AI-008 - PHARMACOKINETIC MODEL-GUIDED ENOXAPARIN DOSING IN THE NICU: RETROSPECTIVE ANALYSIS TO PLAN FOR PROSPECTIVE FEASIBILITY TRIAL.

T. Lewis¹, V. Ivaturri², C. Schentag³, L. Brandao⁴, H. Bunn⁵; ¹The University of Toronto Temerty Faculty of Medicine, ²University of Maryland School of Pharmacy, , , ³The Hospital for Sick Children, ⁴University of Toronto Temerty Faculty of Medicine, , , ⁵PUMAS-AI, , .

Background: Therapeutic enoxaparin dosing for arterial and venous thrombus is increasing in the neonatal intensive care unit (NICU). Population-based mg/kg dosing can result in failure to achieve goal anti-Xa levels, necessitating multiple dose adjustments and lab monitoring. A more personalized approach to dosing, based on individual predicted clearance and volume of distribution, may lead to improved patient outcomes.

Methods: In a retrospective cohort study, infants less than 44 weeks postmenstrual age at first enoxaparin dosing between Jan 2019 - Dec 2022 were identified. Demographics, drug dosing data, PK model covariates and clinical outcomes were collected. Data were analyzed using the PUMAS-AI Lyv dosing tool. The primary outcome was standard-of-care (SOC) first dose versus Lyv-recommended first dose. Secondary outcomes were time to therapeutic anti-Xa level, stratified by appropriate, underdosing or overdosing (SOC vs Lyv). Our objective was to compare enoxaparin standard of care (SOC) dosing to PK-model informed precision dosing and to compare time to therapeutic outcome between these cohorts.

Results: After removing infants who were on enoxaparin for prophylaxis, 168 neonates were included in the analysis. Infant had a median (IQR) birthweight 2.9 kg (2.1,3.4), gestational age 38 (34,39), postnatal age at first LMWH dose 15 days (9,31). Compared with SOC dosing, the Lyv-recommended dose was within +/- 20% for 58% of the infants (Figure 1). 3% of infants would have received at least a 20% lower dose with Lyv, 20% would have received a dose 20-40% higher with Lyv, and 19% would have received a dose >40% higher with Lyv. Thus, 39% of infants would have received a higher dose if their individual clearance and volume were accounted for. For time to therapeutic anti-Xa, infants who were the most underdosed with SOC had the longest time to reach therapeutic (Figure 2), requiring multiple dose adjustments and venipuncture for lab monitoring.

Conclusion: If individual PK parameters are considered, neonates would receive a higher first enoxaparin dose. These data will inform Lyv-recommended dosing in a prospective feasibility trial in a level IV NICU in Canada.