How to manage hyponatremia in patients taking Eslicarbazepine (antiepileptic drug)?

Management of Eslicarbazepine-Induced Hyponatremia

Monitor serum sodium levels regularly in all patients taking eslicarbazepine, and if hyponatremia develops, manage it based on severity while considering dose reduction or discontinuation of the drug. 1

Understanding Eslicarbazepine-Associated Hyponatremia

Eslicarbazepine acetate can reduce serum sodium concentrations, particularly when combined with other medications that lower sodium 1. In clinical trials, ≤3.3% of patients had minimum sodium levels ≤125 mEq/L, <6% experienced hyponatremia-related adverse events, and <2% discontinued treatment due to hyponatremia 2. The incidence increases with higher doses and appears more frequent in monotherapy versus adjunctive therapy 2.

Key risk factors include:

• Age over 40 years 3
• High serum drug levels 3
• Concomitant use of other antiepileptic drugs 4, 3
• Concurrent diuretic use (OR 5.597 for severe hyponatremia) 4
• Female gender (particularly with oxcarbazepine-class drugs) 3

Initial Assessment When Hyponatremia is Detected

Obtain the following immediately:

• Serum sodium level (confirm with laboratory measurement, not just clinical suspicion) 2
• Serum and urine osmolality 5
• Urine sodium concentration 5
• Assessment of extracellular fluid volume status (check for orthostatic hypotension, dry mucous membranes, skin turgor, jugular venous distention, peripheral edema) 5
• Review all concurrent medications, especially diuretics, antidepressants, and other sodium-lowering agents 1, 4

Management Algorithm Based on Severity

Mild Hyponatremia (130-134 mEq/L)

Continue eslicarbazepine with close monitoring:

• Check serum sodium every 1-2 weeks initially 5
• Educate patients to report symptoms: nausea, tiredness, lack of energy, irritability, confusion, muscle weakness/spasms, or increased seizure frequency 1
• Consider dose reduction if sodium continues to decline 2
• No specific treatment required if asymptomatic 5

Moderate Hyponatremia (125-129 mEq/L)

Implement active management:

• For euvolemic patients (most common with eslicarbazepine): Implement fluid restriction to 1-1.5 L/day 5
• Add oral sodium chloride 100 mEq three times daily if fluid restriction alone is insufficient 6
• Consider reducing eslicarbazepine dose by 25-50% 2
• Discontinue any concurrent diuretics or other sodium-lowering medications 5, 4
• Monitor serum sodium every 2-3 days until stable 5
• Target correction rate: 4-6 mEq/L per day, not exceeding 8 mEq/L in 24 hours 5

Severe Hyponatremia (<125 mEq/L) - Asymptomatic

More aggressive intervention required:

• Discontinue eslicarbazepine temporarily 1
• Implement strict fluid restriction to 1 L/day 5
• Administer oral sodium chloride 100 mEq three times daily 6
• Monitor serum sodium every 4-6 hours initially 5
• Do not exceed correction of 8 mEq/L in 24 hours to prevent osmotic demyelination syndrome 5
• Once sodium reaches ≥130 mEq/L, consider restarting eslicarbazepine at a lower dose or switching to an alternative antiepileptic drug 2

Severe Symptomatic Hyponatremia (<125 mEq/L with neurological symptoms)

This is a medical emergency:

• Symptoms include confusion, seizures, altered mental status, or coma 5
• Immediately discontinue eslicarbazepine 1
• Administer 3% hypertonic saline with target correction of 6 mEq/L over 6 hours or until symptoms resolve 5
• Total correction must not exceed 8 mEq/L in 24 hours 5
• Monitor serum sodium every 2 hours during initial correction 5
• Consider ICU admission for close monitoring 5
• Do not restart eslicarbazepine—switch to an alternative antiepileptic drug without sodium-lowering effects 2

Special Considerations

High-risk patients require more cautious management:

• Elderly patients (>65 years) need more frequent monitoring and lower correction rates (4-6 mEq/L per day maximum) 5, 4
• Patients on polytherapy with multiple antiepileptic drugs have 1.5-fold increased risk 4
• Those taking concurrent diuretics have 5.6-fold increased risk and require immediate diuretic discontinuation 4

Monitoring during ongoing eslicarbazepine therapy:

• Check baseline sodium before starting eslicarbazepine 1
• Recheck at 2 weeks, 1 month, then every 3 months during maintenance 2
• More frequent monitoring (every 1-2 weeks) if risk factors present 4
• Always check sodium when symptoms suggestive of hyponatremia develop 1

Common Pitfalls to Avoid

• Never ignore mild hyponatremia (130-135 mEq/L) as it increases fall risk and mortality 5
• Never correct chronic hyponatremia faster than 8 mEq/L in 24 hours—this causes osmotic demyelination syndrome 5
• Never rely solely on clinical symptoms to diagnose hyponatremia—confirm with laboratory measurement 2
• Never continue eslicarbazepine at the same dose if moderate-to-severe hyponatremia develops 2
• Never use fluid restriction alone in severe symptomatic hyponatremia—hypertonic saline is required 5

Alternative Antiepileptic Drugs

If eslicarbazepine must be discontinued due to persistent or severe hyponatremia, consider switching to antiepileptic drugs with lower hyponatremia risk 7. Carbamazepine and oxcarbazepine (structurally related to eslicarbazepine) carry similar or higher hyponatremia risk and should be avoided 3.