Aroneb

Approved Medical Indications:

• Long-term maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

Clinically Accepted (Off-label) Use:

• Severe persistent asthma (off-label, only when combined with inhaled corticosteroids and other controller medications in adults; not first-line therapy).

Note: Arformoterol is not indicated for the relief of acute bronchospasm or rescue therapy.

Adults (including elderly) – COPD:

• 15 mcg twice daily (every 12 hours) via nebulization.
• Maximum recommended dose: 30 mcg per day.
• Administer with a standard jet nebulizer connected to an air compressor capable of delivering a fine mist.

Pediatric Use:

• Not recommended; safety and efficacy in patients under 18 years of age have not been established.

Renal Impairment:

• No specific dose adjustment recommended; use with caution in severe renal impairment due to limited data.

Hepatic Impairment:

• No formal dose adjustment; exercise caution as hepatic clearance data are limited.

Administration Guidance:

• Do not mix with other drugs in the nebulizer.
• Administer at the same time each day.
• Patients should continue treatment even if symptoms improve, as this is a maintenance therapy.

Arformoterol is the (R,R)-enantiomer of formoterol, and it acts as a highly selective long-acting β2-adrenergic receptor agonist (LABA). Upon inhalation, it binds to β2-adrenergic receptors in airway smooth muscle, activating adenylate cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP relaxes bronchial smooth muscle, producing sustained bronchodilation. This action helps improve airflow and reduce airway resistance in COPD patients. The selectivity for β2 receptors reduces β1-mediated cardiac effects, although high doses may still influence cardiovascular parameters.

• Absorption: Rapid onset; peak plasma concentrations achieved within 30 minutes after inhalation.
• Bioavailability: Low oral bioavailability due to extensive first-pass metabolism; therapeutic effects occur locally in the lungs.
• Distribution: Moderate plasma protein binding (~52–65%); wide tissue distribution.
• Metabolism: Primarily metabolized via glucuronidation and sulfation; minor metabolism via CYP2D6 and CYP2C19.
• Elimination: Mostly excreted in urine (approximately 67%) and feces (22%).
• Half-life: Elimination half-life is approximately 26 hours, supporting twice-daily dosing.

• Pregnancy: FDA no longer uses traditional letter categories. Animal studies show no teratogenic effects, but use only if clearly needed during pregnancy. Limited human data available.
• Lactation: Unknown whether arformoterol is excreted in human breast milk. Due to potential for β2-agonist effects in nursing infants, caution is advised. Consider the risk-benefit ratio before prescribing.
• Recommendation: Avoid in pregnancy and lactation unless benefits outweigh risks. Monitor closely if use is necessary.

• Pharmacologic Class: Long-acting β2-adrenergic receptor agonist (LABA)
• Therapeutic Class: Bronchodilator (Respiratory Agent)
• Drug Category: Sympathomimetic agent for maintenance treatment of airway obstruction

• Known hypersensitivity to arformoterol, formoterol, or any component of the formulation
• Use as monotherapy in asthma
• Primary treatment of acute episodes of bronchospasm
• History of life-threatening arrhythmias or severe cardiovascular instability

• Asthma-Related Death: LABAs have been associated with an increased risk of asthma-related death; should not be used alone for asthma.
• Paradoxical Bronchospasm: May occur after initial dosing; discontinue immediately if suspected.
• Cardiovascular Effects: Use cautiously in patients with arrhythmias, coronary insufficiency, hypertension, or other heart diseases.
• Hypokalemia: LABAs may lower serum potassium; monitor in patients receiving diuretics or with renal disease.
• Hyperglycemia: Use with caution in diabetic patients.
• Seizure Risk: β2-agonists may exacerbate seizure disorders.
• Overuse: Do not exceed recommended dose; excessive use can lead to serious adverse cardiac or respiratory events.

Common (≥1%):

• Nervous system: Headache, tremor, dizziness
• Respiratory: Cough, throat irritation, nasopharyngitis
• Cardiovascular: Palpitations, tachycardia
• Gastrointestinal: Nausea, vomiting

Less Common/Rare:

• Chest pain, muscle cramps, back pain
• QT interval prolongation
• Hypokalemia
• Hyperglycemia

Serious/Severe:

• Paradoxical bronchospasm
• Severe arrhythmias (e.g., ventricular tachycardia)
• Hypersensitivity reactions (angioedema, rash)
• Seizures

Note: Severity may be dose-dependent; side effects typically emerge within hours of dosing.

• Other β2-agonists: Increased risk of additive side effects (e.g., tachycardia, tremor).
• MAO Inhibitors/Tricyclic Antidepressants: May potentiate sympathomimetic effects—use cautiously or avoid.
• Beta-blockers: May inhibit therapeutic effects; cardioselective agents may be used with caution.
• Non-potassium-sparing diuretics: Risk of enhanced hypokalemia.
• CYP2D6 Inhibitors: Minor interaction risk; monitor if co-administered with strong inhibitors (e.g., quinidine, fluoxetine).

• FDA Safety Update: Emphasizes that LABAs should not be used alone in asthma due to increased mortality risk. Combination with ICS is mandatory in asthma cases.
• GOLD 2024 COPD Guidelines: Arformoterol is recommended as part of long-term maintenance therapy for moderate-to-severe COPD, often in combination with inhaled anticholinergics or corticosteroids.
• EMA Guidance: Reinforces the limitation of LABA monotherapy to COPD, with specific warnings against off-label monotherapy in asthma.

• Refrigeration Required: Store in a refrigerator at 2°C to 8°C (36°F to 46°F).
• Room Temperature Use: May be stored at 20°C to 25°C for up to 6 weeks. Discard if not used within this period.
• Do Not Freeze: Freezing degrades formulation.
• Protection: Protect from light and moisture.
• Handling: Vials are for single use only; discard any unused solution after opening.