Serum sodium, potassium, and magnesium in children with epilepsy treated with levetiracetam monotherapy: A prospective study

To the Editor,

Levetiracetam (Lev) is a relative new, broad‐spectrum antiepileptic drug whose efficacy and low profile of toxicity in epilepsy treatment are well recognized.1 Lev‐associated hyponatremia, hypokalemia, and hypomagnesemia have been described in adult patients.2, 3, 4, 5, 6, 7, 8 However, there are no reports on the above Lev‐associated disorders in children with epilepsy treated with Lev monotherapy. The objective of this study was to prospectively investigate changes in serum sodium, potassium, and magnesium in children with epilepsy treated with Lev monotherapy. This is the first pediatric study evaluating the effect of Lev on serum electrolytes in a prospective manner.

The study population consisted of 32 children (18 females, 14 males, mean age 5.94 ± 4.1 years, range 1‐15 years) that were treated for new‐onset epilepsy with Lev monotherapy. Twenty‐four children suffered from a localization‐related epilepsy and 8 from a generalized epilepsy. Lev was prescribed at a dose of 10‐45 mg/Kg/day. Apart from epilepsy, all patients were judged to be in good health with nutritionally adequate diets, normal liver and renal function and absence of any other medication. An informed parental consent was obtained, and the study was approved by the Institutional Review Board of “Attikon” University Hospital.

Serum sodium, potassium, and magnesium were measured before and at 2 and 6 months of Lev treatment. A fasting blood sample was obtained in the morning, between 8.00 and 10.00 am. Biochemical measurements were performed at Department of Clinical Biochemistry of “Attikon” University Hospital.

Data were expressed as mean ± SD values and were analyzed using the statistical package for social sciences (SPSS 23.0, Chicago IL). The Wilcoxon signed‐ranks test was used to assess the significance of changes of parameters at base and after treatment with Lev. A P value <0.05 was considered as statistically significant.

Results are shown in Table 1. There were no significant alterations in serum sodium, potassium, and magnesium during Lev treatment. All parameters evaluated were within normal limits. Mean value of drug dosage (mg/Kg) was 18.1 ± 7.14 at 2 months and 20.8 ± 10.1 at 6 months of treatment.

Table 1.

Serum sodium, potassium, and magnesium in 32 children with epilepsy during levetiracetam monotherapy

Parameters	Pretreatment	2 months	P	6 months	P
Sodium (mmol/L)	140 ± 2.72 (140)	140 ± 2.29 (141)	0.991	140 ± 2.24 (140.5)	0.345
Potassium (mmol/L)	4.59 ± 0.33 (4.55)	4.61 ± 0.37 (4.60)	0.922	4.67 ± 0.37 (4.60)	0.450
Magnesium (mg/dL)	2.17 ± 0.15 (2.15)	2.15 ± 0.18 (2.15)	0.314	2.13 ± 0.17 (2.10)	0.208

Values are expressed as mean ± SD, (median).

In the literature, hyponatremia has been reported in 5 asymptomatic adults during Lev treatment.2, 3, 4, 5, 6 Hyponatremia was found as early as 3 days and up to 2 years after initiation of Lev treatment. The disorder has been associated with inappropriate antidiuretic hormone secretion (SIADH),2, 4, 5, 6 although no evident predisposition to SIADH has also been described.3 Advanced age and female gender have been suggested as predisposing factors for Lev‐associated hyponatremia.2, 3, 4, 5, 6

Hypokalemia and hypomagnesemia have been described in 3 asymptomatic adult patients, 2 days to 6 weeks after the administration of Lev. Transcellular shift of K⁺ and renal tubular disorder have been proposed as possible causes for these disorders. However, the exact pathogenetic mechanism of Lev‐induced hypokalemia and hypomagnesemia remains unknown. Advanced age has been suggested as a possible predisposing factor.8

So far, the effect of Lev monotherapy on serum electrolytes has not been investigated in prospective studies. The present study did not show any significant effect of Lev treatment on serum sodium, potassium, and magnesium in children with epilepsy, at 2 and at 6 months of therapy. Young age of our patients may have played a protective role in the prevention of Lev‐induced electrolyte disorders. However, further studies are needed to clarify whether children are less vulnerable than adults in the occurrence of Lev‐associated electrolyte disorders.

There are limitations to this study: the number of patients studied was small and changes in serum/urine osmolality and urine electrolytes were not measured. An advantage of the present report is the prospective design and the homogeneity of the study group and, thus, the absence of confounders such as duration of drug treatment or different antiepileptic drug combination.

CONFLICT OF INTEREST

None of the authors has any conflict of interest to disclose.