risk to the fetus. Women should be advised to contact their physicians if they become pregnant while taking BEVESPI AEROSPHERE.
Glycopyrrolate: There was no evidence of teratogenic effects in rats and rabbits at approximately 18,000 and 270 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults (on a mg/m2 basis at a maternal oral dose of 65 mg/kg/day in rats and at a maternal intramuscular injection dose of 0.5 mg/kg in rabbits).
Single-dose studies in humans found that very small amounts of glycopyrrolate passed the placental barrier.
Formoterol Fumarate: Formoterol fumarate has been shown to be teratogenic, embryocidal, to increase pup loss at birth and during lactation, and to decrease pup weights in rats and teratogenic in rabbits. These effects were observed at approximately 1,500 (rats) and 61,000 (rabbits) times the MRHDID (on a mg/m2 basis at maternal oral doses of 3 mg/kg/day and above in rats and 60 mg/kg/day in rabbits). Umbilical hernia was observed in rat fetuses at approximately 1,500 times the MRHDID (on a mg/m2 basis at maternal oral doses of 3 mg/kg/day and above). Prolonged pregnancy and fetal brachygnathia was observed in rats at approximately 7600 times the MRHDID (on a mg/m2 basis at an oral maternal dose of 15 mg/kg/day in rats). In another study in rats, no teratogenic effects were seen at approximately 600 times the MRHDID (on a mg/m2 basis at maternal inhalation doses up to 1.2 mg/kg/day in rats).
Subcapsular cysts on the liver were observed in rabbit fetuses at an oral dose approximately 61,000 times the MRHDID (on a mg/m2 basis at a maternal oral dose of 60 mg/kg/day in rabbits). No teratogenic effects were observed at approximately 3600 times the MRHDID (on a mg/m2 basis at maternal oral doses up to 3.5 mg/kg/day).
8.2. Labor and Delivery
There are no well-controlled human trials that have investigated the effects of BEVESPI AEROSPHERE on preterm labor or labor at term. Because beta2-agonists may potentially interfere with uterine contractility, BEVESPI AEROSPHERE should be used during labor only if the potential benefit justifies the potential risk.
8.3. Nursing Mothers
It is not known whether BEVESPI AEROSPHERE is excreted in human milk. Because many drugs are excreted in human milk and because formoterol fumarate, one of the active ingredients in BEVESPI AEROSPHERE, has been detected in the milk of lactating rats, caution should be exercised when BEVESPI AEROSPHERE is administered to a nursing woman. Since there are no data from controlled trials on the use of BEVESPI AEROSPHERE by nursing mothers, a decision should be made whether to discontinue nursing or to discontinue BEVESPI AEROSPHERE, taking into account the importance of BEVESPI AEROSPHERE to the mother.
8.4. Pediatric Use
BEVESPI AEROSPHERE is not indicated for use in children. The safety and effectiveness of BEVESPI AEROSPHERE in the pediatric population have not been established.
8.5. Geriatric Use
Based on available data, no adjustment of the dosage of BEVESPI AEROSPHERE in geriatric patients is necessary, but greater sensitivity in some older individuals cannot be ruled out.
The confirmatory trials of BEVESPI AEROSPHERE for COPD included 1,680 subjects aged 65 and older and, of those, 290 subjects were aged 75 and older. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
8.6. Hepatic Impairment
Formal pharmacokinetic studies using BEVESPI AEROSPHERE have n |
