Summary of Use during Lactation

Etanercept is minimally excreted into breastmilk and poorly absorbed by the infant, which would be expected because of its high molecular weight of approximately 150,000 Da. Long-term follow-up data on infants breastfed during maternal etanercept use are not available. The risk of adverse effects in older infants is not known, but thought to be unlikely.[1] Numerous experts and professional guidelines have stated that the drug is a low risk to the nursing infant and acceptable to use during breastfeeding.[2-7] Waiting for at least 2 weeks postpartum to resume therapy may minimize transfer to the infant.[8] Anti-TNF agents appear to reduce the levels of tumor necrosis factor and IP-10 in the milk of mothers with inflammatory bowel disease in the early postpartum period.[9] This reduction in TNF might lead to decreased milk production, so extra lactation support might be necessary in women taking etanercept.

Drug Levels

Maternal Levels. One woman was receiving etanercept 25 mg subcutaneous injections twice weekly. The mother was secreting small amounts of milk, but not breastfeeding. On day 44 after delivery the trough milk etanercept level before the fifth dose was 50 mcg/L. A milk etanercept level one day after the fifth injection was 75 mcg/L and milk levels declined thereafter.[1]

A woman received etanercept 25 mg subcutaneously twice weekly during pregnancy and lactation. At 12 weeks postpartum, a breastmilk sample taken at an unspecified time after a dose was 3.5 mcg/L. Her serum etanercept concentration at the same time was 2872 mcg/L.[10]

A woman with ankylosing spondylitis received etanercept 25 mg subcutaneously once weekly during pregnancy and postpartum. Breastmilk concentrations were measured daily from day 40 to day 47 postpartum following a dose on day 40. Breastmilk concentrations ranged from 2 to 5 mcg/L; the high concentration of 5 mcg/L occurred on day 43 and corresponded with the highest maternal serum etanercept concentration. By day 47, etanercept was not detectable in breastmilk (<2 mcg/L).[11]

A woman with rheumatoid arthritis began etanercept 25 mg subcutaneously twice a week at 3 months postpartum and later switched to a dose of 50 mg subcutaneously once a week. Breastmilk samples were collected over a 2-month period. Before the first dose, the milk level was <1.5 mcg/L. Etanercept milk levels 24 and 48 hours after 25 mg doses were 4.48 and 5.25 mcg/L, respectively. Etanercept milk levels 24 and 72 hours after 50 mg doses were 4.48 and 7.5 mcg/L.[12]

Six women who were receiving etanercept 50 mg per week donated milk samples to a human milk repository. Samples were taken between 5.14 hours (range 1.5 to 10.5 hours) after the last milk expression The median milk etanercept concentration was 12.9 ng/mL (IRQ 6.0 to 46.9 ng/mL). The level in milk was correlated with both the infant and maternal age, but not with any other variable. The estimated average RID was 1.9% with an upper 95% CI of 7.0%.[13]

Infant Levels. An infant was born to a mother who received etanercept 25 mg subcutaneously twice a week during pregnancy and postpartum. At birth, the cord blood etanercept concentration was 81 mcg/L. The infant was completely breastfed. At 1 week postpartum, the infant's serum etanercept level was 21 mcg/L, at 3 weeks postpartum it was 2 mcg/L, and at 12 weeks it was undetectable, despite a breastmilk concentration of 3.5 mcg/L at that time.[10]

An infant was born to a mother with ankylosing spondylitis who received etanercept 25 mg subcutaneously once weekly during pregnancy and postpartum. The infant was fed about 50% breastmilk during days 40 to 47 postpartum following a maternal dose on day 40. Infant serum etanercept concentrations were 40 mcg/L at birth and <4 mcg/L on days 41 to 43.[12]

Effects in Breastfed Infants

A woman with rheumatoid arthritis began etanercept 25 mg subcutaneously twice a week at 3 months postpartum and later switched to a dose of 50 mg subcutaneously once a week. Her infant was breastfed (extent not stated) until 6 months of age. The infant was reportedly healthy at 3 years of age.[12]

A case-control study of women with chronic arthritic conditions found 5 women who received etanercept during pregnancy and lactation (extent not stated). No differences were observed in the 5 infants' growth parameters, developmental milestones, vaccinations and diseases in the first year of life compared to those not exposed to the drugs with lactation.[14]

Six infants were breastfed (2 fully, 4 partially) by mothers with rheumatoid arthritis or ankylosing spondylitis who were receiving etanercept during pregnancy and up to the time they were enrolled in the study. One mother reported a nonserious rash and high-pitched crying in her infant, both of which resolved without intervention. All infants had growth measures within normal range at their 6-month well-child visit.[13]

A national prospective registry of patients with rheumatic diseases who were treated with biological DMARDs was conducted in Spain. Three infants whose mothers were taking etanercept were breastfed (extent not stated) with no mild or severe adverse events reported in the infants.[15]

A woman with ankylosing spondylitis was breastfeeding her infant when subcutaneous etanercept 25 mg weekly was begun at 11 weeks postpartum because of increased disease activity. Her infant developed somnolence, prolonged sleep, feeding difficulty, and hypotonia the day after the first dose. These neurologic symptoms persisted, with some fluctuation in intensity, over the following weeks. About 1 week after their onset, the infant also began to experience intermittent low-grade fever, cough, and nasal congestion. Etanercept was then discontinued. Approximately 4 weeks after the onset of the initial symptoms, the infant developed intermittent fever, cough, diarrhea, and nasal congestion worsened. The infant was diagnosed with an infection and was successfully treated with azithromycin. The initial symptoms of excessive drowsiness, feeding difficulty, and hypotonia were possibly caused by etanercept, but diagnosis was complicated by the respiratory infection in the infant. The mother stopped breastfeeding at 5 months of age and at 9 months, the infant had not experienced any additional health problems.[16]

