Can you take ustekinumab while breastfeeding?

What LactMed would consider instead

LactMed ends this record by naming the drugs it would consider in place of ustekinumab. Whether any of them fits depends on what you are treating — this is the database’s list, not a recommendation from us.

• Adalimumab
• Certolizumab Pegol
• Etanercept
• Infliximab
• Phototherapy
• Tretinoin

How much ustekinumab gets into breastmilk

Maternal Levels. In a multi-center study of women with inflammatory bowel disease in pregnancy (the PIANO registry), 6 women receiving ustekinumab provided milk samples at 1, 12, 24, and 48 hours after drug administration. Some also provided samples at 72, 96, 120, and 168 hours after drug administration. Four of the women had detectable (>0.01 mg/L) ustekinumab levels in milk. Peak concentrations in breastmilk ranged from 0.72 to 1.57 mg/L and occurred at 12 to 72 hours after the dose. Only 3 of the women had a detectable concentration in milk beyond 48 hours.

A woman with treatment-refractory Crohn’s disease was treated during pregnancy with ustekinumab until the third trimester. It was reinitiated 7 weeks postpartum with a loading dose of 390 mg intravenously, then 90 mg every 8 weeks. A breastmilk sample taken 16 weeks after the dose was 3.2 mg/L. After the third dose, breastmilk levels of ustekinumab were 0.82 mg/L within the first day after the dose, 0.18 mg/L at 3 weeks after the third dose and 0.16 mg/L at 4 weeks after the third dose.

Three mothers taking ustekinumab for Crohn’s disease had breastmilk levels of ustekinumab measured 1 hour after a dose and sequentially for up to 2 weeks after the dose. In one patient who was receiving a dose of 90 mg every 4 weeks, the trough milk sample contained 43 mcg/L of ustekinumab and attained a peak level of 43.1 mcg/L two days after the dose. The milk level dropped to 16.7 mcg/L at 4 days after the dose, then rose again to 26.3 mcg/L at 5 days after the dose. The other two women were receiving a dosage of 90 mg every 8 weeks. One had a trough ustekinumab milk level of 40 mcg/L. After the dose, the milk level gradually rose to a level of 45.1 mcg/L at 6 days after the dose. The third woman, who had not had any doses during pregnancy, had a trough milk value of 3 mcg/L. It rose to a peak of 7.4 mcg/L on day 3 and then plateaued between 5.4 and 6.6 mcg/L on days 4 to 6 after the dose.

A pregnant woman with ulcerative colitis received ustekinumab 90 mg 4 times during pregnancy with the last dose at 29 weeks gestation She was also treated with mesalamine 4.8 grams daily during pregnancy and lactation. Postpartum, amlodipine 10 mg daily was begun for hypertension and at 5 days postpartum ampicillin-sulbactam was begun intravenously for suspected endometritis. Subcutaneous ustekinumab was restarted at 48 days postpartum and first detected in milk on day 49 at 1.5 mcg/L. On day 57, the milk concentration was 13.6 mcg/L. Milk concentrations then declined to 10.8, 7.9 and 3.4 mcg/L on days 64, 71 and 78 postpartum, respectively.

Five patients with inflammatory bowel disease were receiving ustekinumab, 4 for maintenance and 1 for induction intravenously. They had been breastfeeding for 6 to 11 months. After 90 mg subcutaneously, ustekinumab appeared in milk within 0 to 2 days, peaking at day 4 to 12 at 9.8 to 31.6 mcg/L. Following 520 ustekinumab intravenously, levels were higher with a peak of 105.3 mcg/L on day 8 and remained detectable throughout the 15-day sampling period. The estimated maximum daily infant dose ranged from 1.5 to 4.7 mcg/kg after subcutaneous injection and was 15.8 mcg/kg after intravenous injection.

Infant Levels. Sixty-nine breastfed infants were born to mothers who received ustekinumab during pregnancy and postpartum. The estimated mean half-life of ustekinumab in infants was 23.2 days (95% CI 21.5 to 24.9 days).

