Pregnancy & Lactation : הריון/הנקה

4.6   Fertility, pregnancy and lactation

Women of childbearing potential
The use of adequate contraception should be considered for women of childbearing potential. For women planning pregnancy, continued contraception may be considered for 5 months after the last Cimzia dose due to its elimination rate (see section 5.2), but the need for treatment of the woman should also be taken into account (see below).

Pregnancy
Data from more than 1300 prospectively collected pregnancies exposed to Cimzia with known pregnancy outcomes, including more than 1000 pregnancies exposed during the first trimester, does not indicate a malformative effect of Cimzia. Further data are being collected as the available clinical experience is still limited to conclude that there is no increased risk associated with Cimzia administration during pregnancy.
Animal studies using a rodent anti-rat TNFα did not reveal evidence of impaired fertility or harm to the foetus. However, these are insufficient with respect to human reproductive toxicity (see section 5.3). Due to its inhibition of TNFα, Cimzia administered during pregnancy could affect normal immune response in the newborn.
Cimzia should only be used during pregnancy if clinically needed.
Non-clinical studies suggest low or negligible level of placental transfer of a homologue Fab- fragment of certolizumab pegol (no Fc region) (see section 5.3).

In a clinical study 16 women were treated with certolizumab pegol (200 mg every 2 weeks or 400 mg every 4 weeks) during pregnancy. Certolizumab pegol plasma concentrations measured in 14 infants at birth were Below the Limit of Quantification (BLQ) in 13 samples; one was 0.042 µg/ml with an infant/mother plasma ratio at birth of 0.09%. At Week 4 and Week 8, all infant concentrations were BLQ. The clinical significance of low levels certolizumab pegol for infants is unknown. It is recommended to wait a minimum of 5 months following the mother’s last Cimzia administration during pregnancy before administration of live or live-attenuated vaccines (e.g. BCG vaccine), unless the benefit of the vaccination clearly outweighs the theoretical risk of administration of live or live- attenuated vaccines to the infants.

Breastfeeding
In a clinical study in 17 lactating women treated with Cimzia, minimal transfer of certolizumab pegol from plasma to breast milk was observed. The percentage of the maternal certolizumab pegol dose reaching an infant during a 24 hour period was estimated to 0.04% to 0.30 %. In addition, since certolizumab pegol is a protein that is degraded in the gastrointestinal tract after oral administration, the absolute bioavailability is expected to be very low in a breastfed infant.
Consequently, Cimzia can be used during breastfeeding.

Fertility
Effects on sperm motility measures and a trend of reduced sperm count in male rodents have been observed with no apparent effect on fertility (see section 5.3).

In a clinical trial to assess the effect of certolizumab pegol on semen quality parameters, 20 healthy male subjects were randomized to receive a single subcutaneous dose of 400 mg of certolizumab pegol or placebo. During the 14-week follow-up, no treatment effects of certolizumab pegol were seen on semen quality parameters compared to placebo.