What are the recommendations for managing levetiracetam and lamotrigine (antiepileptic medications) during pregnancy?

Management of Levetiracetam and Lamotrigine During Pregnancy

Both levetiracetam and lamotrigine are preferred antiepileptic drugs during pregnancy, with levetiracetam classified as FDA Pregnancy Category C and both drugs considered safer alternatives to valproate and other enzyme-inducing anticonvulsants. 1, 2

Monotherapy Recommendations

Levetiracetam

• Levetiracetam monotherapy is a suitable antiepileptic drug in pregnancy with no significantly increased risk of major birth defects or spontaneous abortions. 3
• The FDA label indicates levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus (Category C). 4
• Animal studies showed developmental toxicity at doses similar to or greater than human therapeutic doses, but there are no adequate well-controlled studies in pregnant women. 4
• Male neonates may have significantly lower birth weight after levetiracetam monotherapy compared to lamotrigine monotherapy, which requires monitoring. 3

Lamotrigine

• Lamotrigine is recommended as a preferred medication for seizure disorders during pregnancy when monotherapy is used at the lowest effective dosage. 1, 5
• The drug does not require the same precautions as enzyme-inducing antiepileptic drugs. 2
• Lamotrigine levels decline significantly during pregnancy due to altered pharmacokinetics, requiring proactive dose adjustment in the second and third trimesters. 6, 5

Combination Therapy Considerations

Lamotrigine-Levetiracetam Duotherapy

• Lamotrigine-levetiracetam combination therapy is associated with a 60% lower risk of major congenital malformations compared to valproate monotherapy (adjusted RR 0.41,95% CI 0.24-0.69). 7
• However, this combination showed an unexpectedly increased risk of spontaneous abortion (adjusted HR 3.01,95% CI 1.43-6.33) and a nonsignificant trend toward increased major birth defects (7.7%) compared to nonexposed cohorts. 3
• This combination is increasingly used as an alternative to valproate for generalized epilepsies but requires careful counseling about the mixed risk profile. 7, 3

Avoiding Lamotrigine-Topiramate

• Lamotrigine-topiramate duotherapy was not associated with a reduced risk of major congenital malformations compared to valproate monotherapy (aRR 1.26,95% CI 0.71-2.23). 7

Dose Management During Pregnancy

Therapeutic Drug Monitoring

• Increased monitoring of drug levels is necessary as pregnancy alters pharmacokinetics, particularly for lamotrigine and levetiracetam. 2, 6
• Guidelines recommend proactive dose adjustment in the second and third trimesters alongside therapeutic drug monitoring. 6
• In practice, only 12.4% of women receive therapeutic drug monitoring, and 40% do not have doses increased during pregnancy despite recommendations. 6

Specific Dosing Adjustments

• Lamotrigine levels can decline significantly during pregnancy, with the most pronounced changes requiring dose escalation. 5
• Dosages should be adjusted based on clinical response and serum levels. 2
• Doses should be reduced postpartum to avoid toxicity, though this is often overlooked in clinical practice. 6

Breastfeeding Safety

• Both lamotrigine and levetiracetam can be used during breastfeeding with appropriate monitoring of the infant. 2
• Levetiracetam is excreted in breast milk, and the FDA label recommends considering whether to discontinue nursing or the drug based on the importance of the medication to the mother. 4

Critical Management Principles

Avoid Abrupt Discontinuation

• Never abruptly discontinue antiepileptic medication as this may precipitate status epilepticus, which poses greater risk to mother and fetus than continued medication. 2

Preconception Planning

• Any major change in treatment should ideally be completed before conception. 5
• Monotherapy at the lowest effective dosage is the goal to minimize fetal exposure while preventing generalized tonic-clonic seizures. 1, 5

Valproate Avoidance

• Valproate should be avoided if possible due to higher malformation rates, particularly at doses >1000 mg/day. 1, 5
• The lamotrigine-levetiracetam combination represents a safer alternative for conditions requiring broad-spectrum coverage. 7

Common Pitfalls

• Failing to increase doses during pregnancy: 40% of women do not receive appropriate dose escalation despite declining drug levels. 6
• Neglecting postpartum dose reduction: 43% of women who had dose escalation during pregnancy do not have doses reduced after delivery, risking toxicity. 6
• Inadequate therapeutic drug monitoring: Only 12.4% of pregnancies involve TDM despite guideline recommendations. 6
• Using polytherapy unnecessarily: Polytherapy is associated with increased risk of birth defects compared to monotherapy. 5