What precautions are required for rituximab (Rituxan) use in women of child‑bearing potential and during pregnancy, including contraception, breastfeeding, and neonatal management?

Rituximab Precautions in Pregnancy

Contraception and Pregnancy Planning

Women of childbearing potential must use effective contraception during rituximab treatment and for 12 months after the last dose. 1

• Verify pregnancy status before initiating rituximab in all women of reproductive potential 1
• The 12-month contraception window is based on rituximab's long half-life and potential for prolonged B-cell depletion 2, 1

Risk Assessment When Pregnancy Occurs

If pregnancy occurs during or shortly after rituximab exposure, the decision to continue should be based on whether severe life-threatening or organ-threatening maternal disease exists that cannot be controlled with pregnancy-compatible alternatives. 2

Timing-Dependent Fetal Risk:

• First trimester exposure carries lower risk because rituximab has minimal placental transfer until the second trimester 3
• Second and third trimester exposure poses high risk of neonatal B-cell depletion, as rituximab crosses the maternofetal barrier and actively transfers to the fetus 4, 2, 5
• Dosing in the second half of pregnancy puts the fetus at highest risk of having minimal or absent B cells at delivery 2

Evidence on Maternal Indications:

• ESMO guidelines state rituximab should not be discouraged when postponement would significantly compromise maternal prognosis in B-cell lymphoma 2
• The American College of Rheumatology conditionally recommends continuing rituximab during pregnancy only if severe life- or organ-threatening maternal disease warrants it 2

Neonatal Management After In Utero Exposure

All infants exposed to rituximab in utero must avoid live vaccines for at least 6 months of life, and potentially up to 12 months. 4, 2, 1

Key Neonatal Considerations:

• Rituximab causes B-cell depletion in newborns when administered during pregnancy, particularly in the second and third trimesters 2, 5
• Neonatal B-cell counts spontaneously recover in all reported cases, typically within 6 months 2, 6, 5
• Monitor the infant for signs of infection and manage accordingly 1
• Ensure pediatric providers are informed of in utero exposure to guide vaccination timing 2

Live Vaccines to Avoid:

• BCG, rotavirus, MMR, varicella, and other live-attenuated vaccines must be deferred 2
• Fatal disseminated BCG infection has been reported in an infant whose mother received anti-CD20 therapy during pregnancy and who was vaccinated at 3 months 7

Breastfeeding

Women must not breastfeed during rituximab treatment and for 6 months (FDA label) to 12 months (British guidelines) after the last infusion. 1, 4

• Maternal IgG is excreted in human milk 4
• Rituximab is detected in the milk of lactating primates 1
• The clinical significance of rituximab in breast milk for infants is unknown 1

Pregnancy Outcomes Data

Available safety data show reassuring but limited evidence:

• Among 153 pregnancies with known outcomes in the manufacturer's database, 90 resulted in live births 8
• Only 2 congenital malformations were identified (clubfoot in one twin, cardiac malformation in a singleton) among 90 live births 8
• No pattern of major structural anomalies has been reported in case series 9
• Hematologic abnormalities occurred in 11 neonates, but none had corresponding infections 8
• Preterm delivery and low birthweight are reported risks 4

Common Pitfalls to Avoid

• Do not assume first-trimester exposure is safe enough to continue routinely—while placental transfer is minimal early, the drug's long half-life means exposure continues 3
• Do not give live vaccines to exposed infants based on normal B-cell counts alone—wait the full 6–12 months as rituximab may still be present 2, 5
• Do not reassure patients that "inadvertent exposure is fine"—counsel about B-cell depletion risk and need for neonatal monitoring even when outcomes are generally favorable 8, 9
• Do not forget to document the indication and disease severity—continuation is only justified when maternal disease is severe and uncontrolled by safer alternatives 2