Serum sodium levels and related treatment‐emergent adverse events during eslicarbazepine acetate use in adults with epilepsy

Abstract

Objective To examine the frequency of hyponatremia and potentially related symptoms in clinical trials of eslicarbazepine acetate (ESL) in adults with focal‐ (partial‐) onset seizures. Methods This post hoc, exploratory analysis included data from three controlled phase 3 trials of adjunctive ESL (400‐1200 mg once daily), two phase 3 trials of ESL monotherapy (1200‐1600 mg once daily), and their open‐label extension studies. Exploratory endpoints included clinical laboratory measurements of serum sodium concentrations ([Na+]), incidences of hyponatremia‐related treatment‐emergent adverse events (TEAEs), and incidences of TEAEs that are potential symptoms of hyponatremia. Results The controlled trials of adjunctive ESL and ESL monotherapy included 1447 (placebo, n = 426; ESL, n = 1021) and 365 (ESL, n = 365) patients, respectively; 639 and 274 patients continued onto uncontrolled, open‐label extensions. In the controlled and uncontrolled trials ≤3.3% of patients taking ESL had a minimum postdose [Na+] measurement ≤125 mEq/L, <9% had a >10 mEq/L decrease in [Na+] from baseline, <6% had a hyponatremia‐related TEAE, and <2% discontinued the controlled trials due to a hyponatremia‐related TEAE. Hyponatremia appeared to be more frequent in the monotherapy (vs adjunctive therapy) trials; in the controlled trials of adjunctive ESL and ESL monotherapy, incidence generally increased with increasing ESL dose. The majority of patients with an investigator‐reported TEAE of “hyponatremia” or “blood sodium decreased” did not have a corresponding laboratory [Na+] measurement ≤125 mEq/L. Some symptoms potentially related to hyponatremia (including nausea and vomiting) were more frequent in patients with a minimum postdose [Na+] measurement ≤125 mEq/L. Significance Reductions in serum sodium concentrations and hyponatremia‐related TEAEs occurred in a small number of patients taking ESL. Suspected hyponatremia should be confirmed and monitored via [Na+] measurements.

Seizures and Epilepsy After Stroke: Epidemiology, Biomarkers and Management

“…Hyponatraemia may commonly occur through pharmacodynamic interactions when carbamazepine, oxcarbazepine, or eslicarbazepine acetate are prescribed to patients treated with thiazides or other diuretic drugs [ 123 , 124 ]. Oxcarbazepine has the highest propensity to cause hyponatraemia.…”

Experience with Eslicarbazepine Acetate Treatment at a Pediatric Epilepsy Center

“…Hyponatremia, another dosagerelated AE, was reported in <1% patients. 18,21 Two (6%) patients in our study developed hyponatremia, and both recovered quickly and were able to continue ESL treatment.…”

Eslicarbazepine‐induced severe hyponatremia resulted in generalized tonic‐clonic seizure

“… 17 Furthermore, the latter study reported increased seizure frequency and severity with ESL‐associated hyponatremia, and secondary generalization (3.3% of patients) was only observed in mild to moderate hyponatremia subgroups. 17 …”

“…Convulsions and focal seizures with secondary generalization were described more frequently in patients with serum sodium level below 125 mEq/L. 17 Furthermore, the latter study reported increased seizure and severity with ESL-associated hyponatremia, and secondary generalization (3.3% of patients) was only observed in mild to moderate hyponatremia subgroups. 17 In our case, the patient has had a history of longstanding focal epilepsy which was controlled with ESL, but he came with GTC seizure for the first time which could be primarily generalized or secondary to a focal seizure.…”

“…Convulsions and focal seizures with secondary generalization were described more frequently in patients with serum sodium level below 125 mEq/L. 17 Furthermore, the latter study reported increased seizure frequency and severity with ESL‐associated hyponatremia, and secondary generalization (3.3% of patients) was only observed in mild to moderate hyponatremia subgroups. 17 …”