Pregnancy and epilepsy— managing both, in one patient

As a result, incremental dosing of lamotrigine is usually required early in pregnancy. In some cases, dramatic increases—several multiples of the preconception dosage—may be needed, followed by a rapid decrease after delivery.¹⁸

Monitoring drug levels

Our approach to monitoring AED levels in a pregnant woman who has epilepsy includes the following:

• Check levels at baseline—prior to conception whenever possible—and monthly throughout the pregnancy, with more frequent checks for women who have recurrent seizures and those who are taking lamotrigine
• Use the dosage at which the patient was seizure-free prior to conception as a target level during pregnancy
• Adjust the dosage as needed to maintain the preconception serum drug level.

Drug-specific considerations. Because phenytoin and valproate are highly protein-bound, we follow free levels during pregnancy rather than total levels alone. (If your facility is not equipped to track free drug levels, it is important to realize that total levels of these AEDs may not accurately reflect the drug level.) If your patient is taking phenytoin, and you’re unable to obtain this information, you can use the patient’s albumin level and the total phenytoin level to estimate the corrected level of the drug with the following formula:

Provide vitamin K augmentation late in pregnancy. In addition to routinely prescribing 4 mg/day of folic acid for pregnant women who have epilepsy, we recommend oral augmentation of vitamin K as another protective measure.

AEDs that induce hepatic CYP enzymes also induce vitamin K metabolism, thereby reducing the effectiveness of vitamin K-dependent clotting factors and predisposing newborns to hemorrhagic disease.¹³ It remains unclear whether only women who are taking CYP enzyme-inducing AEDs or all women taking AEDs should receive oral vitamin K supplementation in the last few weeks of pregnancy. We recommend oral vitamin K supplementation for all pregnant women who have epilepsy (phytonadione 10 mg/day), starting at 36 weeks’ gestation and continuing until delivery, despite the lack of a proven benefit, because it is safe and carries little, if any, risk.

An intramuscular injection of 1 mg of vitamin K is generally given to all newborns—regardless of whether the mother has epilepsy and takes an AED—to prevent hemorrhagic disease.¹³

Should women taking an AED breastfeed?

The advantages of breastfeeding are largely undisputed, but women being treated with an AED are generally concerned about the possibility of contaminated breast milk. Although antiepileptic agents such as gabapentin, lamotrigine, levetiracetam, and topiramate are excreted in breast milk in potentially clinically important amounts, no short-term adverse effects have been observed in nursing infants of women being treated with an AED.¹³ Little information is available regarding long-term effects, and the AAN and AES state that further study is needed. Nonetheless, breastfeeding is generally believed to be a relatively safe option for patients who have epilepsy who are being treated with an AED, and it is not contraindicated by AAN/AES guidelines.¹³

Indeed, pregnancy itself is relatively safe for women who have epilepsy. When you’re involved in their care, your awareness of the teratogenicity of various AEDs, the variables to consider in the management of epilepsy and pregnancy, and the steps to take to mitigate risk will help you maximize the chance of a positive outcome.

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