USE OF CARBAMAZEPINE IN PREGNANCY

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(Date of issue: May 2015, Version: 2)

This is a UKTIS monograph for use by health care professionals. For case-specific advice please contact UKTIS on 0344 892 0909. To report an exposure please download and complete a pregnancy reporting form. Please encourage all women to complete an online reporting form.

A corresponding patient information leaflet on carbamazepine use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Carbamazepine is a dibenzazepine derivative licensed to treat paroxysmal pain of trigeminal neuralgia, and as an antiepileptic and mood stabilising medication. It is also used occasionally as an off-license therapy for the treatment of alcohol withdrawal and diabetic neuropathy.

The available data on carbamazepine use in pregnancy are derived mainly from studies of women with epilepsy. Although it is possible that the underlying maternal illness may have confounded some of the findings reported in these studies, similar risks should be assumed for pregnant women using the drug in the treatment of psychiatric or other disorders until proven otherwise.

Carbamazepine monotherapy exposure in pregnancy may increase the risk of congenital malformation in the exposed fetus, although absolute risk estimates range from 3% to 10% (i.e. up to a 3 times increased risk above background). Malformations of the urinary tract, neural tube and respiratory system, and more specific defects including anomalous pulmonary venous return, cleft lip with or without cleft palate, diaphragmatic hernia and hypospadias have all been associated with prenatal exposure. Minor malformations including nail dysplasia and facial dysmorphic features such as hypertelorism, nose hypoplasia or broad/flat nasal bridge, upslanting palpebral fissures, epicanthal folds and elongation of the philtrum have also been attributed to carbamazepine exposure in-utero.

No evidence of an increased risk of spontaneous abortion has been provided from the small number of studies currently available. Increased risk of perinatal death, infants being born small for gestational age, preterm delivery and neonatal complications, including neonatal intensive care admission, specifically with the requirement for respiratory care, have been reported, but the available data are both limited and occasionally conflicting, meaning these associations remain to be confirmed. Carbamazepine monotherapy exposure in pregnancy has also been associated in some but not all studies, with adverse effects on infant neurodevelopment including poorer cognitive and motor functions, and negative behavioural traits.

Some studies have identified associations between the maternal carbamazepine dose and the occurrence of major congenital malformation and neurodevelopmental impairment. Increases in the risk of major congenital malformation have been identified in two out of three studies, specifically following maternal use of ≥1,000 mg/d. Therefore, the lowest effective dose which provides adequate therapeutic control of the maternal condition should be advised. 

In comparison with carbamazepine monotherapy-exposed infants, exposure in polytherapy produces higher rates of major congenital malformation and has been associated with slight intrauterine growth impairment in a single study. However, it is likely that the inclusion of sodium valproate in these regimens has contributed to increased malformation rates, and effects of the underlying maternal epilepsy on fetal growth cannot be excluded. When carbamazepine therapy during pregnancy is required, the drug should preferably be prescribed in monotherapy. Where polytherapy is deemed necessary, the potential for increased risk of adverse pregnancy outcomes should be discussed, particularly where sodium valproate-containing regimens are required.

Carbamazepine has been shown to affect folate metabolism. Given the evidence which has suggested that periconceptual folate supplementation in pregnancy may reduce the risk of neural tube defects, it is currently advised that all women who are either planning a pregnancy, or who become pregnant whilst undergoing carbamazepine therapy, should be advised to commence high dose folic acid supplementation (5mg/d). Patients should, however, be counselled that there is currently no strong scientific evidence that folate supplementation protects against neural tube defects and other congenital malformations, or neurodevelopmental problems as a direct result of carbamazepine exposure.

Exposure to carbamazepine at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors may be present in individual cases which may independently increase the risk of adverse pregnancy outcome. Clinicians are reminded of the importance of consideration of such factors when performing case-specific risk assessments. Although no definitive evidence-based recommendations regarding fetal monitoring can be made on the currently available data, enhanced monitoring of fetal growth may be prudent following exposure to carbamazepine in pregnancy.

This document is regularly reviewed and updated. Only use full UKTIS monographs downloaded directly from TOXBASE.org to be sure you are using the most up-to-date version. The summaries of these monographs are openly available on UKTIS.org.

This is a summary of the full UKTIS monograph for health care professionals and should not be used in isolation. The full UKTIS monograph and access to any hyperlinked related documents is available to health care professionals at www.toxbase.org.

If you have a patient with exposure to a drug or chemical and require assistance in making a patient-specific risk assessment, please telephone UKTIS on 0344 892 0909 to discuss the case with a teratology specialist.

If you would like to report a pregnancy to UKTIS please click here to download our pregnancy reporting form. Please encourage all women to complete an online reporting form.

Disclaimer: Every effort has been made to ensure that this monograph was accurate and up-to-date at the time of writing, however it cannot cover every eventuality and the information providers cannot be held responsible for any adverse outcomes of the measures recommended. The final decision regarding which treatment is used for an individual patient remains the clinical responsibility of the prescriber. This material may be freely reproduced for education and not for profit purposes within the UK National Health Service, however no linking to this website or reproduction by or for commercial organisations is permitted without the express written permission of this service. This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to ensure you are using the most up-to-date version.