Influence of titration schedule and maintenance dose on the tolerability of adjunctive eslicarbazepine acetate: An integrated analysis of three randomized placebo-controlled trials

Objective To examine the influence of titration schedule and maintenance dose on the incidence and type of treatment-emergent adverse events (TEAEs) associated with adjunctive eslicarbazepine acetate (ESL). Methods Data from three randomized, double-blind, placebo-controlled trials were analyzed. Patients with refractory partial-onset seizures were randomized to maintenance doses of ESL 400, 800, or 1200 mg QD (dosing was initiated at 400 or 800 mg QD) or placebo. The incidence of TEAEs was analyzed during the double-blind period (2‐week titration phase; 12-week maintenance phase), according to the randomized maintenance dose and the titration schedule. Results 1447 patients were included in the analysis. During the first week of treatment, 62% of patients taking ESL 800 mg QD had ≥1 TEAE, vs 35% of those taking 400 mg QD and 32% of the placebo group; dizziness, somnolence, nausea, and headache were numerically more frequent in patients taking ESL 800 mg than those taking ESL 400 mg QD. During the double-blind period, the incidences of common TEAEs were lower in patients who initiated ESL at 400 mg vs 800 mg QD. For the 800 and 1200 mg QD maintenance doses, rates of TEAEs leading to discontinuation were lower in patients who began treatment with 400 mg than in those who began taking ESL 800 mg QD. Conclusions Initiation of ESL at 800 mg QD is feasible. However, initiating treatment with ESL 400 mg QD for 1 or 2 weeks is recommended, being associated with a lower incidence of TEAEs, and related discontinuations. For some patients, treatment may be initiated at 800 mg QD, if the need for more immediate seizure reduction outweighs concerns about increased risk of adverse reactions during initiation.