Also known as Avakine, Ig gamma-1 chain C region, Remicade, cA2

A recombinant chimeric, mouse-human monoclonal antibody directed against tumor necrosis factor alpha (TNF-alpha), a protein involved in inflammation, cell survival, and apoptosis. Infliximab may be pro- apoptotic or anti-apoptotic, depending on cell type. (NCI04)

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

Can I take Infliximab while breastfeeding?

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] Although the manufacturer recommends that breastfeeding be discontinued during infliximab therapy, numerous 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]

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.[9] 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.[10] 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).[11] 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.[12] 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.[13] 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.[14] 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.[15] 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.[16] Eleven women who received infliximab (dose unspecified) as part of a large registry study submitted breastmilk samples. Infliximab was detected in levels between 90 and 591 mcg/L between 24 and 48 hours after infusion.[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.[12]

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.[14] 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 mcg/L, which was 2.2% of the simultaneous maternal serum infliximab concentration.[15] 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

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.[9] 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.[10] 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).[11] 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.[12] 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.[13] 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.[14] 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.[15] 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.[16] Eleven women who received infliximab (dose unspecified) as part of a large registry study submitted breastmilk samples. Infliximab was detected in levels between 90 and 591 mcg/L between 24 and 48 hours after infusion.[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.[12]

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.[14] 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 mcg/L, which was 2.2% of the simultaneous maternal serum infliximab concentration.[15] 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]

Possible effects on lactation

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

Alternate drugs to consider

Adalimumab, PMID: 22115374

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

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

4. Mahadevan U, Matro R. Care of the pregnant patient with inflammatory bowel disease. Obstet Gynecol. 2015;126:401-12. PMID: 26241432

5. Nguyen GC, Seow CH, Maxwell C et al. The Toronto Consensus Statements for the Management of IBD in Pregnancy. Gastroenterology. 2016;150:734-57. PMID: 26688268

6. van der Woude CJ, Ardizzone S, Bengtson MB et al. The second European evidenced-based consensus on reproduction and pregnancy in inflammatory bowel disease. J Crohns Colitis. 2015;9:107-24. PMID: 25602023

7. 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

8. 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

9. 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.

10. Forger F, Matthias T, Oppermann M et al. Infliximab in breast milk. Lupus. 2004;13:753 . Abstract.

11. 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

12. 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

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

14. 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

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

16. 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

17. Matro R, Martin CF, Wolf DC et al. Detection of biologic agents in breast milk and implication for infection, growth and development in infants born to women with inflammatory bowel disease: Results from the PIANO registry. Gastroenterology. 2015;148:S141. Abstract.

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 .

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.

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.

Last Revision Date

20160426

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Source: LactMed – National Library of Medicine (NLM)