How to manage hyponatremia (low sodium levels) induced by Phenytoin (Dilantin)?

Management of Phenytoin-Induced Hyponatremia

For phenytoin-induced hyponatremia, discontinue phenytoin if possible and switch to an alternative antiepileptic drug with lower risk of hyponatremia such as lamotrigine or gabapentin, while correcting sodium levels with isotonic fluids and monitoring serum sodium closely. 1

Pathophysiology and Risk Assessment

• Phenytoin is associated with a moderate risk of hospitalization due to hyponatremia, with an adjusted odds ratio of 4.83 compared to controls, making it important to recognize this adverse effect early 1
• Hyponatremia is a common electrolyte abnormality that can lead to serious neurological complications including seizures when severe 2, 3
• While carbamazepine and oxcarbazepine have the highest risk of causing hyponatremia among antiepileptic drugs, phenytoin has been established as a moderate-risk medication 1, 4

Management Algorithm

Step 1: Assess Severity and Symptoms

• Classify hyponatremia severity: mild (126-135 mEq/L), moderate (120-125 mEq/L), or severe (<120 mEq/L) 2
• Evaluate for neurological symptoms such as confusion, seizures, or altered mental status that may require more urgent intervention 2

Step 2: Acute Management

• For severe symptomatic hyponatremia (especially with seizures):
  • Administer 3% hypertonic saline to rapidly increase serum sodium by 4-6 mEq/L to abort seizure activity 5
  • Consider anticonvulsant therapy (such as diazepam) to control seizures while correcting sodium levels 5
  • Monitor serum sodium levels frequently (every 2-4 hours initially) 2

Step 3: Medication Adjustment

• If possible, discontinue phenytoin and switch to an alternative antiepileptic drug with lower risk of hyponatremia 1, 4
• Lamotrigine and gabapentin have the lowest association with hyponatremia (adjusted ORs of 1.67 and 1.61 respectively for newly initiated treatment) and should be considered as preferred alternatives 1
• Avoid switching to carbamazepine, oxcarbazepine, or levetiracetam, which have higher risks of hyponatremia than phenytoin 1

Step 4: Sodium Correction Strategy

• For chronic hyponatremia, correct sodium levels gradually at a rate not exceeding 8-10 mEq/L per 24 hours to avoid osmotic demyelination syndrome 2
• Use isotonic fluids (normal saline) rather than hypotonic fluids to correct sodium levels 2
• Consider fludrocortisone acetate for persistent hyponatremia, as it has been shown to improve sodium levels 2

Step 5: Volume Status Management

• Maintain euvolemic state through careful fluid management 2
• Monitor volume status using central venous pressure, fluid balance, and body weight 2
• Avoid fluid restriction unless specifically indicated for hypervolemic hyponatremia 2

Monitoring and Follow-up

• Check serum sodium levels daily until stable, then weekly for 1 month after switching antiepileptic medications 2
• Monitor for signs of too-rapid correction of hyponatremia, which can lead to central pontine myelinolysis 5
• Assess therapeutic levels of the new antiepileptic drug to ensure seizure control is maintained 2

Special Considerations

• Elderly patients, those with renal impairment, and patients on diuretics are at higher risk for developing severe hyponatremia and require closer monitoring 4, 3
• The risk of hyponatremia is highest during the first 90 days of phenytoin therapy, suggesting more vigilant monitoring during this period 1
• If phenytoin must be continued due to lack of alternatives, consider adding salt supplementation and monitoring sodium levels more frequently 6