VENTOLIN HFA (Brand for ALBUTEROL SULFATE HFA)

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Oral Administration
-Administer with food to minimize gastric irritation.
Oral Solid Formulations
-Extended-release tablets: Swallow whole with the aid of liquids. Do not chew or crush.

Oral Liquid Formulations
-Administer using a calibrated measuring device.




Inhalation Administration
Aerosol inhalation (e.g., ProAir HFA, Ventolin HFA)
-Instruct patient on proper inhalation technique; see the specific product's "Instructions for Use" from the manufacturer.
-Make sure the canister is firmly seated in the plastic mouthpiece adapter before each use.
-Shake the inhaler well. Prime the inhaler before the first use by spraying 4 times into the air, away from the eyes and face. When the inhaler has not been used for a prolonged period, or it has been dropped, prime by spraying 2 to 4 times into the air away from the face, according to the specific inhaler type.
-For patients of any age unable to coordinate inhalation and actuation, a spacer or valved holding chamber (VHC) should be used.
-The choice of using a mouthpiece versus a face mask with a spacer/VHC device must be made based on the skills and understanding of each individual patient. However, in general, children younger than 4 years require administration with a tight-fitting face mask and spacer/VHC device to achieve optimal delivery. If a face mask is used, allow 3 to 5 inhalations per actuation.
-General administration instructions: Shake the inhaler well before each use. Take the cap off the mouthpiece. Hold the inhaler as directed for the inhaler type. The patient will breathe out through the mouth and push as much air from the lungs as the patient can. Put the mouthpiece in the mouth and have patient close their lips around it. Push the top of the canister all the way down while the patient breathes in deeply and slowly through the mouth. Right after the spray comes out, release the canister. After the patient has breathed in all the way, take the inhaler out of the mouth. The patient should hold breath as long as they can, up to 10 seconds, then breathe normally. If prescribed more sprays, wait 1 minute and shake the inhaler again. Repeat inhaler steps. Put the cap back on the mouthpiece after use.
-Following administration, instruct patient to rinse the mouth with water to minimize dry mouth.
-To avoid the spread of infection, do not use the inhaler for more than one person.
-Clean the plastic mouthpiece of the inhaler at least once a week; some manufacturers advocate daily cleaning. After removing the medication canister, wash the mouthpiece in warm running water. Do not allow the medication canister to get wet. Shake excess water from the mouthpiece and verify that all medication build-up has been rinsed away. Allow the mouthpiece to air-dry before next use (e.g., over-night).
-Discard medication and inhaler after expired or once the labeled number of inhalations have been used, whichever comes first; some products may have an inhalation counter. Ventolin HFA expires 12 months after medication removal from the foil pouch. Other products should be discarded when the labeled number of actuations has been used or by the expiration date printed on original packaging; whichever comes first.
Valved holding chamber (VHC) with aerosol inhalation:
-Delivery of a pressurized metered-dose inhaler (MDI) with a spacer with or without a mouthpiece may be preferred in adults and children with asthma exacerbation. Nebulizers can transmit respiratory viral particles.-For infants and children up to 3 years of age, a pressurized MDI plus spacer with face mask is recommended; a nebulizer with a face mask is an alternative.
-For children 4 to 5 years old, a pressurized MDI plus spacer is recommended; a pressurized MDI plus spacer with face mask or a nebulizer with a face mask is an alternative.

-In children 2 years and older with acute asthma, the use of an MDI plus valved holding chamber (VHC) is as effective as nebulized therapy when appropriate administration technique is used. The method of delivery does not result in a significant difference in hospital admission rates in children seen in the emergency department or equivalent community setting. Additionally, the length of stay in the emergency department is shorter when a VHC was used.

Powder for Inhalation (e.g., ProAir RespiClick, ProAir Digihaler)
-Instruct patient on proper inhalation technique; see the specific product's "Instructions for Use" from the manufacturer.
-Before using for the first time, check the dose counter window to ensure that the inhaler is full and the number "200" is in the window. The dose counter will count down each time the mouthpiece cap is opened and closed. The dose counter only displays even numbers (example: 200, 198, 196, etc.) in the window.
-Hold the inhaler upright while opening the cap fully. When the cap is opened, a dose of albuterol will be activated for delivery of the medicine. Make sure a "click" sound is heard; if not, the inhaler may not be activated to give a dose of medicine.
-The cap should not be opened unless the patient is ready to take a dose; opening and closing the cap without inhaling a dose will waste the medicine and may damage the inhaler.
-The patient should breathe out through the mouth and push as much air from the lungs as they can. Be careful that the patient does not breathe out into the inhaler mouthpiece. Put the mouthpiece in the mouth and have the patient close their lips around it. The patient should breathe in deeply through the mouth until their lungs feel completely full of air. Ensure that the vent above the mouthpiece is not blocked by the patient's lips or fingers. The patient should hold their breath for about 10 seconds or as long as they comfortably can.
-Remove the inhaler from the mouth.
-Check the dose counter on the back of the inhaler to make sure the dose was received.
-Close the cap over the mouthpiece after each use of the inhaler; make sure the cap closes firmly into place.
-To inhale another dose, close the cap and then repeat inhaler steps.
-The inhaler contains a powder and must be kept clean and dry at all times. Do not wash or put any part of the inhaler in water. If the mouthpiece needs cleaning, gently wipe it with a dry cloth or tissue.
-When there are "20" doses left, the dose counter will change to red; refill the prescription or contact the doctor for another prescription.
-ProAir Digihaler contains a built-in electronic module which detects, records, and stores data on inhaler events, including peak inspiratory flow rate. A mobile app is required for data transmission but is not required for the administration of albuterol to the patient.
-Throw away the inhaler 13 months after removing it from the foil pouch for the first time, when the dose counter displays "0", or after the expiration date on the package, whichever comes first.

