In a patient with oxcarbazepine‑induced hyponatraemia, should I discontinue oxcarbazepine and start an alternative antiepileptic?

Management of Oxcarbazepine-Induced Hyponatremia

In patients with oxcarbazepine-induced hyponatremia, you should first assess the severity: if serum sodium is <125 mmol/L or the patient is symptomatic, discontinue oxcarbazepine immediately and switch to an alternative antiepileptic drug; if sodium is 125-134 mmol/L and the patient is asymptomatic, reduce the oxcarbazepine dose and monitor closely. 1

Severity Assessment and Decision Algorithm

Immediate discontinuation is required when:

• Serum sodium <125 mmol/L (clinically significant hyponatremia) 1
• Any symptoms of hyponatremia present (nausea, malaise, headache, lethargy, confusion, obtundation, drowsiness, diplopia, apathy, or increased seizure frequency/severity) 1, 2
• Water intoxication develops 3

Dose reduction may be attempted when:

• Serum sodium 125-134 mmol/L with no symptoms 4
• Patient tolerates close monitoring 5

Understanding the Risk Profile

Oxcarbazepine causes clinically significant hyponatremia (sodium <125 mmol/L) in approximately 2.5-3% of patients, typically developing during the first 3 months of therapy, though it can occur after more than 1 year of treatment 1, 5. The overall frequency of any degree of hyponatremia ranges from 22.2% to 50% of patients, but only 5.9% develop symptoms 2.

Key risk factors that increase hyponatremia likelihood:

• Higher oxcarbazepine dosages (each 1 mg increase raises risk by 0.2%) 4
• Concomitant use of multiple antiepileptic drugs 4
• Concurrent medications that lower sodium (diuretics, ACE inhibitors, NSAIDs, oral contraceptives) 5, 2
• Elderly patients 6
• Pre-existing renal disease 5

Alternative Antiepileptic Drug Selection

For partial onset seizures, consider these alternatives:

First-line options:

• Levetiracetam - safest choice with minimal drug interactions and no sodium effects 7
• Lamotrigine - effective for partial seizures without hyponatremia risk 7

Second-line options:

• Carbamazepine - but note that 25-30% of patients with oxcarbazepine hypersensitivity will cross-react 1
• Topiramate, valproic acid 7

Avoid carbamazepine if:

• The patient required strong CYP3A or CYP2C8 inhibitors (carbamazepine, oxcarbazepine, phenobarbital, phenytoin interact significantly) 7
• History of hypersensitivity to oxcarbazepine exists (25-30% cross-reactivity) 1

Critical Monitoring During Transition

After discontinuing oxcarbazepine:

• Serum sodium typically normalizes within a few days without additional treatment 1
• Monitor sodium levels every 2-3 days until normalization 1
• Watch for seizure breakthrough during medication transition 4

If continuing oxcarbazepine at reduced dose:

• Measure serum sodium every 2-4 weeks initially 5
• Check sodium if any new medications are added that may lower sodium 5
• Reassess immediately if symptoms develop 4

Common Pitfalls to Avoid

Do not:

• Continue oxcarbazepine at the same dose when sodium <125 mmol/L, even if asymptomatic - this can progress to dangerous water intoxication 3, 2
• Switch to carbamazepine without considering cross-hypersensitivity risk (25-30% will react) 1
• Assume hyponatremia will resolve spontaneously while continuing the drug at full dose 4
• Overlook concomitant medications that compound the sodium-lowering effect (diuretics, ACE inhibitors) 2

The mechanism involves syndrome of inappropriate antidiuretic hormone secretion (SIADH): oxcarbazepine alters hypothalamic osmoreceptor sensitivity and may increase renal tubule sensitivity to ADH 3. This is why fluid restriction alone is insufficient - the drug itself must be addressed 3.