How to manage hyponatremia (low sodium levels) induced by oxcarbazepine (Trileptal)

From the Guidelines

Oxcarbazepine-induced hyponatremia should be managed by discontinuing the medication in severe cases (below 125 mEq/L) or when symptoms occur, and considering alternative antiepileptic medications like levetiracetam or lamotrigine. For mild to moderate hyponatremia, the approach involves monitoring sodium levels and restricting fluid intake. However, the provided evidence 1 primarily focuses on hyponatremia management in cirrhosis, which may not directly apply to oxcarbazepine-induced hyponatremia. In the context of oxcarbazepine-induced hyponatremia, the following steps can be considered:

• For mild cases (sodium 130-135 mEq/L), monitor sodium levels regularly while restricting fluid intake to 1-1.5 liters daily.
• For moderate hyponatremia (125-130 mEq/L), consider reducing the oxcarbazepine dose by 25-50% while continuing fluid restriction and monitoring.
• In severe cases (below 125 mEq/L) or when symptoms like confusion, headache, or seizures occur, discontinue oxcarbazepine and switch to an alternative antiepileptic medication. Key considerations include:
• Regular monitoring of sodium levels
• Fluid restriction
• Potential dose adjustment or discontinuation of oxcarbazepine
• Alternative antiepileptic medications
• Consultation with specialists for individualized management plans when necessary, as oxcarbazepine's effect on water reabsorption in the kidneys through increased antidiuretic hormone (ADH) activity can lead to dilutional hyponatremia 1.

From the FDA Drug Label

Clinically significant hyponatremia (sodium <125 mmol/L) can develop during oxcarbazepine use. In the 14 controlled epilepsy studies 2. 5% of oxcarbazepine-treated patients (38/1,524) had a sodium of less than 125 mmol/L at some point during treatment, Most patients who developed hyponatremia were asymptomatic but patients in the clinical trials were frequently monitored and some had their oxcarbazepine dose reduced, discontinued, or had their fluid intake restricted for hyponatremia. Whether or not these maneuvers prevented the occurrence of more severe events is unknown Cases of symptomatic hyponatremia and syndrome of inappropriate antidiuretic hormone secretion (SIADH) have been reported during postmarketing use. In clinical trials, patients whose treatment with oxcarbazepine was discontinued due to hyponatremia generally experienced normalization of serum sodium within a few days without additional treatment Measurement of serum sodium levels should be considered for patients during maintenance treatment with oxcarbazepine, particularly if the patient is receiving other medications known to decrease serum sodium levels (e.g., drugs associated with inappropriate ADH secretion) or if symptoms possibly indicating hyponatremia develop (e.g., nausea, malaise, headache, lethargy, confusion, obtundation, or increase in seizure frequency or severity) 2.

To manage hyponatremia induced by oxcarbazepine, the following steps can be taken:

• Monitor serum sodium levels regularly, especially in patients receiving other medications that can lower sodium levels or in those with symptoms indicating hyponatremia.
• Reduce or discontinue oxcarbazepine if hyponatremia occurs, as this may help normalize serum sodium levels.
• Restrict fluid intake in some cases, although the effectiveness of this measure is unknown.
• Be aware of symptoms of hyponatremia, such as nausea, malaise, headache, lethargy, confusion, obtundation, or increased seizure frequency or severity, and report them to a healthcare provider immediately. In general, patients who develop hyponatremia due to oxcarbazepine may experience normalization of serum sodium levels within a few days after discontinuing the medication, without requiring additional treatment 2.

From the Research

Management of Hyponatremia Induced by Oxcarbazepine

To manage hyponatremia induced by oxcarbazepine, the following steps can be taken:

• Monitor serum sodium levels regularly, especially in patients with risk factors such as old age, antiepileptic drug polytherapy, or concomitant use of diuretics 3, 4, 5
• Adjust the dosage of oxcarbazepine or discontinue the drug if symptoms of hyponatremia occur 3, 4
• Be aware of the potential for hyponatremia in patients taking oxcarbazepine, especially in the first few months of treatment 6, 7
• Consider alternative antiepileptic medications if hyponatremia persists or is severe 3, 4

Risk Factors for Hyponatremia

Several risk factors for hyponatremia have been identified, including:

• Age: older patients are at higher risk of developing hyponatremia 3, 5
• Antiepileptic drug polytherapy: taking multiple antiepileptic drugs increases the risk of hyponatremia 3, 4
• Concomitant use of diuretics: taking diuretics with oxcarbazepine increases the risk of hyponatremia 3
• Duration of treatment: longer duration of treatment with oxcarbazepine increases the risk of hyponatremia 5
• Dosage of oxcarbazepine: higher dosages of oxcarbazepine increase the risk of hyponatremia 4

Mechanisms of Hyponatremia

The mechanisms of hyponatremia induced by oxcarbazepine are not fully understood, but possible mechanisms include:

• Direct effect of oxcarbazepine on the renal collecting tubules 7
• Enhancement of the responsiveness of the renal collecting tubules to circulating antidiuretic hormone 7
• Syndrome of inappropriate secretion of antidiuretic hormone (although this has been ruled out in some studies) 7