Gaston TE, et al. – Researchers planned this study to identify potential pharmacokinetic interactions between the pharmaceutical formulation of cannabidiol (CBD; Epidiolex) and the commonly used antiepileptic drugs (AEDs) through an open–label safety study and they monitored serum levels to identify interactions between CBD and AEDs. They observed significantly changed serum levels of clobazam, rufinamide, topiramate, zonisamide, and eslicarbazepine. In participants taking concomitant valproate, abnormal liver function test results were noted. This study highlighted the significance of monitoring serum AED levels and LFTs during treatment with CBD.

• The researchers started CBD dose at 5 mg/kg/day and increased every 2 weeks by 5 mg/kg/day up to a maximum of 50 mg/kg/day in 39 adults and 42 children.
• They obtained serum AED levels at baseline prior to CBD initiation and at most study visits.
• They adjusted AED doses if it was determined that a clinical symptom or laboratory result was related to a potential interaction.
• They used the Mixed Procedure to determine if there was a significant change in the serum level of each of the 19 AEDs with increasing CBD dose.
• They plotted AEDs with interactions seen in initial analysis for mean change in serum level over time.
• They performed subanalyses to determine if the frequency of sedation in participants was related to the mean serum N-desmethylclobazam level, and if aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were different in participants taking concomitant valproate.

• In this study, the researchers observed increases in topiramate, rufinamide, and N-desmethylclobazam and decrease in clobazam (all p < 0.01) serum levels with increasing CBD dose.
• They observed increases in serum levels of zonisamide (p = 0.02) and eslicarbazepine (p = 0.04) with increasing CBD dose in adults.
• All noted mean level changes were within the accepted therapeutic range, except for clobazam and desmethylclobazam.
• In adults, sedation was more frequent with higher N-desmethylclobazam levels (p = 0.02).
• AST/ALT levels were significantly higher in participants taking concomitant valproate (p < 0.01).