USE OF AZATHIOPRINE OR MERCAPTOPURINE IN PREGNANCY

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(Date of issue: July 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 azathioprine or mercaptopurine use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Azathioprine and its active metabolite mercaptopurine are purine analogues which interfere with the synthesis of DNA and RNA precursors. Azathioprine is currently licensed to treat severe refractory eczema, various auto-immune disorders such as inflammatory bowel disease, rheumatoid arthritis and psoriasis, and as an immunosuppressant for the prevention of allograft rejection. Mercaptopurine is currently licensed to treat acute and chronic leukaemia, and as maintenance therapy in acute lymphoblastic and myelogenous leukaemia.

The available data do not suggest that azathioprine/mercaptopurine exposure during early pregnancy increases the risk of congenital malformation, intrauterine death or fetal growth restriction. The risk of spontaneous abortion following azathioprine/mercaptopurine exposure in pregnancy is also not currently thought to be increased. However, the available studies are methodologically limited and more robust epidemiological data are required.

Rates of preterm delivery above those observed in the general population have been described in some studies of azathioprine/mercaptopurine exposure in pregnancy. However, most studies which compare the incidence against unexposed disease-matched controls fail to identify statistically significant associations.

A possible adverse effect on infant neurodevelopment has been demonstrated in one small study. Additional studies using larger datasets are required before firm conclusions can be provided.

Neonatal leucopenia and thrombocytopenia have been reported in a number of case reports following azathioprine exposure in utero but no epidemiological studies assessing this risk have been located.
 
Exposure to azathioprine/mercaptopurine at any stage in pregnancy would not usually be regarded as medical grounds for additional fetal monitoring. 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.

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.