Can Keppra (levetiracetam) cause hyponatremia?

Levetiracetam (Keppra) and Hyponatremia

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

Evidence for Levetiracetam-Induced Hyponatremia

• A population-based case-control study found that newly initiated levetiracetam treatment was 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) 1
• This places levetiracetam among the antiepileptic drugs with the highest risk of causing hyponatremia, comparable to carbamazepine (OR 9.63) 1
• Case reports have documented instances where levetiracetam was associated with hyponatremia severe enough to cause symptoms requiring medical intervention 2, 3

Mechanism and Risk Factors

• The exact mechanism by which levetiracetam causes hyponatremia is not fully understood, but it may involve:
  • Increased sensitivity of renal tubules to antidiuretic hormone (ADH) 4
  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH) 3
• Risk factors that may increase the likelihood of developing hyponatremia while on levetiracetam include:
  • Advanced age 1
  • Concomitant use of other medications known to cause hyponatremia 3
  • Pre-existing conditions like heart failure, cirrhosis, or renal impairment 5

Monitoring and Management

• For patients on levetiracetam therapy:

  • Monitor serum sodium levels, particularly during the first 90 days of treatment when risk appears highest 1
  • Be vigilant for symptoms of hyponatremia (confusion, headache, nausea, fatigue, muscle cramps) 4
  • Consider more frequent monitoring in high-risk patients (elderly, those with heart failure, cirrhosis, or on other medications that can cause hyponatremia) 5

• If hyponatremia develops:

  • Evaluate the severity and symptoms of hyponatremia 5
  • For mild asymptomatic hyponatremia, fluid restriction (1.0-1.5 L/day) may be appropriate 5
  • For more severe or symptomatic cases, consider discontinuing levetiracetam and switching to an alternative antiepileptic with lower risk of hyponatremia 1
  • Lamotrigine and gabapentin have been shown to have the lowest risk of hyponatremia among antiepileptic drugs 1

Clinical Implications

• When prescribing levetiracetam:
  • Inform patients about the potential risk of hyponatremia and symptoms to watch for 3
  • Consider baseline sodium measurement before initiating therapy 3
  • The risk appears highest during the first 90 days of treatment but continues with ongoing therapy 1
  • For patients with pre-existing hyponatremia or at high risk, consider alternative antiepileptics with lower hyponatremia risk 1

While levetiracetam is generally considered to have a favorable side effect profile compared to older antiepileptic drugs, clinicians should be aware of this potentially serious adverse effect and monitor accordingly, especially during the initiation phase of treatment.