Abstracts

Rationale: Since its approval in the fall of 2018, Epidiolex, a purified plant based cannabidiol (CBD), has quickly garnered interest as adjunct therapy in Dravet Syndrome and Lennox Gastaut Syndrome (LGS). It is a substrate of Cytochrome P450 2C19 and 3A4 and can inhibit CYP3 and CYP2C enzymes, thus having the potential to interact with many antiepileptics (AED). The largest case series to date describing drug interactions in a mixed population of adults and children reported Increases in concomitant AED drug levels for Clobazam, Rufinamide, Topiramate, Zonisamide, and Eslicarbazepine1. Another recent case series described a potential interaction between CBD and Brivaracetam2. Absent from this body of literature is experience with Felbamate, a broad-spectrum AED that is highly effective in LGS. We report the changes in felbamate levels following Epidiolex initiation in a single center pediatric ambulatory population. Methods: Inclusion criteria included all pediatric patients (6 months to 18 years of age) who were started on Epidiolex between Dec 2018 and July 2019 with felbamate levels measured within one month prior to and at least 2 weeks after Epidiolex initiation (in which an initial goal of 10 mg/kg/day was reached). Patients were excluded if their antiepileptic drug doses were adjusted within one month prior to Epidiolex initiation or before the first follow up drug levels. Patients were also excluded if they were on artisanal CBD within 1 month of Epidiolex initiation. Drug trough levels, prior to the morning doses of medications, were obtained. Results: Out of our cohort of 46 patients, 35 (76 %) were concomitantly prescribed Felbamate. 13 were excluded due to lack of complete laboratory data or prior artisanal CBD use. 22 patients were included in the final analysis (12 were female; median age 10 years, range 3-18 years). Median Epidiolex dose was 15 mg/kg/day (range 10-20 mg/kg/day). 14 patients (64%) demonstrated a decrease in Felbamate levels following Epidiolex initiation. The median percent change in Felbamate levels was a decrement of 7% (range: +57% to -62%). Other concomitant AEDs included Valproic acid (N=8), Clobazam (N=11), Topiramate (N=3), Levetiracetam (N=2), Zonisamide (N=1), and Vigabatrin (N=1). Interestingly, five out the six patients whose regimens consistent of only Felbamate and Epidiolex experienced a decrement in Felbamate levels. Limitations to our study include inability to rule out non-compliance, natural variations in drug sampling timing in a non-controlled setting, and a small sample size. Conclusions: Due to its high potential for interaction with multiple AEDs, it is difficult to clearly discern the pharmacokinetic effects of Epidiolex on individual AEDs, even in a controlled clinical setting. However, in our cohort of 22 subjects on concomitant Felbamate, 64% demonstrated a decrease in felbamate concentration with Epidiolex initiation. Additionally, of the six subjects who were only taking Epidiolex and Felbamate, five (83%) exhibited decreased Felbamate levels. While the mechanism for the interaction is unknown, these findings suggest that close laboratory monitoring and potential dose adjustments may be required when patients taking felbamate are started on Epidiolex. References: 1. Gaston TE, Bebin EM, Cutter GR. Et al. Interactions between cannabidiol and commonly used antiepileptic drugs. Epilepsia 2017; 58(9):1586-1592. 2. Klotz, K, Hirsch M, Heers M. et al. Effects of cannabidiol on brivaracetam plasma levels. Epilepsia 2019;60: e74-e77. Funding: No funding