94
who resumed treatment with IFX following delivery, breast milk samples were
obtained daily for up to 8 days post-IFX infusion which showed detectable drug
levels as early as 12 h post-infusion with a peak of 90–105 ng/mL on day 2–3 with
serum levels during that same time were 18–64 μg/mL, which correlates to a level
in breast milk of approximately 1/200th of the level in serum [ 90 ]. In a third case
report of three women (two with Crohn’s disease, one with UC) who continued on
IFX postpartum, breast milk samples were obtained at the time of an infusion and
daily for the next 5 days which showed a range in breast milk drug concentrations
from only minimal amounts becoming detectable at day 2 post-infusion to a maxi-
mum drug concentration of 300 ng/mL at day 6 post-infusion [ 91 ]. All of the chil-
dren were healthy with no adverse effects from IFX exposure in the breast milk.
This study did not include the maternal serum drug concentrations for comparison;
however, they did calculate that breastfed infants of mothers being treated with IFX
are estimated to receive an IFX dose of approximately 0.045 mg/kg bodyweight/
day, which is significantly less than the maternal dose.
Looking at ADA in breast milk, a case report of a 26-year-old woman with
Crohn’s disease who resumed ADA postpartum had serum and breast milk samples
collected every 2 days for 8 days which showed a peak in the serum drug concentra-
tion of 4300 ng/mL at day 3 postinjection and a peak in the breast milk level at
31 ng/mL on day 6 postinjection, which corresponded to a level of less than 1/100
the serum level [ 92 ]. In a study case series of four patients, two receiving IFX and
two receiving ADA, the IFX levels in breast milk were found to be 1/20th of the
maternal serum level while the breast milk ADA levels were <1/1000th of the
maternal serum levels [ 93 ]. In all cases, there were no adverse effects from the
medications and no increase in infections or allergic reactions, and all were noted to
have normal weight gain and normal development.
Only one study has measured levels of CZP in breast milk, obtained 4 hours
postinjection, 3 days postinjection, and 6 days postinjection, and all breast milk
samples had undetectable levels of CZP [ 23 ]. There is evidence of excretion of
golimumab in the breast milk of cynomolgus macaques, but no human studies have
yet been reported [ 94 ].
Multiple studies have shown that serum drug levels in the infants continue to
trend down despite breastfeeding from mothers who continue to receive treatment
with anti-TNF agents [ 22 , 26 ]. This provides evidence that the orally absorbed drug
does not result in therapeutic drug levels.
Anti-integrins
The natalizumab prescribing information indicates prior detection of NAT in human
breast milk [ 95 ]. The vedolizumab prescribing information indicates prior detection
of VDZ in the milk of lactating monkey, but no testing in human breast milk has
been performed [ 96 ].
J.K.J. Gaidos and S.V. Kane