Sirolimus is a macrolide immunosuppressant licensed for the prophylaxis of organ rejection in adult renal transplant patients at low-to-moderate immunological risk and the treatment of sporadic lymphangioleiomyomatosis with moderate lung disease or declining lung function.
Preclinical animal studies have identified possible associations between maternal gestational exposure and embryo/fetal lethality, delayed skeletal ossification, decreased fetal weight gain and neurodevelopmental impairment. The available data relating to sirolimus exposure in human pregnancy are, however, highly limited, consisting solely of uncontrolled case reports/series which report outcomes of 30 unique first trimester-exposed pregnancies, a small number of which were also exposed into late pregnancy.
Although adverse outcomes have been reported following human pregnancy exposure, including miscarriage, malformation (with no pattern of defects), low birth weight and preterm delivery, there is currently no signal that sirolimus is a major teratogen. However, the lack of adequately controlled studies prevents an accurate assessment of the risk posed to the developing fetus. Any decision to discontinue sirolimus treatment or switch to an alternative medication must take into consideration the possible risk of subsequent maternal ill health for both mother and fetus.
Exposure to sirolimus 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. As the available data are highly limited, additional/more detailed ultrasound scans to check the morphological development of the fetus may be indicated following first trimester sirolimus exposure.
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.