Abstracts

Rationale: Eslicarbazepine acetate (ESL) is a voltage-gated sodium channel blocker approved in 2009 by the European Medicines Agency as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization. Approved doses are between 800 to 1200 mg/day. ESL has also received US Food and Drug Administration approval as a monotherapy with doses up to 1600 mg/day. However, from routine clinical practice it appears that a wide range of doses (from 400 to 1600 mg/day) can also be useful as adjunctive therapy. Our aim is to describe the plasma levels of ESL and the clinical outcome of patients on doses from 400mg to 1600mg/day. Methods: We performed a retrospective analysis of all patients taking ESL in which ESL plasma levels were done from December 2017 to May 2018. Measurement of (S)-10-Hydroxycarbazepine (ESL) was conducted using an Acquity® UPLC®-TQD® integrated measurement system (Waters, Milford, MA, USA). Following a protein precipitation extraction with acetonitrile, chromatographic separation was achieved using an Acquity® UPLC® BEHTM (2.1x100 mm id, 1.7 µm) reverse-phase C18 column, with a water/acetonitrile non-linear gradient containing 0.1% formic acid at a 0.5 mL/min flow rate. ESL and its internal standard (oxcarbazepine-D4) were detected by electrospray ionization (ESI) mass spectrometry in positive ion multiple reaction monitoring mode (MRM) using mass-to-charge transitions of 254.9®194.3 and 256.8®184.3, respectively. Therapeutic interval was considered between 10-35 mg/l. Results: Thirty-three patients were included. Median dose of ESL was 1200 mg/day, with median plasma levels of 16.1mg/l (range 8.3-37.2). In the patients taking 400mg/day (n=3), median plasma levels were 13.6 mg/l (range 9.5 – 15.4), being the three patients seizure-free (100%) since the introduction of  the drug  Patients taking 800 mg/day (n=11) had median plasma levels of 14 mg/l (range 8.3-22.8) being seizure free six patients (54%) and the ones taking 1200 mg/day (n=14) had a median plasma level of 19.15 mg/l (range 9.1-33-7) being seizure free 2 (14.3%). Among the patients taking 800 or 1200 mg/day, 16% (n=4) had infratherapeutic plasma levels. Regarding patients taking 1600 mg/day (n=5), median plasma levels were 20.4 mg/l (range 11.8-37.2). Only one patient had supratherapeutic levels (37.2 mg/l). Two of them reported an additional 50% reduction in seizure frequency; no one reported any side effects.  Conclusions: Patients could benefit of a wider range of ESL dosage because some patients, the 800 mg/day or 1200 mg/day doses did not reach therapeutic plasma levels According to our data, doses from 400mg/day to 1600mg/day reached therapeutic plasma levels on most of the cases. Funding: No funding