Safety of Tacrolimus and Low-Potency Corticosteroids with Urea During Periconception Period
The combination of tacrolimus and low-potency corticosteroids can be safely used during the periconception period, as both medications are considered compatible with pregnancy and do not require discontinuation before conception. 1
Tacrolimus Safety Profile
Tacrolimus should be continued during the periconception period without interruption. 1 The 2023 EASL guidelines provide strong recommendations that tacrolimus should not be stopped in women planning pregnancy, as there is no significant malformation risk associated with its use. 1
Key Evidence on Tacrolimus:
Fetal malformation rates with tacrolimus are 4-6%, which is comparable to the general population baseline risk of 3-5%. 1 The FDA label reports 8% birth defects in kidney transplant recipients and 5% in liver transplant recipients, though these rates are confounded by concomitant mycophenolate exposure in many cases. 2
Tacrolimus crosses the placenta at approximately 30-71% of maternal blood concentrations, but this does not translate to increased teratogenicity. 1, 3
No preconception washout period is required for tacrolimus, unlike mycophenolate which requires 12 weeks of discontinuation before conception. 1
Important Monitoring Requirements:
Women taking tacrolimus require close monitoring for hypertension and preeclampsia throughout pregnancy, as tacrolimus is associated with 47-54% preeclampsia incidence compared to 68-73% with cyclosporine. 1
Screen for gestational diabetes mellitus, as tacrolimus may increase this risk to approximately 10%. 1
Monitor neonatal kidney function and electrolytes at birth, as transient hyperkalemia and renal dysfunction have been reported in exposed infants. 2, 4, 3
Corticosteroid Safety Profile
Low-potency corticosteroids (prednisolone ≤10 mg daily) are safe during the periconception period and throughout pregnancy. 1
Key Evidence on Corticosteroids:
Only 10% of maternal corticosteroid dose reaches the developing fetus. 1
Older concerns about first-trimester cleft lip/palate associations have not been supported by recent studies. 1
For doses >5 mg prednisolone daily for >3 weeks, be aware of increased gestational diabetes risk and potential adrenal suppression requiring stress-dose coverage at delivery. 1
Screen for gestational diabetes mellitus in all women taking glucocorticoids. 1
Urea Component
The urea component in topical formulations poses no systemic concerns during the periconception period, as it is used for its keratolytic and moisturizing properties without significant systemic absorption.
Clinical Management Algorithm
Before Conception:
- Continue tacrolimus at current dose - no adjustment needed 1
- Continue low-potency corticosteroids if dose ≤10 mg prednisolone equivalent daily 1
- Establish baseline blood pressure, renal function, and glucose tolerance 1
During Conception Attempt:
- No medication changes required 1
- Ensure stable disease control for at least 3 months if this is a transplant patient 1
Common Pitfalls to Avoid:
Do not discontinue tacrolimus thinking it requires a washout period - this applies only to mycophenolate, which requires 12 weeks discontinuation. 1
Do not confuse tacrolimus safety data with sirolimus/everolimus - mTOR inhibitors have limited safety data and higher miscarriage rates (17-31%) and are not recommended. 1
Do not use high-dose corticosteroids (>20 mg prednisolone daily) without adding steroid-sparing agents - aim to taper to <20 mg daily before conception. 1
Contraindicated Medications to Avoid:
If the patient is on mycophenolate mofetil, this must be stopped at least 12 weeks before conception due to 49% miscarriage rates, 23% structural anomaly rates, and specific malformation patterns including hypoplastic nails, microtia, and cleft lip/palate. 1