Usage
Arformoterol + Glycopyrrolate is prescribed for the long-term, twice-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is not indicated for relieving acute bronchospasm or treating asthma. Pharmacologically, this combination drug is classified as a bronchodilator, specifically a combination of a long-acting beta2-adrenergic agonist (LABA) and a long-acting muscarinic antagonist (LAMA). The mechanism of action involves relaxing the muscles around the airways in the lungs, which allows the airways to open, making breathing easier.
Alternate Names
The combination of Arformoterol and Glycopyrrolate is marketed under the brand name Bevespi Aerosphere.
How It Works
Pharmacodynamics: Arformoterol, a LABA, stimulates beta2-adrenergic receptors in the lungs, leading to smooth muscle relaxation and bronchodilation. Glycopyrrolate, a LAMA, blocks the action of acetylcholine at muscarinic receptors, further promoting bronchodilation by inhibiting bronchoconstriction. This dual mechanism provides additive bronchodilatory effects.
Pharmacokinetics: Arformoterol is rapidly absorbed after inhalation, reaching peak plasma concentrations within 5 to 15 minutes. It is metabolized primarily by direct conjugation and excreted via renal and fecal routes. Glycopyrrolate, being a quaternary ammonium compound, exhibits limited systemic absorption after inhalation, minimizing systemic anticholinergic side effects. It is eliminated primarily unchanged in the urine.
Mode of Action: Arformoterol binds to beta2-adrenergic receptors, activating adenylate cyclase, which increases intracellular cyclic AMP levels. This, in turn, leads to smooth muscle relaxation. Glycopyrrolate competitively blocks the binding of acetylcholine to muscarinic M3 receptors on airway smooth muscle, preventing bronchoconstriction.
Elimination Pathways: Arformoterol is eliminated through a combination of renal and hepatic pathways, including direct conjugation and metabolism. Glycopyrrolate, due to its limited systemic absorption, is primarily eliminated unchanged via renal excretion.
Dosage
Standard Dosage
Adults:
The standard dosage for adults is two inhalations (one puff from the inhaler equals one inhalation) twice daily, administered in the morning and evening. Each inhalation from Bevespi Aerosphere delivers 9 mcg of glycopyrrolate and 4.8 mcg of formoterol.
Children:
Use is not recommended for children.
Special Cases:
- Elderly Patients: No dosage adjustment based on age alone is explicitly recommended, however elderly patients might have increased sensitivity to some of the side effects of the medication.
- Patients with Renal Impairment: Dosage modifications might be necessary. Consult drug summary for specific recommendations.
- Patients with Hepatic Dysfunction: Clinical data on patients with hepatic impairment is limited. Dosage adjustment may be necessary. Careful monitoring of liver function and possible adverse events is recommended.
- Patients with Comorbid Conditions: Use with caution in patients with bladder problems, diabetes, enlarged prostate, narrow-angle glaucoma, heart or blood vessel disease, heart rhythm problems (e.g., arrhythmia, QT prolongation), hyperglycemia (high blood sugar), hypertension (high blood pressure), hypokalemia (low potassium in the blood), history of seizures, or thyroid problems.
Clinical Use Cases
This medication is not indicated for:
- Intubation
- Surgical Procedures
- Mechanical Ventilation
- Intensive Care Unit (ICU) Use
- Emergency Situations (e.g., status epilepticus, cardiac arrest)
It is strictly for the maintenance treatment of COPD.
Dosage Adjustments
Dose modifications should be considered based on patient-specific factors such as renal impairment, hepatic dysfunction, and concomitant medications. Consult the relevant drug information resources for detailed guidance on dose adjustments.
Side Effects
Common Side Effects
Common side effects include dry mouth, constipation, cough, headache, sore throat, tremors or shaking, and trouble sleeping.
Rare but Serious Side Effects
Rare but serious side effects include allergic reactions (skin rash, hives, swelling), heart rhythm changes (fast or irregular heartbeat), increased blood pressure, muscle pain or cramps, sudden eye pain or vision changes, difficulty urinating, and worsening wheezing or breathing difficulties after use.
