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Lacosamide response

MedGen UID:
1437479
•Concept ID:
CN781942
•
Sign or Symptom
Synonym: Vimpat response
Drug:
lacosamide
MedGen UID:
170921
•Concept ID:
C0893761
•
Pharmacologic Substance
A functionalized amino acid compound specifically synthesized as an anticonvulsive drug to use as add-on therapy for partial-onset seizures with antinociceptive and neuroprotective activities. Lacosamide selectively enhances slow inactivation of voltage-gated sodium channels without affecting fast inactivation, thereby stabilizing hyperexcitabe neuronal membranes. Furthermore, this agent binds to collapsin response mediator protein 2 (CRMP2; DPYSL2), a cytosolic phosphoprotein expressed in most tissues. In the nervous system, CRMP2 acts as a mediator of growth cone collapse as well as modifies axon number, length, and neuronal polarity. [from NCI]
lacosamide
 
Gene (location): CYP2C19 (10q23.33)

Definition

Lacosamide (brand name Vimpat) is an antiseizure drug indicated for adjunctive therapy for partial-onset seizures in pediatric and adult patients with epilepsy. Lacosamide is thought to work by selectively enhancing slow inactivation of voltage-dependent sodium channels. This stabilizes the neuronal membrane and suppresses the repetitive neuronal firing associated with seizures. Several cytochrome P450 (CYP) enzymes are involved in metabolizing active lacosamide to an inactive metabolite, including CYP2C19. Individuals who have no CYP2C19 enzyme activity are known as "CYP2C19 poor metabolizers". The FDA-approved drug label for lacosamide cites a small study that found plasma levels of lacosamide were similar in CYP2C19 poor metabolizers (n=4) and normal (extensive) metabolizers (n=8). Therefore, the recommended standard doses of lacosamide may be used for CYP2C19 poor metabolizers. [from Medical Genetics Summaries]

Professional guidelines

PubMed

Management of epilepsy in brain tumor patients.
van der Meer PB, Taphoorn MJB, Koekkoek JAF
Curr Opin Oncol 2022 Nov 1;34(6):685-690. Epub 2022 Jul 16 doi: 10.1097/CCO.0000000000000876. PMID: 35838207Free PMC Article
25 years of advances in the definition, classification and treatment of status epilepticus.
Trinka E, Kälviäinen R
Seizure 2017 Jan;44:65-73. Epub 2016 Nov 14 doi: 10.1016/j.seizure.2016.11.001. PMID: 27890484
Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society.
Moulin D, Boulanger A, Clark AJ, Clarke H, Dao T, Finley GA, Furlan A, Gilron I, Gordon A, Morley-Forster PK, Sessle BJ, Squire P, Stinson J, Taenzer P, Velly A, Ware MA, Weinberg EL, Williamson OD; Canadian Pain Society
Pain Res Manag 2014 Nov-Dec;19(6):328-35. doi: 10.1155/2014/754693. PMID: 25479151Free PMC Article

Curated

DailyMed Drug Label, VIMPAT- lacosamide, 2021

Therapeutic recommendations

From Medical Genetics Summaries

This section contains excerpted 1 information on gene-based dosing recommendations. Neither this section nor other parts of this review contain the complete recommendations from the sources.

2016 Statement from the US Food and Drug Administration (FDA):

CYP2C19 Polymorphism

There are no clinically relevant differences in the pharmacokinetics of lacosamide between CYP2C19 poor metabolizers and extensive metabolizers. Results from a trial in poor metabolizers (PM) (N=4) and extensive metabolizers (EM) (N=8) of cytochrome P450 (CYP) 2C19 showed that lacosamide plasma concentrations were similar in PMs and EMs, but plasma concentrations and the amount excreted into urine of the O-desmethyl metabolite were about 70% reduced in PMs compared to EMs.

Please review the complete therapeutic recommendations that are located here: (1).

1 The FDA labels specific drug formulations. We have substituted the generic names for any drug labels in this excerpt. The FDA may not have labeled all formulations containing the generic drug.

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    • Gene
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      Clinical tests in GTR
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