Abstract
OBJECTIVE: To evaluate age, adjunctive antiseizure medication (ASM), and specific ASMs on lacosamide (LCM) weight normalized dose-to-concentration ratio (DCR) and US Food and Drug Administration (FDA) dosing guidelines in pediatric patients. METHODS: Patients 1 mo to ≤18 years with a LCM serum concentration between October 2009 and June 2017 were considered. Demographics, LCM DCR, and adjunctive ASM were recorded. LCM DCR/hr was used as a surrogate for clearance. Data were stratified by age (1 mo-< 2 yr; ≥ 2-6 yr; ≥ 6-12 yr; and ≥12-≤18 yr), FDA dosing weights, and ASM potential to interaction with LCM. RESULTS: There were 646 sera (380 patients) with median dose 8.36 mg/kg/day (IQR, 5.92-11.16). 50.2% of doses were within FDA-weight guidelines; however, 40.4% exceeded recommendations. Most (81.3%) LCM concentrations were between 2 and 12 mg/L. A difference existed in DCR between ages, with those <2 years having the highest DCR (p < 0.001). Moving across age groups, the DCR decreases by 30.7%, 50.5%, and 63.4%. There was a weak (r(2) = 0.073) but significant (p < 0.001) negative correlation between DCR and age. 84.8% received adjunctive ASM consisting of at least one of 31 different ASMs. DCR was higher with adjunctive ASMs compared with monotherapy [0.061 (0.039-0.095) vs 0.043 (0.030-0.062)], respectively (p < 0.001) and was greatest with inducers. Phenobarbital increased DCR by 2.6-fold, topiramate by 72.1%, and clobazam by 32.6%. Inhibitors had no effect. CONCLUSIONS: The correlation between age and DCR was weak, accounting for 6% of variability. Strong inducers significantly increased DCR. Synergy may exist when multiple inducers are given. Weak inhibitors did not affect DCR. Those ≥6 to 11 kg, ≥30 to 50 kg, and those given strong inducers may require larger -initial LCM doses. Serum concentrations should be used to individualize dosing, especially in those receiving strong inducers.