Pregnancy & Lactation : הריון/הנקה

4.6   Fertility, pregnancy and lactation

Women of childbearing potential
Women of childbearing potential should consider the use of appropriate contraception to avoid becoming pregnant during Brenzys therapy and for three weeks after discontinuation of therapy.


Pregnancy
Developmental toxicity studies performed in rats and rabbits have revealed no evidence of harm to the foetus or neonatal rat due to etanercept. The effects of etanercept on pregnancy outcomes have been investigated in two observationsl cohort studies. A higher rate of major birth defects was observed in an observational study comparing pregnancies exposed to etanercept (n=370) during the first trimester, with pregnancies not exposed to etanercept or other TNF-antagonists (n=164) (adjusted odds ratio 2.4, 95% CI: 1.0-5.5). The types of major birth defects were consistent with those most commonly reported in the general population and no particular pattern of abnormalities was identified. No change in the rate of spontaneous abortion, stillbirth, or minor malformations was observed. No change in the rate of spontaneous abortion, stillbirth, or minor malformations was observed. In another observational multi-country registry study comparing the risk of adverse pregnancy outcomes in women exposed to etanercept during the first 90 days of pregnancy (n=425) to those exposed to non-biologic drugs (n=3497), there was no observed increased risk of major birth defects (crude odds ratio [OR]= 1.22, 95% CI: 0.79-1.90; adjusted OR = 0.96, 95% CI: 0.58-1.60 after adjusting for country, maternal disease, parity, maternal age and smoking in early pregnancy). 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. Benepali should only be used during pregnancy if clearly needed.

Etanercept crosses the placenta and has been detected in the serum of infants born to female patients treated with etanercept 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 Brenzys is generally not recommended.

Breast-feeding
Etanercept has been reported to be excreted in human milk following subcutaneous administration. In lactating rats following subcutaneous administration, etanercept was excreted in the milk and detected in the serum of pups. Because immunoglobulins, in common with many medicinal products, can be excreted in human milk, a decision must be made whether to discontinue breast-feeding or to discontinue Brenzys therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility
Preclinical data about peri- and postnatal toxicity of etanercept and of effects of etanercept on fertility and general reproductive performance are not available.