Infliximab use while Breastfeeding

Drugs containing Infliximab: Remicade

Infliximab Levels and Effects while Breastfeeding

Summary of Use during Lactation

Infliximab is usually not detectable in breastmilk and absorption is unlikely because it is probably destroyed in the infant's gastrointestinal tract. Follow-up of infants exposed in utero and breastfed during maternal infliximab therapy have found no adverse effects and normal development. The measurement of minute concentrations in the milk of some women raises the possibility of local immune suppression in the gastrointestinal tact, but levels were not high enough to be of concern for systemic immunosuppression.[1] Numerous US and European experts have stated that the drug is a low risk to the nursing infant and breastfeeding can continue during infliximab use,[2][3][4][5][6][7][8][9]

Drug Levels

Maternal Levels. A nursing mother with Crohn's disease (time postpartum not stated) was given a single 5 mg/kg dose of infliximab by intravenous infusion. Milk samples taken 24 hours and 1 week after the dose had undetectable (<60 mcg/L) levels of infliximab.[10]

A woman who was 4 months postpartum received 2 doses of infliximab. Milk levels were measured after the first dose of 160 mg and second dose of 165 mg, but the time between the 2 doses was not stated. The first milk sample was obtained 10 days after the first dose. Milk infliximab levels increased gradually (values not stated) over the next 10 days. After the second dose, milk infliximab levels increased further, with the highest infliximab concentration of 473 mcg/L measured one day after the second dose.[11]

One group of authors report a personal communication stating that 4 assays of breastmilk (presumably in 4 patients) failed to detect infliximab in any samples (assay sensitivity not specified).[12]

A woman with Crohn's disease received infliximab 10 mg/kg at 2 and 10 weeks postpartum. Infliximab was not detectable in breastmilk with an ELISA assay (assay sensitivity not specified) at 6, 10 or 13 weeks postpartum.[13]

A woman with severe Crohn's disease received infliximab 1000 mg (10 mg/kg) intravenously every 4 weeks during pregnancy and lactation. She received a dose on an unstated day postpartum and breastmilk samples were collected daily (times not stated) once before and daily for 30 days after the dose. None of the samples had detectable infliximab (<5 mcg/L) using an ELISA assay.[14]

Three women with Crohn's disease received infliximab during pregnancy and postpartum. Single breastmilk samples were obtained from each woman after a postpartum dose of 5 mg/kg of infliximab. Samples were collected 7, 5, and 43 days, respectively, after their prior dose. Infliximab was undetectable (<100 mcg/L) in all breastmilk samples.[15]

Three women with Crohn's disease received an intravenous infusion of infliximab 5 mg/kg postpartum for a disease flare and discontinued nursing. Milk samples were obtained before and after the infusion. Milk samples were also obtained from 8 nursing mothers who did not receive infliximab. Infliximab was undetectable (<10 mcg/L) in all of the pre-infusion samples and in those from the untreated mothers. Infliximab was detected in breastmilk samples obtained after the infusion in all 3 women. Infliximab was detectable 12 hours after the infusion and peaked at 75 to 105 mcg/L at 2 to 3 days after the infusion in 2 patients. In a third, one sample obtained 2 days after the infusion was about 20 mcg/L. The assay used in this series was more sensitive than those used previously and allowed the very low infliximab concentrations to be measured.[1]

Two mothers received infliximab 300 mg intravenously for inflammatory bowel disease. Breastmilk infliximab was 200 mcg/L in one mother (time after dose not stated), which was about 4.3% of her serum concentration. The second mother began infliximab at 3 months postpartum. Her breastmilk infliximab levels were 94.6 mcg/L on day 1 after the first dose and 119.7 mcg/L on day 4 after the dose.[16]

Three women with inflammatory bowel disease who received postpartum infliximab infusions (doses not specified) had milk samples analyzed for the drug for 5 days after the infusion. The assay method was somewhat unreliable in this study. In the first patient, infliximab was detectable in breastmilk only on days 4 and 6 after the infusion, with values of about 100 mcg/L. After the second infusion, the highest milk concentration of about 130 mcg/L occurred after about 30 hours. Subsequent levels were lower over the next 5 days. In a second patient, infliximab was found in milk shortly after the infusion with the highest concentration of 300 mcg/L occurring at 3.3 days after the dose. A third patient had detectable infliximab in milk on days 2 and 4, with the highest level of about 100 mcg/L on day 4.[17]

