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.

• Authors: Robert T Wechsler, Rodney A Radtke, Michael Smith, David G Vossler, Laura Strom, Eugen Trinka, Hailong Cheng, Todd Grinnell, David Blum, Mariana Vieira, Joana Moreira, Francisco Rocha
• Journal: Epilepsia (Epilepsia) Vol. 60 Issue 7 Pg. 1341-1352 (07 2019) ISSN: 1528-1167 [Electronic] United States
• PMID: 31260089 (Publication Type: Clinical Trial, Phase III, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

Chemical References

• Anticonvulsants
• Dibenzazepines
• Sodium
• eslicarbazepine

Topics

• Adolescent
• Adult
• Aged
• Anticonvulsants (adverse effects, therapeutic use)
• Dibenzazepines (adverse effects, therapeutic use)
• Epilepsies, Partial (drug therapy)
• Epilepsy (drug therapy)
• Humans
• Hyponatremia (chemically induced)
• Middle Aged
• Sodium (blood)
• Young Adult