BEVESPI AEROSPHERE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BEVESPI AEROSPHERE (BEVESPI AEROSPHERE).
BEVESPI AEROSPHERE is a combination of glycopyrrolate, a long-acting muscarinic antagonist (LAMA), and formoterol fumarate, a long-acting beta2-adrenergic agonist (LABA). Glycopyrrolate inhibits acetylcholine at M3 muscarinic receptors in bronchial smooth muscle, leading to bronchodilation. Formoterol stimulates beta2-adrenergic receptors, increasing cyclic AMP and relaxing bronchial smooth muscle.
| Metabolism | Glycopyrrolate: primarily metabolized by CYP2D6 and CYP3A4; formoterol: metabolized by direct glucuronidation and O-demethylation via CYP2D6 and CYP2C19. |
| Excretion | Renal: 15% to 30% as unchanged drug after intravenous administration for glycopyrrolate; fecal: 65% to 80% as unchanged drug after oral administration for glycopyrrolate. For formoterol, renal: 10% to 20% as unchanged drug; bile/fecal: 60% to 70%. |
| Half-life | Glycopyrrolate: terminal elimination half-life 3.2 to 4.1 hours after inhalation; formoterol: terminal elimination half-life approximately 10 hours after inhalation. Context: Steady-state achieved within 2 to 3 days. |
| Protein binding | Glycopyrrolate: 45% to 55% bound to plasma proteins (albumin); formoterol: 40% to 50% bound to albumin. |
| Volume of Distribution | Glycopyrrolate: Vd approximately 1.3 L/kg after intravenous administration, indicating extensive tissue distribution. Formoterol: Vd approximately 3.5 L/kg after inhalation, suggesting wide distribution. |
| Bioavailability | Inhalation: Glycopyrrolate absolute bioavailability 10-15%; formoterol absolute bioavailability 10-20%. |
| Onset of Action | Inhalation: Improvement in FEV1 observed within 5 minutes, with peak effect at 1-2 hours. |
| Duration of Action | Inhalation: Duration of bronchodilation 12 hours, supporting twice-daily dosing. |
Two inhalations (glycopyrrolate 18 mcg / formoterol fumarate 9.6 mcg per inhalation) twice daily, administered orally via inhalation.
| Dosage form | AEROSOL, METERED |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min; contraindicated in severe renal impairment (GFR <30 mL/min). |
| Liver impairment | No dose adjustment required for Child-Pugh A or B; insufficient data for Child-Pugh C, use with caution. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established in individuals under 18 years of age. |
| Geriatric use | No dose adjustment based solely on age; monitor for anticholinergic effects (e.g., urinary retention) and formoterol-related cardiovascular effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BEVESPI AEROSPHERE (BEVESPI AEROSPHERE).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. Both glycopyrrolate and formoterol are expected to be excreted into milk. Caution advised; consider developmental and health benefits of breastfeeding alongside maternal need for drug. |
| Teratogenic Risk | FDA Pregnancy Category C. No adequate and well-controlled studies in pregnant women. In animal studies, glycopyrrolate (anticholinergic) showed no teratogenicity at exposures 10x MRHDID; formoterol (beta-agonist) caused fetal harm (delayed ossification, increased resorptions) at maternal toxic doses. Risk cannot be ruled out; use only if benefit justifies potential risk. |
■ FDA Black Box Warning
LABA use increases the risk of asthma-related death. BEVESPI AEROSPHERE is not indicated for asthma.
| Serious Effects |
["Hypersensitivity to glycopyrrolate, formoterol, or any component of the product"]
| Precautions | ["Not for acute bronchospasm or as rescue therapy","Paradoxical bronchospasm","Cardiovascular effects (tachycardia, arrhythmia, hypertension)","Worsening of narrow-angle glaucoma","Worsening of urinary retention","Hypokalemia and hyperglycemia associated with beta2-agonists"] |
| Food/Dietary | No significant food interactions reported. Avoid grapefruit juice as it may increase systemic exposure of formoterol? (Lack of specific data; theoretical risk with CYP3A4 inhibition). No dietary restrictions. |
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| Fetal Monitoring | Monitor maternal respiratory status (lung function, exacerbations). Monitor fetal growth and well-being via ultrasound if prolonged use. Assess for signs of preterm labor or uterine contractions given beta-agonist activity of formoterol. |
| Fertility Effects | No human data on fertility. Animal studies: glycopyrrolate had no adverse fertility effects; formoterol decreased fertility in rats at high doses (maternal toxicity). Effect on human fertility unknown. |
| Clinical Pearls | Bevespi Aerosphere (glycopyrrolate/formoterol fumarate) is a fixed-dose combination LAMA/LABA for maintenance treatment of COPD. Not indicated for asthma or acute bronchospasm. Use with caution in patients with narrow-angle glaucoma, urinary retention, or severe cardiovascular disorders. The propellant HFA-134a may cause bronchospasm in hypersensitive patients. Instruct patients not to use more than 2 inhalations twice daily. |
| Patient Advice | Use exactly as prescribed: 2 inhalations twice daily (morning and evening). · Do not use for sudden breathing problems; have a rescue inhaler available. · Prime the inhaler before first use or if not used for more than 7 days. · Rinse mouth with water after each dose to reduce risk of oral thrush. · Seek medical attention immediately if symptoms of narrow-angle glaucoma (eye pain, blurred vision) or urinary retention (difficulty urinating) occur. · Store at room temperature (20-25°C); avoid exposure to extreme heat or cold. |