Abstracts

Rationale: Epidiolex (CBD) is purified cannabidiol that is FDA approved for the treatment of seizures associated with Dravet, Lennox Gastaut and Tuberous Sclerosis. Pharmacokinetic (PK) interactions involving CBD and CYP450 isoforms have been extensively studied, but those involving glucuronidation (UGT) less so. Lamotrigine (LTG) is primarily metabolized via UGT2B7 and 1A4. In-vitro data suggests CBD inhibits UGT2B7, but it is unclear whether this is clinically meaningful. An increase in plasma concentrations of LTG potentially increases the risk of treatment emergent adverse effects (TEAE). Our objective was to evaluate whether addition of CBD to a stable ASM regimen including LTG, resulted in changes in steady-state LTG plasma concentrations in both pediatric and adult patients with epilepsy.

Methods: A retrospective analysis was conducted on patients with epilepsy, seen at the University of Wisconsin-Madison Dept. of Neurology. 282 patients on CBD were identified as concomitantly on LTG. Only patient with stable LTG daily doses (minimum 30 days) prior to initiation of CBD were included. Further, patients must have been on stable doses of both ASMs for a minimum of 30 days. Excluded patients were those who had insufficient laboratory or clinical data, utilized other cannabis products, or were reported as non-adherent to LTG. The resulting pool of n=29 was then stratified based on concomitant valproic acid (VPA) treatment due to known inhibition of LTG apparent oral clearance. To assess potential changes in apparent oral clearance, LTG concentration:dose ratios (CDR) were calculated pre- and post-introduction of CBD. Statistical analysis included the Wilcoxon signed-rank test, with significance assigned at p< 0.05. TEAEs were abstracted from clinical records and stratified based on the presence or absence of clobazam (CLB) treatment, given the known kinetic/dynamic interaction between these medications. All data are presented as mean (SD). This study was approved by the University of Wisconsin IRB.