Also known as Anhydrous tacrolimus, FK 506, Fujimycin, Hecoria, Prograf, Protopic, Tacrolimus anhydrous, Tacrolimus, anhydrous

A macrolide isolated from Streptomyces tsukubaensis. Tacrolimus binds to the FKBP-12 protein and forms a complex with calcium-dependent proteins, thereby inhibiting calcineurin phosphatase activity and resulting in decreased cytokine production. This agent exhibits potent immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation. Tacrolimus possesses similar immunosuppressive properties to cyclosporine, but is more potent.

Originator: NCI Thesaurus | Source: The website of the National Cancer Institute (http://www.cancer.gov)

Can I take Tacrolimus while breastfeeding?

Limited data indicate that amounts of systemically administered tacrolimus are low in breastmilk and probably do not adversely affect the breastfed infant. European experts consider tacrolimus to be probably safe to use for inflammatory bowel disease during breastfeeding.[1] US investigators and clinicians from the National Transplantation Pregnancy Registry and other experts consider tacrolimus acceptable to use during breastfeeding following transplant.[2][3][4][5][6][7] Exclusively breastfed infants should be monitored if this drug is used during lactation, possibly including measurement of serum levels to rule out toxicity if there is a concern.

Topical tacrolimus presents a low risk to the nursing infant because it is poorly absorbed after topical application and peak blood concentrations are less than 2 mcg/L in most patients. Ensure that the infant’s skin does not come into direct contact with the areas of skin that have been treated. If the breast is to be treated, an alternate drug is preferred; do not apply to the nipple area while nursing.[8][9][10]

Drug levels

Maternal Levels. Random tacrolimus colostrum levels in 10 samples from 6 mothers averaged 1.7 mcg/L (range 0.3 to 1.9 mcg/L) which was about 50% of maternal serum levels. Tacrolimus dosages in these mothers were not reported.[11]

One mother taking 3 mg twice daily (0.1 mg/kg per day), had a peak milk level of 0.57 mcg/L one hour after the dose. The half-life in milk was estimated to be 12.85 hours. The authors estimated that her breastfed infant would receive 0.06% of the maternal weight-adjusted dosage or 0.06 mcg/kg daily, which is 0.03 to 0.04% of the oral starting dosage for pediatric patients.[12]

One mother who had been taking tacrolimus for a kidney transplant 5 years earlier was 3 months postpartum and exclusively breastfeeding her infant. She had been taking a dosage of 2 mg orally twice daily (0.05 mg/kg per day) for at least 2 months. She was also taking atenolol 100 mg, azathioprine 100 mg, diltiazem 180 mg, furosemide 20 mg, and prednisone 5 mg daily. Milk samples obtained over a 12-hour dosage interval found little change throughout the day, with the highest levels of 2.1 mcg/L at 4 and 8.5 hours after the dose. The average milk concentration was 1.8 mcg/L. The authors calculated that an exclusively breastfed infant would receive a daily dosage of 0.27 mcg/kg which is about 0.5% of the maternal weight-adjusted dosage and less than 0.2% of the pediatric dosage for organ transplant rejection.[13]

Eleven women who took tacrolimus (exact dosages not specified, but assumed to be 6 mg daily) during pregnancy and postpartum donated 22 breastmilk samples (times unspecified) for analysis. The median breastmilk concentration was 0.8 mcg/L (range 0.1 to 1.6 mcg/L). Two women took samples before and 4 or more hours after a dose; no difference in milk levels was seen. The authors estimated that the maximum dosage that an exclusively breastfed infant would receive would be 0.56 mg daily, equivalent to 0.23% of the maternal weight-adjusted dosage. Additionally, comparing infants who were breastfed to those who were not, the serum tacrolimus concentrations fell at about the same rate over the first 2 weeks postpartum, regardless of breastfeeding status, indicating that breastfeeding did not prolong infant tacrolimus levels[14]

Eleven breastmilk samples were obtained via breast pump over a 12-hour dosage interval in a nursing mother who was 45 weeks postpartum and receiving tacrolimus 1.5 mg twice daily after a liver transplant. The peak tacrolimus milk level of 1.11 mcg/L occurred 6 hours after the dose. The average tacrolimus level in milk was 0.93 mcg/L. The milk concentration of the active metabolite, 13-demethyl tacrolimus, averaged 0.03 mcg/L (range 0.01 to 0.04 mcg/L). The authors estimated that a fully breastfed infant would receive 0.14 mcg/kg daily or 0.3 % of the maternal weight-adjusted dosage.[2]

