Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a dibenzazepine derivative, like carbamazepine (CBZ) and oxcarbazepine (OXC) with a structural difference at the 10,11-position. ESL was licensed for add-on treatment of adults with focal epilepsies by the EMA in 2009. The active metabolite of ESL enhances the slow inactivation of the fast voltage gated sodium channel, whereas CBZ inactivates it. Though both leading to ESL as the active metabolite metabolisation differs, with ESL being directly converted, while OXC-peaks in plasma and CSF about 1-2 hours after intake. This OXC peak may cause intolerable dose dependent adverse events such as dizziness, diplopia, headache or nausea, which could resolve after switching to ESL. Therefore we performed a study to investigate the safety and tolerability of an overnight switch from OXC to ESL. Methods: We included 10 patients (6 women) with focal epilepsy, median age 38 years (yrs) (range 21-85), had median of five previously failed AEDs (range 1-14), and were not seizure free, had dose limiting adverse events under OXC, or both. Median age at epilepsy onset was 12 yrs (range 1-74), aetiology was symptomatic in eight and unknown in two, 8 patients had temporal lobe epilepsy (6 left, 3 bilateral, 1 right), 4 patients received polytherapy of three additional AEDs, 5 of two AEDs, and 1 was on monotherapy. We applied the Adverse Event Profile (AEP), standardized test for alertness, and the QOLIE 10 immediately before and 5 days after the switch. Serum levels of MHD, eslicarbazepine and OXC were measured on the day of the neuropsychological assessments. Results: Median Dose of OXC before the switch was 900 (range 600-1800) mg. The individual conversion ratio between OXC and ESL ranged from 1:1.1 to 1:1.9. After conversion the median dose of ESL was 800 mg (range 800-1600); 2/10 pts had a reduction of seizure frequency after the switch (FU 3 to 10 months); Serum level of eslicarbazepine was median 15.8 mg/l (range 7.3-31.3). After switch to ESL patients had significantly lower sum scores on the AEP (p=0.005). The reduction was most prominent in the following domains: unsteadiness, problems with the stomach, weight gain, dizziness, diplopia or blurred vision, difficulties in concentration. Seven pts. continued treatment with ESL. One discontinued due to lack of efficacy, one because of concentration difficulties (which were also present before the switch, and one due to increased thirst, probably unrelated to ESL). Alertness improved, but did not reach significant levels (p=0.09). QOLIE 10 showed no significant difference (p=0.08). Conclusions: Overnight switch from OXC to ESL was safe and easy to perform. Clinical improvements were seen immediately after the switch. Most pts. continued treatment with ESL.