Levalbuterol

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Aerosol, Inhalation, as tartrate [strength expressed as base]:

Xopenex HFA: 45 mcg/actuation (15 g)

Generic: 45 mcg/actuation (15 g)

Nebulization Solution, Inhalation, as hydrochloride [strength expressed as base]:

Generic: 0.31 mg/3 mL (3 mL); 0.63 mg/3 mL (3 mL); 1.25 mg/3 mL (3 mL); 1.25 mg/0.5 mL (1 ea, 30 ea)

Nebulization Solution, Inhalation, as hydrochloride [strength expressed as base, preservative free]:

Xopenex: 0.31 mg/3 mL (3 mL); 0.63 mg/3 mL (3 mL); 1.25 mg/3 mL (3 mL)

Xopenex Concentrate: 1.25 mg/0.5 mL (1 ea, 30 ea)

Generic: 0.31 mg/3 mL (3 mL); 0.63 mg/3 mL (3 mL); 1.25 mg/3 mL (3 mL); 1.25 mg/0.5 mL (1 ea, 30 ea)

Pharmacology

Mechanism of Action

Relaxes bronchial smooth muscle by action on beta₂-receptors with little effect on heart rate

Pharmacokinetics/Pharmacodynamics

Absorption

A portion of inhaled dose is absorbed to systemic circulation

Metabolism

Metabolized primarily in the gastrointestinal tract via SULT1A3 (sulfotransferase)

Excretion

Urine (80% to 100%), feces (<20%)

Onset of Action

Measured as a 15% increase in FEV₁:

Metered-dose inhaler: 5.5 to 10.2 minutes; Peak effect: 76 to 78 minutes

Nebulization solution: 10 to 17 minutes; Peak effect: 1.5 hours

Time to Peak

Nebulization solution: Children: 0.3 to 0.6 hours, Adults: 0.2 hours

Duration of Action

Measured as a 15% increase in FEV₁:

Metered-dose inhaler: 3 to 4 hours (up to 6 hours in some patients)

Nebulization solution: 5 to 6 hours (up to 8 hours in some patients)

Half-Life Elimination

3.3 to 4 hours

Use in Specific Populations

Special Populations: Renal Function Impairment

Racemic albuterol clearance decreased by 67% in patients with creatinine clearance of 7 to 53 mL/minute.

Use: Labeled Indications

Bronchospasm: Treatment or prevention of bronchospasm in patients with reversible obstructive airway disease

Contraindications

Hypersensitivity to levalbuterol, albuterol, or any component of the formulation

Dosage and Administration

Dosing: Adult

Bronchospasm:

Metered-dose inhaler: 2 inhalations (90 mcg) every 4 to 6 hours as needed; in some patients, 1 inhalation (45 mcg) every 4 hours may be sufficient (maximum: 2 inhalations every 4 hours)

Nebulization solution: Initial: 0.63 mg 3 times daily at intervals of 6 to 8 hours; dosage may be increased to 1.25 mg 3 times daily with close monitoring for adverse effects (maximum: 1.25 mg 3 times daily)

Exacerbation of asthma (acute, severe) (off-label; NAEPP, 2007):

Metered-dose inhaler: 4 to 8 inhalations every 20 minutes for up to 4 hours, then every 1 to 4 hours as needed

Nebulization solution: 1.25 to 2.5 mg every 20 minutes for 3 doses, then 1.25 to 5 mg every 1 to 4 hours as needed

Dosing: Geriatric

Refer to adult dosing, starting with lowest dose; titrate cautiously.

Dosing: Pediatric

Note: Dosage expressed in terms of mg levalbuterol.

Asthma, acute exacerbation (NAEPP 2007):

Nebulization:

Infants and Children: 0.075 mg/kg/dose (minimum dose: 1.25 mg/dose) every 20 minutes for 3 doses, then 0.075 to 0.15 mg/kg/dose (maximum dose: 5 mg/dose) every 1 to 4 hours as needed

Adolescents: 1.25 to 2.5 mg every 20 minutes for 3 doses, then 1.25 to 5 mg every 1 to 4 hours as needed

Inhalation, aerosol (metered dose inhaler): 45 mcg/spray:

Infants and Children: 4 to 8 puffs every 20 minutes for 3 doses, then every 1 to 4 hours

Adolescents: 4 to 8 puffs every 20 minutes for up to 4 hours, then every 1 to 4 hours as needed

Asthma, maintenance therapy (nonacute) (NAEPP 2007): Note: Not recommended for long-term, daily maintenance treatment; regular use exceeding 2 days/week for symptom control indicates the need for additional long-term control therapy.

