Can Keppra (levetiracetam) cause hyponatremia?

Levetiracetam (Keppra) and Hyponatremia

Levetiracetam (Keppra) can cause hyponatremia, with recent evidence showing a strong association between newly initiated levetiracetam treatment and hospitalization due to hyponatremia. 1

Risk Assessment and Evidence

Strength of Association

• Levetiracetam has been associated with a significantly increased risk of hospitalization due to hyponatremia with an adjusted odds ratio of 9.76 (95% CI: 4.02-27.59) for newly initiated treatment 1
• This risk is comparable to carbamazepine (OR 9.63) and higher than several other antiepileptic drugs like lamotrigine (OR 1.67) and gabapentin (OR 1.61) 1

Risk Factors for Hyponatremia with Antiepileptic Drugs

• Advanced age
• Female gender
• Low body weight
• Concomitant use of other medications that can cause hyponatremia
• Higher dosages of the medication
• Early treatment period (first 90 days) 2

Monitoring Recommendations

When to Monitor Sodium Levels

• Baseline measurement before starting levetiracetam
• During the first 90 days of therapy (highest risk period)
• After dose increases
• In elderly patients or those with low body weight
• In patients on multiple medications 3

Clinical Signs to Monitor

• Early signs: headache, nausea, vomiting, lethargy
• Advanced signs: confusion, somnolence, seizures, coma 3
• Note that chronic hyponatremia (developing over >48 hours) may present with more subtle symptoms than acute hyponatremia 2

Management of Levetiracetam-Induced Hyponatremia

When to Intervene

• For mild asymptomatic hyponatremia: close monitoring may be sufficient
• For moderate to severe hyponatremia (sodium <130 mmol/L) or symptomatic cases:
  1. Consider dose reduction
  2. If hyponatremia persists, consider switching to an alternative antiepileptic drug

Alternative Antiepileptic Options

• Lamotrigine and gabapentin have shown the lowest risk of hyponatremia both during initiation and ongoing treatment 1
• These may be advantageous alternatives in patients at risk of developing hyponatremia

Correction of Hyponatremia

• If severe hyponatremia occurs, correction should not exceed 8 mmol/L per day to avoid central pontine myelinolysis 3

Clinical Perspective

While carbamazepine and oxcarbazepine are more commonly known to cause hyponatremia, the evidence shows that levetiracetam also carries a significant risk, particularly during treatment initiation. The risk appears to decrease during ongoing treatment but remains clinically relevant.

Important Caveats

• Hyponatremia can be multifactorial, so consider other potential causes even when a patient is taking levetiracetam
• The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is the likely mechanism for most antiepileptic drug-induced hyponatremia
• Patients with epilepsy often require long-term treatment, making awareness of this potential adverse effect particularly important for ongoing monitoring

Regular monitoring of serum sodium levels is essential, particularly in high-risk patients and during the initial treatment period with levetiracetam, to detect and manage this potentially serious adverse effect early.