Introduction
Xopenex HFA (levalbuterol tartrate) is an inhaled short-acting beta₂-adrenergic agonist (SABA) used for the treatment and prevention of bronchospasm in patients with reversible obstructive airway disease. It is the (R)-enantiomer of racemic albuterol, formulated as a hydrofluoroalkane (HFA) metered-dose inhaler. This formulation provides bronchodilation with potentially reduced systemic beta-adrenergic effects compared to racemic albuterol.
Mechanism of Action
Levalbuterol selectively stimulates beta₂-adrenergic receptors in bronchial smooth muscle. This activation leads to the activation of adenylate cyclase, increasing intracellular cyclic AMP (cAMP) concentrations. Elevated cAMP levels result in relaxation of bronchial smooth muscle and inhibition of immediate hypersensitivity mediator release from mast cells. The (R)-enantiomer is responsible for the bronchodilatory effects, while the (S)-enantiomer (present in racemic albuterol) may contribute to pro-inflammatory effects and increased airway hyperresponsiveness.
Indications
Xopenex HFA is indicated for:
- Treatment or prevention of bronchospasm in patients 4 years of age and older with reversible obstructive airway disease
- Exercise-induced bronchospasm prophylaxis in patients 4 years of age and older
Dosage and Administration
Adults and adolescents 12 years and older:- 1-2 inhalations (45-90 mcg) every 4-6 hours as needed
- Maximum dose: 8 inhalations (360 mcg) per 24 hours
- 1 inhalation (45 mcg) every 4-6 hours as needed
- Maximum dose: 4 inhalations (180 mcg) per 24 hours
- Prime inhaler before first use or if not used for more than 3 days
- Shake well before each use
- Use spacer device if recommended by healthcare provider
- Rinse mouth after inhalation to minimize systemic absorption
- Hepatic impairment: Use with caution
- Renal impairment: Use with caution
- Geriatric patients: Start at lower end of dosing range
Pharmacokinetics
Absorption: Levalbuterol is rapidly absorbed following inhalation. Peak plasma concentrations occur within approximately 0.5-1 hour after inhalation. Distribution: The drug is approximately 55-65% plasma protein bound. The volume of distribution is approximately 180-200 L. Metabolism: Levalbuterol undergoes extensive presystemic metabolism in the gut wall and liver via conjugation with sulfate and glucuronide. The (R)-enantiomer is not interconverted to the (S)-enantiomer. Elimination: Primarily excreted in urine (60-70% of dose) as metabolites, with less than 5% excreted unchanged. Elimination half-life is approximately 3.3-4.0 hours.Contraindications
- Hypersensitivity to levalbuterol, albuterol, or any component of the formulation
- History of hypersensitivity reactions to milk proteins (contains lactose)
Warnings and Precautions
Paradoxical bronchospasm: Can occur with immediate worsening of breathing after dosing. Discontinue immediately and institute alternative therapy if this occurs. Cardiovascular effects: May cause significant increases in pulse rate, blood pressure, and ECG changes. Use with extreme caution in patients with cardiovascular disorders (coronary artery disease, arrhythmias, hypertension), and in patients unusually responsive to sympathomimetic amines. Hypokalemia: May decrease serum potassium levels through intracellular shifting. Use with caution in patients at risk for hypokalemia. Hyperglycemia: May increase blood glucose levels. Monitor diabetic patients carefully. Coexisting conditions: Use with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus. Asthma-related death: Long-acting beta₂-agonists may increase the risk of asthma-related death. Xopenex HFA should not be used for long-term control of asthma.Drug Interactions
Beta-blockers: May antagonize bronchodilator effects and produce severe bronchospasm (especially non-selective beta-blockers). Diuretics: Concomitant use may potentiate ECG changes and hypokalemia. Monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants: May potentiate cardiovascular effects. Other sympathomimetic agents: Additive cardiovascular effects may occur. Digoxin: May decrease serum digoxin concentrations; monitor levels. Corticosteroids, xanthine derivatives: May potentiate hypokalemic effects.Adverse Effects
Common (≥2%):- Nervousness (8-12%)
- Tremor (4-8%)
- Headache (6-8%)
- Tachycardia/palpitations (4-6%)
- Dizziness (2-4%)
- Pharyngitis (2-4%)
- Cough (2-4%)
- Paradoxical bronchospasm
- Angina pectoris
- Hypertension or hypotension
- Arrhythmias (including atrial fibrillation, supraventricular tachycardia, extrasystoles)
- Anaphylaxis
- Hypokalemia
- Hyperglycemia
Monitoring Parameters
- Pulmonary function (FEV₁, peak flow)
- Heart rate and rhythm
- Blood pressure
- Serum potassium levels (especially with high-dose or frequent use)
- Blood glucose in diabetic patients
- Signs of paradoxical bronchospasm
- Asthma symptoms and rescue medication use
- Inhaler technique assessment at each visit
Patient Education
Proper use:- Demonstrate and observe return demonstration of proper inhaler technique
- Prime inhaler before first use and if not used for more than 3 days
- Shake well before each use
- Wait at least 1 minute between inhalations
- Rinse mouth with water after each use to prevent oral candidiasis
- Use as needed for symptom relief, not on a regular schedule
- Do not exceed maximum daily dose
- Seek medical attention if symptoms worsen or if needing more frequent doses
- Store at room temperature (20-25°C/68-77°F)
- Do not puncture or incinerate
- Discard when counter reads "0" or after 200 actuations
- Report chest pain, rapid heartbeat, tremors, or worsening breathing
- Inform all healthcare providers of all medications being taken
- Keep all medical appointments for monitoring
References
1. Xopenex HFA [package insert]. Marlborough, MA: Sunovion Pharmaceuticals Inc; 2021. 2. Nelson HS, Bensch G, Pleskow WW, et al. Improved bronchodilation with levalbuterol compared with racemic albuterol in patients with asthma. J Allergy Clin Immunol. 1998;102(6):943-952. 3. Truitt T, Witko J, Halpern M. Levalbuterol compared to racemic albuterol: efficacy and outcomes in patients hospitalized with COPD or asthma. Chest. 2003;123(1):128-135. 4. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2023. 5. National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. NIH Publication No. 07-4051. Bethesda, MD: National Institutes of Health; 2007. 6. Kelly HW. Comparison of inhaled levalbuterol and racemic albuterol in patients with asthma. J Allergy Clin Immunol. 2003;111(2):277-283.