Dibenzazepine Agents in Epilepsy: How Does Eslicarbazepine Acetate Differ?

Abstract

Carbamazepine (CBZ), oxcarbazepine (OXC), and eslicarbazepine acetate (ESL) belong to the dibenzazepine family of antiepileptic drugs and are all thought to primarily act as sodium channel blockers (SCBs). However, ESL is structurally distinct from CBZ and OXC, resulting in differences in metabolism, pharmacokinetics, and pharmacodynamics. Despite a lack of direct comparative data, evidence for potential differences in effectiveness and tolerability within the dibenzazepine family has emerged from studies in which patients being treated with one dibenzazepine agent have received adjunctive treatment with another (having achieved insufficient seizure control with the first) or have transitioned from one dibenzazepine agent to another because of lack of effectiveness or poor tolerability. Most of these studies have been conducted in the real-world clinical practice setting. ESL has been shown to be effective as adjunctive therapy in patients who have previously achieved inadequate seizure control with CBZ, indicating that the use of different dibenzazepine agents in combination can provide additive effectiveness benefits, which may reflect underlying differences in their mechanisms of action. Similarly, ESL monotherapy can be effective in patients who have switched from another dibenzazepine, such as CBZ or OXC, because of inadequate efficacy. There is also considerable evidence to demonstrate that patients transitioning from OXC or CBZ to ESL as a result of adverse events experience improvements in tolerability, which may also be associated with improvements in quality of life, alertness, and/or lipid profiles. Current evidence therefore demonstrates that ESL differs from other dibenzazepine agents in terms of effectiveness and tolerability.Funding: Eisai Ltd.

Long‐term efficacy and safety of eslicarbazepine acetate monotherapy for adults with newly diagnosed focal epilepsy: An open‐label extension study

“…Studies conducted primarily in the clinical practice setting have demonstrated that ESL monotherapy can be effective in patients who have transitioned from CBZ monotherapy due to lack of efficacy or poor tolerability. 23 The current study demonstrated that ESL monotherapy maintained seizure control in the majority of patients who transitioned from CBZ-CR to ESL, but the higher risk of seizures observed in the CBZ-CR/ESL group during the first 3-4 months, compared with the ESL/ESL group, illustrates the challenges associated with switching patients from one ASM to another. Published guidance has highlighted that transitioning patients from CBZ to ESL requires careful consideration on a patient-by-patient basis, primarily because CBZ may have a different mechanism of action than ESL [24][25][26] and is a stronger inducer of cytochrome P450 enzymes.…”

“…Studies conducted primarily in the clinical practice setting have demonstrated that ESL monotherapy can be effective in patients who have transitioned from CBZ monotherapy due to lack of efficacy or poor tolerability 23 . The current study demonstrated that ESL monotherapy maintained seizure control in the majority of patients who transitioned from CBZ‐CR to ESL, but the higher risk of seizures observed in the CBZ‐CR/ESL group during the first 3‐4 months, compared with the ESL/ESL group, illustrates the challenges associated with switching patients from one ASM to another.…”

The evidence for switching dibenzazepines in people with epilepsy

“…CBZ is commonly associated with increased serum lipid levels, and there is potential for severe rebound seizures with both CBZ and OXC when adherence is low. 3,4 A key difference between ESL and CBZ is the pharmacokinetic profile and metabolism which conveys real clinical utility. Eslicarbazepine acetate has high bioavailability reaching peak concentration within 2-3 hours, with a significantly longer half-life of 20-24 hours (depending on population studied).…”

“…CBZ specifically has major potential for significant drug to drug interactions. CBZ is commonly associated with increased serum lipid levels, and there is potential for severe rebound seizures with both CBZ and OXC when adherence is low 3,4 . A key difference between ESL and CBZ is the pharmacokinetic profile and metabolism which conveys real clinical utility.…”

Clinical outcomes of eslicarbazepine acetate monotherapy for focal‐onset seizures: A multicenter audit

“…Eslicarbazepine acetate (ESL) is a voltage‐gated sodium channel blocker antiepileptic drug that belongs to the dibenzazepine family. However, compared to carbamazepine and oxcarbazepine, also members of the same family, ESL has a variety of advantages that include better metabolic and tolerability profiles, lower risk of allergic reactions, and drug interactions . Additional properties of ESL such as its simple titration schedule and the possibility of once‐daily dosing make it a suitable option for monotherapy treatment in patients with focal epilepsy.…”