Risks and Recommendations for Carbamazepine and Clobazam During Pregnancy
Both carbamazepine and clobazam should be used with caution during pregnancy, with carbamazepine carrying a specific risk of neural tube defects while clobazam has limited safety data but potential signals for increased major congenital malformations. 1, 2
Carbamazepine in Pregnancy
Risks
- Carbamazepine increases the risk of neural tube defects specifically, but does not appear to increase the risk of other major malformations 1
- Unlike valproic acid, carbamazepine is not associated with an increased risk of developmental delay in exposed children 1
- The risks of carbamazepine appear to be dose-dependent, with higher doses carrying greater risk 3
Recommendations
- For women with mild manifestations of conditions treated with carbamazepine, consider discontinuing therapy prior to or during pregnancy due to the fetal risks 4
- If treatment is necessary, use the lowest effective dose to minimize fetal exposure while maintaining seizure control 5
- A comprehensive evaluation of risks and benefits should be conducted prior to conception when possible 6
- Monotherapy is preferred over polytherapy, as combination therapy with other antiepileptic drugs increases the risk of birth defects 5
Clobazam in Pregnancy
Risks
- Limited data exists on clobazam use during pregnancy, but there appears to be a signal for increased risk of major congenital malformations (MCMs) in infants of women with epilepsy who use clobazam 2
- The FDA label for clobazam warns that its use during pregnancy can cause fetal harm which may occur early in pregnancy 7
- Risk appears lower when clobazam is used as part of polytherapy compared to monotherapy, though data is limited 2
Recommendations
- Women should be advised that clobazam use during pregnancy can cause fetal harm 7
- Healthcare providers should counsel pregnant women and women of childbearing potential about alternative therapeutic options when appropriate 7
- Women should be instructed to notify their healthcare provider if they become pregnant or intend to become pregnant during therapy 7
- Abrupt discontinuation of clobazam should be avoided as it may precipitate withdrawal reactions or increase seizure risk 7
General Considerations for Both Medications
Balancing Maternal and Fetal Risks
- The decision to continue, adjust, or discontinue anticonvulsant therapy during pregnancy requires careful balancing of maternal and fetal risks 5
- Uncontrolled seizures pose potential hazards to both mother and fetus, potentially more harmful than the teratogenic effects of the medications 5
- For women with bipolar disorder treated with these medications, illness relapse can occur if medications are discontinued, which itself carries risks 8
Monitoring and Management
- Regular monitoring of drug concentrations is recommended during pregnancy 5
- Any major change in treatment should ideally be completed before conception 5
- Women taking these medications during pregnancy should be enrolled in pregnancy registries when available 7
- Close monitoring for seizures or mood episodes is essential as pregnancy can affect medication levels 8
Breastfeeding Considerations
- Clobazam is excreted in breast milk, and mothers should observe their infants for poor sucking and somnolence 7
- For both medications, infants should be monitored for potential adverse effects if the mother chooses to breastfeed while on treatment 7, 5
Clinical Approach
- Evaluate the necessity of the medication for the specific condition being treated
- Consider the severity of the underlying condition and risks of untreated disease
- Use the lowest effective dose of medication when treatment is necessary
- Provide appropriate folic acid supplementation, particularly with carbamazepine due to the risk of neural tube defects 5
- Consider switching to medications with better pregnancy safety profiles when possible and clinically appropriate 6