USE OF CICLOSPORIN IN PREGNANCY

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.

Guidance from the British Society for Rheumatology (BSR) and European Alliance of Associates for Rheumatology (EULAR) states that ciclosporin is compatible for use throughout pregnancy at the lowest effective dose.

Human data predominantly deriving from transplant recipients and women with immune-mediated disorders include approximately 4,000 unique pregnancies, around 2,000 of which were exposed in the first trimester. Interpretation of this evidence is limited by a predominance of uncontrolled studies, as well as the likelihood of concomitant medication exposures and confounding from underlying maternal medical conditions. A further ~3,500 predominantly early pregnancy exposures are provided from experimental studies of ciclosporin use to reduce recurrent pregnancy loss, with the main outcome reported being miscarriage risk.

The available data do not suggest that use of ciclosporin during pregnancy increases the risk of miscarriage or congenital malformation. Increased rates of preterm delivery and intrauterine growth restriction have been identified; however, the underlying maternal medical condition likely contributes to these findings. Data relating to intrauterine death, neonatal complications, and neurodevelopmental outcomes are very limited but do not suggest an increased risk.

There are no pregnancy exposure data relating specifically to topical administration of ciclosporin, although this route of exposure is unlikely to lead to significant systemic absorption.

Women treated with ciclosporin who are planning a pregnancy or who become pregnant should be offered a specialist medication review. 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 associated with pregnancy.

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.