Inhalation Solution for Nebulization
-To administer a 0.63 mg dose of albuterol, use 3 mL of the commercially available (0.63mg/3mL) solution.
-To administer a 1.25 mg dose of albuterol, dilute 0.25 mL of a 0.5% solution for nebulization to a final volume of 3 mL with sterile 0.9% Sodium Chloride Injection or use 3 mL of the commercially available (1.25mg/3mL) solution.
-To administer a 2.5 mg dose of albuterol, dilute 0.5 mL of a 0.5% solution for nebulization to a final volume of 3 mL with sterile 0.9% Sodium Chloride Injection or use 3 mL of the commercially available 0.083% solution for nebulization.
-Deliver solution by nebulization over 5 to 15 minutes.
-The choice of using a mouthpiece versus a face mask must be made based on the skills and understanding of each individual patient.
-Using the 'blow by' technique (i.e., holding the face mask or open tube near the patient's nose and mouth) is not recommended.
-To avoid microbial contamination, aseptic technique should be used each time a multi-dose bottle is opened. Precautions should be taken to prevent contact of dropper tip with any surface, including nebulizer reservoir and ventilatory equipment. Each multi-dose bottle should be used for only 1 patient.
-Unit-dose vials should be stored in protective foil pouch at all times. Specific products may be good for up to 1 week outside the foil pouch, but should remain protected from light.
-Discard the vial if the solution changes color or becomes cloudy.

The most common adverse reactions associated with albuterol use are related to its sympathomimetic effects, although certain cardiovascular effects may be less common with albuterol than with sympathomimetics that have less selectivity for beta2-adrenergic receptors. In general, the sympathomimetic effects of albuterol are dose-related and are more frequent with oral dosage forms than with the inhalation aerosol or solution for inhalation.

Central nervous system (CNS) stimulation is common with all forms of albuterol. Tremor (10 to 24%) and nervousness or anxiety (4 to 20%) are some of the most common adverse effects reported with albuterol use; these may occur early in treatment initiation and lessen with continued use. During clinical trials with extended-release albuterol tablets, tremor occurred less frequently in adolescents than in their adult counterparts; incidence increased with increasing patient age. The incidence of tremor in young children is unclear. Tremor development in children receiving inhaled albuterol may be more common when the drug is delivered via nebulization compared to valved holding chamber (VHC) (RR 0.64; 95% CI, 0.44 to 0.95). Excitability and nervousness appear to occur more frequently in young children (20% and 15%, respectively) than in older children and adolescents (2% and 9%, respectively) receiving oral albuterol. During clinical trials of albuterol syrup, tremor (10%), shakiness (9%), and hyperactivity (2%) occurred in older children and adolescents; in addition, hyperkinesis (4%) was reported in younger children. Restlessness (less than 1%) and insomnia (1% to 3%) have also been reported with albuterol use. Other central nervous system (CNS) effects associated with albuterol use include headache (3% to 19%), migraine (1% to 2%), dizziness/lightheadedness (7% or less), vertigo, weakness (2% or less), drowsiness (less than 1%), sleep disturbance, not specified (2% or less), and nightmares. Agitation (1%), irritability (less than 1%), emotional lability (1%), and aggressive behavior (1%) have also been reported, specifically in pediatric patients.

Like other sympathomimetics, albuterol can cause various adverse cardiovascular effects including palpitations (5% or less), sinus tachycardia (1% to 5%), hypertension (3% or less), chest pain (unspecified) (less than 3%), and angina. Increases in pulse rate may be less significant when albuterol is administered via valved holding chamber (VHC) compared to nebulization. Peripheral vasodilation (e.g., hypotension) may occur from beta-2 stimulation of the vasculature. Arrhythmia exacerbation or precipitation, such as atrial fibrillation, supraventricular tachycardia (SVT), and extrasystole have been reported with albuterol use. In addition, beta-agonists have been reported to produce ECG changes, ST-T wave changes (e.g., flattening of the T wave, ST segment depression), and QT prolongation. Cardiac effects may be related to sympathomimetic effects and/or beta-agonist-induced hypokalemia. Stimulation of beta-2 receptors results in gluconeogenesis and intracellular movement of potassium, which may cause hyperglycemia and hypokalemia. Significant metabolic effects occur most commonly with relatively large doses of nebulized albuterol or with enteral products. In general, cardiovascular reactions are transient and more common with systemic albuterol therapy. Clinically significant effects are uncommon after administration of albuterol at recommended doses; however, if they occur the drug should be discontinued.