Nebulization:

Infants and Children ≤4 years: 0.31 to 1.25 mg every 4 to 6 hours as needed

Children 5 to <12 years: 0.31 to 0.63 mg every 8 hours as needed

Children ≥12 years and Adolescents: 0.63 to 1.25 mg every 8 hours as needed

Inhalation, aerosol (metered dose inhaler): 45 mcg/spray: Children ≥4 years and Adolescents: 2 inhalations every 4 to 6 hours as needed; per the manufacturer, 1 inhalation every 4 hours may be sufficient in some patients; maximum dose: 2 inhalations every 4 hours

Reconstitution

Concentrated solution should be diluted with 2.5 mL NS prior to use.

Administration

Inhalation: For oral inhalation only.

Metered-dose inhaler: Shake well before use, avoid spraying in the eyes. Prime with 4 test sprays prior to first use or if inhaler has not been used for more than 3 days. Clean actuator (mouthpiece) weekly with warm water and air dry thoroughly. A spacer device or valved holding chamber is recommended when using a metered-dose inhaler. Each inhaler contains 200 actuations, discard when the display window shows zero.

Nebulization solution: Safety and efficacy were established when administered with the following nebulizers: PARI LC Jet, PARI LC Plus, as well as the following compressors: PARI Master, Dura-Neb 2000, and Dura-Neb 3000. Concentrated solution should be diluted prior to use. Blow-by administration is not recommended, use a mask device if patient unable to hold mouthpiece in mouth for administration.

Storage

Metered-dose inhaler: Store at 20°C to 25°C (68°F to 77°F); protect from freezing and direct sunlight. Store with mouthpiece down. Discard when the dose indicator display shows zero, corresponding to 200 actuations. Do not store near heat or open flame or expose to temperatures >120°F. Do not puncture or incinerate.

Nebulization solution: Store in protective foil pouch at 20°C to 25°C (68°F to 77°F). Protect from light and excessive heat. Vials should be used within 2 weeks after opening protective pouch. Use within 1 week and protect from light if removed from pouch. Vials of concentrated solution should be used immediately after removing from protective pouch.

Drug Interactions

AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Haloperidol: QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of Haloperidol. Monitor therapy

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy

Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination

Methacholine: Beta2-Agonists (Short-Acting) may diminish the therapeutic effect of Methacholine. Management: Hold short-acting beta₂ agonists for 6 hours before methacholine use. Consider therapy modification

Monoamine Oxidase Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Caution) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Adverse Reactions

>10%:

Central nervous system: Headache (children: 12%)

Gastrointestinal: Vomiting (children: 11%)

Infection: Viral infection (≤12%)

Respiratory: Rhinitis (6% to 11%)

>2% to 10%:

Cardiovascular: Tachycardia (adolescents and adults: 3%)

Central nervous system: Nervousness (adolescents and adults: 3% to 10%), dizziness (adolescents and adults: 3%), migraine (adolescents and adults: 3%), anxiety (adolescents and adults: ≤3%), pain (adolescents and adults: ≤3%)

Dermatologic: Skin rash (children: 8%), urticaria (children: 3%)

Gastrointestinal: Diarrhea (children: 2% to 6%; adolescents and adults: <2%), dyspepsia (adolescents and adults: ≤3%)

Hematologic & oncologic: Lymphadenopathy (≤3%)

Neuromuscular & skeletal: Tremor (adolescents and adults: ≤7%), leg cramps (adolescents and adults: ≤3%), weakness (children: 3%), myalgia (≤2%)

Respiratory: Pharyngitis (7% to 10%), asthma (9%), cough (adolescents and adults: 4%), sinusitis (adolescents and adults: 4%), flu-like symptoms (adolescents and adults: ≤4%), bronchitis (children: 3%), nasal mucosa swelling (1% to 3%)

Miscellaneous: Fever (children: 9%), accidental injury (children 5% to 9%; adolescents and adults: 3%)

Frequency not defined:

Endocrine & metabolic: Decreased serum potassium, increased heart rate, increased serum glucose, paradoxical bronchospasm

