What is the safety profile of Levetiracetam (Keppra) during pregnancy?

From the Guidelines

Levetiracetam (Keppra) is considered a relatively safe antiepileptic medication to use during pregnancy, with a lower risk of major congenital malformations compared to older antiepileptic drugs. According to the provided evidence, many major antiepileptic drugs are teratogenic, but Levetiracetam is not explicitly mentioned as a teratogenic medication in the study 1. The study recommends monotherapy at the lowest effective dosage for seizure disorders, which is in line with the general approach to using Levetiracetam during pregnancy.

Key Considerations

• The risk of major congenital malformations with Levetiracetam appears to be relatively low, similar to the general population (approximately 2-3%)
• Levetiracetam crosses the placenta and is present in breast milk, but it has not been strongly associated with specific birth defects
• For pregnant women with epilepsy, the risks of uncontrolled seizures often outweigh the potential risks of the medication
• Seizures during pregnancy can cause oxygen deprivation to the fetus and increase the risk of miscarriage or other complications

Recommendations

• Dosage adjustments may be necessary during pregnancy as the body's clearance of the drug can change
• Regular monitoring of drug levels and close collaboration between neurologists and obstetricians is recommended
• Folic acid supplementation (at least 1 mg daily) is also important for all women taking antiepileptic medications during pregnancy to reduce the risk of neural tube defects, although this is not explicitly mentioned in the provided study, it is a general recommendation for pregnant women taking antiepileptic medications.

From the FDA Drug Label

Pregnancy Category C In animal studies, levetiracetam produced evidence of developmental toxicity at doses similar to or greater than human therapeutic doses Administration to female rats throughout pregnancy and lactation was associated with increased incidences of minor fetal skeletal abnormalities and retarded offspring growth pre- and/or postnatally at doses ≥350 mg/kg/day There are no adequate and well-controlled studies in pregnant women Levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The safety profile of Levetiracetam (Keppra) during pregnancy is not well established, as there are no adequate and well-controlled studies in pregnant women. However, animal studies have shown evidence of developmental toxicity at doses similar to or greater than human therapeutic doses. Pregnancy Category C indicates that levetiracetam should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Key points to consider include:

• Increased incidences of minor fetal skeletal abnormalities and retarded offspring growth
• Increased pup mortality and offspring behavioral alterations at higher doses
• No overt maternal toxicity at the doses used in animal studies
• The developmental no effect dose was 70 mg/kg/day (0.2 times the MRHD on a mg/m2 basis) 2 2 2

From the Research

Safety Profile of Levetiracetam During Pregnancy

The safety profile of Levetiracetam (Keppra) during pregnancy has been evaluated in several studies.

• A hospital-based, retrospective study from a tertiary care hospital in North Eastern India found that levetiracetam taken in monotherapy can be considered a safer alternative for women with epilepsy of childbearing age 3.
• A prospective study on therapeutic drug monitoring of levetiracetam in pregnant women with epilepsy found that serum levels of levetiracetam vary during pregnancy, and a well-conducted, intensive pharmacokinetic sampling study is needed to evaluate the whole pharmacokinetic profile of levetiracetam and to correlate the clinical outcome 4.
• A review on therapeutic drug monitoring of antiepileptic drugs in women with epilepsy before, during, and after pregnancy found that levetiracetam concentrations decrease during pregnancy, and monitoring of levetiracetam is recommended during and after pregnancy 5.
• A retrospective study on levetiracetam use during pregnancy in women with epilepsy found that none of the children born to pregnant women receiving levetiracetam had any congenital malformation, and levetiracetam is a first-line antiepileptic drug during pregnancy 6.
• A study on fetal growth restriction and birth defects with newer and older antiepileptic drugs during pregnancy found that levetiracetam had a low malformation rate, and children exposed to levetiracetam did not have a significant risk of birth defects 7.

Key Findings

• Levetiracetam is considered a safer alternative for women with epilepsy of childbearing age 3.
• Serum levels of levetiracetam vary during pregnancy, and therapeutic drug monitoring is recommended 4, 5.
• Levetiracetam has a low malformation rate, and children exposed to levetiracetam do not have a significant risk of birth defects 6, 7.
• Monitoring of levetiracetam is recommended during and after pregnancy to ensure optimal seizure control and minimize the risk of birth defects 5.