Symptomatology of carbamazepine‐ and oxcarbazepine‐induced hyponatremia in people with epilepsy

Abstract

Objective To ascertain whether adverse effects experienced by people taking carbamazepine or oxcarbazepine could be attributed to carbamazepine‐ or oxcarbazepine‐induced hyponatremia (COIH). Methods We performed an observational study, collecting data between 2017 and 2019 on serum sodium levels and adverse effects retrospectively in people with epilepsy while receiving treatment with either carbamazepine (CBZ) or oxcarbazepine (OXC). We defined hyponatremia as sodium level ≤134 mEq/L and severe hyponatremia as sodium level ≤128 mEq/L. Adverse effects experienced were compared between groups of individuals with and without hyponatremia. Results A total of 1370 people using CBZ or OXC were identified, of whom 410 had at least one episode of hyponatremia. We checked for symptoms related to the use of CBZ and OXC in 710 people (410 with and 300 without hyponatremia) and found relevant information in 688. Adverse effects occurred in 65% of people with hyponatremia compared to 21% with normal sodium levels (odds ratio [OR] 7.5, P ≤ .001) and in 83% of people with severe hyponatremia compared to 55% in those with mild hyponatremia (P ≤ .001). Significant predictors of adverse effects were the drug (OXC vs CBZ), and the number of concomitant anti‐seizure medications. Dizziness (28% vs 6%), tiredness (22% vs 7%), instability (19% vs 3%), and diplopia (16% vs 4%) were reported more often in the hyponatremia group than in patients with normal levels. Significance People with COIH had a 7‐fold increased risk of developing adverse effects during treatment. Clinicians should consider ascertainment of sodium levels in patients taking CBZ and OXC and act upon findings.

Thirteen years of experience with eslicarbazepine acetate in the United Kingdom and Republic of Ireland: A safety perspective

“…16 Acute symptomatic seizures, dizziness, tiredness (fatigue), instability, and diplopia have been reported more often in hyponatremia groups than in patients with normal levels of sodium. 17 In the current study, seizure (4.5%), hyponatremia (4.2%), dizziness (2.7%), rash (2.5%), and fatigue (2.5%) were also among the most common AEs identified.…”

“…The safety profile observed in this long‐term PMS analysis supports the results from a previous worldwide 6 years PMS analysis, 16 in which the most commonly identified AEs were hyponatremia (10.2%), seizure (5.8%), dizziness (4.1%), rash (2.6%), fatigue (2.1%), and nausea (1.8%) 16 . Acute symptomatic seizures, dizziness, tiredness (fatigue), instability, and diplopia have been reported more often in hyponatremia groups than in patients with normal levels of sodium 17 . In the current study, seizure (4.5%), hyponatremia (4.2%), dizziness (2.7%), rash (2.5%), and fatigue (2.5%) were also among the most common AEs identified.…”

Characterization in Inhibitory Effectiveness of Carbamazepine in Voltage-Gated Na+ and Erg-Mediated K+ Currents in a Mouse Neural Crest-Derived (Neuro-2a) Cell Line

“…CBZ has been increasingly demonstrated to cause hyponatremia, which mimics the syndrome of inappropriate antidiuretic hormone secretion [ 11 , 12 , 13 , 14 , 15 , 16 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 27 ]. Esaxerenone, known to be a nonsteroidal mineralocorticoid receptor blocker, was demonstrated to modify the magnitude and gating of I Na [ 38 ], while sparsentan, a dual antagonist of endothelial type A receptor and angiotensin II receptor, could suppress I Na [ 41 ].…”

“…Of additional notice, although CBZ is safe and effective in anti-convulsant activities, the unwanted events following CBZ treatment, such as hyponatremia, QT-interval prolongation, hyperprolactinemia, change in pitch perception and idiosyncratic reactions, have gradually emerged [ 5 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ]. The effectiveness of CBZ in inhibiting the activity of ATP-sensitive K + (K ATP ) channels has also been demonstrated [ 29 , 30 ].…”

Oxcarbazepine and Hyponatremia

“…This hypothesis was analyzed in a previous study where 1370 patients treated with CBZ or OXC were identified, 410 of whom had at least one episode of hyponatremia. Authors found that adverse effects (dizziness, tiredness, instability, and diplopia) occurred in 65% of participants with hyponatremia compared to 21% with normal sodium levels (odds ratio 7.5, p ≤ 0.001) and in 83% of people with severe hyponatremia compared to 55% in those with mild hyponatremia ( p ≤ 0.001) [ 18 ]. Previous studies also found that even mild chronic hyponatremia can cause neurocognitive deficits and gait disturbance falls, and the treatment of this disturbance of electrolytes improved neurocognitive and neuromuscular function [ 19 , 20 ].…”