Characterization of lacosamide pharmacokinetics in older adults with epilepsy (P4-1.007)

Abstract

<h3>Objective:</h3> This study aimed to characterize the relationship between lacosamide pharmacokinetics and renal function in older adults with epilepsy. <h3>Background:</h3> Lacosamide is an anti-seizure medication (ASM) indicated for focal-onset seizures which is primarily excreted through the renal route. Changes in clearance with increased age could lead to pharmacokinetic changes in medications that are eliminated via the kidney; therefore, older adults, being more sensitive to these changes may need lower doses than younger adults. <h3>Design/Methods:</h3> Data on patients diagnosed with epilepsy according to ICD10 codes and having at least one steady-state lacosamide concentration measurement between January 2015 and July 2020 met inclusion. A linear mixed model was developed to characterize differences in lacosamide dose normalized concentrations (DNCs = blood concentration/total daily dose) with respect to creatinine clearance (CLCR). CLCR was calculated using the Cockcroft-Gault equation as indicated for lacosamide dosing (package insert), thus incorporating the effect of patient age and sex. The model was controlled for covariates including ethnicity, route of administration (oral/intravenous), aspartate aminotransferase concentration, alanine aminotransferase concentration, regime (monotherapy/polytherapy), presence of CYP450 inducers &amp; inhibitors, and critically ill status as signified by prescription. Model significance was set to α≤0.05 (R software (version 4.1.2)). <h3>Results:</h3> 2291 lacosamide DNCs from 676 patients were included. The median[range] dose and DNC were 300 mg [50–1000 mg] and 23(ug/L)/mg [1–480(ug/L)/mg], respectively. For a given subject the mean DNC of lacosamide decreased by 6% (95% confidence interval: 3.5–8.9%, p&lt;0.01) per unit increase in the CLCR. Route of administration (p=0.01) and presence of a CYP450 inducer (p&lt;0.01) showed a statistically significant effect on DNCs. <h3>Conclusions:</h3> Creatinine clearance was a significant predictor of lacosamide DNCs in older patients with epilepsy. Thus, as CLCR changes are more pronounced as one ages, modification in dosing regimens may be required to maintain lacosamide concentrations in the tolerable and effective range. <b>Disclosure:</b> Miss Avachat has nothing to disclose. The institution of Dr. Reeder has received research support from American Epilepsy Society . Mr. Long has received personal compensation for serving as an employee of PharmaVelox. Dr. Leppik has nothing to disclose. The institution of Dr. Patel has received research support from Ucb. The institution of Dr. Birnbaum has received research support from National Institutes of Health. Dr. Birnbaum has received intellectual property interests from a discovery or technology relating to health care.