Metabolic acidosis has been reported in post-marketing experience with albuterol inhalation solution and aerosol. A causal relationship has not been established. Diabetic ketoacidosis has been reported after administration of large doses of intravenous albuterol; the potential for this adverse event after the use of other albuterol dosage forms is unknown.

Anaphylactoid reactions, including rare cases of angioedema, difficulty breathing, oropharyngeal edema, urticaria, and rash (unspecified) have been reported with albuterol use. In clinical trials of albuterol inhalation, allergic reactions (1% to 3%) and urticaria (1% to 2%) were infrequently reported. Rarely, oral albuterol has been associated with cases of Stevens-Johnson syndrome and erythema multiforme in children.

Paradoxical bronchospasm can occur after treatment with albuterol inhalations and can be life threatening. Patients who continue to have dyspnea, cough, and/or wheezing after albuterol administration with no relief of symptoms should stop using albuterol immediately and seek emergency medical attention. Paradoxical bronchospasm appears more likely to occur with the first few uses of a new canister of inhaled albuterol pressurized inhalation or MDI. Asthma exacerbation/lack of efficacy (11% to 13%), bronchospasm (8% to 15%), cough (2% or more), wheezing (1%), dyspnea (less than 3%) have been reported during clinical trials of inhaled albuterol.

Nausea (4% or less) and vomiting (3% to 4%) are sympathomimetic effects that may occur with any albuterol dosage form; these reactions are usually transient and may respond to temporary dose reduction. Though gastrointestinal symptoms such as appetite stimulation (3%), anorexia (1%), and abdominal pain (less than 1%) are more common with systemic albuterol, dyspepsia (1% to 1.5%) and diarrhea (less than 3%) have been reported with inhaled albuterol use. Flatulence (less than 3%) and eructation (less than 3%) have also been reported.

Musculoskeletal pain (5% or less), muscle spasm (less than 1%), leg pain, and muscle cramps (3%) have been reported with albuterol use. During clinical trials with extended-release albuterol tablets, muscle cramps occurred less frequently in adolescents than in their adult counterparts; incidence increased with increasing patient age. Muscle cramps may be related to beta-agonist-induced hypokalemia.

Oropharyngeal/throat irritation is a sympathomimetic effects that may occur with any albuterol dosage form; however, local nose, and throat effects are more likely to occur with the inhaled formulations. Xerostomia and throat irritation (10% or less), oropharyngeal pain (2% or more), sinusitis (5% or more), sinus headache (1%), naso-pharyngitis (2% or more), pharyngitis (14% or less), rhinitis (4% to 5%), upper respiratory inflammation (5%), laryngitis, hoarseness, dysphonia (less than 3%), glossitis (less than 3%), nasal congestion (1%), epistaxis (1% to 3%), tongue oral ulceration, and gagging have been reported with inhaled albuterol use. Systemic sympathomimetic effects (e.g., oropharyngeal irritation) are usually transient and may respond to temporary dose reduction. Local effects due to oral inhalation may be limited by rinsing the mouth with water after drug administration. Infections have also been reported with all albuterol dosage forms. Viral respiratory tract infection (4% to 7%), upper respiratory tract infection (5% or more), bronchitis (5% or more), lung disorders (less than 3%), and increased sputum (1.5%) have been reported as respiratory infectious adverse events of inhaled albuterol therapy. Miscellaneous infectious events such as cold symptoms (3%), flu-like syndrome (3%), fever (5% or more), lymphadenopathy (1% to 3%), gastroenteritis (1% to 3%), skin/appendage infection (2%), and urinary tract infection (less than 3%) have also been reported.

Taste disturbance (dysgeusia, less than 3%) may occur with albuterol use, especially with inhaled formulations. Conjunctivitis has been reported in 1% of patients receiving albuterol oral solution ; conjunctivitis or ocular irritation may also occur if formulations for inhalation are inadvertently sprayed in the eyes. Unusual taste and mydriasis (1.5%) are sympathomimetic effects that may occur with any albuterol dosage form. Other sensory system effects are more likely to occur with the inhaled formulations. Otitis media (1% to 4%), ear pain or otalgia (less than 3%), tinnitus, and tooth discoloration (1%) have been reported with inhaled albuterol use. Rinsing the mouth with water after inhaled albuterol administration helps to limit any localized effects.

