USE OF TACROLIMUS IN PREGNANCY

View printable version
(Date of issue: May 2016, 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 tacrolimus use in pregnancy is available at www.medicinesinpregnancy.org.

Summary

Tacrolimus is a potent immunosuppressive macrolide antibiotic used as prophylactic immunosuppression therapy in solid organ transplant recipients and as treatment for allograft rejection which has proven resistant to treatment with other immunosuppressive agents. Topical tacrolimus preparations have been used to treat moderate to severe atopic eczema.

The available data concerning the safety of maternal tacrolimus use in pregnancy mainly consists of uncontrolled case reports/series which describe the pregnancy outcomes of women with solid organ transplants. These data are likely limited by reporting bias and uncontrolled confounding resulting from concomitant medication exposures and the underlying or associated maternal medical conditions. A small number of controlled studies are also available but collectively report on less than 100 exposed pregnancies. There are no pregnancy exposure data available concerning topical administration of tacrolimus.

The available data do not suggest an association between spontaneous abortion, congenital malformation or intrauterine death and exposure to tacrolimus during pregnancy, but are limited and potentially confounded, therefore an increased risk of these outcomes cannot be excluded. 

Intrauterine growth restriction, small for gestational age at delivery, low infant birth weight, preterm delivery and neonatal complications, including hyperbilirubinaemia and hyperkalaemia, have all been described in uncontrolled case reports/series of maternal tacrolimus use in pregnancy. However, maternal transplant-associated comorbidities may heavily confound these data. Furthermore, no evidence of a significantly increased risk of small for gestational age, low infant birth weight or preterm delivery was provided from studies which utilised disease-matched control groups to limit the impact of confounding by indication.

The available data concerning neurodevelopmental impairment following in utero tacrolimus exposure are currently too limited to permit an assessment of the risk.

Although it is not possible to state that there is no increased risk to the fetus following maternal tacrolimus use during pregnancy, the available data does not currently provide evidence that tacrolimus is a major human teratogen. Women being treated with tacrolimus who are considering pregnancy or who become pregnant should discuss their options for immunosuppressive therapy during pregnancy with their specialist. 

Exposure to tacrolimus 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. Close monitoring of allograft function and immunosuppressive status with regular surveillance of the maternal obstetric condition, fetal growth and development is advised.
                     
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.