Can Tripletal (Oxcarbazepine) cause hyponatremia?

Can Trileptal (Oxcarbazepine) Cause Hyponatremia?

Yes, Trileptal (oxcarbazepine) is a well-established cause of hyponatremia, with clinically significant hyponatremia (sodium <125 mmol/L) occurring in approximately 2.5% of treated patients, typically within the first 3 months of therapy. 1

Mechanism and Incidence

Oxcarbazepine causes hyponatremia through inappropriate antidiuretic hormone (ADH) secretion, leading to water retention and subsequent dilutional hyponatremia 1. The overall frequency of any degree of hyponatremia (sodium ≤134 mEq/L) ranges from 24.7% to as high as 51% in cross-sectional studies, though most cases are asymptomatic 2, 3. Severe hyponatremia (sodium ≤128 mEq/L) occurs in approximately 8.2% of patients, while symptomatic hyponatremia requiring intervention occurs in 6.8% of cases 2.

Risk Factors to Identify

You should specifically assess for these risk factors before and during oxcarbazepine therapy:

• Advanced age - Each additional year increases risk by 1.4% for severe hyponatremia and 3.4% for symptomatic hyponatremia 2
• Polytherapy with other antiepileptic drugs - Increases risk of severe hyponatremia by 54% 2, 4
• Concomitant diuretic use - Increases risk of severe hyponatremia 5.6-fold and symptomatic hyponatremia 2.2-fold 2
• Higher oxcarbazepine dosages - Doses above 30 mg/kg/day significantly increase hyponatremia risk, with each 1 mg increase raising risk by 0.2% 4, 3
• Medications that lower sodium - Including oral contraceptives and NSAIDs 5
• Pre-existing renal disease 5

Clinical Presentation

Most patients with oxcarbazepine-induced hyponatremia are asymptomatic 1. When symptoms occur, they include nausea, malaise, headache, lethargy, confusion, obtundation, gait disturbance, somnolence, or increased seizure frequency 1, 4. Rare cases can progress to syndrome of inappropriate antidiuretic hormone secretion (SIADH) 1.

Monitoring Algorithm

Baseline assessment:

• Measure serum sodium before initiating oxcarbazepine if the patient has renal disease, takes medications that lower sodium (diuretics, oral contraceptives, NSAIDs), or has any clinical symptoms suggesting hyponatremia 5

During maintenance therapy:

• Monitor serum sodium at least every 3 months, particularly during the first 3 months when hyponatremia most commonly develops 1, 2
• Increase monitoring frequency in elderly patients, those on polytherapy, or those taking concomitant diuretics 2
• Check sodium immediately if symptoms develop (headache, malaise, gait disturbance, somnolence, confusion, nausea, or increased seizures) 1, 4

Management When Hyponatremia Occurs

For asymptomatic mild hyponatremia (sodium 126-134 mEq/L):

• Continue oxcarbazepine with close monitoring 5
• Consider fluid restriction if appropriate 6

For severe hyponatremia (sodium ≤125 mEq/L) or any symptomatic hyponatremia:

• Reduce oxcarbazepine dose or discontinue the drug 1, 4
• Restrict fluid intake 1
• Serum sodium generally normalizes within a few days after discontinuation without additional treatment 1

For severe symptomatic hyponatremia with neurological symptoms:

• Follow standard hyponatremia correction protocols with 3% hypertonic saline if needed 6
• Correct by 6 mmol/L over 6 hours or until symptoms resolve 6
• Never exceed 8 mmol/L correction in 24 hours to prevent osmotic demyelination syndrome 6

Critical Pitfall to Avoid

The most common error is failing to monitor sodium levels in high-risk patients (elderly, polytherapy, diuretic use) during the first 3 months of therapy when hyponatremia most frequently develops 2. Even asymptomatic hyponatremia can progress to symptomatic cases if unrecognized, and the clinically significant symptomatic hyponatremia rate of 2.8% among all oxcarbazepine-treated patients is substantial enough to warrant vigilant monitoring 2.