Tacrolimus is a potent immunosuppressive macrolide antibiotic used as prophylactic therapy in solid organ transplant recipients and as treatment for allograft rejection which has proven resistant to treatment with other immunosuppressive agents. Topical tacrolimus is used in the treatment of atopic eczema and psoriasis.
The available data relating to maternal tacrolimus use in pregnancy mainly consist 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 associated maternal medical conditions. A small number of controlled studies are also available but collectively report only 139 confirmed unique exposed pregnancies. There are no pregnancy exposure data available relating to topical administration of tacrolimus.
The available data do not suggest associations between gestational tacrolimus exposure and miscarriage, congenital malformation or intrauterine death, but are limited and potentially confounded, therefore increased risks of these outcomes cannot be excluded. Studies using disease-matched control groups do not suggest that tacrolimus use in pregnancy increases the risks of preterm delivery or low infant birth weight. Uncontrolled case reports have described neonatal complications including hyperbilirubinaemia, hyperkalaemia, oliguria and respiratory complications, although some of these were observed in conjunction with preterm delivery.
The available data relating to neurodevelopmental impairment following in utero tacrolimus exposure are reassuring but are too limited to rule out any increased risk.
Although it is not possible to state that there is no increased risk to the fetus following maternal systemic tacrolimus use during pregnancy, the available data do not currently provide evidence that tacrolimus is a major human teratogen. Women being treated with tacrolimus who are planning a pregnancy or who become pregnant should be offered a medication review by their specialist.
There are no pregnancy exposure data relating specifically to topical administration of tacrolimus, therefore a meaningful assessment of any risks posed by its use is not possible. Given the mode of administration, it is unlikely that significant systemic absorption will occur. Where topical tacrolimus is the only medication which controls a condition, use can be considered.
Exposure to tacrolimus at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. Additional fetal monitoring may be required due to the underlying maternal conditions that tacrolimus is used to treat. 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.
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.