Beviprex

Glycopyrronium Bromide + Formoterol Fumarate is a combination bronchodilator used for the maintenance treatment of chronic obstructive pulmonary disease (COPD) and certain asthma patients who require dual therapy.

Approved Indications:

• Maintenance treatment of moderate to severe COPD, including chronic bronchitis and emphysema, to improve lung function and reduce exacerbations.
• Long-term management of persistent asthma in adults inadequately controlled with inhaled corticosteroids plus a single long-acting bronchodilator.

Clinically Accepted Off-Label Uses:

• Symptomatic relief in patients with overlap COPD-asthma syndrome (ACO).
• Adjunct therapy to reduce rescue medication use in patients with frequent exacerbations.

Adults (≥18 years):

• Dose: 1 inhalation twice daily (morning and evening).
• Maximum daily dose: 2 inhalations.
• Administer via dry powder inhaler or pressurized metered-dose inhaler depending on formulation.

Elderly:

• Same as adult dose; monitor for anticholinergic and cardiovascular side effects.

Pediatrics (<18 years):

• Safety and efficacy not established; use only if specifically recommended by a specialist.

Special Populations:

• Renal Impairment: No dose adjustment required; caution in severe impairment.
• Hepatic Impairment: No dose adjustment for mild to moderate; caution in severe impairment.

Administration Notes:

• Instruct patient on proper inhaler technique.
• Rinse mouth after inhalation to reduce risk of oral thrush if co-administered with corticosteroids.
• Do not use for acute bronchospasm; rescue inhaler required.

• Glycopyrronium Bromide: A long-acting muscarinic antagonist (LAMA) that competitively inhibits acetylcholine at M3 receptors in bronchial smooth muscle, reducing bronchoconstriction and airway resistance.
• Formoterol Fumarate: A long-acting β2-adrenergic agonist (LABA) that stimulates β2-receptors in bronchial smooth muscle, causing smooth muscle relaxation and bronchodilation.
• Combination Effect: The dual mechanism results in enhanced bronchodilation, improved airflow, reduced hyperinflation, and better symptom control compared to either component alone.

Glycopyrronium Bromide:

• Absorption: Rapidly absorbed; systemic bioavailability ~10–15% after inhalation.
• Distribution: Low plasma protein binding; volume of distribution 20–30 L.
• Metabolism: Minimal hepatic metabolism; primarily unchanged.
• Elimination: Renal excretion (~50%) and fecal elimination.
• Half-life: ~33–57 hours (bronchodilatory effect sustained due to receptor binding).

Formoterol Fumarate:

• Absorption: Rapid after inhalation; systemic bioavailability 20–30%.
• Distribution: Plasma protein binding 61–64%; volume of distribution 4.8 L/kg.
• Metabolism: Hepatic via CYP2D6 and CYP2C19; forms inactive metabolites.
• Elimination: Urine and feces (~50% renal).
• Half-life: ~10 hours; onset of action within 1–3 minutes, peak at 1–2 hours.

• Pregnancy: Category C — animal studies show no teratogenic effects, but human data are limited. Use only if benefits outweigh risks.
• Lactation: Both drugs are excreted in small amounts in breast milk; caution advised. Monitor infant for anticholinergic or β2-agonist effects.
• Note: Avoid high-dose or prolonged therapy in pregnancy and lactation.

• Primary Class: Combination bronchodilator
• Subclasses:
• Glycopyrronium Bromide: Long-acting muscarinic antagonist (LAMA)
• Formoterol Fumarate: Long-acting β2-adrenergic agonist (LABA)

• Known hypersensitivity to glycopyrronium, formoterol, or excipients.
• Acute bronchospasm (rescue therapy required).
• Severe hypersensitivity to other anticholinergic or β2-agonist drugs.
• Cardiovascular conditions prone to tachyarrhythmia or ischemia may require caution.

• High-risk patients:
• Cardiovascular disease (arrhythmias, ischemic heart disease) — monitor heart rate and ECG.
• Glaucoma or urinary retention — glycopyrronium may exacerbate.
• Serious risks:
• Paradoxical bronchospasm (rare).
• Hypokalemia and hyperglycemia (formoterol).
• Monitoring:
• Pulmonary function, blood pressure, heart rate, and potassium levels in high-risk patients.
• Early signs: Chest pain, palpitations, severe shortness of breath — require immediate medical attention.

Common:

• Dry mouth, throat irritation
• Cough, nasopharyngitis
• Headache
• Tremor or palpitations

Serious/Rare:

• Paradoxical bronchospasm
• Angina, arrhythmias
• Urinary retention
• Glaucoma exacerbation
• Hypokalemia, hyperglycemia

Onset & Dose Dependence: Usually mild; LABA effects dose-related and may increase with concomitant β-agonist use.

• Drug-Drug:
• Other β-agonists or anticholinergics — additive effects.
• MAO inhibitors or tricyclic antidepressants — increased cardiovascular risk.
• CYP2D6 or CYP2C19 inhibitors — may increase formoterol levels.
• Drug-Food: No significant interactions.
• Drug-Alcohol: No significant interaction, but alcohol may exacerbate CNS effects.
• Enzyme Systems: Formoterol metabolized by CYP2D6/CYP2C19; glycopyrronium minimally metabolized.

• Recommended as maintenance therapy for moderate to severe COPD in GOLD guidelines.
• LABA/LAMA combinations preferred over monotherapy in patients with persistent symptoms or frequent exacerbations.
• Short-acting rescue inhalers remain necessary for acute bronchospasm.
• Emphasis on correct inhaler technique to optimize therapeutic effect.

• Store at 20°C–25°C (room temperature).
• Protect from moisture, light, and heat.
• Keep inhaler tightly closed when not in use.
• Do not freeze.
• Keep out of reach of children.