Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)
USE IN SPECIFIC POPULATIONS
- There are no randomized clinical studies of FLOVENT HFA in pregnant women. There are clinical considerations with the use of FLOVENT HFA in pregnant women. In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight, and/or skeletal variations in rats, mice, and rabbits were observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the maximum recommended human daily inhaled dose (MRHDID) on a mg/m2 basis. However, fluticasone propionate administered via inhalation to rats decreased fetal body weight, but did not induce teratogenicity at a maternal toxic dose approximately 0.5 times the MRHDID on a mg/m2 basis. Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans.
- The estimated risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
- 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.
- In embryofetal development studies with pregnant rats and mice dosed by the subcutaneous route throughout the period of organogenesis, fluticasone propionate was teratogenic in both species. Omphalocele, decreased body weight, and skeletal variations were observed in rat fetuses, in the presence of maternal toxicity, at a dose approximately 0.5 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 100 mcg/kg/day). The rat no observed adverse effect level (NOAEL) was observed at approximately 0.17 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 30 mcg/kg/day). Cleft palate and fetal skeletal variations were observed in mouse fetuses at a dose approximately 0.1 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 45 mcg/kg/day). The mouse NOAEL was observed with a dose approximately 0.04 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 15 mcg/kg/day).
- In an embryofetal development study with pregnant rats dosed by the inhalation route throughout the period of organogenesis, fluticasone propionate produced decreased fetal body weights and skeletal variations, in the presence of maternal toxicity, at a dose approximately 0.5 times the MRHDID (on a mg/m2 basis with a maternal inhalation dose of 91 mcg/kg/day); however, there was no evidence of teratogenicity. The NOAEL was observed with a dose approximately 0.13 times the MRHDID (on a mg/m2 basis with a maternal inhalation dose of 23 mcg/kg/day).
- In an embryofetal development study in pregnant rabbits that were dosed by the subcutaneous route throughout organogenesis, fluticasone propionate produced reductions of fetal body weights, in the presence of maternal toxicity, at doses approximately 0.006 times the MRHDID and higher (on a mg/m2 basis with a maternal subcutaneous dose of 0.57 mcg/kg/day).
- Teratogenicity was evident based upon a finding of cleft palate for 1 fetus at dose approximately 0.04 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 4 mcg/kg/day). The NOAEL was observed in rabbit fetuses with a dose approximately 0.001 times the MRHDID (on a mg/m2 basis with a maternal subcutaneous dose of 0.08 mcg/kg/day).
- Fluticasone propionate crossed the placenta following subcutaneous administration to mice and rats and oral administration to rabbits.
- In a pre- and post-natal development study in pregnant rats dosed from late gestation through delivery and lactation (Gestation Day 17 to Postpartum Day 22), fluticasone propionate 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 0.3 times the MRHDID (on a mg/m2 basis with maternal subcutaneous doses up to 50 mcg/kg/day).
- There are no available data on the presence of fluticasone propionate in human milk, the effects on the breastfed child, or the effects on milk production. Other corticosteroids have been detected in human milk. However, fluticasone propionate concentrations in plasma after inhaled therapeutic doses are low and therefore concentrations in human breast milk are likely to be correspondingly low. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for FLOVENT HFA and any potential adverse effects on the breastfed child from FLOVENT HFA or from the underlying maternal condition.
- Subcutaneous administration of tritiated fluticasone propionate at a dose in lactating rats approximately 0.05 times the MRHDID for adults (on a mg/m2 basis) resulted in measurable levels in milk.
- Infections and Infestations: Esophageal candidiasis
6 ADVERSE REACTIONS
6.2 Postmarketing Experience
- Gastrointestinal Disorders: Dental caries and tooth discoloration