Infant Levels. A woman with Crohn's disease received infliximab during pregnancy, with the last of five 10 mg/kg doses 2 weeks before delivery. Doses were also given 2 and 10 weeks postpartum. She breastfed her infant from birth to 6 weeks, discontinued breastfeeding for 3 weeks and then restarted breastfeeding (extent not stated) at week 11 postpartum. Maternal and infant serum infliximab levels were equal when they were first measured at 6 weeks postpartum. The infant's serum infliximab steadily decreased over the next 7 weeks. The authors concluded that the initial high infant serum level was from transplacental passage of infliximab because the drug was undetectable in milk and the serum level dropped despite breastfeeding.[13]

Two infants were breastfed (extent not stated) by mothers who received 5 mg/kg doses of infliximab during pregnancy and breastfeeding. Infliximab was discontinued at or before 32 weeks of the pregnancy and restarted within 2 weeks postpartum. Infant serum samples were obtained 5 days after the mother's previous infliximab dose in one when the infant was 15 days old and 43 days after the mother's dose at 57 days of age in the other infant. Infliximab was undetectable (<100 mcg/L) in both infants' serum.[15]

A woman exclusively breastfed her infant for 3 months, then received a single intravenous dose of infliximab 300 mg and began partially breastfeeding her infant. Four weeks after beginning infliximab and 5 days after the second infliximab dose, her infant had a serum concentration of 1.7 mg/L, which was 2.2% of the simultaneous maternal serum infliximab concentration.[16]

An infant was born at week 37 of gestation to a mother with ulcerative colitis was receiving long-term therapy with mesalamine 4 grams daily throughout pregnancy received inductions series of infliximab 5 mg/kg in weeks 20 and 31 of pregnancy for disease flares. She continued to receive infliximab infusions every 8 to 12 weeks, while the baby was breastfed (extent not stated) until 14 weeks of age. The infant's infliximab serum concentration at 16 weeks after birth was 0.6 mg/L, but was undetectable (<0.05mg/L) at 28 weeks of age. The serum concentration at 16 weeks was judged to have been a result of placental passage of the drug from mother to infant.[18]

Effects in Breastfed Infants

A retrospective chart review of patients who received infliximab during pregnancy found that 5 mothers breastfed their infants during infliximab therapy at a dose of 5 mg/kg. No other patient details were reported and no adverse effects were reported in the infants, although observation during breastfeeding was not the purpose of the study.[12]

A woman with Crohn's disease received infliximab 5 mg/kg intravenously every 8 weeks throughout pregnancy and during lactation. The infant was reported to be good condition without any evidence of illnesses.[19]

An infant was born to a mother who received infliximab 10 mg/kg 5 times during pregnancy at 6- to 8-week intervals. A maternal dose of 10 mg/kg was given at 2 weeks postpartum. The infant was breastfed for 6 weeks, discontinued for 3 weeks and then reinstated at 9 weeks of age (extent of nursing not stated). Another 10 mg/kg dose was given to the mother at 10 weeks postpartum. The infant underwent a formal evaluation of the immune system and found to have normal immune markers and responses. The infant reportedly grew and developed normally throughout the first year of life.[13]

An infant was breastfed (extent not stated) for up to 4 months by a mother who was taking infliximab (dosage not stated) and azathioprine 150 mg daily for inflammatory bowel diseases. The infant was followed regularly for 22 months of age and found to have a normal growth rate, and no history of recurrent infections.[20]

A woman with severe Crohn's disease received infliximab 1000 mg (10 mg/kg) intravenously every 4 weeks during pregnancy and lactation. The extent and duration of breastfeeding were not reported. The child had no developmental abnormalities noted at 27 months of age.[14]

Three infants were breastfed after their mothers received infliximab during the third trimester of pregnancy. No immune system deficits were noted on follow-up.[21]

Three infants were breastfed (extent not stated) during maternal infliximab therapy at a dose of 5 mg/kg every 8 weeks. Infants were followed for almost 1 year and found to have no unusual number or types of infections and all seroconverted after their routine childhood immunizations.[15]

A 24-year-old woman with Crohn's disease received infliximab 5 mg/kg every 8 weeks during pregnancy until 33 weeks gestation. After delivering at term, she received her next infliximab dose at 1 week postpartum. The infant was breastfed (extent not stated) and received all vaccinations, except rotavirus, on schedule.[22]

