Safety, tolerability and effectiveness of transition to eslicarbazepine acetate from carbamazepine or oxcarbazepine in clinical practice.

2020-01-07

PURPOSE:

To assess the efficacy, safety and tolerability of eslicarbazepine acetate (ESL) in patients transitioning from carbamazepine or oxcarbazepine to ESL in clinical practice, by analysing data from the Euro-Esli study.

METHODS:

Euro-Esli was a pooled analysis of 14 European clinical practice studies. Effectiveness assessments included responder rate (?50 % seizure frequency reduction) and seizure freedom rate (seizure freedom at least since prior visit), assessed after 3, 6 and 12 months of ESL treatment, and at the last visit. Safety and tolerability were assessed throughout follow-up by evaluating adverse events (AEs) and ESL discontinuation due to AEs, respectively. Data were analysed for cohorts of patients who transitioned from carbamazepine and oxcarbazepine to ESL either due to lack of efficacy or poor tolerability.

RESULTS:

Euro-Esli included 2058 patients, of whom 233 (11.3 %) transitioned from carbamazepine to ESL and 134 (6.5 %) transitioned from oxcarbazepine to ESL. After 12 months of ESL treatment, responder and seizure freedom rates for patients transitioning from carbamazepine due to lack of efficacy (n?=?163) were 70.0 % and 30.9 %, respectively. Corresponding values for patients transitioning from oxcarbazepine due to lack of efficacy (n?=?90) were 57.1 % and 25.0 %, respectively. Among patients who transitioned from carbamazepine and oxcarbazepine to ESL due to poor tolerability (n?=?64 and n?=?61, respectively), 26.6 % and 39.5 % experienced AEs, and 8.3 % and 6.8 % discontinued ESL due to AEs, respectively.

CONCLUSION:

ESL was efficacious and generally well tolerated in patients transitioning from carbamazepine or oxcarbazepine in clinical practice due to inadequate seizure control or intolerable AEs with these agents.

~tCarvacrol inhibits the neuronal voltage-gated sodium channels Nav1.2, Nav1.6, Nav1.3, Nav1.7, and Nav1.8 expressed in Xenopus oocytes with different potencies.

Carvacrol is the predominant monoterpene in essential oils from many aromatic plants. Several animal studies showing analgesic effects of carvacrol indicate potential of carvacrol as a new medication for patients with refractory pain. Voltage-gated sodium channels (Nav) are thought to have crucial roles in the development of inflammatory and neuropathic pain, but there is limited information about whether the analgesic mechanism of carvacrol involves Nav. We used whole-cell, two-electrode, voltage-clamp techniques to examine the effects of carvacrol on sodium currents in Xenopus oocytes expressing ? subunits of Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8. Carvacrol dose-dependently suppressed sodium currents at a holding potential that induced half-maximal current. The half-maximal inhibitory concentration values for Nav1.2, Nav1.3, Nav1.6, Nav1.7, and Nav1.8 were 233, 526, 215, 367, and 824 ?mol/L, respectively, indicating that carvacrol had more potent inhibitory effects towards Nav1.2 and Nav1.6 than Nav1.3, Nav1.7, and Nav1.8. Gating analysis showed a depolarizing shift of the activation curve and a hyperpolarizing shift of the inactivation curve in all five ? subunits following carvacrol treatment. Furthermore, carvacrol exhibits a use-dependent block for all five ? Nav subunits. These findings provide a better understanding of the mechanisms associated with the analgesic effect of carvacrol.

Authors: Rocamora R, Peltola J, Assenza G, McMurray R, Villanueva V
; Full Source: Seizure. 2020 Feb;75:121-128. doi: 10.1016/j.seizure.2019.12.022. Epub 2019 Dec 23.
; Authors: Horishita T, Ogata Y, Horishita R, Fukui R, Moriwaki K, Ueno S, Yanagihara N, Uezono Y, Sudo Y, Minami K