PATERNAL USE OF AZATHIOPRINE OR MERCAPTOPURINE

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(Date of issue: August 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.

Summary

Azathioprine and its active metabolite mercaptopurine are purine analogues which interfere with the synthesis of DNA and RNA precursors. Azathioprine is used either alone or in combination with other immunosuppressive medications in the prevention of organ rejection following renal, cardiac or hepatic transplantation, and in the treatment of various autoimmune disorders. Mercaptopurine is licensed for the treatment of leukaemia.

Due to the anti-metabolite effects of azathioprine/mercaptopurine (AZA/MP), there are theoretical concerns that periconceptual paternal use could result in genetic abnormalities in the sperm and disorders in subsequent offspring. As such, the manufacturers of both azathioprine and mercaptopurine advise use of adequate contraceptive precautions in cases where either partner is undergoing AZA/MP treatment.

The available data concerning pregnancy outcomes following periconceptual paternal AZA/MP exposure are currently limited (<500 fathered pregnancies). Although isolated case reports have described adverse pregnancy outcomes, overall the data do not currently provide evidence that paternal use of AZA/MP is associated with an increased risk of spontaneous abortion, congenital malformation, low birth weight or preterm delivery. Single cases of impaired motor development and carcinogenicity (Wilms tumour) in the offspring following paternal AZA/MP use have been reported in the literature. Epidemiological studies assessing the risk of these specific outcomes or the risk of stillbirth following paternal AZA/MP exposure are currently unavailable.

The available evidence base is currently too limited to accurately assess whether the risk of adverse pregnancy outcomes differs with paternal periconceptual use in comparison with discontinued use prior to conception. It is therefore not possible to state whether paternal use of AZA/MP should be discontinued prior to attempting conception. As spermatogenesis takes approximately three months to complete, it is often advised that male patients exposed to medication for which there may be theoretical mutagenic concerns should wait six months (approximately two sperm cycles) after exposure cessation before attempting conception. However, the lack of evidence of adverse effects and the need for continued control of the paternal condition should be considered when discussing preconception discontinuation with patients.

Paternal exposure to AZA/MP would not usually be regarded as medical grounds for termination of pregnancy or any 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.