A woman with severe psoriasis was treated during pregnancy and postpartum with infliximab 5 mg/kg intravenously every 8 weeks. Her last doses of infliximab before delivery were at weeks 20 and 29 of pregnancy. The drug was continued postpartum, although the timing of the first postpartum dose was not stated. Her infant was breastfed for 1 month and developed normally.[23]

A woman with Crohn's disease used infliximab 5 mg/kg every 8 weeks during pregnancy and postpartum. During breastfeeding (extent not stated) she also received sulfasalazine 4 g/day and prednisone 60 mg/day in a tapering schedule. At 6 months of age, the infant was asymptomatic with regular weight gain.[24]

Two women received infliximab 300 mg intravenously for treatment of inflammatory bowel disease. One woman nursed her infant (extent not stated) and the other began partial breastfeeding her infant at 3 months of age when infliximab was begun. She breastfed for approximately 5 weeks (2 doses) before discontinuing breastfeeding. At 22 and 18 months of age, respectively, neither infant had any signs of adverse drug reactions, allergic reactions or severe infections leading to hospitalization. The first infant had a low birth weight, but caught up and reached the 75th percentile at the age of 11 months. Developmental milestones were reached on time by both infants.[16]

A prospective cohort study followed pregnant women with inflammatory bowel disease throughout pregnancy and for 12 months postpartum. Women were assigned to one of the following groups: unexposed (no thiopurines or anti-TNF agents); group A (azathioprine or mercaptopurine); group B (infliximab, adalimumab or certolizumab) and group AB (both a thiopurine and an anti-TNF agent). Of 1052 women enrolled in the study, 72% breastfed their infants, although the extent and duration were not stated in the abstract. A total of 102 women were exposed to an anti-TNF agent and 59 were exposed to a thiopurine plus an anti-TNF agent. The use of an anti-TNF alone was not associated with any complication in the infants and their growth and development were normal throughout the 12 months. Infants exposed to both a thiopurine and an anti-TNF agent had a 50% increase in the number of infections between 9 and 12 months of age. The relationship of this increase with breastfeeding could not be determined from the available data.[25] A woman with ulcerative colitis was receiving long-term therapy with mesalamine 4 grams daily throughout pregnancy received inductions series of infliximab 5 mg/kg in weeks 20 and 31 of pregnancy for disease flares. She continued to receive infliximab infusions every 8 to 12 weeks, while the baby was breastfed (extent not stated) until 14 weeks of age. The infant received routine vaccinations (diphtheria, tetanus, pertussis, injectable polio, Haemophilus influenzae b, and pneumococcal vaccines) at 3, 5 and 12 months with no signs of adverse effects from them, or signs of allergic or infectious diseases. Development at 13 months of age was normal.[18]

Possible Effects on Lactation

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

Alternate Drugs to Consider

(Inflammatory Bowel Disease) Adalimumab, Certolizumab, (Rheumatoid Arthritis) Adalimumab, Certolizumab, Etanercept

References

1. Ben-Horin S, Yavzori M, Kopylov U et al. Detection of infliximab in breast milk of nursing mothers with inflammatory bowel disease. J Crohns Colitis. 2011;5:555-8. PMID: 22115374

2. Ostensen M. Management of early aggressive rheumatoid arthritis during pregnancy and lactation. Expert Opin Pharmacother. 2009;10:1469-79. PMID: 19505214

3. Mottet C, Vader JP, Felley C et al. Appropriate management of special situations in Crohn's disease (upper gastro-intestinal; extra-intestinal manifestations; drug safety during pregnancy and breastfeeding): Results of a multidisciplinary international expert panel-EPACT II. J Crohns Colitis. 2009;3:257-63.

