crit Care. 2018 Nov 14;50:50-53. doi: 10.1016/j.jcrc.2018.11.010. [Epub ahead of print] PubMed PMID: 30471561.)). 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 ((Gómez-Argüelles JM, Bermejo PE, Lara M, Almajano J, Aragón E, García del Carrizo F, Blanco MV, Valenzuela-Rojas FJ, Colás J, Sánchez-Del Valle O, Ceballos MÁ, Toribio-Díaz ME, Latorre-González G, Costa-Frossard L, Morin-Martin Mdel M. [Effectiveness of lacosamide in the treatment of refractory neuropathic pain: an open observational trial]. Rev Neurol. 2014 Oct 1;59(7):289-93. Spanish. PubMed PMID: 25245872.)). ---- 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 ((Kart PÖ, Gürgen SG, Esenülkü G, Dilber B, Yıldız N, Yazar U, Sarsmaz HY, Topsakal AS, Kamaşak T, Arslan EA, Şahin S, Cansu A. An Investigation of the Effects of Chronic Zonisamide, Sultiam, Lacosamide, Clobazam, and Rufinamide Antiseizure Drugs on Foliculogenesis in Ovarian Tissue in Prepubertal Non-Epileptic Rats. Int J Dev Neurosci. 2022 Jun 9. doi: 10.1002/jdn.10200. Epub ahead of print. PMID: 35680420.)). ---- [[Brain tumor-related epilepsy]] ===== Dose ===== ℞ Adult: 200–400 mg. Supplied: mg tabs. ===== Pharmacokinetics ===== 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 polymorphism]]s 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 ((Ahn SJ, Oh J, Kim DY, Son H, Hwang S, Shin HR, Kim EY, Lee HS, Lee WJ, Moon J, Lee ST, Jung KH, Park KI, Jung KY, Lee S, Yu KS, Chu K, Lee SK. Effects of CYP2C19 genetic polymorphisms on the pharmacokinetics of lacosamide in Korean patients with epilepsy. Epilepsia. 2022 Aug 21. doi: 10.1111/epi.17399. Epub ahead of print. PMID: 36039802.)). ===== Risk factors ===== 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 ((Onodera M, Saito T, Fukui A, Nitta M, Tsuzuki S, Koriyama S, Masamune K, Kawamata T, Muragaki Y. The high incidence and risk factors of levetiracetam and lacosamide-related skin rashes in glioma patients. Clin Neurol Neurosurg. 2022 Jul 14;220:107366. doi: 10.1016/j.clineuro.2022.107366. Epub ahead of print. PMID: 35878560.)).