Benefit should outweigh risk

AU TGA pregnancy category: A (inhalation); B3 (oral)
US FDA pregnancy category: Not assigned

Comments:
-The possibility of fetal ham with inhaled corticosteroids appears remote; but data are insufficient with oral and rectal administration to inform a drug-associated risk for major birth defects and miscarriage.
-Hypoadrenalism may occur in neonates exposed to glucocorticosteroids in utero; carefully observe neonates for signs and symptoms of hypoadrenalism.

Teratogenicity and embryocidal effects have been observed in rabbits and rats administered subcutaneous doses that represent 0.05 and 0.5 times the maximum recommended human doses, respectively. These effects have been reported as increased fetal loss, decreased pup weights, and skeletal abnormalities. Higher doses administered by inhalation to rats have not shown to be teratogenic. Experience with oral corticosteroids at pharmacologic doses suggests rodents are more prone to teratogenic effect than humans.

Results from a large population-based prospective cohort epidemiological study reviewing data from 3 Swedish registries covering approximately 99% of the pregnancies from 1995-1997 indicate no increased risk for congenital malformations from the use of inhaled drug during early pregnancy. These same data were used in a second study bringing the total to 2,534 infants whose mothers were exposed to inhaled budesonide. In this study, the rate of congenital malformations among infants whose mother were exposed to inhaled budesonide during early pregnancy was not different from the rate for all newborn babies during the same period (3.6%).

There are few data on pregnancy outcomes after oral or rectal administration in humans. The maximal concentration of budesonide in plasma is expected to be higher with oral compared to inhaled use. Prolonged or repeated exposure may increase the risk of intra-uterine growth retardation. When considering use, risk benefit analysis should take into consideration disease-associated maternal and/or embryo/fetal risks. Inhaled glucocorticosteroids offer lower systemic effects compared to oral glucocorticosteroids and achieve similar pulmonary responses. There are no adequate and well controlled studies in pregnant women. 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%.


AU TGA pregnancy category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed.

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.

See references

Most experts consider inhaled corticosteroids acceptable during breastfeeding as the presence in breast milk is expected to be low and infant exposure negligible. A fully breastfed infant is expected to receive a maximum 0.3% to 1% of the weight-adjusted maternal dosage; a milk to plasma ratio between 0.4 and 0.5. Drug levels have not been detected in breastfed infants following maternal use of the inhaled drug. Oral drug at the recommended daily dose is expected to produce plasma concentrations up to 10 times higher than the inhaled drug. Due to lack of specific data with the oral or rectal formulations, some manufacturers recommend therapy be avoided.

The manufacturer makes no recommendation regarding use during lactation.

Excreted into human milk: Yes

Comment:
-The breastfed infant is exposed to approximately 0.3 to 1% of the dose received via a dry powder inhaler by the patient.
-Extrapolating from inhaled drug exposure, data suggest therapeutic oral doses could expose a breastfeeding infant to drug levels 10 times higher than those from inhalation.
-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.

See references