Enbrel Use In Pregnancy & Lactation

Effects on fertility: Long-term animal studies have not been conducted to evaluate the effects of Enbrel on fertility.
Use in pregnancy - Pregnancy Category D: The safe use of Enbrel during pregnancy has not been established. Enbrel should only be used during pregnancy if the potential benefits to the mother outweigh the potential risks to the fetus. If Enbrel is used during pregnancy, or if the patient becomes pregnant while taking it, the woman should be advised of the possible risk to the fetus.
Developmental toxicity studies have been performed in rats and rabbits at doses resulting in AUC-based systemic exposure levels of etanercept that were at least 12-fold higher than in humans at the highest proposed therapeutic dose of 50 mg and have revealed no evidence of harm to the fetus due to Enbrel. There are, however, no studies in pregnant women. Animal studies are not always predictive of human response.
Etanercept crosses the placenta and has been detected in the serum of infants born to female patients treated with Enbrel during pregnancy. The clinical impact of this is unknown, however, infants may be at increased risk of infection. Administration of live vaccines to infants for 16 weeks after the mother's last dose of Enbrel is generally not recommended.
The effects of etanercept on pregnancy outcomes have been investigated in two observational cohort studies. One pregnancy registry examined the risk of major birth defects and other pregnancy outcomes in mothers with rheumatic diseases or psoriasis exposed to Enbrel in the first trimester (n=319) versus those who were unexposed to Enbrel or other TNF-antagonists (n=144). The all-inclusive odds ratio for major birth defects in those exposed to Enbrel was 2.77 (95% CI 1.04-7.35) compared to non-exposed mothers with inflammatory disease. The findings showed no clear pattern of major or minor malformations. There was no increase in rates of intrauterine or postnatal growth deficits or delayed postnatal development.
In a second observational multi-country registry study comparing the risk of adverse pregnancy outcomes in women exposed to etanercept (n=522) to those exposed to non biologic drugs (n=3508), there was no observed increased risk of major birth defects (adjusted odds ratio 0.96, 95% CI: 0.58-1.60). This study also showed no increased risks of minor birth defects, preterm birth, stillbirth or infections in the first year of life for infants born to women exposed to etanercept during pregnancy.
Use in lactation: In lactating rats, following subcutaneous administration etanercept was detected in the serum of the pups. Limited information from the published literature indicates etanercept has been detected at low levels in human milk. Use of etanercept during breastfeeding should be assessed taking into account the risks and benefits of breastfeeding for the child and therapy for the mother.
While systemic exposure in a breastfed infant is expected to be low because etanercept is largely degraded in the gastrointestinal tract, limited data regarding systemic exposure in the breastfed infant are available. Therefore, the administration of live vaccines (e.g. BCG) to a breastfed infant when the mother is receiving etanercept could be considered 16 weeks after stopping breastfeeding (or at an earlier timepoint if the infant etanercept serum levels are undetectable).