Abstracts

Rationale: Disturbances in serum lipid profiles have been reported following treatment with some anti epileptic drugs (AEDs) (Chuang YC et al, Epilepsia 2012;53:120 8). Eslicarbazepine acetate (ESL) is a once-daily antiepileptic, extensively and rapidly converted to eslicarbazepine after oral administration. Eslicarbazepine stabilizes the inactivated state of voltage-gated sodium channels and blocks T-type voltage-gated calcium channels. ESL was approved in 2009 by the European Medicines Agency as adjunctive therapy in adults with partial-onset seizures (POS), with or without secondary generalization. ESL is in clinical development for the treatment of POS in the United States but it is not approved. Interaction studies have shown that ESL decreases exposure to simvastatin and rosuvastatin. This post-hoc analysis assessed the effect of ESL on serum lipid profiles, according to statin use at baseline.Methods: A post-hoc analysis of 8 placebo-controlled trials (3 phase III epilepsy trials and 5 phase II non-epilepsy trials) was performed. The epilepsy trials recruited patients aged 16 or 18 years with POS not adequately controlled with 1 2 or 1 3 AEDs. After an 8-week baseline, patients were randomized to QD placebo or ESL 400mg (2 studies only), 800mg, or 1200mg. Patients then entered a 2-week, double-blind titration phase followed by a 12-week double-blind, fixed-dose maintenance phase. Non-epilepsy phase II trials were performed in patients with bipolar disorder, postherpetic neuralgia, migraine, and fibromyalgia and featured treatment periods of 3 14 weeks; ESL was administered QD or BID at doses of 400 2400mg/day. For both epilepsy and non-epilepsy trials, changes in serum lipid levels from baseline to the final visit were calculated and pooled by use or non-use of statins at baseline. Results: A total of 426 placebo-treated and 1021 ESL-treated patients were included in the epilepsy trials analysis, of whom 18 (4.2%) and 46 (4.5%), respectively, were statin users. Concomitant statin use in the ESL-treated patients included simvastatin (n=23), atorvastatin (n=12), fluvastatin (n=2), lovastatin (n=3), pravastatin (n=6) and rosuvastatin (n=4). The non-epilepsy trials analysis included 411 placebo-treated patients and 1294 ESL-treated patients (median daily dose in the ESL group, 755mg; median duration of ESL exposure, 64 days). In these trials, 19 (4.6%) and 98 (7.6%) of placebo- and ESL-treated patients, respectively, were statin users. Changes in serum lipid levels are shown in Tables 1 and 2.Conclusions: In non-statin users, ESL did not have a clinically significant impact on serum lipid levels. Although only a low number of statin users participated in the analyzed trials, the impact of ESL on serum lipids in these patients was small, despite the fact that over half were taking a statin known to be induced by ESL. This suggests that the induction of statin metabolism by ESL may not be clinically relevant, thereby obviating dose adjustment or alternative lipid-lowering therapy in ESL-treated patients.