Five patients with inflammatory bowel disease were receiving ustekinumab, 4 for maintenance and 1 for induction intravenously. All infants were exposed to ustekinumab in utero and during breastfeeding. In cases 2 to 5, ustekinumab was cleared from infant serum despite ongoing breastfeeding. Infants 3 and 4 had undetectable levels by 3 months. Infants 2 and 5 had low levels at 3 months, and undetectable levels at 6 months. Infant 1 was not assessed.

What has been seen in breastfed infants

One woman receiving ustekinumab for severe psoriasis breastfed her infant. No adverse effects were reported in the infant, although the dosage of ustekinumab and the extent of breastfeeding were not reported.

In a multi-center study of women with inflammatory bowel disease in pregnancy (the PIANO registry), 6 women received a ustekinumab while breastfeeding their infants. Among those who received ustekinumab or another biologic agent while breastfeeding, infant growth, development or infection rate was no different from infants whose mothers received no treatment. An additional 68 women received a biologic agent plus a thiopurine. Infant outcomes were similar in this group.

A woman with treatment-refractory Crohn’s disease was treated during pregnancy with ustekinumab until the third trimester. It was reinitiated 7 weeks postpartum with a loading dose of 390 mg intravenously, then 90 mg every 8 weeks. She breastfed her infant (extent and duration not reported). Follow-up of the infant at 12 months of age was normal.

A woman with severe psoriasis was treated with ustekinumab 45 mg subcutaneously every 12 weeks until pregnancy was confirmed. After delivery ustekinumab was restarted while she was breastfeeding (extent and duration not stated). The infant reportedly had no complications and a normal growth curve.

Three mothers taking ustekinumab for Crohn’s disease breastfed (extent not stated) their infants. Their dosages were 90 mg every 4 weeks in one and 90 mg every 8 weeks in the other two. Infants were followed for 3 to 6 months and no developmental delays or excess infections of hospital admissions were noted.

A pregnant woman with ulcerative colitis received ustekinumab 90 mg 4 times during pregnancy with the last dose at 29 weeks gestation. She was also treated with mesalamine 4.8 grams daily during pregnancy and lactation. Postpartum, amlodipine 10 mg daily was begun for hypertension and at 5 days postpartum ampicillin-sulbactam was begun intravenously for suspected endometritis. Subcutaneous ustekinumab was restarted at 7 weeks postpartum. The infant was partially (>50%) breastfed for 3 months. The infant had no adverse drug events at the 1 and 3-month checkups and received routine infant vaccinations with no adverse events.

The DUMBO registry in Spain followed 526 newborns whose mothers had inflammatory bowel disease. During breastfeeding 4% of the mothers were receiving ustekinumab. Of children breastfed at least until month 6 and whose mothers were taking a biologic, 60% received the first and second 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 first dose of MMR vaccine; and from children breastfed at least until month 15 and whose mothers were under biologics, 84% received the first dose of varicella vaccine. No serious adverse events related to live vaccines were reported.

In a prospective multicenter study, 20 infants were born to mothers taking ustekinumab during pregnancy. Of these, 18 were breastfed for a median of 7 months (range 0.5 to 27 months). Infants were followed for at least 6 months and a median of 18 months. All children had normal growth and normal psychomotor development. All but one child exposed to ustekinumab receive mandatory vaccinations with non-live vaccines without any serious or unexpected adverse events.

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. Twelve infants were exposed to ustekinumab during lactation for a mean duration of 39.5 weeks. No adverse impact of biologics exposure was found on the psychomotor development of infants for up to 1 year of age.

Five nursing mothers with inflammatory bowel disease were receiving ustekinumab, 4 for maintenance and 1 for induction intravenously. No adverse events were reported in the nursing infants at 4.6 to 6.7 years of age. No serious infections occurred. All infants completed the Danish National Immunization Program, including the live-attenuated measles, mumps, and rubella (MMR) vaccine without adverse effects at 15 months and 4 years. All mothers reported age-appropriate infant development at 4 to 6 years. ASQ-3 scores at 12 months showed no deviations from the reference population across 5 developmental domains, except higher gross motor scores, among ustekinumab-exposed infants.

Effects on milk supply

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