General adverse events reported in albuterol clinical trials include back pain (2%), pain (2%), edema (less than 3%), ataxia (less than 3%), increased sweating (hyperhidrosis, less than 3%), flushing (less than 1%), pallor (1%), and rigors or chills (less than 3%). Urinary retention (less than 1%) has also rarely been reported.

Do not exceed recommended dosages of beta-agonists; fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest after an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.

Paradoxical bronchospasm can occur after treatment with albuterol and can be life-threatening. If this occurs, albuterol should be discontinued immediately and supportive care provided as necessary. In addition, increased albuterol use (more than 2 days/week, not including exercise-induced bronchospasm) may indicate asthma destabilization. Asthma may deteriorate acutely over a period of hours or chronically over several days or weeks. If deterioration of asthma occurs appropriate evaluation of the patient and the treatment strategy is warranted, giving special consideration to corticosteroid therapy. Albuterol has no anti-inflammatory activity and is not a substitute for inhaled or oral corticosteroid therapy. The use of beta-agonists alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents (e.g., corticosteroids) to the therapeutic regimen. Corticosteroids should not be stopped or reduced when albuterol therapy is instituted.

Albuterol is contraindicated in patients with albuterol hypersensitivity, levalbuterol hypersensitivity, or hypersensitivity to any component of the specific dosage formulation. Albuterol inhalation powder (i.e., ProAir RespiClick and ProAir Digihaler), is contraindicated in patients with severe milk protein hypersensitivity because the formulation contains lactose, which contains milk proteins. Immediate hypersensitivity reactions may occur after administration of racemic albuterol, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Like other beta-agonists, albuterol can produce paradoxical bronchospasm, which may be life-threatening. If paradoxical bronchospasm occurs, albuterol should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister or vial.

Albuterol, like other sympathomimetic amines, should be used cautiously in patients with a history of seizure disorder, hyperthyroidism (thyrotoxicosis), pheochromocytoma, or unusual responsiveness to other sympathomimetic amines.

Monitor heart rate and blood pressure in patients receiving high doses of albuterol for acute asthma exacerbations; cardiovascular adverse effects are more likely to occur when aggressive doses are used. Albuterol, like other beta2-agonists and sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency (coronary artery disease), cardiac arrhythmias, and hypertension. Albuterol can produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and cardiac arrhythmias, such as supraventricular tachycardia and extrasystoles. If such effects occur, albuterol may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiographic (ECG) changes, such as flattening of the T wave, QT prolongation, and ST segment depression, although the clinical significance of these findings is unknown. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Beta-adrenergic agonist therapies like albuterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation. After repeated dosing of albuterol inhalation solution in normokalemic pediatric patients (5 to 17 years), an asymptomatic 20% to 25% decrease in serum potassium concentrations was noted.

Use albuterol with caution in patients with diabetes mellitus. Large doses of intravenous racemic albuterol have been reported to aggravate preexisting diabetes mellitus and diabetic ketoacidosis. Also, patients with diabetic ketoacidosis (DKA) typically have a severe electrolyte imbalance. Serum potassium concentrations must be closely monitored during the treatment of DKA and albuterol may contribute to changes in serum potassium concentrations.

Description: Albuterol is a moderately selective short-acting beta2-agonist (SABA). It is a racemic mixture of R- and S-isomers and is widely used as a bronchodilator. Albuterol is indicated for the management of acute bronchospasm due to asthma and other chronic obstructive airway diseases. It is also used off-label as an adjuvant treatment for hyperkalemia in certain clinical situations. Albuterol is similar in structure to terbutaline, and when compared to non-selective beta-agonists, produces equivalent bronchodilation with less cardiac stimulation. Orally inhaled SABAs are recommended for the management of asthma exacerbations. SABAs should not be used alone to manage asthma, but continue to be an option for reliever therapy in pediatric patients with intermittent asthma and those with mild or moderate persistent asthma who are taking controller therapy such as inhaled corticosteroid (ICS) or ICS-long-acting beta-agonist (LABA) regimens. SABAs remain a key reliever therapy for infants and very young children (less than 4 years of age). However, guidelines now promote the use of "SMART" (single maintenance and reliever therapy) inhaler dosing strategies as preferred asthma management for selected older pediatric patients; such regimens usually combine an ICS with formoterol. SABAs also prevent exercise-induced bronchospasm (EIB), however, tolerance can develop with regular use and the incidence of EIB can usually be reduced with maintenance ICS therapy. Although historically a trial of albuterol was an option for infants and young children presenting with bronchiolitis, this practice is no longer recommended due to a lack of clinical benefit. Outside the United States, albuterol is referred to as salbutamol. Albuterol sulfate inhalation solution is FDA-approved in children 2 years and older; other albuterol products are FDA-approved for use in pediatric patients of varying ages depending on the specific product. Oral albuterol is not a preferred medication for any indication, given the risk for systemic side effects vs. inhaled therapy.

