USE OF CLOZAPINE IN PREGNANCY

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(Date of issue: March 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 clozapine use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Clozapine is an atypical antipsychotic used in the treatment of schizophrenia, and psychosis associated with Parkinson’s disease.

Published data on the use of clozapine in pregnancy are extremely limited and are derived mainly from case reports, cohort studies of antipsychotics as a class, and manufacturer adverse event monitoring. Although there is currently no signal for an increase in rates of spontaneous abortion, congenital malformation, intrauterine death, low birth weight or preterm delivery following in utero clozapine exposure, the number of published clozapine exposures and quality of the available evidence are not sufficient to enable an accurate assessment of risk. Neurodevelopment in the offspring following maternal use of clozapine during pregnancy has not been investigated. 

Weight gain and diabetes are recognised side-effects of clozapine therapy but have not been systematically studied in pregnant populations. However, this together with early reports of an increased mean birth weight of infants exposed to atypical antipsychotics, raised concerns regarding risk of maternal diabetes, obesity and high infant birth weight, all which are associated with various adverse pregnancy outcomes. Data from subsequent studies on infant birth weight are conflicting, with some supporting an association while others find no difference between exposed and unexposed infant cohorts, or show an association with low infant birth weight. Until more robust data are available, additional maternal, fetal and neonatal monitoring may be prudent.

Use of clozapine throughout pregnancy or near delivery has been associated with withdrawal symptoms in the neonate and/or poor neonatal adaptation syndrome (PNAS). These symptoms are likely to be more severe in infants exposed in utero to more than one CNS acting drug. Delivery should be planned in a unit with adequate neonatal facilities.

Prescribers and patients should consider this lack of human pregnancy safety data when weighing up the risks and benefits of use in human pregnancy. It is, however, important to ensure that maternal mental health is treated appropriately. Where a patient is stabilised on clozapine, either prior to conception or during pregnancy, the risk of relapse of the maternal condition as a result of discontinuing or changing medication, or reducing the dose, should be carefully considered on a case-by-case basis. Where clinically appropriate, clinicians are encouraged to discuss these factors with the patient. Where the benefit of continued treatment is considered to outweigh any potential or known risks, clozapine may be prescribed for use in pregnancy.

This document is regularly reviewed and updated. Only use UKTIS monographs downloaded directly from TOXBASE.org or UKTIS.org to be sure you are using the most up-to-date version.

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.