What are the considerations and guidelines for using Tacrolimus (immunosuppressive medication) in women of childbearing age?

From the Guidelines

Tacrolimus can be used in women of childbearing age, but it requires careful consideration and monitoring due to its potential effects on pregnancy and fetal development. Women taking tacrolimus who are planning pregnancy should not discontinue this medication without consulting their transplant team or specialist, as maintaining immunosuppression is critical for organ preservation 1. According to the most recent guidelines, tacrolimus is generally considered acceptable during pregnancy when medically necessary, with no significant malformation risk 1.

Key Considerations

• Women should use effective contraception while taking tacrolimus unless actively trying to conceive under medical supervision 1.
• Dosing typically requires more frequent monitoring during pregnancy, as physiological changes may alter drug metabolism, often necessitating dose adjustments 1.
• Patients should be counseled about potential risks including slightly increased rates of preterm birth, low birth weight, and gestational hypertension, though the absolute risk of congenital malformations does not appear significantly elevated compared to the general population 1.
• Breastfeeding while on tacrolimus is generally discouraged by many practitioners, though limited data suggests minimal infant exposure 1.

Recommendations

• The immunosuppressive drugs azathioprine, cyclosporine, tacrolimus, and prednisolone should not be stopped in pregnant women 1.
• Women taking cyclosporine and tacrolimus should be closely monitored for hypertension and preeclampsia throughout pregnancy 1.
• Pre-conceptional counselling is recommended for liver transplant recipients, in order to assess graft function, rule out risk of drug-related teratogenic effects, and perform genetic tests if needed 1.

Monitoring and Follow-up

• Women taking glucocorticoid treatment should be screened for gestational diabetes mellitus 1.
• Clinicians should be aware that women taking >5 mg prednisolone per day for more than 3 weeks are at increased risk of adrenal suppression and there should be consideration of increased glucocorticoid dose at the time of delivery, and if there is intercurrent infection, vomiting or hyperemesis gravidarum 1.
• A multidisciplinary counselling between the transplant team, obstetricians, and neonatologists is recommended to plan the pregnancy and also the follow-up after pregnancy 1.

From the FDA Drug Label

Administration of oral tacrolimus to pregnant rabbits throughout organogenesis produced maternal toxicity and abortion at 0.32 mg/kg (0.5 to 1.4 times the recommended clinical dose range [0.2 to 0.075 mg/kg/day], on a mg/m2 basis). Tacrolimus can cause fetal harm when administered to pregnant women. Advise female and male patients of reproductive potential to speak to their healthcare provider on family planning options including appropriate contraception prior to starting treatment with tacrolimus

Considerations for Women of Childbearing Age:

• Contraception: Tacrolimus can cause fetal harm, so female patients of reproductive potential should discuss family planning options with their healthcare provider before starting treatment.
• Fetal Risk: Tacrolimus has been shown to cause fetal harm in animal studies, including embryofetal lethality and fetal malformations.
• Pregnancy Risks: Diabetes and hypertension during pregnancy have been reported in transplant patients receiving tacrolimus.
• Breastfeeding: Tacrolimus is excreted in human milk, and the effects on the breastfed infant are unknown, so the benefits of breastfeeding should be weighed against the potential risks 2.

From the Research

Considerations for Using Tacrolimus in Women of Childbearing Age

• Tacrolimus is an immunosuppressive medication that can be used in women of childbearing age, but its use requires careful consideration and monitoring 3, 4, 5, 6, 7.
• The safety of tacrolimus during pregnancy and lactation has been reported in several studies, with most suggesting that it is relatively safe for the mother, fetus, and allograft 3, 4, 6, 7.
• However, tacrolimus may increase the risk of hypertension, preeclampsia, preterm birth, and low birth weight 4.
• Infants exposed to tacrolimus during lactation will ingest very small amounts of the drug via breast milk, but no adverse outcomes have been reported in children exposed to tacrolimus during lactation 4.

Guidelines for Using Tacrolimus in Women of Childbearing Age

• Women who are trying to conceive and are taking mycophenolic acid (MPA) are strongly recommended to switch to azathioprine, as MPA is teratogenic 4.
• Tacrolimus treatment during conception, pregnancy, and lactation seems to be relatively safe, but requires monitoring of serum levels for dose adjustment, particularly during pregnancy 4, 5, 6.
• The general target range for tacrolimus is 5-15 ng/mL, and pregnant patients may require higher doses to achieve therapeutic levels 5.
• Adherence to prescribed immunosuppressive regimens is crucial to prevent graft rejection and autoimmune disorder flare-ups 5.

Special Considerations

• Patients with a history of kidney or pancreas transplantation may require special consideration when using tacrolimus during pregnancy, as they may be at higher risk for complications such as hyperkalemia and renal impairment in infants exposed to tacrolimus in utero 6, 7.
• LifeCycle Pharma tacrolimus (LCPT) has been reported to be safe during pregnancy in a kidney-pancreas transplanted patient, but further studies are needed to expand the empirical knowledge surrounding tacrolimus 7.