Levetiracetam Use in Pregnancy: Safety and Management
Levetiracetam is considered one of the safer antiepileptic medications for use during pregnancy, with a low risk of major congenital malformations when used as monotherapy. 1
Safety Profile in Pregnancy
Levetiracetam is classified as FDA Pregnancy Category C, indicating that:
- Animal studies have shown evidence of developmental toxicity at doses similar to or greater than human therapeutic doses
- There are no adequate well-controlled studies in pregnant women
- The medication should be used only if the potential benefit justifies the potential risk to the fetus 2
Evidence on Fetal Risk
- Monotherapy use shows a very low major congenital malformation rate of 0.70% (95% CI 0.19%-2.51%) 1
- Risk increases significantly when used in polytherapy combinations:
- With lamotrigine: 1.77% (lower risk)
- With valproate: 6.90% (higher risk)
- With carbamazepine: 9.38% (highest risk) 1
Recent Research Findings
- A 2024 study confirmed levetiracetam as a suitable antiepileptic drug in pregnancy 3
- However, this study noted:
- Lower birth weight in male neonates with levetiracetam monotherapy compared to lamotrigine
- Higher risk of spontaneous abortion with levetiracetam-lamotrigine dual therapy 3
Pharmacokinetic Changes During Pregnancy
Pregnancy significantly affects levetiracetam levels, requiring close monitoring:
- Levetiracetam clearance increases throughout pregnancy, resulting in decreased blood concentrations 4, 5
- Most significant concentration/dose decrease occurs in the first trimester 5
- Dose increases of approximately 75% are often needed during pregnancy compared to preconception 5
- After delivery, there is an abrupt increase in concentration/dose ratio, requiring dose reduction 5
Management Recommendations
Therapeutic Drug Monitoring
- Monthly monitoring of levetiracetam levels is strongly recommended throughout pregnancy 4, 5
- Target concentration should be maintained at least 65% of preconceptional concentration for women who had seizures in the year before pregnancy 4
- For seizure-free patients, maintaining levels at approximately 46% of preconceptional concentration may be sufficient 4
Dosing Considerations
- Dose adjustments should be made based on serum level monitoring and clinical response
- Extended-release formulations may require twice-daily dosing during pregnancy due to increased clearance 6
- After delivery, doses should be reduced by approximately 24% compared to third-trimester dosing to avoid toxicity 5
Breastfeeding Considerations
- Levetiracetam is excreted in breast milk
- A decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother 2
Clinical Pitfalls to Avoid
- Failure to monitor drug levels: Not performing monthly therapeutic drug monitoring can lead to breakthrough seizures due to decreased drug levels
- Inadequate dose adjustments: Failing to increase doses during pregnancy or decrease doses postpartum
- Inappropriate formulation: Using once-daily extended-release formulations without considering the increased clearance during pregnancy
- Polytherapy risks: Combining levetiracetam with other antiepileptic drugs, especially valproate, significantly increases the risk of congenital malformations
Conclusion
When seizure control is essential during pregnancy, levetiracetam monotherapy represents one of the safer antiepileptic options with appropriate monitoring and dose adjustments. The benefit of seizure control generally outweighs the potential risks to the fetus when levetiracetam is used as monotherapy with proper therapeutic drug monitoring.