Infant Levels. Four breastfed (3 exclusive, 1 partial) infants whose mothers took tacrolimus during breastfeeding had serum tacrolimus concentrations measured between day 15 and 27 of age. The mothers’ mean daily tacrolimus dosage during breastfeeding was 9.6 mg daily (range 4.5 to 15 mg daily). Tacrolimus was undetectable (<1.9 mcg/L) in all of the infants.[15] A woman was taking tacrolimus 6 mg twice daily during pregnancy to prevent rejection of an small intestine transplant. Her dosage was adjusted to maintain an optimal tacrolimus blood level postpartum, although the exact dosage was not stated. She breastfed (extent not stated) her infant and at 1 week of age, the infant’s tacrolimus blood level was less than 1 mcg/L.[16] Twelve infants were exclusively breastfed by mothers taking tacrolimus (exact dosages not specified) during pregnancy and postpartum. Twenty-four infant blood samples were obtained from the infants at various times. The median infant blood tacrolimus concentration was 1.3 mcg/L (range 0.0-4.0 mcg/L). In infants in whom serial blood levels were obtained, levels declined at about 15% daily. Blood tacrolimus levels in breastfed infants were no higher than those in 3 additional infants who were not breastfed. Eight breast-fed infants with serial blood samples had undetectable (<0.1 mcg/L) tacrolimus blood levels at a median of day 14 (interquartile range day 11-22) postpartum.[14] Two mothers with systemic lupus erythematosus were reported who took tacrolimus during pregnancy and lactation. One took tacrolimus 3 mg and prednisolone 40 mg daily and the other took tacrolimus 3 mg and prednisolone 30 mg daily during breastfeeding. The infants’ blood tacrolimus levels measured 1 hour after breastfeeding were 0.2 mcg/L in the first infant at 10 days of age, and 0.5 mcg/L in the second at 7 days of age.[17]

Effects in breastfed infants

Maternal Levels. Random tacrolimus colostrum levels in 10 samples from 6 mothers averaged 1.7 mcg/L (range 0.3 to 1.9 mcg/L) which was about 50% of maternal serum levels. Tacrolimus dosages in these mothers were not reported.[11]

One mother taking 3 mg twice daily (0.1 mg/kg per day), had a peak milk level of 0.57 mcg/L one hour after the dose. The half-life in milk was estimated to be 12.85 hours. The authors estimated that her breastfed infant would receive 0.06% of the maternal weight-adjusted dosage or 0.06 mcg/kg daily, which is 0.03 to 0.04% of the oral starting dosage for pediatric patients.[12]

One mother who had been taking tacrolimus for a kidney transplant 5 years earlier was 3 months postpartum and exclusively breastfeeding her infant. She had been taking a dosage of 2 mg orally twice daily (0.05 mg/kg per day) for at least 2 months. She was also taking atenolol 100 mg, azathioprine 100 mg, diltiazem 180 mg, furosemide 20 mg, and prednisone 5 mg daily. Milk samples obtained over a 12-hour dosage interval found little change throughout the day, with the highest levels of 2.1 mcg/L at 4 and 8.5 hours after the dose. The average milk concentration was 1.8 mcg/L. The authors calculated that an exclusively breastfed infant would receive a daily dosage of 0.27 mcg/kg which is about 0.5% of the maternal weight-adjusted dosage and less than 0.2% of the pediatric dosage for organ transplant rejection.[13]

Eleven women who took tacrolimus (exact dosages not specified, but assumed to be 6 mg daily) during pregnancy and postpartum donated 22 breastmilk samples (times unspecified) for analysis. The median breastmilk concentration was 0.8 mcg/L (range 0.1 to 1.6 mcg/L). Two women took samples before and 4 or more hours after a dose; no difference in milk levels was seen. The authors estimated that the maximum dosage that an exclusively breastfed infant would receive would be 0.56 mg daily, equivalent to 0.23% of the maternal weight-adjusted dosage. Additionally, comparing infants who were breastfed to those who were not, the serum tacrolimus concentrations fell at about the same rate over the first 2 weeks postpartum, regardless of breastfeeding status, indicating that breastfeeding did not prolong infant tacrolimus levels[14]

Eleven breastmilk samples were obtained via breast pump over a 12-hour dosage interval in a nursing mother who was 45 weeks postpartum and receiving tacrolimus 1.5 mg twice daily after a liver transplant. The peak tacrolimus milk level of 1.11 mcg/L occurred 6 hours after the dose. The average tacrolimus level in milk was 0.93 mcg/L. The milk concentration of the active metabolite, 13-demethyl tacrolimus, averaged 0.03 mcg/L (range 0.01 to 0.04 mcg/L). The authors estimated that a fully breastfed infant would receive 0.14 mcg/kg daily or 0.3 % of the maternal weight-adjusted dosage.[2]

