Pregnancy & Lactation : הריון/הנקה

4.6   Fertility, pregnancy and lactation

Pregnancy


There are no or limited amount of data from the use of budesonide, glycopyrronium and formoterol in pregnant women.

Data on the use of inhaled budesonide in more than 2,500 exposed pregnancies indicate no increased teratogenic risk associated with budesonide. Single-dose studies in humans found that very small amounts of glycopyrronium passed the placental barrier.

There is no experience with or evidence of safety issues on the use of the propellant norflurane (HFA134a) during human pregnancy or lactation. However, studies on the effect of HFA134a on the reproductive function and embryofoetal development in animals revealed no clinically relevant adverse effects.

No animal reproductive toxicology studies have been conducted with this medicinal product.
Budesonide has been shown to induce embryofoetal toxicity in rats and rabbits, a class effect of glucocorticoids. At very high doses/systemic exposure levels, formoterol caused implantation losses as well as decreases in birth weight and early postnatal survival, whereas glycopyrronium had no significant effects on reproduction (see section 5.3).

Administration of this medicinal product to pregnant women should only be considered if the expected benefit to the mother justifies the potential risk to the foetus.

Breast-feeding

A clinical pharmacology study has shown that inhaled budesonide is excreted in breast milk. However, budesonide was not detected in nursing infant blood samples. Based on pharmacokinetic parameters, the plasma concentration in the child is estimated to be less than 0.17% of the mother’s plasma concentration. Consequently, no effects due to budesonide are anticipated in breast-fed children whose mothers are receiving therapeutic doses of this medicinal product. It is not known whether glycopyrronium or formoterol are excreted in human milk. Evidence of transfer of glycopyrronium and formoterol into maternal milk in rats has been reported.

Administration of this medicinal product to women who are breast-feeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

Fertility

Studies in rats have shown adverse effects on fertility only at dose levels higher than the maximum human exposure to formoterol (see section 5.3). Budesonide and glycopyrronium individually, did not cause any adverse effects on fertility in rats. It is unlikely that this medicinal product administered at the recommended dose will affect fertility in humans.