Animal studies are not available for the combination product. There are no controlled data in human pregnancy. The background birth defect and miscarriage risk for the indicated population is not known. In the US general population, the estimated major birth defect risk is 2 to 4% and the miscarriage risk is 15 to 20%.

Aclidinium:
-Animal studies at approximately 15 times the maximum recommended human daily inhaled dose (MRHDID) administered during organogenesis (gestation days 6 to 17) showed no evidence of structural alteration, however a pre- and post-natal study (gestation day 6 through lactation) at inhaled doses approximately 5 times the MRHDID showed decreased pup weight. Maternal toxicity was seen at inhaled doses equal to 0.2 mg/kg/day or higher. An embryo-fetal development study of inhaled doses approximately 20 times the MRHDID during organogenesis (gestation days 6 to 19) show not structural alteration, but another study during organogenesis (gestation days 6 to 19) at doses approximately 1400 times the MRHDID showed increased incidences of additional liver lobes, with decreased fetal weights seen at approximately 2300 times the MRHDID. Fetal findings were seen in the presence of maternal toxicity.

Formoterol:
-An animal fertility and reproduction study using oral formoterol dosed male rats for 9 weeks and female rats for 2 weeks prior to pairing and throughout mating, with female dosing continuing up to gestation day 19 or until offspring were weaned and males dose for up to 25 weeks showed umbilical hernias in the fetuses at 1200 times the MRHDID and up; brachygnathia and abnormal mandible shortness were seen at 6000 times the MRHDID as well as prolonged pregnancy; fetal and pup death occurred at about 1200 times the MRHDID and higher during gestation.
-An embryofetal study at doses up to 280 times the MRHDID during organogenesis (gestation days 6 to 15) was not teratogenic or embryocidal, and no developmental effects were seen.
-An embryofetal study at doses up to 2800 times the MRHDID during organogenesis (gestation days 6 to 18) showed not teratogenic effects, but at 49,000 times the MRHDID subcapsular cysts on the liver of the fetuses were seen.
-A pre- and post-natal study of oral doses administered from gestation through lactation showed decreased pup survival at 85 times the MRHDID and higher; no treatment-related effects were seen on the physical, functional or behavioral development.

AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned

Comments:
-Animal studies of aclidinium bromide at inhaled doses 15 to 20 times the maximum recommended human daily inhaled dose (MRHDID) during organogenesis did not show adverse developmental effects, but reduced pup weights were seen at 5 times the MRHDID; adverse developmental effects were seen at about 1400 times the MRHDID.
-Animal studies of oral formoterol showed teratogenicity at 1200 to 49,000 times the MRHDID; 85 times the MRHDID was embryocidal, increased pup loss at birth and during lactation, and decreased pup weight.
-Animals studies of inhaled formoterol at up to 280 times the MRHDID was not embryocidal, teratogenic, and no developmental effects were seen.
-Since beta-agonists can interfere with uterine contractility, use during labor only if benefits clearly outweigh risks.

See references

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Unknown
Excreted into animal milk: Yes (aclidinium, formoterol)

Comments:
-There is no information regarding this drug on the presence in human milk, the effects on a breastfed infant, or effects on milk production.
-Because both drugs are found in animal milk, they are likely to be present in human milk.
-Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for this medication as well as any potential adverse effects from this drug or the underlying maternal condition.

Animals administered 1 mg/kg radiolabeled aclidinium bromide intravenously on approximately post-natal day 14 showed maximum milk concentrations of radioactivity 6 hours post dose at concentrations 10 to 14 times higher than in plasma.
Plasma levels of formoterol measured on post-natal day 15 estimated 4.4% of the maternal dose of 15 mg/kg reached the pups.

See references