Effects of adjunctive eslicarbazepine acetate on serum lipids in patients with partial-onset seizures: Impact of concomitant statins and enzyme-inducing antiepileptic drugs.

Abstract

PURPOSE:

To evaluate the effects of eslicarbazepine acetate (ESL) on lipid metabolism and to determine whether reduced statin exposure during ESL therapy has clinical consequences.

SUBJECTS AND METHODS:

We conducted a post-hoc analysis of pooled data for serum lipids (laboratory values) from three phase III, multicenter, randomized, double-blind, placebo-controlled trials of adjunctive ESL therapy (400, 800, or 1200 mg once daily) in patients with treatment-refractory partial-onset seizures. Changes from baseline in serum lipid levels were analyzed according to use of statins and/or enzyme-inducing antiepileptic drugs (EIAEDs) during the baseline period.

KEY FINDINGS:

In total, 426 and 1021 placebo- and ESL-treated patients, respectively, were included in the analysis. With regard to the changes from baseline in serum concentrations, there were statistically significant differences between the placebo and ESL 1200 mg QD groups, for both total cholesterol (TC) and high-density lipoprotein cholesterol (HDL-C), but the effect sizes were small (+4.1 mg/dL and +1.8 mg/dL, respectively). A small but significant difference in low-density lipoprotein cholesterol (LDL-C; -5.0 mg/dL) was observed between the ESL 400 mg QD group and the placebo group. In patients not taking a concomitant EIAED, there were no changes with ESL 400 mg QD, but modest and statistically significant increases in cholesterol fractions (TC, LDL-C and HDL-C) with ESL 800 mg QD (<6 mg/dL) and ESL 1200 mg QD (<10 mg/dL). ESL had no consistent effect on lipids in patients taking a concomitant EIAED. In patients taking statins during baseline, there were no clinically relevant changes in serum lipids during use of ESL, although the subgroups were small.

SIGNIFICANCE:

These results suggest that ESL does not appear to have clinically significant effects on serum lipids, nor does the pharmacokinetic interaction between ESL and statins have an impact on serum lipid concentrations.

• Authors: Scott Mintzer, Robert T Wechsler, Joanne B Rogin, Barry E Gidal, Matthias Schwab, Elinor Ben-Menachem, Mar Carreño, Patrício Soares da Silva, Joana Moreira, Yan Li, David Blum, Todd Grinnell
• Journal: Epilepsy research (Epilepsy Res) Vol. 141 Pg. 83-89 (03 2018) ISSN: 1872-6844 [Electronic] Netherlands
• PMID: 29499473 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Anticonvulsants
• Dibenzazepines
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Lipids
• eslicarbazepine acetate

Topics

• Adolescent
• Adult
• Aged
• Anticonvulsants (pharmacology, therapeutic use)
• Dibenzazepines (pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Enzyme Induction (drug effects)
• Female
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, pharmacology)
• Lipids (blood)
• Male
• Middle Aged
• Seizures (blood, drug therapy)
• Treatment Outcome
• Young Adult