4. 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

5. Van Assche G, Dignass A, Reinisch W et al. The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Special situations. J Crohns Colitis. 2010;4:63-101. PMID: 21122490

6. Gisbert JP, Chaparro M. Safety of anti-TNF agents during pregnancy and breastfeeding in women with inflammatory bowel disease. Am J Gastroenterol. 2013;108:1426-38. PMID: 23752881

7. Hassid B, Mahadevan U. The use of biologic therapy in pregnancy: a gastroenterologist's perspective. Curr Opin Rheumatol. 2014;26:347-53. PMID: 24625373

8. Nielsen OH, Maxwell C, Hendel J. IBD medications during pregnancy and lactation. Nat Rev Gastroenterol Hepatol. 2014;11:116-27. PMID: 23897285

9. Hyrich KL, Verstappen SM. Biologic therapies and pregnancy: The story so far. Rheumatology (Oxford). 2014;53:1377-85. PMID: 24352337

10. Peltier M, James D et al. Infliximab levels in breast-milk of a nursing Crohn's patient. Am J Gastroenterol. 2001;96 (9 suppl 1):S312. Abstract.

11. Forger F, Matthias T, Oppermann M et al. Infliximab in breast milk. Lupus. 2004;13:753 . Abstract. DOI: doi:10.1191/0961203304lu2014xx

12. Mahadevan U, Kane S, Sandborn WJ et al. Intentional infliximab use during pregnancy for induction or maintenance of remission in Crohn's disease. Aliment Pharmacol Ther. 2005;21:733-8. PMID: 15771759

13. Vasiliauskas EA, Church JA, Silverman N et al. Case report: evidence for transplacental transfer of maternally administered infliximab to the newborn. Clin Gastroenterol Hepatol. 2006;4:1255-8. PMID: 17045211

14. Stengel JZ, Arnold HL. Is infliximab safe to use while breastfeeding? World J Gastroenterol. 2008;14:3085-7. PMID: 18494064

15. Kane S, Ford J, Cohen R, Wagner C. Absence of infliximab in infants and breast milk from nursing mothers receiving therapy for Crohn's disease before and after delivery. J Clin Gastroenterol. 2009;43:613-6. PMID: 19142167

16. Fritzsche J, Pilch A, Mury D et al. Infliximab and adalimumab use during breastfeeding. J Clin Gastroenterol. 2012;46:718-9. PMID: 22858514

17. Grosen A, Julsgaard M, Kelsen J, Christensen LA. Infliximab concentrations in the milk of nursing mothers with inflammatory bowel disease. J Crohn's Colitis. 2014;8:175-6. PMID: 24090905

18. Steenholdt C, Al-Khalaf M, Ainsworth MA, Brynskov J. Therapeutic infliximab drug level in a child born to a woman with ulcerative colitis treated until gestation week 31. J Crohns Colitis. 2012;6:358-61. PMID: 22405174

19. Tursi A. Effect of intentional infliximab use throughout pregnancy in inducing and maintaining remission in Crohn's disease. Dig Liver Dis. 2010;38:439-40. PMID: 16563889

20. Bernard N, Garayt C, Chol F et al. Prospective clinical and biological follow-up of three breastfed babies from azathioprine-treated mothers. Fundam Clin Pharmacol. 2007;21 (Suppl 1):62-3. Abstract . DOI: doi:10.1111/j.1472-8206.2007.00481.x

21. Mahadevan U, Kane SV, Church JA et al. The effect of maternal peripartum infliximab use on neonatal immune response. Gastroenterology. 2008;134 (Suppl 1):A69. Abstract. DOI: doi.org/10.1016/S0016-5085(08)60323-6

22. Hou JK, Mahadevan U. A 24-year-old pregnant woman with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2009;7:944-7. PMID: 19410016

23. Puig L, Barco D, Alomar A. Treatment of psoriasis with anti-TNF drugs during pregnancy: case report and review of the literature. Dermatology. 2010;220:71-6. PMID: 19940453

24. Correia LM, Bonilha DQ, Ramos JD et al. Inflammatory bowel disease and pregnancy: report of two cases treated with infliximab and a review of the literature. Eur J Gastroenterol Hepatol. 2010;22:1260-4. PMID: 20671559

25. Mahadevan U, Martin CF, Sandler RS et al. PIANO: a 1000 patient prospective registry of pregnancy outcomes in women with IBD exposed to immunomodulators and biologic therapy . Gastroenterology . 2012;142 (Suppl 1):S149. Abstract 865. DOI: doi.org/10.1016/S0016-5085(12)60561-7

Infliximab Identification

Substance Name

Infliximab

CAS Registry Number

170277-31-3

Drug Class

Administrative Information

LactMed Record Number

476

Information from the National Library of Medicine's LactMed Database.

Last Revision Date

2014-08-01

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