The Basics
What is Cyclosporine?
Used with other medications to prevent kidney, liver, and heart transplant rejection.
Brand names for Cyclosporine
Sandimmune
How Cyclosporine is classified
Immunosuppressive Agents
Cyclosporine During Pregnancy
Cyclosporine pregnancy category
Category CNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Cyclosporine while pregnant
Animal studies have shown reproductive toxicity in rats and rabbits. Cyclosporine gave no evidence of mutagenic or teratogenic effects in the standard test systems with oral application (rats up to 17 mg/kg and rabbits up to 30 mg/kg per day orally). Sandimmune Oral Solution (cyclosporine oral solution, USP) has been shown to be embryo-and fetotoxic in rats and rabbits when given in doses 2-5 times the human dose. At toxic doses (rats at 30 mg/kg/day and rabbits at 100 mg/kg/day), Sandimmune Oral Solution (cyclosporine oral solution, USP) was embryo-and fetotoxic as indicated by increased pre-and postnatal mortality and reduced fetal weight together with related skeletal retardations. In the well-tolerated dose range (rats at up to 17 mg/kg/day and rabbits at up to 30 mg/kg/day), Sandimmune Oral Solution (cyclosporine oral solution, USP) proved to be without any embryolethal or teratogenic effects. There are no adequate and well-controlled studies in pregnant women and therefore, Sandimmune (cyclosporine) should not be used during pregnancy unless the potential benefit to the mother justifies the potential risk to the fetus. In pregnant transplant recipients who are being treated with immunosuppressants, the risk of premature birth is increased. The following data represent the reported outcomes of 116 pregnancies in women receiving Sandimmune (cyclosporine) during pregnancy, 90% of whom were transplant patients, and most of whom received Sandimmune (cyclosporine) throughout the entire gestational period. Since most of the patients were not prospectively identified, the results are likely to be biased toward negative outcomes. The only consistent patterns of abnormality were premature birth (gestational period of 28 to 36 weeks) and low birth weight for gestational age. It is not possible to separate the effects of Sandimmune (cyclosporine) on these pregnancies from the effects of the other immunosuppressants, the underlying maternal disorders, or other aspects of the transplantation milieu. Sixteen fetal losses occurred. Most of the pregnancies (85 of 100) were complicated by disorders; including, preeclampsia, eclampsia, premature labor, abruptio placentae, oligohydramnios, Rh incompatibility and fetoplacental dysfunction. Preterm delivery occurred in 47%. Seven malformations were reported in 5 viable infants and in 2 cases of fetal loss. Twenty-eight percent of the infants were small for gestational age. Neonatal complications occurred in 27%. In a report of 23 children followed up to 4 years, postnatal development was said to be normal. More information on cyclosporine use in pregnancy is available from Novartis Pharmaceuticals Corporation. A limited number of observations in children exposed to cyclosporine in utero are available, up to an age of approximately 7 years. Renal function and blood pressure in these children were normal. The alcohol content of the Sandimmune formulations should also be taken into account in pregnant women. (See WARNINGS, Special Excipients)
Taking Cyclosporine While Breastfeeding
What are recommendations for lactation if you're taking Cyclosporine?
Cyclosporine concentration in milk is variable. With typical maternal cyclosporine blood levels, a completely breastfed infant would usually receive no more than about 2% of the mother’s weight-adjusted dosage or pediatric transplantation maintenance dosage, and often less than 1%. Most infants studied have not had detectable cyclosporine blood levels, but 2 infants have had measurable levels, 1 with blood levels in the therapeutic range despite relatively low maternal milk levels. Numerous infants have been breastfed during maternal cyclosporine use, usually with a concurrent corticosteroid and sometimes with concurrent azathioprine. At least 2 mothers successfully breastfed a second infant after successfully breastfeeding the first infant. No reports of adverse effects on infants growth, development or kidney function have been reported, although thorough follow-up examinations have not always been performed or reported. Some reviewers believe breastfeeding should be discouraged during cyclosporine use, but these opinions appear to be based on limited, early data.[1][2] European experts, the National Transplantation Pregnancy Registry and other experts consider cyclosporine to be probably safe to use for inflammatory bowel disease during breastfeeding,[3][4][5][6][7] although others have expressed concern.[8] 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. Because absorption from the eye is limited, ophthalmic cyclosporine would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.