For the treatment of asthma exacerbation:
Respiratory (Inhalation) dosage (inhalation aerosol; e.g., ProAir HFA, Proventil HFA, Ventolin HFA):
Infants*: 180 to 540 mcg (2 to 6 actuations of 90 mcg/actuation) inhaled by mouth every 20 minutes for the first hour, then 180 to 270 mcg (2 to 3 actuations of 90 mcg/actuation) every hour as needed. Delivery should occur with a spacer, with face mask for children younger than 3 years.
Children 1 to 5 years: 180 to 540 mcg (2 to 6 actuations of 90 mcg/actuation) inhaled by mouth every 20 minutes for the first hour, then 180 to 270 mcg (2 to 3 actuations of 90 mcg/actuation) every hour as needed. Delivery should occur with a spacer, with face mask for children younger than 3 years.
Children and Adolescents 6 to 17 years: 360 to 900 mcg (4 to 10 actuations of 90 mcg/actuation) inhaled by mouth every 20 minutes for the first hour for mild to moderate exacerbations, then 360 to 900 mcg (4 to 10 actuations of 90 mcg/actuation) every 3 to 4 hours up to 540 to 900 mcg (6 to 10 actuations of 90 mcg/actuation) every 1 to 2 hours, or more often.
Respiratory (Inhalation) dosage (inhalation solution):
Infants* and Children* 1 year: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
Children 2 to 12 years: 2.5 mg inhaled by nebulizer every 20 minutes for the first hour, then 0.15 to 0.3 mg/kg/dose (Max: 10 mg/dose) inhaled by nebulizer every 1 to 4 hours as needed.
Adolescents: 2.5 to 5 mg inhaled by nebulizer every 20 minutes for the first hour, then 2.5 to 10 mg inhaled by nebulizer every 1 to 4 hours as needed.

For the treatment of transient increase in bronchospasm (e.g., episodic wheezing) as asthma reliever therapy:
Respiratory (Inhalation) dosage (inhalation aerosol; e.g., ProAir HFA, Proventil HFA, Ventolin HFA):
Children and Adolescents 4 to 17 years: 180 mcg (2 actuations of 90 mcg/actuation) inhaled by mouth every 4 to 6 hours as needed. In some patients, 90 mcg (1 actuation) every 4 hours may be sufficient. Max: 1,080 mcg/day (12 actuations/day).
Respiratory (Inhalation) dosage (inhalation powder; e.g., ProAir RespiClick, ProAir Digihaler):
Children and Adolescents 4 to 17 years: 180 mcg (2 actuations of 90 mcg/actuation) inhaled by mouth every 4 to 6 hours as needed. In some patients, 90 mcg (1 actuation) every 4 hours may be sufficient. Max: 1,080 mcg/day (12 actuations/day).
Respiratory (Inhalation) dosage (inhalation solution):
Children 2 to 5 years weighing less than 15 kg: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed. Those with more severe asthma (baseline FEV1 less than 60% predicted) may achieve a better initial response with the 1.25 mg dose.
Children 2 to 5 years weighting 15 kg or more: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed. Those with more severe asthma (baseline FEV1 less than 60% predicted) may achieve a better initial response with the 1.25 mg dose. Children weighing at least 15 kg may receive up to 2.5 mg inhaled by nebulizer 3 to 4 times daily if needed.
Children 6 to 12 years weighing less than 15 kg: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed. Those with more severe asthma (baseline FEV1 less than 60% predicted) or patients 11 to 12 years of age may achieve a better initial response with the 1.25 mg dose.
Children 6 to 12 years weighing 15 kg or more: 0.63 or 1.25 mg inhaled by nebulizer 3 or 4 times daily as needed. Those with more severe asthma (baseline FEV1 less than 60% predicted), weight more than 40 kg, or patients 11 to 12 years of age may achieve a better initial response with the 1.25 mg dose. Children weighing at least 15 kg may receive up to 2.5 mg inhaled by nebulizer 3 to 4 times daily if needed.
Adolescents: 2.5 mg inhaled by nebulizer 3 to 4 times daily as needed. Usual Max: 10 mg/day.
Oral dosage (oral solution or syrup):
Infants* and Children* younger than 2 years: Safety and efficacy have not been established; not FDA-approved; 0.1 to 0.2 mg/kg/dose PO every 8 hours has been used in neonates and young children.
Children 2 to 5 years: 0.1 mg/kg/dose PO 3 times per day. If an adequate response is not obtained, may gradually increase to 0.2 mg/kg/dose PO 3 times per day. Max: 12 mg/day. Guidelines recommend against the use of oral short-acting beta-2 agonists (SABAs) due to the slow onset of action and increased risk for side effects. Use inhaled SABAs for acute bronchospasm; do not use oral agents.
Children and Adolescents 6 to 14 years: 2 mg PO 3 to 4 times per day. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 24 mg/day. Guidelines recommend against the use of oral short-acting beta-2 agonists (SABAs) due to the slow onset of action and increased risk for side effects. Use inhaled SABAs for acute bronchospasm; do not use oral agents.
Adolescents 15 to 17 years: 2 to 4 mg PO 3 to 4 times daily. If adequate response not obtained, dose may be increased gradually with caution to 8 mg PO 4 times daily. Max: 32 mg/day. Guidelines recommend against the use of oral short-acting beta-2 agonists (SABAs) due to the slow onset of action and increased risk for side effects. Use inhaled SABAs for acute bronchospasm; do not use oral agents.
Oral dosage (immediate-release tablet):
Children 6 to 12 years: 2 mg PO 3 to 4 times per day. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 24 mg/day. Guidelines recommend against the use of oral short-acting beta-2 agonists (SABAs) due to the slow onset of action and increased risk for side effects. Use inhaled SABAs for acute bronchospasm; do not use oral agents.
Adolescents: 2 to 4 mg PO 3 to 4 times daily. If an adequate response is not obtained, may gradually increase with caution, up to 8 mg PO 4 times daily. Max: 32 mg/day. Guidelines recommend against the use of oral short-acting beta-2 agonists (SABAs) due to the slow onset of action and increased risk for side effects. Use inhaled SABAs for acute bronchospasm; do not use oral agents.
Oral dosage (extended-release tablets):
Children 6 to 12 years: 4 mg ER PO every 12 hours. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 24 mg/day. DOSE CONVERSION: 2 mg immediate-release PO every 6 hours = 4 mg extended-release PO every 12 hours. Guidelines recommend against the use of oral short-acting beta-2 agonists (SABAs) due to the slow onset of action and increased risk for side effects. Use inhaled SABAs for acute bronchospasm; do not use oral agents.
Adolescents : 4 to 8 mg ER PO every 12 hours. If an adequate response is not obtained, dose may be increased gradually with caution. Max: 32 mg/day. DOSE CONVERSION: 2 mg immediate-release PO every 6 hours = 4 mg extended-release PO every 12 hours. Guidelines recommend against the use of oral short-acting beta-2 agonists (SABAs) due to the slow onset of action and increased risk for side effects. Use inhaled SABAs for acute bronchospasm; do not use oral agents.

