What are the precautions and dosage recommendations for Tacrolimus (Tacrolimus) XL in women of childbearing age?

From the Guidelines

Tacrolimus XL should be used with caution in women of childbearing age, with careful consideration of the potential risks and benefits, and women should use effective contraception before, during, and for 6 weeks after discontinuing tacrolimus therapy. The standard dosage for tacrolimus XL typically starts at 0.1-0.15 mg/kg/day as a once-daily morning dose, though this must be individualized based on clinical response and blood level monitoring, with target trough blood levels generally ranging from 5-15 ng/mL depending on the transplant type and time post-transplant, as recommended by the EASL clinical practice guidelines on liver transplantation 1. Women planning pregnancy should consult their transplant specialist and obstetrician before conception to evaluate risks versus benefits, as maintaining immunosuppression is often necessary despite pregnancy risks. According to the reproductive health and liver disease practice guidance by the American Association for the Study of Liver Diseases, tacrolimus is classified as pregnancy category C, meaning potential risks to the fetus cannot be ruled out 1. Additionally, the EASL clinical practice guidelines on the management of liver diseases in pregnancy 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.

Some key points to consider when using tacrolimus XL in women of childbearing age include:

• The medication can pass into breast milk, so breastfeeding decisions require careful discussion with healthcare providers
• Women should use effective contraception before, during, and for 6 weeks after discontinuing tacrolimus therapy
• The standard dosage for tacrolimus XL typically starts at 0.1-0.15 mg/kg/day as a once-daily morning dose, though this must be individualized based on clinical response and blood level monitoring
• Target trough blood levels generally range from 5-15 ng/mL depending on the transplant type and time post-transplant, with levels checked regularly
• Women planning pregnancy should consult their transplant specialist and obstetrician before conception to evaluate risks versus benefits, as maintaining immunosuppression is often necessary despite pregnancy risks.

It is essential to weigh the potential benefits of tacrolimus XL against the potential risks, particularly in women of childbearing age, and to carefully monitor and adjust the dosage as needed to minimize adverse effects, as recommended by the EASL clinical practice guidelines on liver transplantation 1 and the reproductive health and liver disease practice guidance by the American Association for the Study of Liver Diseases 1.

From the FDA Drug Label

Tacrolimus can cause fetal harm. The FDA drug label does not answer the question.

From the Research

Precautions for Tacrolimus XL in Women of Childbearing Age

• Women of childbearing age taking Tacrolimus XL should be aware of the potential risks and benefits of the medication during pregnancy and lactation 2, 3.
• The current available information does not suggest that tacrolimus increases the risk of major congenital malformations above the baseline risk in the general population 3.
• However, premature birth and low birth weight are often reported in pregnant transplant patients treated with tacrolimus, which may reflect the effects of the maternal condition rather than the medication itself 3.
• Women taking tacrolimus during pregnancy should be monitored for kidney function and electrolytes, as there are reports of hyperkalemia and renal impairment in infants exposed to tacrolimus in utero 3.

Dosage Recommendations for Tacrolimus XL in Women of Childbearing Age

• The dosage of tacrolimus XL should be adjusted based on therapeutic drug monitoring to maintain a stable blood concentration 4.
• The C/D ratio (expressed as the blood concentration normalized by the dose) can be used to classify patients into two major metabolism groups, which can help guide dosage adjustments 4.
• Women of childbearing age taking tacrolimus XL should be closely monitored by a multidisciplinary team to ensure the best possible outcomes for both the mother and the fetus 5.

Pregnancy and Lactation Considerations

• Tacrolimus can be continued during pregnancy if the patient is stable, but the risks and benefits should be carefully considered 3.
• Breastfeeding is possible while taking tacrolimus, but the infant should be monitored for potential adverse effects 2.
• Women with kidney transplants who become pregnant should have good kidney function, controlled blood pressure, and general good health to minimize the risks of complications 5.