Azathioprine is a prodrug and is rapidly metabolised to its active metabolite mercaptopurine (6-MP). Mercaptopurine is a purine analogue which interferes with the synthesis of DNA and RNA and has immunosuppressant properties. Azathioprine is licensed to treat various auto-immune disorders such as inflammatory bowel disease, rheumatoid arthritis and psoriasis, and for the prevention of allograft rejection. It is also used off-licence to treat severe refractory eczema. Mercaptopurine is licensed to treat acute and chronic leukaemia, as maintenance therapy in acute lymphoblastic and myelogenous leukaemia, and is used off-license to treat severe ulcerative colitis and Crohn’s disease.
The available data do not demonstrate that azathioprine/mercaptopurine exposure during early pregnancy increases the risk of congenital malformation, preterm delivery, or adversely affects fetal growth. There is also no robust evidence of increased risks of intrauterine death, miscarriage, or altered neurodevelopment following gestational azathioprine exposure. However, as the available data for many of these outcomes are limited in quantity and sometimes also methodologically, more robust epidemiological data are ideally required.
Neonatal leucopoenia and thrombocytopenia have been reported in a number of case reports following azathioprine exposure in utero but no epidemiological studies quantifying these risks are available. There is therefore a theoretical concern that the use of azathioprine/mercaptopurine during pregnancy could result in immunosuppression in the neonate, leading to an increased risk of infection and adverse effects following administration of live vaccines. Advice from the MHRA states that infants exposed in utero to certain immunosuppressive medications should not receive live vaccines until they are least 6 months old, although no specific advice relating to azathioprine exposure was issued.
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 NHS health care professionals who are logged in.
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.