For bronchospasm prophylaxis, including exercise-induced bronchospasm prophylaxis and bronchospasm prophylaxis in persons with cystic fibrosis*:
-for exercise-induced bronchospasm prophylaxis:
Respiratory (Inhalation) dosage (inhalation aerosol; e.g., ProAir HFA, Proventil HFA, Ventolin HFA):
Children* 1 to 3 years: 90 to 180 mcg (1 to 2 actuations of 90 mcg/actuation) inhaled by mouth 15 minutes (range: 5 to 20 minutes) before exercise.
Children and Adolescents 4 to 17 years: 180 mcg (2 actuations of 90 mcg/actuation) inhaled by mouth 15 to 30 minutes before exercise. A controller agent (e.g., daily inhaled corticosteroid) is recommended to be used along with as-needed and pre-exercise short-acting beta-agonists like albuterol.
Respiratory (Inhalation) dosage (inhalation powder; ProAir RespiClick, ProAir Digihaler):
Children and Adolescents 4 to 17 years: 180 mcg (2 actuations of 90 mcg/actuation) inhaled by mouth 15 to 30 minutes before exercise. A controller agent (e.g., daily inhaled corticosteroid) is recommended to be used along with as-needed and pre-exercise short-acting beta-agonists like albuterol.
-for bronchospasm prophylaxis prior to the administration of other inhaled medications in persons with cystic fibrosis*:
Respiratory (Inhalation) dosage (inhalation aerosol; e.g., ProAir HFA, Proventil HFA, Ventolin HFA):
Children and Adolescents 6 to 17 years: 180 mcg (2 actuations of 90 mcg/actuation) inhaled by mouth prior to other inhaled medications, every 8 to 24 hours depending on regimen.

For adjunctive treatment of neonatal respiratory illness, such as those with suspected airway reactivity*, bronchopulmonary dysplasia*, or chronic lung disease (CLD)*:
Respiratory (Inhalation) dosage (inhalation solution):
Neonates*: 1.25 to 2.5 mg inhaled by nebulizer was the most common dose reported in a survey of 68 academic medical center neonatal intensive care units (NICUs). While significantly less common, weight-based dosing of 0.05 to 0.1 mg/kg/dose was also reported by some NICUs as their usual dose. Published reports describe a wide range of effective doses; 0.2 to 5 mg/dose and 0.02 to 0.2 mg/kg/dose administered every 4 to 8 hours have been reported to improve pulmonary compliance and/or resistance in ventilator-dependent neonates. The optimal frequency of administration has not been clearly defined in the neonatal population. Of note, significantly larger doses of albuterol are used in nebulization when compared to administration with metered-dose inhalers (MDIs) due to the inefficiency of nebulized drug delivery.
Respiratory (Inhalation) dosage (inhalation aerosol):
Neonates*: 90 to 180 mcg (1 to 2 actuations of 90 mcg/actuation) via the inspiratory limb of the mechanical ventilator circuit appeared to improve pulmonary mechanics in ventilator-dependent neonates. In a survey of 68 academic medical center neonatal intensive care units (NICUs), 95% reported 1 to 2 actuations as the average dose used. Frequency of administration has not been clearly defined in the neonatal population. Of note, MDIs with inline spacers have demonstrated superior drug delivery when compared to jet nebulizers in simulated neonatal lung models.
Oral dosage (oral solution or syrup):
Neonates*: Limited data. 0.15 mg/kg/dose enterally every 8 hours for 96 hours improved pulmonary resistance in ventilator-dependent premature neonates at risk for developing chronic lung disease (n = 30). Major cardiovascular side effects did not occur; heart and respiratory rate increases were deemed clinically unimportant by investigators.

