Is Trileptal (Oxcarbazepine) safe during pregnancy?

From the Guidelines

Trileptal (oxcarbazepine) should be used with caution during pregnancy, as it is associated with a slightly increased risk of birth defects, particularly neural tube defects, and may cause decreased fetal growth, but it may be necessary for seizure control in some cases. When considering the use of Trileptal during pregnancy, it is essential to weigh the benefits of seizure control against the potential risks to the fetus, as uncontrolled seizures pose significant risks to both mother and baby 1. According to the American Family Physician guidelines, many major antiepileptic drugs, including carbamazepine, are teratogenic, and monotherapy should be used when possible at the lowest effective dosage 1.

Key Considerations

• Trileptal is associated with a slightly increased risk of birth defects, particularly neural tube defects, with a risk of 2-3% compared to 1-2% in the general population.
• Decreased fetal growth is also a potential risk associated with Trileptal use during pregnancy.
• If Trileptal is necessary for seizure control, a higher dose of folic acid (4-5 mg daily) may be recommended before and during pregnancy to reduce the risk of neural tube defects.
• During pregnancy, drug levels should be monitored more frequently due to changes in metabolism that can affect medication effectiveness.
• Breastfeeding while taking Trileptal is generally considered acceptable, as only small amounts of the medication pass into breast milk.

Recommendations

• Consult a neurologist and obstetrician to discuss the specific situation and determine the best course of action.
• Do not stop Trileptal suddenly, as this can increase the risk of seizures.
• Monitor drug levels and adjust the dosage as needed to ensure effective seizure control and minimize potential risks to the fetus.

From the FDA Drug Label

There are no adequate data on the developmental risks associated with the use of oxcarbazepine in pregnant women; however, oxcarbazepine is closely related structurally to carbamazepine, which is considered to be teratogenic in humans Data on a limited number of pregnancies from pregnancy registries suggest that oxcarbazepine monotherapy use is associated with congenital malformations (e.g., craniofacial defects such as oral clefts and cardiac malformations such as ventricular septal defects) Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose (MRHD)

Oxcarbazepine use during pregnancy is not considered safe due to the potential risk of congenital malformations and developmental toxicity. The FDA drug label recommends that women who become pregnant while taking oxcarbazepine should enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry to monitor pregnancy outcomes 2. Women of childbearing potential should use effective birth control and consult their healthcare provider before becoming pregnant while taking oxcarbazepine.

• Key points: + Oxcarbazepine is closely related to carbamazepine, which is teratogenic in humans + Limited data suggest oxcarbazepine monotherapy use is associated with congenital malformations + Animal studies show increased incidences of fetal structural abnormalities and developmental toxicity + Women who become pregnant while taking oxcarbazepine should enroll in the NAAED Pregnancy Registry + Effective birth control should be used by women of childbearing potential taking oxcarbazepine

From the Research

Safety of Trileptal During Pregnancy

• The safety of Trileptal (oxcarbazepine) during pregnancy has been assessed in several studies 3, 4.
• A literature review of 248 pregnancies involving maternal exposure to oxcarbazepine monotherapy found a malformation rate of 2.4%, which is similar to the rate in the general population 3.
• However, the number of pregnancies studied was not sufficient to draw definitive conclusions, and additional information from large-scale pregnancy registries is needed to confirm the safety profile of oxcarbazepine during pregnancy 3.
• Another study found that oxcarbazepine is among the first-choice options for the initial treatment of focal-onset seizures in several countries, including the US and China, and is widely used in many countries 4.
• The pharmacokinetics of oxcarbazepine during pregnancy may be altered, with an increase in clearance and a decrease in concentrations, which may have consequences for fetal exposure and seizure control 5.
• Monitoring of oxcarbazepine concentrations during and after pregnancy is recommended to ensure adequate seizure control and minimize the risk of teratogenic effects 5.

Key Findings

• Oxcarbazepine monotherapy does not appear to increase the risk of malformations in newborns compared to the general population 3.
• The malformation rate associated with oxcarbazepine adjunctive therapy is higher, but the number of pregnancies studied is limited 3.
• Oxcarbazepine is generally well tolerated during monotherapy and adjunctive therapy, but may interact with other drugs and decrease plasma levels of oral contraceptives 6.
• Additional research is needed to confirm the safety profile of oxcarbazepine during pregnancy and to provide guidance on dose modification and therapeutic drug monitoring 5, 7.