SAN FRANCISCO — Third-generation antiepileptic drugs such as lamotrigine and oxcarbazepine are less likely than earlier treatments to cause congenital malformations, but serum levels of the newer drugs must be monitored more closely during pregnancy to avoid other problems.
“The good news is that the third-generation drugs seem to have a spectrum of safety that we did not see with earlier generations,” said Dr. Yasser Y. El-Sayed. “It took awhile for this to be evaluated, as many of these third-generation drugs were part of polytherapy. They were add-on treatments. It seems that with these newer drugs, the incidence of congenital malformation is within the expected range for the general population.”
The risk of birth defects with older antiepileptics has been reported to be 4%-9%, double to triple the 2%-3% rate of birth defects in the general population. Therapy with four or more antiepileptic drugs boosts the risk for malformations to as high as 25%, said Dr. El-Sayed, professor of maternal-fetal medicine and obstetrics at Stanford (Calif.) University. High peak serum levels of the drugs also increase risk, he said.
Valproic acid, in particular, stands out among older antiepileptics for elevating risk of congenital malformations. A 2009 report by the quality standards subcommittee of the American Academy of Neurology and the American Epilepsy Society recommended that physicians avoid valproic acid and polytherapy for women in their first trimesters of pregnancy, if possible, to reduce overall risk of congenital malformations.
The report also said to avoid phenytoin, carbamazepine, and phenobarbital during the first trimester to reduce risks of specific anomalies, Dr. El-Sayed said at the meeting, which was sponsored by the University of California, San Francisco.”
“Having said that, the majority of women on these drugs will not have malformations, so if that's the drug you need to use to control the seizure, then so be it,” he added. Many women hear about the teratogenic potential of antiepileptics and decide to stop epilepsy treatment entirely. “The problem is that seizure activity is hugely problematic” in pregnancy, with potentially grave consequences for both mother and baby.
The most practical approach to treating pregnant women with epilepsy is to pick the single most effective drug and use it at the lowest possible dose, Dr. El-Sayed suggested.
Unlike the older drugs, third-generation antiepileptics have not shown their risks for anomalies to be dose dependent, he added. It's important with the older antiepileptics to keep the whole clinical picture in mind and not respond only to changes in serum levels.
The story is very different with the newer agents. “Their management in pregnancy is much more problematic. The drop in serum levels can be dramatic, and unlike with the older drugs, we tend to see an increase in seizures,” he said. “They require much more stringent monitoring in pregnancy and a much more reactionary approach to lower serum levels.”
Assessing a patient's therapeutic serum level for a drug before conception helps guide treatment during pregnancy. At a minimum, check serum levels at the beginning of each trimester, or monthly for lamotrigine or oxcarbazepine, Dr. El-Sayed advised. Check levels again in the last month of pregnancy and through postpartum week 8, with close attention to third-generation agents because “there tends to be a reactive toxicity post partum. If you've increased the dose during pregnancy, post partum you may run into some toxicity.” Get free fraction levels, if available, and not just total fraction measurements, he said.
Besides sticking to monotherapy and more closely monitoring newer antiepileptic drug levels, good management involves partnering between obstetricians and neurologists in the care of these patients, Dr. El-Sayed added.
Most women with epilepsy give birth safely and successfully, but 1%-2% will develop tonic-clonic seizure during labor, and another 1%-2% will do so during the 24 hours after delivery.
“This can be from stress or lack of sleep, but also from failure to continue adequate administration of antiepileptic drugs during labor,” Dr. El-Sayed said.
Don't forget to give medicine in labor, and consider intravenous or intramuscular administration if needed, he noted.
Disclosures: Dr. El-Sayed said he has no relevant conflicts of interest.