For the adjunctive acute treatment of hyperkalemia*:
NOTE: Place patients on a cardiac monitor. Avoid in patients with preexisting cardiac arrhythmias. Adjuvant or alternative therapy is warranted for patients experiencing ECG changes or significantly elevated serum potassium concentrations (e.g., more than 7.5 mmol/L). Albuterol decreases serum potassium by approximately 1 to 1.5 mEq/L within an hour of administration. Concentrations begin to fall within 30 minutes of administration and may remain depressed up to 300 minutes when albuterol is nebulized.
Respiratory (Inhalation) dosage (inhalation solution):
Neonates: 400 mcg inhaled by nebulizer administered every 2 hours was effective in a study of mechanically ventilated neonates weighing less than 2,000 grams (n = 19). Doses were repeated every 2 hours until serum potassium concentrations fell to less than 5 mmol/L, the patient experienced adverse effects, or the maximum of 12 doses was reached.
Infants: 2.5 mg/dose inhaled by nebulizer every 20 minutes for 1 to 2 doses. In a small study (n = 11), doses were repeated every 2 hours as needed. Smaller doses for younger/premature infants may be necessary (e.g., 400 mcg every 2 hours).
Children weighing less than 25 kg: 2.5 mg/dose inhaled by nebulizer every 20 minutes for 1 to 2 doses. In a small study (n = 11), doses were repeated every 2 hours as needed.
Children and Adolescents weighing 25 to 50 kg: 5 mg/dose inhaled by nebulizer every 20 minutes for 1 to 2 doses. In a small study (n = 11), doses were repeated every 2 hours as needed.
Children and Adolescents weighing more than 50 kg: 10 mg/dose inhaled by nebulizer every 20 minutes for 1 to 2 doses.

For the treatment of respiratory symptoms in anaphylaxis* not responding to epinephrine:
Respiratory (Inhalation) dosage (inhalation solution):
Children and Adolescents: 2.5 mg inhaled by nebulizer; repeat every 15 minutes as necessary.

Maximum Dosage Limits:
-Neonates
Safety and efficacy have not been established; nebulizer inhalation maximum dependent on patient response and formulation used.
-Infants
Safety and efficacy have not been established; nebulizer inhalation maximum dependent on patient response and formulation used.
-Children
1 year: Safety and efficacy have not been established; nebulizer inhalation maximum dependent on patient response and formulation used.
2 to 3 years: 0.6 mg/kg/day PO (Max: 12 mg/day PO) for albuterol syrup; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.
4 to 5 years: 0.6 mg/kg/day PO (Max: 12 mg/day PO) for albuterol syrup; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.
6 to 12 years: 24 mg/day PO for syrup and tablets; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.
-Adolescents
13 to 14 years: 24 mg/day PO for syrup; 32 mg/day PO for tablets; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.
15 to 17 years: 32 mg/day PO for syrup and tablets; FDA-approved labeling for inhaler recommends not exceeding 12 puffs/day; FDA-approved labeling for nebulizer solution for oral inhalation recommends not exceeding 4 doses/day or 10 mg/day (0.083% or 0.5% nebulizer solution), 2.5 mg/day (0.63 mg/3 mL nebulizer solution), and 5 mg/day (1.25 mg/3 mL nebulizer solution). Higher maximum dosages for inhalation products have been recommended in NAEPP guidelines for acute exacerbations of asthma.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Albuterol is a moderately selective beta2-adrenergic agonist that stimulates receptors of the smooth muscle in the lungs, uterus, and vasculature supplying skeletal muscle. Albuterol is a racemic beta2-agonist, comprised of an equal mixture of R- and S-isomers.
Relief of Bronchoconstriction
The R-isomer, known as levalbuterol, is primarily responsible for bronchodilation. Although not confirmed during clinical trials in humans, the S-isomer of albuterol has been shown to increase airway reactivity in animal models. The net result of beta2-receptor agonism in the lungs is relaxation of bronchial and tracheal smooth muscles, which in turn relieves bronchospasm, reduces airway resistance, facilitates mucous drainage, and increases vital capacity. Stimulation of beta2-receptors on peripheral vascular smooth muscle can cause vasodilation and a modest decrease in diastolic blood pressure. Intracellularly, the actions of albuterol are mediated by cyclic-3',5'-adenosine monophosphate (cAMP), the production of which is augmented by beta2-stimulation. Albuterol is believed to work by activating adenyl cyclase, the enzyme responsible for generating cAMP, an intracellular mediator. Increased cAMP leads to activation of protein kinase A, which inhibits phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in bronchial smooth muscle relaxation. Increased cAMP also inhibits the release of histamine, leukotriene, and prostaglandin D2, and tumor necrosis factor alpha from mast cells. Inhibition of mediator release is believed to inhibit bronchoconstriction secondary to exercise and cold dry air.
Treatment of Hyperkalemia
Albuterol is an effective adjunctive treatment for hyperkalemia; beta2-adrenergic stimulation results in intracellular accumulation of serum potassium due to stimulation of the sodium-potassium adenosine triphosphatase (Na/K ATPase) pump, leading to moderate degrees of hypokalemia.

