Can you take vedolizumab while breastfeeding?

How much vedolizumab gets into breastmilk

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.

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.

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.

Data from a clinical lactation study show the presence of vedolizumab in human milk. The mean calculated daily infant dosage was 0.02 mg/kg/day orally (see Data). Systemic exposure in a breastfed infant is expected to be low because monoclonal antibodies are largely degraded in the gastrointestinal tract. There are no data on the effects of vedolizumab on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ENTYVIO and any potential adverse effects on the breastfed infant from ENTYVIO or from the underlying maternal condition.

Data

A milk-only lactation study was conducted in 9 adult lactating women being treated for active ulcerative colitis or Crohn’s disease with intravenous ENTYVIO every 8 weeks after reaching steady state and completing the induction phase (ENTYVIO administration at 0, 2, and 6 weeks). Mean concentrations of ENTYVIO in human milk ranged from 0.03 to 0.26 mcg/mL. The mean calculated daily infant oral dosage was 0.02 mg/kg/day calculated as a product of the average concentration over the 8-week dosing interval and the standardized milk consumption of 150 mL/kg/day.

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.

What has been seen 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.

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.

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. 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.

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. 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.

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 and 2 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 dose of varicella vaccine. No serious adverse events related to live vaccines were reported.

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.

A woman with ulcerative colitis received vedolizumab (dose not stated) during pregnancy and postpartum, delivering twins by cesarean section at 34 weeks of gestation. She breastfed (extent not stated) her infants who maintained adequate developmental growth for their age.

An infant whose mother was taking tofacitinib 5 mg twice daily and vedolizumab 300 mg every 4 weeks for ulcerative colitis postpartum was followed. She breastfed her infant exclusively for the first 6 months postpartum, and continued breastfeeding for at least 16 months. The child demonstrated normal growth and psychomotor development. The infant received 3 doses of a required hexavalent vaccine (tetanus, diphtheria, polio, pertussis, hepatitis B, and Haemophilus influenza type B) as well as optional non-live vaccines (pneumococcal and meningococcal vaccines) on schedule at 3, 5, and 14 months, with no adverse events reported. At 12 months of age, the child contracted chickenpox, which had a mild course. No other infectious complications were noted. A blood sample was collected from the child at 15 months. Laboratory analysis revealed normal levels of immunoglobulin classes, except for a slightly reduced total IgG antibody level and non-significant anemia. The titers of post-vaccination antibodies were within the typical range for a healthy population, indicating a normal response to vaccination. Extended T-cell and B-cell immunophenotyping was normal, except for mild, non-significant deviations in some T-cell and B-cell populations. The neonatal screening for severe combined immunodeficiency (SCID) was negative. No severe or clinically meaningful pathological findings were observed.

A multicenter study in Spain prospectively followed women treated for inflammatory bowel disease with biological agents, mostly anti-TNF agents. Overall, 29% of infants exposed to a biologic agent were also exposed to azathioprine or mercaptopurine and almost all were exposed during both pregnancy and lactation. Seven infants were exposed to vedolizumab during lactation for a mean duration of 30.4 weeks. No adverse impact of biologics exposure was found on the psychomotor development of infants for up to 1 year of age.

Effects on milk supply

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.