Is lamotrigine (anticonvulsant) safe to use during pregnancy?

Lamotrigine Use During Pregnancy

Lamotrigine is considered safe to use during pregnancy for women with epilepsy or other indications, with evidence showing it has among the lowest risks of teratogenicity compared to other anticonvulsants. 1

Safety Profile

• Lamotrigine has consistently demonstrated favorable safety in pregnancy registries, making it likely the first choice anticonvulsant for women planning pregnancy when clinically appropriate 1
• No drug interactions have been reported among epileptic women taking lamotrigine and using progestin-only contraceptives, indicating good compatibility with hormonal medications that might be used periconceptionally 2
• Unlike certain other anticonvulsants (phenytoin, carbamazepine, barbiturates, primidone, topiramate, oxcarbazepine), lamotrigine does not reduce the effectiveness of progestin-only contraceptives 2

Dosing Considerations During Pregnancy

• Pregnancy significantly alters lamotrigine pharmacokinetics, with increased metabolism and clearance that can lead to subtherapeutic levels 3, 4
• Lamotrigine clearance increases progressively across trimesters, with the most pronounced changes in the second and third trimesters 4
• Mean steady-state trough plasma concentrations decrease significantly during pregnancy compared to non-pregnant levels:
  • Non-pregnant: 4.31 ± 1.14 mg/L
  • First trimester: 3.17 ± 0.93 mg/L
  • Second trimester: 2.14 ± 0.86 mg/L
  • Third trimester: 1.51 ± 0.65 mg/L 3

Monitoring and Dose Adjustment Recommendations

• Therapeutic drug monitoring (TDM) should be performed every 4 weeks throughout pregnancy to maintain stable lamotrigine concentrations 5
• When lamotrigine plasma concentration falls below the pre-pregnancy reference concentration, the dose should be increased by 20-25% 5
• For optimal management, establish a reference concentration before pregnancy or as early in pregnancy as possible 5
• Simulation studies suggest the following twice-daily dosing regimen to maintain therapeutic levels:
  • Pre-conception: 150 mg
  • First trimester: 175 mg
  • Second trimester: 225 mg
  • Third trimester: 250 mg 3

Postpartum Considerations

• After delivery, lamotrigine plasma concentration should be measured within the first or second week 5
• If plasma concentration exceeds the reference concentration, reduce the dose by 20-25% and repeat measurements until the reference concentration is re-established 5
• Failure to reduce doses postpartum is common but important to prevent toxicity, as approximately 43% of women who had dose increases during pregnancy did not have appropriate postpartum dose reductions 6

Special Considerations

• For women with mild manifestations of paroxysmal kinesigenic dyskinesia (PKD), discontinuing lamotrigine prior to or during pregnancy may be considered due to the fetal risk, though this risk is lower than with many other anticonvulsants 2
• The decision to use any medication during pregnancy needs to balance maternal risk of therapy versus no therapy and the fetal risk of uncontrolled maternal disease against the risk of therapy on the newborn 2

Common Pitfalls

• Inadequate monitoring: Only 12.4% of pregnant women on lamotrigine receive therapeutic drug monitoring, despite guidelines recommending proactive monitoring 6
• Failure to increase doses: Approximately 40% of pregnant women do not receive appropriate dose increases during pregnancy, potentially leading to breakthrough seizures 6
• Neglecting postpartum dose reduction: Many women do not have their doses appropriately reduced after delivery, increasing the risk of toxicity 6

By following a systematic approach to lamotrigine management during pregnancy with regular monitoring and appropriate dose adjustments, the risks of seizure deterioration during pregnancy and lamotrigine toxicity postpartum can be minimized.