Ciclosporin (cyclosporin, cyclosporine, cyclosporine A) is a calcineurin inhibitor used systemically for graft rejection prophylaxis and management, and in the treatment of ulcerative colitis, rheumatoid arthritis, atopic dermatitis, psoriasis, nephrotic syndrome, and endogenous uveitis. It is also used topically as an eye drop solution for severe keratitis in adults with dry eye disease.
A guideline produced by the British Society for Rheumatology (BSR) and British Health Professionals in Rheumatology (BHPR) states that ciclosporin is compatible for use throughout pregnancy (and breastfeeding) at the lowest effective dose.
The available data relating to the safety of maternal ciclosporin use in human pregnancy mainly consist of uncontrolled case series and a smaller number of controlled studies, which collectively describe the pregnancy outcomes of approximately 4,000 unique pregnancies in women with solid organ transplants or immune mediated diseases. Around 2,000 of these relate to exposure in the first trimester. Uncontrolled data are likely limited by reporting bias and confounding resulting from concomitant medication exposures and associated maternal medical conditions.
The available data do not currently provide evidence that systemic use of ciclosporin during pregnancy increases the risk of congenital malformation. Increased rates of preterm delivery and intrauterine growth restriction have been identified among women receiving systemic treatment; however, it is unclear to what extent these findings are confounded by the underlying maternal medical condition.
The currently available data do not suggest an increased risk of miscarriage, intrauterine death, neonatal complications, or neurodevelopmental impairment following ciclosporin use in pregnancy.
There are no pregnancy exposure data relating specifically to topical administration of ciclosporin. However, given the mode of administration, it is unlikely that significant systemic absorption will occur. Topical ciclosporin treatment can therefore be considered when there is no alternative with a better established pregnancy safety profile.
Women being treated with ciclosporin who are planning a pregnancy or who become pregnant should be offered a medication review by their specialist. Regular clinical review and monitoring of maternal whole blood ciclosporin concentration is recommended both during and after pregnancy due to the risk of subtherapeutic or toxic blood concentrations as a consequence of the pharmacokinetic changes which may be associated with pregnancy. Close monitoring of the maternal graft function and immunosuppressive status, with regular observations of the maternal obstetric condition and fetal growth, is advised.
Exposure to ciclosporin at any stage in pregnancy would not usually be regarded as medical grounds for termination of pregnancy. However, other risk factors present in individual cases 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.