Hypersensitivity: Hypersensitivity reaction (including bronchospasm, oropharyngeal edema)

<2%, postmarketing, and/or case reports: Acne vulgaris, anaphylaxis, angina pectoris, angioedema, atrial fibrillation, cardiac arrhythmia, chest pain, chills, constipation, conjunctivitis, dry throat, dysmenorrhea, dyspnea, ECG abnormality, epistaxis, extrasystoles, eye pruritus, gastroenteritis, gastroesophageal reflux disease, hematuria, hyperesthesia (hand), hypertension, hypokalemia, hypotension, insomnia, metabolic acidosis, nausea, otalgia, paresthesia, pulmonary disease, supraventricular cardiac arrhythmia, syncope, vertigo, voice disorder, vulvovaginal candidiasis, xerostomia

Warnings/Precautions

Concerns related to adverse effects:

• Bronchospasm: Rarely, life-threatening paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response. Discontinue immediately and treat with an alternative therapy. Paradoxical bronchospasm is frequently associated with first use of a new canister or vial.
• Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm, anaphylaxis, oropharyngeal edema) have been reported.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, or hypertension); beta agonists may cause elevation in blood pressure and heart rate and result in CNS stimulation/excitation. Beta-2 agonists may also increase risk of arrhythmias and electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression.
• Diabetes: Use with caution in patients with diabetes mellitus; beta₂-agonists may increase serum glucose and aggravate ketoacidosis.
• Hyperthyroidism: Use with caution in hyperthyroidism; may stimulate thyroid activity.
• Hypokalemia: Use with caution in patients with hypokalemia; beta₂-agonists may decrease serum potassium.
• Renal impairment: Use with caution in patients with renal impairment; drug clearance is decreased.
• Seizures: Use with caution in patients with seizure disorders; beta-agonists may result in CNS stimulation/excitation.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.
• Asthma: Optimize anti-inflammatory treatment before initiating maintenance treatment with levalbuterol. Do not use as a component of long-term therapy without an anti-inflammatory agent. Only the mildest form of asthma (step 1 and/or exercise-induced) would not require concurrent use based on asthma guidelines (NAEPP 2007). If patients need more doses than usual, this may be a sign of asthma destabilization; patient should be reevaluated.
• Patient information: Patients must be instructed to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use may indicate deterioration of asthma, and treatment must not be delayed. A spacer device or valved holding chamber is recommended when using a metered-dose inhaler.

Monitoring Parameters

Asthma symptoms; FEV₁, peak flow, and/or other pulmonary function tests; heart rate, blood pressure, CNS stimulation; arterial blood gases (if condition warrants); serum potassium, serum glucose (in selected patients)

Pregnancy

Pregnancy Considerations

Pregnant women with poorly controlled asthma or asthma exacerbations may have a greater fetal/maternal risk than what is associated with appropriately used medications. Uncontrolled asthma is associated with an increased risk of perinatal mortality, pre-eclampsia, preterm birth, and low birth weight infants. Acute asthma exacerbations should be treated aggressively with short-acting beta-2 agonists (SABA) to prevent fetal hypoxia (GINA 2018; Namazy 2016). If high doses of SABA are needed during the last 48 hours of labor and delivery, monitor blood glucose in the newborn for 24 hours after birth (GINA 2018). If initiating treatment during pregnancy, use of an agent with more data in pregnant women may be preferred (Namazy 2016). Levalbuterol is not approved for the management of preterm labor.

Data collection to monitor pregnancy and infant outcomes following exposure to levalbuterol is ongoing. Females exposed to levalbuterol during pregnancy are encouraged to enroll in the MotherToBaby Asthma and Pregnancy Study (1-877-311-8972 or www.mothertobaby.org/ongoing-study/asthma).

Patient Education

What is this drug used for?

• It is used to open the airways in lung diseases where spasm may cause breathing problems.

Frequently reported side effects of this drug

• Runny nose
• Diarrhea
• Tremors
• Sore throat

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Low potassium like muscle pain or weakness, muscle cramps, or an abnormal heartbeat.
• Chest pain
• Fast heartbeat
• Vision changes
• Severe dizziness
• Passing out
• Severe anxiety
• Severe headache
• Difficulty breathing
• Wheezing
• Cough
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.