Ultibro Breezhaler Use In Pregnancy & Lactation

Effects on fertility: No studies on the effect on fertility have been conducted with the indacaterol/glycopyrronium combination.
Information related to indacaterol: No adverse effects on fertility were observed in male and female rats given indacaterol by subcutaneous injection at doses up to 2 mg/kg/day (yielding greater than 450-times [males] and 340-times [females] the serum AUC in humans at the maximum recommended dose of 110 μg/day provided by Ultibro Breezhaler).
Information related to glycopyrronium: Male and female fertility were unaffected in rats given glycopyrronium bromide by subcutaneous administration at doses up to 1.5 mg/kg/day (yielding plasma AUC levels approximately 900-times [males] and 500-times [females] that of humans at the maximum recommended clinical dose of 50 μg). Slight inhibition of ovulation (decreased corpora lutea) and increased pre-implantation loss were evident at this highest dose, but not at 0.5 mg/kg/day (relative exposure based on AUC, 162).
Use in pregnancy: Pregnancy Category B3: There are no data from the use of Ultibro Breezhaler in pregnant women available. Likewise there are no data from the use of either indacaterol or glycopyrronium in pregnant women.
No adverse embryofetal effects were seen following inhalational administration of glycopyrronium and indacaterol in combination in rats. Plasma AUC values at the highest dose tested were 79 and 125 times the human AUC for indacaterol and glycopyrronium, respectively.
Information related to indacaterol: Indacaterol was not teratogenic in rats or rabbits following subcutaneous administration at doses up to 1 and 3 mg/kg/day in the respective species. An increase in the incidence of a rib skeletal variation and retarded ossification were observed in the rabbit, possibly secondary to maternal toxicity. The plasma AUC at the no effect level in animals was at least 170 times the AUC in humans at the maximum recommended dose of indacaterol provided by Ultibro Breezhaler.
Information related to glycopyrronium: Glycopyrronium bromide was not teratogenic in rats or rabbits following inhalational administration at doses up to 3.05 and 3.5 mg/kg/day in the respective species (yielding plasma AUC values 730-times and 250-times higher than in patients at the maximum recommended human dose). Glycopyrronium bromide and its metabolites did not significantly cross the placental barrier of pregnant mice, rabbits and dogs. In human parturients undergoing Caesarean section, 86 minutes after a single intramuscular injection of 0.006 mg/kg glycopyrronium bromide, umbilical plasma concentrations were low.
The potential risk for humans is unknown. Therefore as there is no adequate experience in pregnant women, ULTIBRO BREEZHALER should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the fetus.
Use in lactation: It is not known whether indacaterol and/or glycopyrronium passes into human breast milk. Indacaterol and glycopyrronium (including their metabolites) have been detected in the milk of lactating rats. Reduced body weight gain was observed in pups of rats treated with indacaterol or glycopyrronium, while impaired learning and decreased fertility were observed in pups of rats treated with indacaterol during pregnancy and lactation. Therefore the use of Ultibro Breezhaler by breastfeeding women should only be considered if the expected benefit to the woman is greater than any possible risk to the infant.
Labor and delivery: Information related to indacaterol: Like other beta₂-adrenergic agonist containing drugs, Ultibro Breezhaler may inhibit labor due to a relaxant effect on uterine smooth muscle.