Infant Levels. Four breastfed (3 exclusive, 1 partial) infants whose mothers took tacrolimus during breastfeeding had serum tacrolimus concentrations measured between day 15 and 27 of age. The mothers’ mean daily tacrolimus dosage during breastfeeding was 9.6 mg daily (range 4.5 to 15 mg daily). Tacrolimus was undetectable (<1.9 mcg/L) in all of the infants.[15] A woman was taking tacrolimus 6 mg twice daily during pregnancy to prevent rejection of an small intestine transplant. Her dosage was adjusted to maintain an optimal tacrolimus blood level postpartum, although the exact dosage was not stated. She breastfed (extent not stated) her infant and at 1 week of age, the infant’s tacrolimus blood level was less than 1 mcg/L.[16] Twelve infants were exclusively breastfed by mothers taking tacrolimus (exact dosages not specified) during pregnancy and postpartum. Twenty-four infant blood samples were obtained from the infants at various times. The median infant blood tacrolimus concentration was 1.3 mcg/L (range 0.0-4.0 mcg/L). In infants in whom serial blood levels were obtained, levels declined at about 15% daily. Blood tacrolimus levels in breastfed infants were no higher than those in 3 additional infants who were not breastfed. Eight breast-fed infants with serial blood samples had undetectable (<0.1 mcg/L) tacrolimus blood levels at a median of day 14 (interquartile range day 11-22) postpartum.[14] Two mothers with systemic lupus erythematosus were reported who took tacrolimus during pregnancy and lactation. One took tacrolimus 3 mg and prednisolone 40 mg daily and the other took tacrolimus 3 mg and prednisolone 30 mg daily during breastfeeding. The infants’ blood tacrolimus levels measured 1 hour after breastfeeding were 0.2 mcg/L in the first infant at 10 days of age, and 0.5 mcg/L in the second at 7 days of age.[17]

Possible effects on lactation

Relevant published information was not found as of the revision date.

Alternate drugs to consider

Azathioprine, Cyclosporine , Pimecrolimus

References

1. van der Woude CJ, Kolacek S, Dotan I et al. European evidenced-based consensus on reproduction in inflammatory bowel disease. J Crohn’s Colitis. 2010;4:493-510. PMID: 21122553

2. Zheng S, Easterling TR, Hays K et al. Tacrolimus placental transfer at delivery and neonatal exposure through breast milk. Br J Clin Pharmacol. 2013;76:988-96. PMID: 23528073

3. Armenti VT, Moritz MJ, Davison JM. Breastfeeding and tacrolimus: is it a reasonable approach? Expert Rev Clin Immunol. 2013;9:623-6. PMID: 23899232

4. Thiagarajan KM, Arakali SR, Mealey KJ et al. Safety considerations: breastfeeding after transplant. Prog Transplant. 2013;23:137-46. PMID: 23782661

5. Constantinescu S, Pai A, Coscia LA et al. Breast-feeding after transplantation. Best Pract Res Clin Obstet Gynaecol. 2014;28:1163-73. PMID: 25271063

6. Flint J, Panchal S, Hurrell A et al. BSR and BHPR guideline on prescribing drugs in pregnancy and breastfeeding-Part I: standard and biologic disease modifying anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford). 2016. PMID: 26750124

7. Gotestam Skorpen C, Hoeltzenbein M, Tincani A et al. The EULAR points to consider for use of antirheumatic drugs before pregnancy, and during pregnancy and lactation. Ann Rheum Dis. 2016;75:795-810. PMID: 26888948

8. Strober B, Berger E, Cather J et al. A series of critically challenging case scenarios in moderate to severe psoriasis: a Delphi consensus approach. J Am Acad Dermatol. 2009;61 (Suppl 1):S1-S46. PMID: 19527820

9. Barrett ME, Heller MM, Fullerton Stone H, Murase JE. Dermatoses of the breast in lactation. Dermatol Ther. 2013;26:331-6. PMID: 23914890

10. Butler DC, Heller MM, Murase JE. Safety of dermatologic medications in pregnancy and lactation: Part II Lactation. J Am Acad Dermatol. 2014;70:417.e1-417.e10. PMID: 24528912

11. Jain A, Venkataramanan R et al. Pregnancy after liver transplantation under tacrolimus. Transplantation. 1997;64:559-65. PMID: 9293865

12. French AE, Soldin SJ et al. Milk transfer and neonatal safety of tacrolimus. Ann Pharmacother. 2003;37:815-8. PMID: 12773068

13. Gardiner SJ, Begg EJ. Breastfeeding during tacrolimus therapy. Obstet Gynecol. 2006;107 (2 pt. 2):453-5. PMID: 16449146

14. Bramham K, Chusney G, Lee J et al C. Breastfeeding and tacrolimus: Serial monitoring in breast-fed and bottle-fed infants. Clin J Am Soc Nephrol. 2013;8:563-7. PMID: 23349333

15. Gouraud A, Bernard N, Millaret A et al. Follow-up of tacrolimus breastfed babies. Transplantation. 2012;94:e38-40. PMID: 22996303

16. Gomez-Lobo V, Landy HJ, Matsumoto C, Fishbein TM. Pregnancy in an intestinal transplant recipient. Obstet Gynecol. 2012;120 (2 Pt 2):497-500. PMID: 22825278

17. Izumi Y, Miyashita T, Migita K. Safety of tacrolimus treatment during pregnancy and lactation in systemic lupus erythematosus: A report of two patients. Tohoku J Exp Med. 2014;234:51-6. PMID: 25175032

Last Revision Date

20160426

Disclaimer:Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

Source: LactMed – National Library of Medicine (NLM)

3D Model of the Tacrolimus molecule

MolView – data visualization platform