Effects on Lactation and Breastmilk

An analysis of the US Food and Drug Administration’s FAERS database of 7,022 spontaneous adverse reaction reports of anti-TNF drugs found that they may cause an increased risk of lactation insufficiency and disorders. Drugs that were studied included adalimumab, infliximab, golimumab, certolizumab, and etanercept. The authors noted that TNF alpha is involved in milk production, adding biological plausibility to the findings.[17]

Alternate Drugs to Consider

(Psoriasis) Adalimumab, Certolizumab Pegol, Infliximab, Phototherapy, Tretinoin; (Rheumatoid Arthritis) Adalimumab, Certolizumab Pegol, Infliximab, Tocilizumab

References

1.

Østensen M, Eigenmann GO. Etanercept in breast milk. J Rheumatol 2004;31:1017. [PubMed: 15124283]

2.

Mahadevan U, Robinson C, Bernasko N, et al. Inflammatory bowel disease in pregnancy clinical care pathway: A report from the American Gastroenterological Association IBD Parenthood Project Working Group. Gastroenterology 2019;156:1508–24. [PubMed: 30658060]

3.

Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Rheumatol 2020;72:529–56. [PubMed: 32090480]

4.

Yeung J, Gooderham MJ, Grewal P, et al. Management of plaque psoriasis with biologic therapies in women of child-bearing potential consensus paper. J Cutan Med Surg 2020;24 (1_Suppl):3S–14S. [PubMed: 32500730]

5.

Russell MD, Dey M, Flint J, et al. British Society for Rheumatology guideline on prescribing drugs in pregnancy and breastfeeding: Immunomodulatory anti-rheumatic drugs and corticosteroids. Rheumatology (Oxford) 2023;62:e48–e88. [PMC free article: PMC10070073] [PubMed: 36318966]

6.

Torres J, Chaparro M, Julsgaard M, et al. European Crohn's and Colitis Guidelines on Sexuality, Fertility, Pregnancy, and Lactation. J Crohns Colitis 2023;17:1–27. [PubMed: 36005814]

7.

Rüegg L, Pluma A, Hamroun S, et al. EULAR recommendations for use of antirheumatic drugs in reproduction, pregnancy, and lactation: 2024 update. Ann Rheum Dis 2025;84:910–26. [PubMed: 40287311]

8.

Krysko KM, Dobson R, Alroughani R, et al. Family planning considerations in people with multiple sclerosis. Lancet Neurol 2023;22:350–66. [PubMed: 36931808]

9.

Sepiashvili L, Brydon A, Koroshegyi C, et al. Reduction of tumor necrosis factor (TNF) in milk of women receiving anti-TNF antibody. Pediatr Res 2025;97:1935–42. [PubMed: 39487320]

10.

Murashima A, Watanabe N, Ozawa N, et al. Etanercept during pregnancy and lactation in a patient with rheumatoid arthritis: Drug levels in maternal serum, cord blood, breast milk and the infant's serum. Ann Rheum Dis 2009;68:1793–4. [PubMed: 19822717]

11.

Berthelsen BG, Fjeldsoe-Nielsen H, Nielsen CT, et al. Etanercept concentrations in maternal serum, umbilical cord serum, breast milk and child serum during breastfeeding. Rheumatology (Oxford) 2010;49:2225–7. [PubMed: 20581374]

12.

Keeling S, Wolbink GJ. Measuring multiple etanercept levels in the breast milk of a nursing mother with rheumatoid arthritis. J Rheumatol 2010;37:1551. [PubMed: 20595298]

13.

Bertrand K, Rossi S, Wells A, et al. The concentration of etanercept in human milk and infant outcomes. J Rheumatol 2023;50:712–4. [PMC free article: PMC10159878] [PubMed: 36379569]

14.

Dall'ara F, Reggia R, Bazzani C, et al. Safety of anti-TNF alfa agents during pregancy and breastfeeding: longterm follow up of exposed children in a case-series of mothers with chronic arthritides. Ann Rheum Dis 2016;75 (Suppl 2):493. doi:10.1136/annrheumdis-2016-eular.4123 [CrossRef]

15.

Membrive-Jiménez C, Sánchez-Piedra C, Martínez-González O, et al. Safety and effectiveness of bDMARDs during pregnancy in patients with rheumatic diseases: Real-world data from the BIOBADASER registry. Reumatol Clin (Engl Ed) 2023;19:500–6. [PubMed: 37945183]

16.

Eskiyurt B, Horoz E, Bakırlı DC, et al. Possible association between etanercept use during breastfeeding and infant somnolence, hypotonia, and feeding difficulties: A case report and literature review. Breastfeed Med 2026:15568253261446227. [PubMed: 42093128]

17.

Yan Z, Chen H, Sun J, et al. Divergent safety profiles of TNF inhibitors in pregnancy: A comprehensive pharmacovigilance analysis of the FAERS database. J Autoimmun 2026;160:103553. [PubMed: 41932089]

Substance Name

Etanercept

CAS Registry Number

185243-69-0

Drug Class

Breast Feeding

Lactation

Milk, Human

Antirheumatic Agents

Dermatologic Agents

Gastrointestinal Agents

Tumor Necrosis Factor Inhibitors