Respiratory Drug (Bronchodilator)
PREGNANCY RECOMMENDATION: No Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
No reports describing the use of indacaterol in human pregnancy have been located. The animal reproduction data suggest low risk, but the absence of human pregnancy experience prevents a more complete assessment of embryo–fetal risk. Nevertheless, only small amounts reach the systemic circulation, so if the drug is indicated, it should not be withheld because of pregnancy.
FETAL RISK SUMMARY
Indacaterol is a long-acting β2-adrenergic agonist that is available as an inhalation powder. It is indicated for long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. The absolute bioavailability after an inhaled dose was, on average, 43–45%.
Indacaterol is extensively metabolized to apparently inactive metabolites. The human serum and plasma protein binding is about 95% and 96%, respectively. The average terminal half-life ranges from 45.5 to 126 hours (1).
Reproduction studies have been conducted with SC doses in rats and rabbits. In these species, indacaterol doses that were about 130 and 260 times, respectively, the human 75 mcg dose based on BSA were not teratogenic (1).
In carcinogenic studies, the drug showed no statistically significant increase in tumor formation in mice or rats. However, similar to other β2-adrenergic agonists, lifetime treatment in female rats resulted in an increased incidence of benign ovarian leiomyomas. Multiple assays for mutagenic or clastogenic effects were negative. The drug did not impair fertility of rats in reproduction studies (1).
It is not known if indacaterol crosses the human placenta. The molecular weight (about 509) and long terminal half-life suggest that exposure of the embryo–fetus will occur. However, the high serum and plasma protein binding might limit the exposure. Moreover, a relatively small amount of the drug will reach the systemic circulation.
BREASTFEEDING SUMMARY
No reports describing the use of indacaterol during human lactation have been located. The molecular weight (about 509) and long terminal half-life (45.5–126 hours) suggest that the drug will be excreted into breast milk. However, the high serum and plasma protein binding (about 95% and 96%) might limit the exposure. Moreover, a relatively small amount of the drug will reach the systemic circulation. Taken in sum, the drug is probably compatible with breastfeeding.
Reference
1.Product information. Arcapta. Novartis Pharmaceuticals, 2011.