Levetiracetam and Hypernatremia
Levetiracetam does not cause hypernatremia; it is associated with hyponatremia (low sodium), not hypernatremia (high sodium).
Evidence for Hyponatremia, Not Hypernatremia
The available evidence consistently demonstrates that levetiracetam is linked to decreased sodium levels, not elevated ones:
Case reports document levetiracetam-induced hyponatremia in patients predisposed to syndrome of inappropriate antidiuretic hormone secretion (SIADH), with hyponatremia developing after levetiracetam challenges 1.
A 2024 case report describes a patient who developed significant hyponatremia while on levetiracetam, which resolved after switching to lacosamide, demonstrating a clear temporal relationship between levetiracetam use and low sodium levels 2.
Population-based evidence shows strong association with hyponatremia: A Swedish case-control study of 14,359 patients hospitalized for hyponatremia found that newly initiated levetiracetam had an adjusted odds ratio of 9.76 (95% CI: 4.02-27.59) for hospitalization due to hyponatremia compared to controls 3.
Comparative Risk Profile
When comparing levetiracetam to other antiepileptic drugs:
Levetiracetam carries one of the highest risks for hyponatremia among newer antiepileptic drugs, with a risk comparable to carbamazepine (OR 9.63) and oxcarbazepine during treatment initiation 3.
In traumatic brain injury patients, a retrospective study of 846 patients found no clinically significant difference in hyponatremia rates between levetiracetam and phenytoin, though there was increased intervention for hyponatremia in the levetiracetam group 4.
Clinical Implications
Monitor sodium levels when initiating levetiracetam, particularly in patients with:
- Pre-existing risk factors for SIADH 1
- Central diabetes insipidus or other sodium regulation disorders 2
- Concurrent use of other medications that affect sodium balance (opioids, NSAIDs, diuretics) 2
The risk is highest during treatment initiation (within 90 days), with lower risk during ongoing treatment 3.
Drugs That Actually Cause Hypernatremia
A comprehensive review of drug-induced hypernatremia identifies specific medications that elevate sodium levels, but levetiracetam is not among them 5. The guideline literature discussing hypernatremia management in traumatic brain injury and cirrhosis does not implicate levetiracetam as a causative agent 6.