Maternal / infant drug levels
Cyclosporine concentration in milk is variable. With typical maternal cyclosporine blood levels, a completely breastfed infant would usually receive no more than about 2% of the mother’s weight-adjusted dosage or pediatric transplantation maintenance dosage, and often less than 1%. Most infants studied have not had detectable cyclosporine blood levels, but 2 infants have had measurable levels, 1 with blood levels in the therapeutic range despite relatively low maternal milk levels. Numerous infants have been breastfed during maternal cyclosporine use, usually with a concurrent corticosteroid and sometimes with concurrent azathioprine. At least 2 mothers successfully breastfed a second infant after successfully breastfeeding the first infant. No reports of adverse effects on infants growth, development or kidney function have been reported, although thorough follow-up examinations have not always been performed or reported. Some reviewers believe breastfeeding should be discouraged during cyclosporine use, but these opinions appear to be based on limited, early data.[1][2] European experts, the National Transplantation Pregnancy Registry and other experts consider cyclosporine to be probably safe to use for inflammatory bowel disease during breastfeeding,[3][4][5][6][7] although others have expressed concern.[8] 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. Because absorption from the eye is limited, ophthalmic cyclosporine would not be expected to cause any adverse effects in breastfed infants. To substantially diminish the amount of drug that reaches the breastmilk after using eye drops, place pressure over the tear duct by the corner of the eye for 1 minute or more, then remove the excess solution with an absorbent tissue.
Possible effects of Cyclosporine on milk supply
Relevant published information was not found as of the revision date.
Possible alternatives to Cyclosporine
Azathioprine, Tacrolimus.
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. Ramsey-Goldman R, Schilling E. Optimum use of disease-modifying and immunosuppressive antirheumatic agents during pregnancy and lactation. Clin Immunother. 1996;5:40-58. DOI: doi:10.1007/BF03259314
2. Janssen NM, Genta MS. The effects of immunosuppressive and anti-inflammatory medications on fertility, pregnancy and lactation. Arch Intern Med. 2000;160:610-9. PMID: 10724046
3. 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
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;55:1693-7. 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. Bar-Gil Shitrit A, Grisaru-Granovsky S, Ben Ya’acov A et al. Management of inflammatory bowel disease during pregnancy. Dig Dis Sci. 2016;61:2194-204. PMID: 27068171
9. Lewis GJ, Lamont CAR, Lee HA et al. Successful pregnancy in a renal transplant recipient taking cyclosporin A. Br Med J. 83;286:603. Letter.
10. Flechner SM, Katz AR, Rogers AJ et al. The presence of cyclosporine in body tissues and fluids during pregnancy. Am J Kidney Dis. 1985;5:60-3. PMID: 3155592
11. Ziegenhagen DJ, Crombach G, Dieckmann M et al. [Pregnancy during cyclosporin medication following a kidney transplant]. Dtsch Med Wochenschr. 88;113:260-3. PMID: 3277831
12. Behrens O, Kohlhaw K, Gunter H et al. [Detection of cyclosporin A in breast milk–is breast feeding contraindicated?] Geburtshilfe Frauenheilkd. 1989;49:207-9. PMID: 2649410
13. Moretti ME, Ito S, Koren G. Therapeutic drug monitoring in the lactating patient. Reprod Toxicol. 95;9(6):580-1. Abstract.
14. Madill JE, Levy G, Greig P. Pregnancy and breast-feeding while receiving cyclosporine A. In: Williams BAH S-GD, eds. Trends in organ transplantation. New York: Springer Publishing Company, 1996:109-21.
15. Thiru Y, Bateman DN, Coulthard MG. Successful breast feeding while mother was taking cyclosporin. BMJ. 1997;315:463. PMID: 9284666
16. Nyberg G, Haljamae U, Frisenette-Fich C et al. Breast-feeding during treatment with cyclosporine. Transplantation. 1998;65:253-5. PMID: 9458024
17. Munoz-Flores-Thiagarajan KD, Easterling T, Davis C et al. Breast-feeding by a cyclosporine-treated mother. Obstet Gynecol. 2001;97(5 pt 2):816-8. PMID: 11336764
18. Moretti ME, Sgro M, Johnson DW et al. Cyclosporine excretion into breast milk. Transplantation. 2003;75:2144-6. PMID: 12829927
19. Osadchy A, Koren G. Cyclosporine and lactation: when the mother is willing to breastfeed. Ther Drug Monit. 2011;33:147-8. PMID: 21240055
20. Mazzuoccolo LD, Andrada R, Pellerano G et al. Levels of cyclosporine in breast milk and passage into the circulation of the infant of a mother with psoriasis. Int J Dermatol. 2014;53:355-6. PMID: 23336105
21. Fiocchi R, D’Elia E, Vittori C et al. First report of a successful pregnancy in an everolimus-treated heart-transplanted patient: Neonatal disappearance of immunosuppressive drugs. Am J Transplant. 2016;16:1319-22. PMID: 26555407
22. Morton A. Cyclosporine and lactation. Nephrology (Carlton). 2011;16:249. PMID: 21272141
23. Lahiff C, Moss AC. Cyclosporine in the management of severe ulcerative colitis while breast-feeding. Inflamm Bowel Dis. 2011;17:E78. PMID: 21538721
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
