Summary of Use during Lactation

Maternal vedolizumab injections appear to produce low levels in breastmilk and to not adversely affect the nursing infant. Because vedolizumab is a large protein molecule with a molecular weight of about 147,000 Da, the amount in milk is likely to be very low.[1] It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal.[2] Additionally, vedolizumab does not affect SIgA, SIgM levels in milk in women with inflammatory bowel disease. Most experts and guidelines consider vedolizumab to be probably acceptable during nursing.[3-6] Until more data become available, vedolizumab should be used with caution during breastfeeding, especially while nursing a newborn or preterm infant. Waiting for at least 2 weeks postpartum to resume therapy may minimize transfer to the infant.[7]

Drug Levels

Maternal Levels. Five lactating women who were receiving vedolizumab for inflammatory bowel disease donated milk samples at various times after receiving a dose of 300 mg intravenously. Four were on maintenance therapy every 1 to 2 months and 1 was in the induction phase and had received 2 doses of the drug 2 weeks apart. Peak breastmilk levels occurred from day 2 to 4 after the dose with a median of day 3. Peak milk concentrations averaged 354 mcg/L (range 108 to 478 mcg/L). One woman collected milk daily for 15 days. Her breastmilk levels slowly decreased from a peak of 405 mcg/L on day 3 to 101 mcg/L on day 15.[8]

Five nursing mothers were receiving vedolizumab 300 mg intravenously at unspecified intervals for inflammatory bowel disease. Breastmilk samples were collected before a dose, 30 minutes after a dose and twice daily thereafter for up to 14 days. Trough samples contained 124 to 228 mcg/L of vedolizumab. Most breastmilk levels were between 150 and 250 mcg/L The highest breastmilk vedolizumab milk levels were variable and ranged from 196 to 318 mcg/L on days 3 through 7. Using the highest level measured, the authors calculated that an infant would receive an oral dose of 0.048 mg/kg of vedolizumab daily.[9]

Eleven women with inflammatory bowel disease were receiving vedolizumab 300 mg intravenously at various intervals, nine every 8 weeks, and one each at 4 and 6 week intervals. Complete expression of breastmilk from both breasts was done before the dose on day 1 of therapy, then at 1 hour after the infusion and on days 1, 4, 8, 15, 29, and 57 after the dose. The median time to peak milk level was 3 to 4 days after the dose with a mean peak value of 252 mcg/L (range, 98 to 561 mcg/L) in the 9 women receiving the drug every 8 weeks. The mean trough level at 57 days after the dose was 47.1 mcg/L. The average daily milk concentration over the 8-week dosing interval was 129 mcg/L (range 0.032 to 0.26 mcg/L). The geometric mean daily infant dosage was 0.019 mg/kg daily. In the patient receiving the drug every 6 weeks, the peak milk level was 165 mcg/L. In the patient receiving the drug every 4 weeks, the peak milk level was 305 mcg/L and the trough level was 154 mcg/L.[10]

Infant Levels. Forty-three women who received vedolizumab 300 mg at a median of every 8 weeks (range 4-8 weeks) and delivered a live newborn were studied. They continued to receive vedolizumab at similar intervals postpartum with the first treatment given at median 3 (range 0-18) weeks after delivery. Thirty-six of the women breastfed (extent not stated) their infants for a median of 4 months (range 0.5 to 19 months). The study found no correlation between the rate of infant serum vedolizumab level decline and whether they were breastfed.[11]

Effects in Breastfed Infants

Eight women who were receiving vedolizumab for inflammatory bowel disease were breastfeeding their infants (extent not stated). Dosages were 300 mg intravenously, at 1 to 2 month intervals for 6 and starting during induction for 2 women. No increase in general or gastrointestinal tract infections were seen in the newborns up to 10 months of age and all infants reached their development milestones.[8]

Five infants were breastfed by mothers receiving vedolizumab 300 mg intravenously at regular intervals. The infants all had normal developmental milestones at 3.5 to 10 months of age. All of the infants received routine inactivated vaccines without complications.[9]

A multicenter, retrospective study in Belgium reported on women with inflammatory bowel disease during pregnancy and postpartum who received vedolizumab (n = 23). Twelve infants were breastfed by their mothers and were followed for a median of 23 weeks (IQR 10 to 60 weeks). Twenty of the 23 infants were vaccinated with the standard Belgian protocol, with 9 also receiving rotavirus vaccination. No serious infections or malignancies were reported.[12] In an extension of this study, 70 women who received vedolizumab were compared to those who received a TNF antagonist (n = 162) and to those who received no biological or immunologic therapy (n = 163). Sixty-two percent of women on vedolizumab breastfed their infants compared to 60% and 64% in the other groups. No malignancies were reported in any of the children during the first year of life and the number of infant infections were not statistically different between the groups. The extent of breastfeeding and postpartum dosage regimens were not stated.[13]

The manufacturer’s database of adverse drug events up to May 2019 included 21 adverse events in breastfed infants whose mothers were taking vedolizumab. None of them were judged to be serious.[10] No details of the types of reactions were reported.

