Safe Usage of Levetiracetam (Keppra) in Pregnancy
Levetiracetam is considered a safer antiepileptic medication option during pregnancy with a low risk of major congenital malformations when used as monotherapy, though therapeutic drug monitoring is recommended due to decreased drug concentrations during pregnancy.
Safety Profile
- Levetiracetam has demonstrated a low risk of major congenital malformations (0.70%) when used as monotherapy during pregnancy, making it a safer alternative to other antiepileptic medications like valproate 1.
- In animal studies, levetiracetam produced developmental toxicity at doses similar to or greater than human therapeutic doses, with evidence of minor fetal skeletal abnormalities and retarded offspring growth at higher doses 2.
- The FDA classifies levetiracetam as Pregnancy Category C, indicating that it should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus 2.
Dosing Considerations During Pregnancy
- Levetiracetam concentrations significantly decrease throughout pregnancy due to physiological pharmacokinetic changes 3.
- Therapeutic drug monitoring is strongly recommended for all pregnant patients on levetiracetam to maintain effective seizure control 3.
- For patients who had seizures within 12 months before pregnancy, it's advisable to maintain levetiracetam concentration above 65% of the preconceptional concentration 3.
- For seizure-free patients (no seizures for >12 months before pregnancy), maintaining levetiracetam at approximately 46% of the preconceptional concentration is recommended 3.
Monotherapy vs. Polytherapy
- Levetiracetam monotherapy is associated with a significantly lower risk of major congenital malformations (0.70%) compared to polytherapy regimens (5.56%) 1.
- When levetiracetam must be used in combination with other antiepileptic drugs, the combination with lamotrigine appears to have a lower risk of malformations (1.77%) compared to combinations with valproate (6.90%) or carbamazepine (9.38%) 1.
- However, dual therapy with levetiracetam and lamotrigine has been associated with an increased risk of spontaneous abortion in some studies 4.
Breastfeeding Considerations
- Levetiracetam is excreted in breast milk, and the FDA advises that 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.
Monitoring Recommendations
- Monthly monitoring of drug levels is recommended throughout pregnancy 3.
- Dose adjustments may be necessary as pregnancy progresses to maintain therapeutic levels 3.
- Enrollment in the North American Antiepileptic Drug (NAAED) pregnancy registry is advised for pregnant patients taking levetiracetam to provide information regarding in utero exposure effects 2.
Clinical Implications
- Maintaining seizure control during pregnancy is critical as uncontrolled seizures pose significant risks to both mother and fetus 5.
- Male neonates born to mothers on levetiracetam monotherapy may have lower birth weights compared to those exposed to lamotrigine monotherapy 4.
- No significant increase in the risk of spontaneous abortions has been observed with levetiracetam monotherapy 4.
Comparative Safety
- Levetiracetam is considered a first-line antiepileptic drug during pregnancy due to its favorable safety profile compared to older antiepileptic medications 5.
- Studies have shown no congenital malformations in children born to pregnant women receiving levetiracetam monotherapy in some cohorts 5.
- When considering antiepileptic medications during pregnancy, levetiracetam is a safer alternative to valproate, which has a higher risk of major congenital malformations (13.3%) 5.