How kidney and liver health can change CBD seizure-medication dosing

Ten newer antiseizure medications (ASMs) approved since 2000 and selected for this review (cenobamate, brivaracetam, eslicarbazepine acetate, lacosamide, perampanel, fenfluramine, ganaxolone, cannabidiol, stiripentol, and rufinamide) have broadened treatment options for drug-resistant epilepsy. However, concurrent renal or hepatic impairment alters drug disposition through diminished clearance, shifted protein binding equilibria, accumulation of active metabolites, and variable dialytic removal that standard dosing fails to accommodate. Despite the rising clinical overlap of epilepsy with chronic kidney and liver diseases, consolidated prescribing guidance for these agents in organ-impaired populations remains limited. This narrative review synthesizes pharmacokinetic data from pivotal development programs together with current regulatory labeling issued by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) through 2025 for all ten agents across graded severities of renal and hepatic impairment. Brivaracetam, rufinamide, and cannabidiol proved minimally susceptible to renal decline, whereas eslicarbazepine acetate required no hepatic dose adjustment in mild-to-moderate disease. Conversely, cenobamate and perampanel necessitate strict dose caps or avoidance in severe organ dysfunction, and stiripentol is precluded in any degree of organ impairment owing to unpredictable nonlinear Michaelis-Menten kinetics. Regulatory discrepancies between FDA and EMA labeling were identified for all ten agents, notably divergent hepatic dose caps for perampanel and cenobamate, conflicting renal recommendations for fenfluramine, and discordant guidance for eslicarbazepine acetate in severe renal impairment. These agents exhibit no uniform class effect in organ impairment; prescribing must be governed by agent-specific disposition profiles, organ-function severity, and free-drug monitoring for highly protein-bound agents like perampanel and ganaxolone.