Long-Term Effects
Potential long-term side effects with chronic use are not extensively documented.
Adverse Drug Reactions (ADR)
Clinically significant ADRs requiring immediate intervention include severe allergic reactions, paradoxical bronchospasm, and cardiovascular effects like tachycardia and QT interval prolongation.
Contraindications
Arformoterol + Glycopyrrolate is contraindicated in patients with hypersensitivity to glycopyrrolate, formoterol, or any components of the product. It is also contraindicated in patients with asthma who are not also taking an inhaled corticosteroid.
Drug Interactions
Arformoterol + Glycopyrrolate can interact with other medications, including anticholinergics (e.g., tiotropium, ipratropium), beta-blockers, some diuretics, and certain antidepressants. Concomitant use of other LABAs is not recommended. Consult a comprehensive drug interaction resource for detailed information.
Pregnancy and Breastfeeding
The safety of Arformoterol + Glycopyrrolate during pregnancy has not been established. Animal studies with formoterol suggest potential fetal harm at high doses. Data on glycopyrrolate are insufficient for pregnant women. Therefore, use during pregnancy should only be considered if the potential benefits outweigh the risks. It is unknown whether arformoterol or glycopyrrolate is excreted in human milk. Caution is recommended during breastfeeding. Consult individual drug information for arformoterol and glycopyrrolate.
Drug Profile Summary
- Mechanism of Action: Bronchodilation via beta2-adrenergic receptor agonism (arformoterol) and muscarinic receptor antagonism (glycopyrrolate).
- Side Effects: Common: Dry mouth, constipation. Serious: Allergic reactions, heart rhythm changes, worsening breathing problems.
- Contraindications: Hypersensitivity, asthma without concomitant inhaled corticosteroid.
- Drug Interactions: Anticholinergics, beta-blockers, some diuretics, antidepressants, other LABAs.
- Pregnancy & Breastfeeding: Use with caution. Limited safety data available.
- Dosage: Two inhalations twice daily.
- Monitoring Parameters: Lung function (FEV1), heart rate, blood pressure, adverse events.
Popular Combinations
Arformoterol + Glycopyrrolate is itself a combination product. It is not typically combined with additional bronchodilators. For patients requiring further treatment intensification, a combination of an ICS/LAMA/LABA such as Breztri Aerosphere might be considered.
Precautions
- General Precautions: Assess for allergies, pre-existing medical conditions (especially cardiovascular, respiratory, or metabolic disorders), and concomitant medications.
- Specific Populations:
- Pregnant Women: Limited safety data. Weigh benefits against risks.
- Breastfeeding Mothers: Potential for neonatal exposure. Caution advised.
- Children & Elderly: Not recommended for children. Elderly patients may have increased sensitivity.
FAQs (Frequently Asked Questions)
A: Two inhalations twice daily (morning and evening).
A: No, it is not indicated for asthma, particularly without concurrent inhaled corticosteroid therapy.
Q3: What are the most common side effects?
A: Dry mouth, constipation, cough, and headache.
Q4: What should patients do if they miss a dose?
A: Skip the missed dose and resume their regular dosing schedule. Do not double the dose.
Q5: Can patients with renal or hepatic impairment use this medication?
A: Use with caution. Dosage adjustments may be needed. Close monitoring is essential.
Q6: Can this medication be used with other LABAs?
A: No, concomitant use with other LABAs is generally not recommended due to increased risk of adverse events.
Q7: Are there any specific drug interactions to be aware of?
A: Yes, it can interact with other anticholinergic drugs, some beta-blockers, diuretics and certain antidepressants. Consult a comprehensive drug interaction resource.
A: Safety during pregnancy and breastfeeding has not been fully established. Use with caution if benefits outweigh risks. Consult specific drug information for arformoterol and glycopyrrolate.
A: It combines a LABA and a LAMA, offering dual bronchodilation in a single inhaler. Some other COPD inhalers might contain only a LABA, LAMA, or an ICS/LABA.
Q10: What monitoring parameters are important for patients on this medication?
A: Lung function (FEV1), heart rate, blood pressure, and monitoring for any adverse effects.
