Infliximab

Drug Levels and Effects:




Summary of Use during Lactation:


Infliximab is usually not detectable in breastmilk and is is poorly absorbed orally. Follow-up of infants exposed in utero and breastfed during maternal infliximab therapy have found no adverse effects and normal development. 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,[1][2][3][4][5][6] although Australian experts note that the data are inadequate to absolutely assure safety.[7] 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.[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.[8]

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]

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


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.[11]

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.[16]

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.[12]

An infant was breastfed (extent not stated) for up to 4 months by a mother who was taking infliximab (dosage not stated) andazathioprine150 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.[17]

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.[13]

Three infants were breastfed after their mothers received infliximab during the third trimester of pregnancy. No immune system deficits were noted on follow-up.[18]

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.[14]

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.[19]

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.[20]

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.[21]

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.[15]


Possible Effects on Lactation:


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


Alternate Drugs to Consider:


(Inflammatory Bowel Disease)Azathioprine,Budesonide,Mesalamine,Prednisone,(Rheumatoid Arthritis) Auranofin,Etanercept,Gold Sodium Thiomalate,Hydroxychloroquine,Methotrexate,Penicillamine,Sulfasalazine


References:


1. Ostensen M. Management of early aggressive rheumatoid arthritis during pregnancy and lactation. Expert Opin Pharmacother. 2009;10:1469-79. PMID:19505214
2. 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.
3. Mahadevan U. Pregnancy and inflammatory bowel disease. Med Clin North Am. 2010;94:53-73. PMID:19944798
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. Mahadevan U, Cucchiara S, Hyams JS et al. The London Position Statement of the World Congress of Gastroenterology on Biological Therapy for IBD With the European Crohn's and Colitis Organisation: Pregnancy and Pediatrics. Am J Gastroenterol. 2010. PMID:21157441
6. 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
7. Miehsler W, Novacek G, Wenzl H et al. A decade of infliximab: the Austrian Evidence Based Consensus on the Safe Use of Infliximab in Inflammatory Bowel Disease. J Crohns Colitis. 2010;4:221-56.
8. 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
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. 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
17. Bernard N, Garayt C, Chol F et al. Prospective clinical and biological follow-up of three breastfed babies fromazathioprine-treated mothers. Fundam Clin Pharmacol. 2007;21 (Suppl. 1):62-3. Abstract .
18. 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.
19. Hou JK, Mahadevan U. A 24-year-old pregnant woman with inflammatory bowel disease. Clin Gastroenterol Hepatol. 2009;7:944-7. PMID:19410016
20. 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
21. 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



Substance Identification:




Substance Name:

Infliximab

CAS Registry Number:

170277-31-3

Drug Class:


  • Antibodies, Monoclonal

  • Antirheumatic Agents

  • Dermatologic Agents

  • Gastrointestinal Agents


  • Administrative Information:




    LactMed Record Number:


    476


    Last Revision Date:


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