led albuterol use do notconsistently demonstrate a risk of major birth defects or miscarriage. There are clinical considerations with use ofalbuterol in pregnant women [see Clinical Considerations]. In animal reproduction studies, when albuterol sulfate wasadministered subcutaneously to pregnant mice there was evidence of cleft palate at less than and up to 9 times themaximum recommended human daily inhalation dose (MRHDID) [see Data].
The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In theU.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2to 4% and 15 to 20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryo/Fetal Risk
In women with poorly or moderately controlled asthma, there is an increased risk of preeclampsia in the mother andprematurity, low birth weight, and small for gestational age in the neonate. Pregnant women should be closely monitoredand medication adjusted as necessary to maintain optimal control.
Labor or Delivery
Because of the potential for beta-agonist interference with uterine contractility, use of ProAir Digihaler for relief ofbronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk. ProAirDigihaler has not been approved for the management of pre-term labor. Serious adverse reactions, including pulmonaryedema, have been reported during or following treatment of premature labor with beta2-agonists, including albuterol.
Data
Animal Data
In a mouse reproduction study, subcutaneously administered albuterol sulfate produced cleft palate formation in 5 of111 (4.5%) fetuses at an exposure nine-tenths the maximum recommended human dose (MRHDID) for adults (on amg/m2 basis at a maternal dose of 0.25 mg/kg) and in 10 of 108 (9.3%) fetuses at approximately 9 times the MRHDID (ona mg/m2 basis at a maternal dose of 2.5 mg/kg). Similar effects were not observed at approximately one-eleventh theMRHDID for adults (on a mg/m2 basis at a maternal dose of 0.025 mg/kg). Cleft palate also occurred in 22 of 72 (30.5%)fetuses from females treated subcutaneously with isoproterenol (positive control).
In a rabbit reproduction study, orally administered albuterol sulfate induced cranioschisis in 7 of 19 fetuses (37%) atapproximately 750 times the MRHDID (on a mg/m2 basis at a maternal dose of 50 mg/kg).
In a rat reproduction study, an albuterol sulfate/HFA-134a formulation administered by inhalation did not produce anyteratogenic effects at exposures approximately 80 times the MRHDID (on a mg/m2 basis at a maternal dose of 10.5mg/kg).
A study in which pregnant rats were dosed with radiolabeled albuterol sulfate demonstrated that drug-related material istransferred from the maternal circulation to the fetus.
8.2 Lactation
Risk Summary
There are no available data on the presence of albuterol in human milk, the effects on the breastfed child, or the effects onmilk production. However, plasma levels of albuterol after inhaled therapeutic doses are low in humans, and if present inbreast milk, albuterol has a low oral bioavailability [see Clinical Pharmacology (12.3)].
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need forProAir Digihaler and any potential adverse effects on the breastfed child from albuterol or from the underlying m |