Forty-three women who received vedolizumab 300 mg at a median of every 8 weeks (range 4-8 weeks) and delivered a live newborn were studied. They continued to receive vedolizumab at similar intervals postpartum with the first treatment given at median 3 (range 0-18) weeks after delivery. Thirty-six of the women breastfed (extent not stated) their infants for a median of 4 months (range 0.5 to 19 months). The study found no correlation between breastfeeding and infection rate among the infants and normal development in the infants.[11]

The DUMBO registry in Spain followed 526 newborns whose mothers had inflammatory bowel disease. During breastfeeding 2% of the mothers were receiving vedolizumab. Of children breastfed at least until month 6 and whose mothers were taking a biologic, 60% received the 1^st and 2^nd dose of rotavirus vaccine, and 17% the 3rd dose. Of children breastfed at least until month 12 and whose mothers were taking a biologic, 97% received the 1st dose of MMR vaccine; and from children breastfed at least until month 15 and whose mothers were under biologics, 84% received the 1^st dose of varicella vaccine. No serious adverse events related to live vaccines were reported.[14]

In a prospective, multicenter study, 16 infants were born to mothers taking vedolizumab during pregnancy. Of these, 12 were breastfed for a median of 11 months (range 1 to 21 months). Infants were followed for at least 6 months and a median of 18 months. All children had normal growth and normal psychomotor development at 12 or more months of age. All but one child exposed to ustekinumab receive mandatory vaccinations with non-live vaccines without any serious or unexpected adverse events.[15]

Effects on Lactation and Breastmilk

A study of the milk of women with or without inflammatory bowel disease (IBD) found that the use of vedolizumab to treat IBD did not affect the amount of SIgA or SIgM in the milk.[16]

References

1.

Stratigakis A, Paty D, Zou P, et al. A regression approach for assessing large molecular drug concentration in breast milk. Reprod Breed 2023;3:199-207. doi:10.1016/j.repbre.2023.10.003 [CrossRef]

2.

Anderson PO. Monoclonal antibodies during breastfeeding. Breastfeed Med 2021;16:591-3. [PubMed: 33956488]

3.

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]

4.

Picardo S, Seow CH. A pharmacological approach to managing inflammatory bowel disease during conception, pregnancy and breastfeeding: Biologic and oral small molecule therapy. Drugs 2019;79:1053-63. [PubMed: 31183768]

5.

Laube R, Selinger CP, Seow CH, et al. Australian inflammatory bowel disease consensus statements for preconception, pregnancy and breast feeding. Gut 2023;72:1040-53. [PubMed: 36944479]

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.

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

8.

Lahat A, Shitrit AB, Naftali T, et al. Vedolizumab levels in breast milk of nursing mothers with inflammatory bowel disease. J Crohns Colitis 2018;12:120-3. [PubMed: 28961712]

9.

Julsgaard M, Kjeldsen J, Bibby BM, et al. Vedolizumab concentrations in the breast milk of nursing mothers with inflammatory bowel disease. Gastroenterology 2018;154:752-754 e1. [PubMed: 28988916]

10.

Sun W, Fennimore B, Beaulieu DB, et al. Vedolizumab concentrations in breast milk: Results from a prospective, postmarketing, milk-only lactation study in nursing mothers with inflammatory bowel disease. Clin Pharmacokinet 2021;60:811–8. [PMC free article: PMC8195772] [PubMed: 33544318]

11.

Julsgaard M, Baumgart DC, Baunwall SMD, et al. Vedolizumab clearance in neonates, susceptibility to infections and developmental milestones: a prospective multicentre population-based cohort study. Aliment Pharmacol Ther 2021;54:1320-9. [PubMed: 34472644]

12.

Moens A, Van Hoeve K, Humblet E, et al. Outcome of pregnancies in female patients with inflammatory bowel diseases treated with vedolizumab. J Crohns Colitis 2019;13:12-8. [PubMed: 30281093]

13.

Moens A, van der Woude CJ, Julsgaard M, et al. Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti-TNF or conventional therapy: results of the European CONCEIVE study. Aliment Pharmacol Ther 2020;51:129-38. [PubMed: 31692017]

14.

Chaparro Sanchez M, García Donday M, Rubio S, et al. Live vaccines in children exposed to biological agents for IBD in utero and/or during breastfeeding: Are they safe? Results from the Dumbo registry of GETECCU. United European Gastroenterol J 2022;10:757-8. doi:10.1002/ueg2.12295 [CrossRef]

15.

Mitrova K, Pipek B, Bortlik M, et al. Safety of ustekinumab and vedolizumab during pregnancy-pregnancy, neonatal, and infant outcome: A prospective multicentre study. J Crohns Colitis 2022;16:1808-15. [PubMed: 35708729]

16.

Urrete J, Mitra T, Boland BS, et al. Vedolizumab does not affect antibody secreting cell recruitment to the lactating mammary gland of mothers with inflammatory bowel disease. Inflamm Bowel Dis 2024. [PubMed: 38334263]

Substance Name

Vedolizumab

CAS Registry Number

943609-66-3

Drug Class

Breast Feeding

Lactation

Milk, Human

Antibodies, Monoclonal, Humanized

Gastrointestinal Agents