USE OF MYCOPHENOLATE MOFETIL IN PREGNANCY

View printable version
(Date of issue: January 2016, Version: 2.1)

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 mycophenolate use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Mycophenolate mofetil (MMF) is the pro-drug of mycophenolic acid (MPA), an antiproliferative agent that interferes with purine synthesis, thereby suppressing the immune response. It is indicated for the prophylaxis of organ rejection in patients receiving transplants and is generally used concomitantly with cyclosporine and corticosteroids. Mycophenolate has also been used off-license to control autoimmune conditions such as psoriasis and lupus nephritis.

Mycophenolate is not recommended for use during pregnancy due to an increased risk of first trimester pregnancy loss and confirmed human teratogenic effects including craniofacial anomalies (cleft lip and/or palate, microtia, external auditory canal atresia,  micrognathia); microphthalmia, coloboma of iris and retina, and hypertelorism; complex congenital cardiac anomalies including septal defects, conotruncal and outflow tract anomalies; oesophageal atresia, diaphragmatic hernia, and various vertebral and skeletal anomalies. Prospective data from the two larger cohort studies report malformation rates of between 21% and 27% amongst MMF-exposed offspring. No studies have investigated neurodevelopmental outcomes following exposure in utero, and risk of effects on learning and development remain undefined. 

Women of childbearing potential who are prescribed MMF or MPA should be informed of the associated risks to the fetus and therefore the importance of adequate contraception.  European Medicines Agency guidelines for male and female patients, published in October 2015 following a periodic safety update review, recommend additional measures to prevent fetal exposure to mycophenolate and should be read prior to prescribing MMF.

Patients wishing to become pregnant (or who become pregnant and wish to continue the pregnancy) while being treated with MMF are advised to consider alternative treatments, taking into account the risk of graft rejection. Women for whom there is no suitable alternative, or the risk of rejection is high, must be informed of the increased risk of structural teratogenesis and miscarriage with MMF treatment in the first trimester. 

Mycophenolate should only be used during pregnancy if there is no effective alternative. Women exposed to mycophenolate during early pregnancy should be offered detailed anomaly scans. Patients should also be counselled about the unknown risk of adverse neurodevelopmental outcomes and the fact that these will not be detected by ultrasound examination. Other risk factors may also 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. Please report all cases of MMF exposure to UKTIS.

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.