Pharmacokinetics: Albuterol can be administered as oral tablets or syrup, but is more commonly administered by oral inhalation. Intravenous studies in animals have shown that albuterol crosses the blood-brain barrier, reaching brain concentrations that amount to 5% of the plasma concentrations. After systemic administration to healthy adult volunteers, the volume of distribution was found to be is relatively large (156 +/- 381 L), indicating extensive extravascular uptake. Protein binding is negligible (10%). Albuterol is preferentially metabolized in the gastrointestinal tract via sulfotransferase to inactive compounds; however, a significant amount (25% to 45%) is excreted as unchanged drug. The primary route of elimination is through renal excretion; a small amount (< 20%) can be detected in the feces. In adults, the elimination half-life of albuterol is approximately 4 to 6 hours, with the extended release oral product having a longer half-life of approximately 9 hours.

Affected cytochrome P450 isoenzymes and drug transporters: None


-Route-Specific Pharmacokinetics
Oral Route
Immediate-release formulations
Immediate-release albuterol is rapidly absorbed after oral administration, obtaining Cmax (14 to 18 ng/mL) within 2 to 3 hours. Onset of pulmonary improvement can usually be seen within 30 minutes. Clinically significant improvement (defined as maintaining at least a 15% increase in FEV1 and a 20% increase in mid-expiratory flow rate over baseline) was recorded for up to 6 hours in a controlled clinical trial of 55 children. Elimination half-life is 5 hours.

Extended-release formulations
The bioavailability of extended-release (ER) tablets is 100% relative to the immediate-release (IR) tablets at steady state. Albuterol ER has a lower mean Cmax (14 ng/mL) and longer Tmax (6 hours) when compared to IR formulations. Fluctuations in plasma concentrations are similar for albuterol extended-release tablets administered at 12-hour intervals and immediate-release tablets administered at 6-hour intervals. AUC for both formulations is similar (130 ng x hr/mL). Elimination half-life of the ER formulation is approximately 9 hours. Food decreases the rate of absorption without altering the extent of bioavailability. Single dose studies have indicated administration with food causes a more gradual increase in the fraction of the dose absorbed compared to fasting conditions.

Inhalation Route
During studies, the majority of the nebulized albuterol dose administered has been recovered from the nebulizer apparatus and/or expired air; less than 20% of albuterol administered is systemically absorbed. At recommended doses, the bioavailability of inhaled albuterol is low. Onset of pulmonary improvement occurs within 2 to 20 minutes. After a 3 mg nebulized dose, peak concentrations of 2.1 ng/mL (range: 1.4 to 3.2 ng/mL) are reached in approximately 30 minutes and peak pulmonary improvement is seen at 1 to 2 hours. Duration of action is 2 to 6 hours. Half-life is approximately 4.6 to 6 hours. Administration via nebulization does not appear to significantly alter the pharmacokinetics of albuterol. The systemic exposure in children 6 to 11 years of age is similar to that of adults after 180 mcg single dose oral inhalation. A small study in 11 healthy children (aged 4 to 11 years) who received a single dose of albuterol inhalation aerosol 180 mcg via metered-dose inhaler, demonstrated a least square mean (SE) Cmax and AUC of 1100 (+/-1.18) pg/mL and 5120 (+/-1.15) pg x hr/mL, respectively. The least square mean (SE) terminal plasma half-life was 166 (+/-7.8) minutes. In a cumulative dose study, the AUC of the dry powder inhalation was similar to the aerosol formulation (metered dose inhaler); however, the Cmax was about one-third higher in the dry powder inhalation group.


-Special Populations
Renal Impairment
The pharmacokinetics of albuterol were studied in a small number of subjects with creatinine clearances between 7 to 53 mL/minute in comparison to healthy volunteers. The half-life was unchanged; however, albuterol clearance was decreased by 67% in those with renal impairment. Caution should be used when administering high doses of inhaled albuterol to patients with renal impairment.