Corticosteroids and beta2-agonists have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. In mouse reproduction assays, fluticasone propionate by the subcutaneous route at a dose approximately 3/5 the maximum recommended human daily inhalation dose (MRHDID) combined with oral salmeterol at a dose approximately 410 times the MRHDID produced cleft palate, fetal death, increased implantation loss, and delayed ossification. These observations are characteristic of glucocorticoids. No developmental toxicity was observed at combination doses of fluticasone propionate subcutaneously up to approximately 1/6 the MRHDID and doses of salmeterol up to approximately 55 times the MRHDID. In rats, combining fluticasone propionate subcutaneously at a dose equivalent to the MRHDID and a dose of salmeterol at approximately 810 times the MRHDID produced decreased fetal weight, umbilical hernia, delayed ossification, and changes in the occipital bone. These effects were not seen when combining fluticasone propionate subcutaneously at a dose less than the MRHDID and an oral dose of salmeterol at approximately 80 times the MRHDID. There are no controlled data in human pregnancy.

Fluticasone Propionate and Salmeterol:
The combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol during the period of organogenesis, in rats and mice were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. Omphalocele, increased embryofetal deaths, decreased body weight, and skeletal variations were observed in rat fetuses in the presence of maternal toxicity when combining fluticasone propionate at a dose approximately equivalent to the MRHDID and salmeterol at a dose approximately 970 times the MRHDID. Cleft palate, fetal death, increased implantation loss, and delayed ossification were observed in mouse fetuses when combining fluticasone propionate at a dose approximately 0.7 times the MRHDID and salmeterol at a dose approximately 490 times the MRHDID.

Salmeterol xinafoate crossed the placenta following oral administration to mice and rats.

Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits. It was not associated with decreases in pup body weight, and had no effects on developmental landmarks, learning, memory, reflexes, or fertility at doses up to 0.5 times the MRHDID.

Data Human Data:
Fluticasone Propionate: Following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery.

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 not be used during pregnancy unless the benefit outweighs the risk to the fetus.

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

Risk Summary:
-There are no randomized clinical studies of this combination drug or individual monoproducts in pregnant women.
-Disease-Associated Maternal and/or Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.

Comments:
-Patients should contact their physician if pregnancy occurs while taking this drug.
-If needed, the lowest effective dose of this drug should be used.
-Closely monitor pregnant patients and adjust medications to optimize asthma control.
-There are no human studies of the effects of this drug on labor and delivery.
-Beta-agonists may interfere with uterine contractility.

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 and any potential adverse effects on the breastfed child.

Excreted into human milk: Unknown (fluticasone-salmeterol)
Excreted into animal milk: Yes (fluticasone-salmeterol)

Comments: The effects in the nursing infant are unknown.

Fluticasone-salmeterol:
After inhaled therapeutic doses, plasma levels are low and therefore concentrations in human breast milk are likely to be correspondingly low.

Salmeterol:
Oral administration of salmeterol in lactating rats at 10,000 mcg/kg/day (approximately 973 times the MRHDID for adults) resulted in measurable levels in milk.

Fluticasone:
Subcutaneous administration of 10 mcg/kg/day to lactating rats of tritiated fluticasone propionate resulted in measurable radioactivity in the milk.

There are no controlled data on the use of this drug by nursing mothers.

See references