How to manage severe ongoing hypomagnesemia in a patient with epilepsy on Keppra (levetiracetam) and Vimpat (lacosamide), and hypothyroidism?

Management of Severe Ongoing Hypomagnesemia in a Patient with Epilepsy

For severe ongoing hypomagnesemia in a patient with epilepsy on Keppra and Vimpat, intravenous magnesium supplementation with 1-2 g of MgSO4 is recommended, while investigating potential medication-related causes, particularly Keppra (levetiracetam) which may be contributing to the electrolyte abnormality. 1, 2, 3

Evaluation of Persistent Hypomagnesemia

Step 1: Assess the severity and clinical manifestations

• Check for neuromuscular symptoms: weakness, tremors, muscle cramps, tetany
• Evaluate for cardiac manifestations: arrhythmias, particularly polymorphic ventricular tachycardia
• Monitor for neurological symptoms: seizures, confusion, ataxia
• Check for associated electrolyte abnormalities, particularly hypokalemia 1

Step 2: Identify potential causes

1. Medication-related causes:

   • Levetiracetam (Keppra) has been reported to cause hypomagnesemia and hypokalemia 2, 3
   • Other potential contributors: proton pump inhibitors, diuretics

2. Gastrointestinal losses:

   • Assess for diarrhea, malabsorption syndrome
   • Check for symptoms of gastrointestinal disease

3. Renal losses:

   • Calculate fractional excretion of magnesium (FEMg)
   • FEMg > 2% indicates renal magnesium wasting
   • FEMg < 2% suggests extrarenal causes 4

4. Endocrine factors:

   • Evaluate thyroid function (patient has hypothyroidism)
   • Assess for diabetes, alcoholism 1

Treatment Algorithm

For severe hypomagnesemia (< 0.4 mmol/L or < 1.0 mg/dL):

1. Immediate IV replacement:

   • Administer 1-2 g of MgSO4 IV push for cardiotoxicity and severe hypomagnesemia (Class I, LOE C) 1
   • For ongoing replacement: 5 g (approximately 40 mEq) added to 1 liter of 5% Dextrose or 0.9% Sodium Chloride for slow IV infusion over 3 hours 5
   • Monitor serum magnesium levels frequently during replacement

2. Maintenance therapy:

   • After initial correction, provide 1 g (8.12 mEq) IM every 6 hours for 4 doses 5
   • Transition to oral supplementation when levels stabilize

For moderate hypomagnesemia (0.4-0.7 mmol/L or 1.0-1.7 mg/dL):

• Oral magnesium supplements (magnesium oxide, magnesium citrate)
• Typical dose: 300-400 mg elemental magnesium daily in divided doses
• Monitor serum levels weekly until stabilized 4

Addressing Medication-Related Causes

Given the patient's persistent hypomagnesemia despite multiple grams of replacement, medication-related causes should be strongly considered:

1. Evaluate Keppra (levetiracetam) as a potential cause:

   • Multiple case reports have linked levetiracetam to hypomagnesemia and hypokalemia 2, 3
   • Consider consulting neurology for potential medication adjustment

2. Potential medication changes:

   • If hypomagnesemia persists despite adequate replacement, consider switching from levetiracetam to an alternative antiepileptic medication
   • Lacosamide (Vimpat) alone may be sufficient if the patient has been stable on dual therapy 2
   • Any medication change should be done gradually under neurological supervision

Special Considerations

• Monitor for associated electrolyte abnormalities:

  • Hypomagnesemia often coexists with hypokalemia
  • Correct magnesium deficiency first, as hypokalemia may be refractory until magnesium is repleted 2

• Renal function assessment:

  • Ensure adequate renal function before aggressive magnesium supplementation
  • Adjust dosing in renal impairment 4

• Cardiac monitoring:

  • Severe hypomagnesemia can lead to life-threatening arrhythmias
  • ECG monitoring is recommended during correction of severe deficiency 1

• Hypothyroidism management:

  • Ensure adequate thyroid replacement therapy, as thyroid dysfunction can contribute to magnesium abnormalities 1

Pitfalls and Caveats

1. Avoid rapid IV administration: Do not exceed 150 mg/minute for IV magnesium to prevent hypotension and flushing 5

2. Watch for overcorrection: Monitor for signs of hypermagnesemia (hyporeflexia, respiratory depression, hypotension)

3. Don't ignore the medication cause: Simply replacing magnesium without addressing the underlying cause will lead to continued losses and treatment failure

4. Consider consultation: In cases of severe, refractory hypomagnesemia, nephrology consultation may be beneficial to rule out rare tubular disorders

5. Recognize the seizure risk: Untreated hypomagnesemia can worsen seizure control, creating a dangerous cycle in patients with epilepsy 1