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Budesonide / formoterol / glycopyrrolate Pregnancy and Breastfeeding Warnings

Budesonide / formoterol / glycopyrrolate is also known as: Breztri Aerosphere

Medically reviewed by Drugs.com. Last updated on Sep 14, 2020.

Budesonide / formoterol / glycopyrrolate Pregnancy Warnings

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%.

Budesonide alone:
Human data do not show increases in abnormalities when used during pregnancy. A large population-based prospective cohort from 3 Swedish registries showed no increased risk for congenital malformations with use of inhaled drug during early pregnancy. A 2014 study of inhaled budesonide for asthma in early pregnancy (usually 10 to 12 weeks after last menstrual period - when most major organ malformations occur) showed congenital malformations at a similar rate to the general population (3.8% vs. 3.5% respectively) and infants with orofacial clefts was similar to the normal population.
Animal data of subcutaneous administration to both males and females prior to mating and throughout the mating period and up to weaning showed a decrease in prenatal viability and viability of offspring at birth and during lactation and decreased maternal body weight gain at doses 0.3 times the maximum recommended human daily inhaled dose (MRHDID); no such effects were seen at 0.08 times the MRHDID. In an embryofetal study (gestation days 6 to 15/during organogenesis) of subcutaneous administration fetal loss, decreased fetal weight, and skeletal abnormalities occurred at 0.75 times the MRHDID with similar results seen in another study at 8 times the MRHDID. Another animal study showed no structural abnormalities or embryocidal effect at up to 4 times the MRHDID. A peri- and post-natal development study (gestation day 15 to postpartum day 21) showed no effects on delivery, but reduced offspring survival and decreased mean body weight at birth and during lactation in survivors, with effects seen in the presence of maternal toxicity.

Formoterol Fumarate alone:
An animal fertility and reproduction study of oral dosing of male and female rates prior to pairing and throughout the mating period, with drug stopped in females either at gestation day 19 or weaning, showed umbilical hernias at 1500 times the MRHDID, prolonged pregnancy at 8000 times the MRHDID, and fetal and pup death at doses 1500 times the MRHDID and higher. An embryofetal development study (dosed during gestation days 6 to 15/organogenesis) showed no structural abnormalities, embryocidal effects, or developmental effects at up to 350 times the MRHDID. Another embryofetal development study (dosed during gestation days 6 to 18/organogenesis) showed subcapsular cysts on fetal livers at 61,000 times the MRHDID, but no teratogenicity at up to 3500 times the MRHDID. A pre- and post-partum study (gestation day 6 to lactation) showed decreased pup survival (birth to postpartum day 26) at 110 times the MRHDID or higher, although there was no evidence of a dose-response relationship, but no treatment related effects on pup physical, functional , or behavioral development.

Glycopyrrolate alone:
An animal of subcutaneous administration did not show structural abnormalities or affect fetal survival at approximately 2700 and 5400 times the MRHDID respectively. No effects on physical, functional, or behavioral development was seen at up to 2700 times the MRHDID.


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.

The manufacturer makes no recommendation regarding use during pregnancy.

US FDA pregnancy category: Not assigned

Comments:
-There is no data on use in pregnant women to know this drugs risks, including the risk of fetal harm or reproductive effects.
-Animal studies of budesonide alone via the subcutaneous route showed structural abnormalities, was embryocidal, and reduced fetal weights at 0.3 and 0.75 times the maximum recommended human daily inhaled dose (MRHDID) respectively in rats and rabbits, but these effects were not seen in rats at inhaled doses up to 4 times the MRHDID; experience with oral corticosteroids suggests rodents are more sensitive to corticosteroid teratogenicity than humans.
-Human studies of inhaled budesonide alone during pregnancy have not shown increased abnormalities.
-Animal studies of oral formoterol fumarate alone showed structural abnormalities at 1500 and 61,000 times the MRHDID in rats and rabbits respectively; it was embryocidal increased pup loss at birth and during lactation, and decreased pup weight at 110 times the MRHDID; effects generally occurred at large multiples of the MRHDID given orally for high systemic exposure.
-Animal studies of inhaled formoterol fumarate alone did not show structural abnormalities or developmental effects and was not embryocidal at up to 350 times the MRHDID.
-Animal studies of subcutaneous glycopyrrolate alone did not show structural abnormalities or affect fetal survival at 2700 and 5400 times the MRHDID; no effects on physical, functional, or behavioral development was seen at up to 2700 times the MRHDID.
-Because of the potential for beta-agonist interference with uterine contractility, use during labor only if benefits clearly outweigh risks.

See references

Budesonide / formoterol / glycopyrrolate Breastfeeding Warnings

The manufacturer makes no recommendation regarding use during lactation.

Excreted into human milk: Yes (budesonide)/Data not available (formoterol, glycopyrrolate)
Excreted into animal milk: Yes (formoterol, glycopyrrolate)

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.
-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.

Budesonide: Human data with this drug (via dry powder inhaler) indicated approximately 0.3 to 1% of the parental inhaled dose is available in breast milk.

Formoterol: Animal data estimated at the highest dose (15 mg/kg) nursing pups had a maximum plasma concentration of 4.4% (0.24 nmol/L for a litter vs. 5.5 nmol/L for the dam).

Glycopyrrolate: Animal data estimated at the highest dose (10 mg/kg/day) nursing pups had a maximum plasma concentration of 6% (9 ng/mL in pup plasma 1 hour after dosing vs. 1610 ng/mL in dam plasma 0.5 hour after dosing).

See references

References for pregnancy information

  1. "Product Information. Breztri Aerosphere (budesonide/formoterol/glycopyrrolate)." Astra-Zeneca Pharmaceuticals, Wilmington, DE.

References for breastfeeding information

  1. "Product Information. Breztri Aerosphere (budesonide/formoterol/glycopyrrolate)." Astra-Zeneca Pharmaceuticals, Wilmington, DE.

Further information

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