Summary of Use during Lactation

The excretion of exogenous epoetin alfa (recombinant human erythropoietin; EPO) in breastmilk has not been studied. Erythropoietin is a normal component of human milk. Although some studies have shown an improve response of postpartum anemia when epoetin alfa was used with iron therapy, current consensus is that epoetin alfa has no clinically important effect on the increase in hemoglobin concentration over iron alone.[1] No adverse reactions were reported in the breastfed infants of mothers who received epoetin alfa. Based on theoretical considerations, the manufacturer recommends avoiding the use of epoetin alfa multiple-dose vials for lactating women because of its benzyl alcohol content and to avoid breastfeeding for 2 weeks after a dose that contains benzyl alcohol. No special precautions are required during breastfeeding if mothers receive epoetin alfa from a single-use vial without preservatives.[2]

Some authors have hypothesized that erythropoietin in milk might help maintain the integrity of the lining of the mammary epithelium and the infant gastrointestinal tract, thereby reducing the risk of mother-to-child transmission of HIV infection (MTCT).[3] A case-control study in Tanzania supports the protective role of erythropoietin in breastmilk against MTCT.[4] Erythropoietin might also have a modest beneficial effect on the infant's red cell production.[5]

Drug Levels

Maternal Levels. Relevant published information on exogenous administration of epoetin alfa was not found as of the revision date. However, breastmilk normally contains erythropoietin. Erythropoietin concentrations in human milk are in the range of approximately 4 to 5 units/L in the first 1 to 2 months postpartum and increase to 20 to 40 units/L by the third month and to 100 to 150 units/L by 12 months.[3]

Infant Levels. Published information on absorption of epoetin alfa from breastmilk was not found as of the revision date. However, several studies in which oral doses of epoetin alfa and other recombinant forms of erythropoietin were given to preterm infants found that epoetin is absorbed to a small extent. Increases in hematocrit in infants treated with oral epoetin alfa have been small to negligible.[5-10] However, one study found that hospitalized preterm infants taking enteral feedings and given 400 units daily of recombinant human erythropoietin by mouth with ferrous sulfate had higher reticulocyte counts and serum erythropoietin concentrations upon hospital discharge than control infants given only ferrous sulfate.[11]

Effects in Breastfed Infants

Enhancement of gastrointestinal tract maturation has been proposed as a function of erythropoietin in breastmilk.[3,11]

In a study of 40 women with postpartum anemia, 19 of 20 women who received iron and subcutaneous recombinant human erythropoietin (generic name and brand not specified) 200 IU/kg daily for 15 days were able to breastfeed their infants. This regimen is more aggressive than the approved three times/week regimen. In the control group that received only oral iron and folic acid, only 10 were able to breastfeed their infants. No adverse reactions were reported among the infants of women who receive epoetin.[2]

Effects on Lactation and Breastmilk

In small studies, epoetin alfa administration decreased serum prolactin in patients with amyotrophic lateral sclerosis,[12] but had no effect in normal subjects or in patients with renal failure undergoing chronic ambulatory peritoneal dialysis.[13,14] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

References

1.

Milman N. Postpartum anemia II: prevention and treatment. Ann Hematol 2012;91:143-54. [PubMed: 22160256]

2.

Makrydimas G, Lolis D, Lialios G, et al. Recombinant human erythropoietin treatment of postpartum anemia. Preliminary results. Eur J Obstet Gynecol Reprod Biol 1998;81:27-31. [PubMed: 9846709]

3.

Semba RD, Juul SE. Erythropoietin in human milk: Physiology and role in infant health. J Hum Lact 2002;18:252-61. [PubMed: 12192960]

4.

Arsenault JE, Aboud S, Manji KP, et al. Vitamin supplementation increases risk of subclinical mastitis in HIV-infected women. J Nutr 2010;140:1788-92. [PMC free article: PMC2937574] [PubMed: 20739447]

5.

Pasha YZ, Ahmadpolir-Kacho M, Hajiahmadi M, Hosseini M. Enteral erythropoietin increases plasma erythropoietin level in preterm infants: A randomized controlled trial. Indian Pediatr 2008;45:25-8. [PubMed: 18250501]

6.

Calhoun DA, Christensen RD. Hematopoietic growth factors in neonatal medicine: The use of enterally administered hematopoietic growth factors in the neonatal intensive care unit. Clin Perinatol 2004;31:169-82. [PubMed: 15183665]

7.

Ballin A, Bilker-Reich A, Arbel E, et al. Erythropoietin, given enterally, stimulates erythropoiesis in premature infants. Lancet 1999;353:1849. [PubMed: 10359412]

8.

Juul SE. Enterally dosed recombinant human erythropoietin does not stimulate erythropoiesis in neonates. J Pediatr 2003;143:321-6. [PubMed: 14517513]

9.

Juul SE, Christensen RD. Absorption of enteral recombinant human erythropoietin by neonates. Ann Pharmacother 2003;37:782-6. [PubMed: 12773061]

10.

Britton JR, Christensen RD. Enteral administration of recombinant erythropoietin to preterm infants. J Perinatol 1995;15:281-3. [PubMed: 8558334]

11.

Miller M, Iliff P, Stoltzfus RJ, Humphrey J. Breastmilk erythropoietin and mother-to-child HIV transmission through breastmilk. Lancet 2002;360:1246-8. [PubMed: 12401271]

12.

Tokgöz B, Utas C, Dogukan A, et al. Influence of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid axis in patients undergoing CAPD. Ren Fail 2002;24:315-23. [PubMed: 12166698]

13.

Bernini GP, Mariotti F, Brogi G, et al. Effects of erythropoietin administration on prolactin secretion in normal subjects. Nephron 1993;65:522-6. [PubMed: 8302403]

14.

Markianos M, Kosmidis ML, Sfagos C. Reductions in plasma prolactin during acute erythropoietin administration. Neuro Endocrinol Lett 2006;27:355-8. [PubMed: 16816832]

Substance Name

Epoetin Alfa

CAS Registry Number

113427-24-0

Drug Class

Breast Feeding

Lactation

Milk, Human

Colony-Stimulating Factors

Hematinics

Hematopoietic Cell Growth Factors