From the Guidelines
Lamotrigine is the preferred drug of choice for an epileptic woman who is pregnant due to its relatively low risk of congenital malformations. When considering the management of epilepsy in pregnant women, it's crucial to balance the risks of uncontrolled seizures against the potential teratogenic effects of antiepileptic drugs. According to the guidelines for preconception counseling and care 1, seizure disorders in pregnancy are associated with increased risks of miscarriage, low birth weight, developmental disabilities, and congenital anomalies, whether or not the mother is taking medication.
Given these risks, the selection of an antiepileptic drug during pregnancy is critical. Key considerations include the drug's efficacy in controlling seizures, its safety profile, particularly regarding teratogenicity, and the need for dose adjustments during pregnancy due to changes in drug metabolism. Lamotrigine stands out for its favorable profile, with studies indicating a lower risk of congenital malformations compared to other antiepileptic drugs like valproate. The typical dosage of lamotrigine starts at 25mg daily, increasing to 100-400mg daily in divided doses, with the need for potential dose adjustments and blood level monitoring due to pregnancy-induced changes in drug metabolism.
It's also important to note the recommendation for folic acid supplementation at a dose of 4mg daily, initiated at least one month before conception and continued through the first trimester, to mitigate the risk of neural tube defects associated with antiepileptic drug use 1. The principle of using the lowest effective dose of a single antiepileptic drug (monotherapy) is preferred to minimize fetal exposure while maintaining adequate seizure control. This approach is guided by the understanding that uncontrolled seizures pose significant risks to both the mother and the fetus, including trauma, status epilepticus, and pregnancy complications. Therefore, continuing effective treatment with lamotrigine or switching to lamotrigine when possible is recommended for pregnant women with epilepsy.
From the FDA Drug Label
In humans, transplacental passage of carbamazepine is rapid (30 to 60 minutes), and the drug is accumulated in the fetal tissues, with higher levels found in liver and kidney than in brain and lung Retrospective case reviews suggest that, compared with monotherapy, there may be a higher prevalence of teratogenic effects associated with the use of anticonvulsants in combination therapy Therefore, if therapy is to be continued, monotherapy may be preferable for pregnant women.
The FDA drug label does not answer the question.
From the Research
Drug of Choice for Epileptic Women During Pregnancy
The drug of choice for an epileptic woman who is pregnant is lamotrigine, due to its low teratogenicity and effectiveness against a broad spectrum of seizure types 2.
Key Characteristics of Lamotrigine
- Lamotrigine is a sodium-channel-modulating, antiepileptic drug (AED) that has gained widespread use in the USA as both an immediate and an extended-release agent 2.
- It has a favorable metabolic profile, with few but significant drug interactions 2.
- Pregnancy registries have consistently demonstrated lamotrigine to be among the safest medications for a developing fetus, both in terms of fetal malformations and postpartum cognitive development 2.
Considerations for Lamotrigine Use During Pregnancy
- There is an increased metabolism and clearance of lamotrigine in pregnancy, contributing to suboptimal drug therapy and poor disease control, prompting the need for proactive dosage adjustments 3.
- Therapeutic drug monitoring (TDM) is recommended to control for changes in the disposition of lamotrigine during pregnancy, as it can help reduce seizure deterioration 4, 5.
- The dosage of lamotrigine may need to be adjusted during pregnancy to achieve target concentrations, with simulated studies suggesting doses of 150 mg, 175 mg, 225 mg, and 250 mg twice daily in the preconception stage and the 3 trimesters, respectively 3.
Comparison with Other AEDs
- Other AEDs, such as oxcarbazepine and levetiracetam, may also experience changes in pharmacokinetics during pregnancy, but less is known about these alterations compared to lamotrigine 5.
- Valproate is generally avoided in pregnant women due to its high teratogenic potential, and polytherapy is also discouraged if possible 6.