Abstracts

Rationale: Intravenous lacosamide (IV LCM) could be useful for seizure management in neonates given its quick mode of administration and established safety profile in older children and adults. However, the safety of IV LCM in treating neonatal seizures is unknown. LCM is not approved for the treatment of neonatal seizures. The extrapolated dose used in the neonatal population was calculated from the recommended dose in adults. Any LCM dose higher than the dose extrapolated from the recommended dose in adults was defined as the higher dose. The off-label use of higher doses in neonates has not been studied yet. We evaluated the safety of initiating IV LCM at extrapolated dose vs higher dose in neonates with drug-resistant seizures.

Methods: This retrospective cohort study used electronic health record data (01Jan2009–29Feb2020) from PEDSnet (7 large pediatric hospitals in the United States). Patients aged < 30 days, treated with ≥ 1 IV LCM dose and not exposed to either oral or IV LCM before the index date (first IV LCM dose) were included. Based on first IV LCM dose and patient age and weight, neonates were classified into initial extrapolated dose cohort and higher dose cohort and followed until discharge, transfer or death for a maximum of 37 days. Newly diagnosed health conditions were extracted by trained personnel who were blinded to full study protocol. Incidence rate ratios were adjusted for possible confounders by Poisson regression with inverse probability treatment weights.

Results: 28 patients were identified in PEDSnet database; 16 vs 12 received extrapolated dose vs higher dose, respectively (mean age: 14.2 vs 16.2 days; male; 43.8% vs 41.7%). Almost all patients (except one in the extrapolated dose cohort) were treated in an intensive care unit, and 56.2% vs 50.0% of patients in the extrapolated dose cohort vs higher dose cohort received ≥ 4 administrations of IV LCM. In the extrapolated dose and higher dose cohorts, 100% and 91.7% had ≥ 1 benzodiazepine antiseizure medication (ASM) before the index date, respectively. In the extrapolated dose cohort and higher dose cohort, 81.2% and 66.7% received ≥ 1 concomitant benzodiazepine ASM, respectively. In patients in the extrapolated dose and higher dose cohorts, health conditions occurred in eight and two patients, respectively during the median follow-up of 26 days (IQR 8–32 vs 13–35). The crude incidence rates per 1000 person-days of overall health conditions in the extrapolated and higher dose cohort were 36.04 (95% confidence interval [CI]: 15.56–71.01) vs 8.85 (95% CI: 1.07–31.97), respectively. For predefined health conditions of special interest with regard to LCM, one health condition (cardiac arrest) was reported in the extrapolated dose cohort (crude incidence rate per 1000 person-days: 12.86 [95% CI: 3.50–32.93]). No health condition was reported in the higher dose cohort. Seven deaths were reported in these critically ill patients, none attributed to LCM. Crude mortality rates per 1000 person-days in the extrapolated and higher dose cohort were 14.75 (95% CI: 4.81–34.08) and 7.14 (95% CI: 0.87–25.56), respectively.

Conclusions: IV LCM in this study appeared to have a favorable safety profile in neonates.

Funding: Please list any funding that was received in support of this abstract.: UCB Pharma-funded.