Ixifi Use In Pregnancy & Lactation

Pregnancy: Infliximab products should be given to a pregnant woman only if clearly needed.
Published data suggest that there is an increased risk of adverse pregnancy outcomes in women with inflammatory bowel disease (IBD) or rheumatoid arthritis associated with increased disease activity. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2.5 kg) and small for gestational age at birth.
No evidence of maternal toxicity, embryotoxicity or teratogenicity was observed in a developmental toxicity study conducted in mice using an analogous antibody that selectively inhibits the functional activity of mouse TNFα. Infliximab has been detected in the serum of infants up to 6 months following birth. Consequently, these infants may be at increased risk of infection, including disseminated infection which can become fatal.
Women of childbearing potential should use adequate contraception to prevent pregnancy and continue its use for at least 6 months after the last infliximab treatment.
Two prospective cohort studies were conducted assessing birth outcomes as well as the health status of infants up to the age of one year in women exposed to infliximab compared to non-biologic comparators including methotrexate, azathioprine, 6-mercaptopurine and systemic corticosteroids used for the treatment of similar diseases. The first study was conducted in an IBD pregnancy registry in the United States and assessed pregnancy outcomes in 294 women with inflammatory bowel disease exposed to infliximab during pregnancy compared with 515 women on a non-biologic treatment. Infliximab exposure was not associated with increased rates of major congenital malformations, miscarriage/stillbirth, infants of low birth weight, small for gestational age, or infection in the first year of life. The second study among IBD and non-IBD patients in Sweden, Finland, and Denmark compared 97, 7, and 166 women exposed to infliximab to 2693, 2499, and 1268 women on non-biologic systemic therapy, respectively. In this study, comparing pooled data across the three countries, exposure to infliximab was not associated with increased rates of congenital anomalies or infant death. Infliximab in combination with immunosuppressants (mainly systemic corticosteroids and azathioprine) was associated with increased rates of preterm birth, small for gestational age, low birth weight, and infant hospitalization for infection compared with non-biologic systemic treatment. Although the study did not show any associations with infliximab monotherapy, the analyses could have been underpowered to detect an association.
There were additional methodological limitations with these studies that may account for the study findings in both studies: the concomitant use of other medications or treatments was not controlled and disease severity was not assessed; in the U.S. study, patient reported outcomes were collected without clinical validation. These methodological limitations hinder interpretation of the study results.
As with other IgG antibodies, infliximab crosses the placenta. Infliximab has been detected in the serum of infants up to 12 months following birth. The clinical significance of low serum levels of infliximab on the immune status in infants is unknown. After in utero exposure to infliximab, infants may be at increased risk of infection, including disseminated infection that can become fatal. At least a 12-month waiting period following birth is recommended before the administration of live vaccines (e.g., BCG vaccine or other live vaccines, such as the rotavirus vaccine) to these infants (see Precautions).
Cases of agranulocytosis in infants exposed in utero have also been reported (see Adverse Reactions).
Breastfeeding: Infliximab has been detected at low levels in human milk and in infant serum via breast milk. While systemic exposure in a breastfed infant is expected to be low because infliximab is largely degraded in the gastrointestinal tract, the administration of live vaccines to a breastfed infant when the mother is receiving infliximab is not recommended unless infant infliximab serum levels are undetectable. Limited data from published literature reported that infants exposed to infliximab through breast milk had no increase in rates of infections and developed normally. The consideration of infliximab use during breastfeeding should take into account the importance of the drug to the mother and health benefits of breastfeeding for the infant.
Fertility: It is not known whether infliximab can impair fertility in humans. No impairment of fertility or reproductive performance indices were observed in male or female mice that received cV1q, an analogous mouse antibody, at intravenous doses up to 40 mg/kg given (see Pharmacology: Toxicology: Preclinical safety data under Actions).