Introduction
Levalbuterol is the (R)-enantiomer of the racemic albuterol mixture, representing the pharmacologically active component. It is a selective short-acting beta₂-adrenergic receptor agonist (SABA) used primarily for the treatment and prevention of bronchospasm in patients with reversible obstructive airway disease. As the purified isomer, levalbuterol offers a potentially improved therapeutic profile compared to racemic albuterol, with reduced beta₁-mediated side effects.
Mechanism of Action
Levalbuterol exerts its therapeutic effects by selectively binding to and activating beta₂-adrenergic receptors on bronchial smooth muscle. This activation stimulates adenylate cyclase, increasing intracellular cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP promotes smooth muscle relaxation through protein kinase A-mediated phosphorylation of various proteins, resulting in bronchodilation. The drug also inhibits the release of mast cell mediators such as histamine and leukotrienes, providing additional bronchoprotective effects.
Indications
- Treatment and prevention of bronchospasm in patients with reversible obstructive airway disease (e.g., asthma)
- Exercise-induced bronchospasm prevention
- FDA-approved for use in adults and children 4 years of age and older
Dosage and Administration
Inhalation Solution (0.31 mg, 0.63 mg, 1.25 mg in 3 mL vial):- Adults and adolescents ≥12 years: 0.63 mg administered three times daily by nebulization, every 6-8 hours
- Maximum dose: 1.25 mg three times daily
- Children 6-11 years: 0.31 mg administered three times daily by nebulization
- Children 4-5 years: 0.31 mg administered three times daily by nebulization
- Hepatic impairment: Use with caution; consider dose reduction
- Renal impairment: No specific dosage adjustment recommended
- Geriatric patients: Initiate at lower end of dosing range
- Pregnancy: Category C; use only if potential benefit justifies potential risk
Pharmacokinetics
Absorption: Rapidly absorbed following inhalation; onset of action within 5-15 minutes Distribution: Moderate plasma protein binding (55-65%); distributes minimally to tissues Metabolism: Extensively metabolized in the liver via sulfation and cytochrome P450 metabolism Elimination: Primarily excreted in urine (70-90%) as metabolites; elimination half-life approximately 3.3-4 hoursContraindications
- Hypersensitivity to levalbuterol, albuterol, or any component of the formulation
- History of hypersensitivity reactions to sympathomimetic amines
Warnings and Precautions
- Paradoxical bronchospasm: Can occur; discontinue immediately if occurs
- Cardiovascular effects: May cause significant blood pressure increases, tachycardia, and palpitations
- Hypokalemia: May occur due to intracellular shifting of potassium
- Hyperglycemia: May increase blood glucose levels
- Asthma exacerbations: Not recommended as first-line treatment for status asthmaticus
- Coexisting conditions: Use with extreme caution in patients with cardiovascular disorders, diabetes, hyperthyroidism, or seizure disorders
Drug Interactions
- Beta-blockers: May antagonize bronchodilating effects (non-selective beta-blockers particularly)
- Diuretics: Enhanced risk of hypokalemia with non-potassium-sparing diuretics
- Digoxin: Increased risk of hypokalemia-induced digoxin toxicity
- MAO inhibitors and tricyclic antidepressants: May potentiate cardiovascular effects
- Other sympathomimetic agents: Additive cardiovascular effects
Adverse Effects
Common (≥5%):- Nervousness (8-12%)
- Tremor (5-9%)
- Headache (6-8%)
- Tachycardia (5-7%)
- Pharyngitis (5-6%)
- Angina pectoris
- Cardiac arrhythmias
- Hypertension
- Hypokalemia
- Paradoxical bronchospasm
- Anaphylaxis
Monitoring Parameters
- Pulmonary function tests (FEV₁, peak flow)
- Heart rate and rhythm
- Blood pressure
- Serum potassium levels (especially with frequent dosing)
- Blood glucose in diabetic patients
- Clinical signs of bronchospasm
- Therapeutic response and symptom control
Patient Education
- Use exactly as prescribed; do not exceed recommended dosage
- Understand proper nebulizer technique
- Recognize signs of worsening asthma requiring medical attention
- Rinse mouth after inhalation to reduce systemic absorption
- Report palpitations, chest pain, or nervousness
- Keep regular follow-up appointments with healthcare provider
- Have a rescue inhaler available at all times
- Understand difference between maintenance and rescue medications
- Do not use with other inhaled medications without healthcare provider approval
References
1. 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. 2. Milgrom H, Skoner DP, Bensch G, et al. Low-dose levalbuterol in children with asthma: safety and efficacy in comparison with placebo and racemic albuterol. J Allergy Clin Immunol. 2001;108(6):938-945. 3. FDA Prescribing Information: Xopenex® (levalbuterol HCl) Inhalation Solution. 4. Global Initiative for Asthma (GINA). Global Strategy for Asthma Management and Prevention, 2023. 5. 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. 6. Drug Facts and Comparisons. Facts & Comparisons [database online]. St. Louis, MO: Wolters Kluwer Health; 2023.