From the Guidelines
Cyclosporin levels should be closely monitored during pregnancy, with adjustments made as needed to maintain therapeutic levels, as pregnancy can alter cyclosporin pharmacokinetics, and both subtherapeutic and excessive levels can have adverse effects on the mother and fetus.
Key Considerations
- The recommended therapeutic range for cyclosporin during pregnancy is typically 100-150 ng/mL for whole blood trough concentrations, though this may vary based on the specific transplant type and clinical situation 1.
- Pregnancy alters cyclosporin pharmacokinetics due to increased plasma volume, altered drug metabolism, and changes in protein binding, often necessitating higher doses to maintain therapeutic levels.
- Renal function should be closely monitored, as both pregnancy and cyclosporin can affect kidney function.
- Blood pressure should be regularly checked since cyclosporin can cause hypertension, which is particularly concerning during pregnancy.
- Liver function tests should also be performed periodically.
Monitoring and Management
- Cyclosporin levels should be monitored more frequently during pregnancy, typically every 1-2 weeks, with dose adjustments as needed to maintain therapeutic levels.
- A multidisciplinary approach involving transplant specialists, obstetricians, and pharmacists is essential for optimal management of pregnant transplant recipients on cyclosporin.
- According to the easl clinical practice guidelines on the management of liver diseases in pregnancy, cyclosporine crosses the placenta with concentrations in the fetus reported to be between 30-60% of maternal concentration, and there is no significant malformation risk with either cyclosporine or tacrolimus 1.
- The guidelines also suggest that tacrolimus use in pregnancy has been shown to lower incidences of hypertension and preeclampsia when compared to cyclosporine, whilst renal toxicity and glucose intolerance during pregnancy may also be prevalent 1.
From the Research
Pregnancy and Cyclosporin Levels
- Cyclosporin is an immunosuppressive drug used to prevent rejection in organ transplantation and to treat various autoimmune diseases, including psoriasis, rheumatoid arthritis, and systemic lupus erythematosus 2.
- The use of cyclosporin during pregnancy has been associated with premature delivery and low birthweight infants, as well as comorbidities such as hypertension, pre-eclampsia, and gestational diabetes mellitus 2, 3.
- However, some studies suggest that cyclosporin therapy during pregnancy may be a safe alternative for patients with autoimmune disease refractory to conventional treatment, with a live birth rate of 86.2% and no significant increase in maternal-fetal complications 4.
- Cyclosporin crosses the placental barrier and enters the fetal circulation, posing a risk for fetal development, but the literature suggests that it does not appear to be a major human teratogen 3, 5.
- The risk of prematurity and low birth weight associated with cyclosporin use during pregnancy is still a concern, with an overall prevalence rate of 56.3% for prematurity and an odds ratio of 1.52 (CI 1.00-2.32) 5.
- Continued monitoring of patients exposed to cyclosporin during pregnancy is necessary to understand the risk factors associated with its use and to minimize potential adverse effects on the fetus 2, 4, 3.