Short-acting, nebulized beta2-adrenergic bronchodilators are FDA-approved for use in the relief of acute, potentially recurrent bronchospasm in patients with reversible obstructive airway disease^1-6. Long-acting, nebulized beta2-adrenergic agents are FDA-approved for use as maintenance therapy in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema^1,2,7,8. Revefenacin (Yupelri®) is FDA-approved as a maintenance therapy for COPD^1,2,9. A nebulized formulation of the long acting antimuscarinic anticholinergic agent glycopyrrolate (Lonhala Magnair®) was approved by the FDA in 2017 for the long-term maintenance treatment of airflow obstruction in patients with COPD^1,2,10. The anticholinergic, ipratropium, is FDA-approved to manage bronchospasm associated with exacerbations of COPD, including bronchitis and emphysema, either as monotherapy or in combination with beta adrenergic agents^1,2,11. While not FDA-approved, the Expert Panel 3 guidelines from the National Heart Lung and Blood Institute document benefit when multiple ipratropium doses are administered adjunctively with beta2-agonists in the emergency department to manage more severe acute asthma exacerbations¹². Additionally, the Global Initiative for Asthma (GINA) guidelines state that ipratropium may be considered a potential alternative bronchodilator for routine relief of asthma symptoms, and it may be used in combination with a short-acting beta2-adrenergic agonist in the emergency treatment of moderate to severe exacerbations.13 Ipratropium/racemic albuterol combination therapy is FDA-approved for use as second-line therapy in adult COPD patients who continue to experience bronchospasm with an aerosol bronchodilator and require a second bronchodilator^1,2,14. Recommended adult dosages are summarized in Tables 1-5. Patient profiles with dosages exceeding these recommendations will be reviewed.

Table 1. Maximum Recommended Nebulized Bronchodilator Dosages in Adults: Monotherapy: Short-Acting Sympathomimetics^1-6

Treatment Indication	Drug Name	Dosage Strength	Maximum Recommended Dosage
Bronchospasm in reversible obstructive airway disease (e.g., asthma)	Racemic albuterol (various generics)	2.5 mg/3 mL; (0.083%); 2.5 mg/0.5 mL (0.5%)	2.5 mg four times daily by nebulization* (maximum dose per day: 10 mg)
Bronchospasm in reversible obstructive airway disease (e.g., asthma)	Levalbuterol (Xopenex®, generics)	0.31 mg/3 ml; 0.63 mg/3 ml; 1.25 mg/3 ml; 1.25 mg/0.5 ml	1.25 mg three times daily by nebulization^

Legend:

• *Manufacturers of racemic albuterol state that more frequent administration or higher doses not recommended; however, in severe asthma exacerbations, the National Asthma Education and Prevention Program Expert Panel (NAEPPEP) recommends racemic albuterol doses of 2.5-5 mg every 20 minutes for 3 doses, then 2.5-10 mg every 1-4 hours as needed, or 10-15 mg/hour by continuous nebulization¹²
• ^For acute asthma exacerbations, NAEPPEP recommends levalbuterol doses of 1.25-2.5 mg every 20 minutes for 3 doses, then 1.25-5 mg every 1-4 hours as needed¹²

Table 2. Maximum Recommended Nebulized Bronchodilator Dosages in Adults: Monotherapy: Short-Acting Anticholinergics^1,2,11

Treatment Indication	Drug Name	Dosage Strength	Maximum Recommended Dosage
Chronic obstructive pulmonary disease (COPD)	Ipratropium (various generics)	500 mcg/2.5 ml (0.02%)	500 mcg four times daily, with doses 6 hours apart

Table 3. Maximum Recommended Nebulized Bronchodilator Dosages in Adults: Monotherapy: Long-Acting Sympathomimetics^1,2,7,8

Treatment Indication	Drug Name	Dosage Strength	Maximum Recommended Dosage
Chronic obstructive pulmonary disease (COPD)	Arformoterol (Brovana®, generic)	15 mcg/2 ml	15 mcg twice daily by nebulization
COPD	Formoterol (Perforomist®, generic)	20 mcg/2 ml	20 mcg twice daily by nebulization

Table 4. Maximum Recommended Nebulized Bronchodilator Dosages in Adults: Monotherapy: Long-Acting Anticholinergics^1,2,9,10

Treatment Indication	Drug Name	Dosage Strength	Maximum Recommended Dosage
Chronic obstructive pulmonary disease (COPD) – maintenance therapy	Glycopyrrolate (Lonhala® Magnair®)	25 mcg/ mL	25 mcg twice daily by nebulization!
COPD – maintenance therapy	Revefenacin (Yupelri®)	175 mcg/3 ml	175 mcg once daily

Legend:

• ! Lonhala® Magnair® is approved for use with the Magnair® nebulization system¹⁰

Table 5. Maximum Recommended Nebulized Bronchodilator Dosages in Adults: Combination Therapy^1,2,14

Treatment Indication	Drug Name	Dosage Strength	Maximum Recommended Dosage
Bronchospasm associated with chronic obstructive pulmonary disease (COPD) for patients requiring a second bronchodilator	Ipratropium/ racemic albuterol (generic)	0.5 mg/3 mg# per 3 ml	3 ml 6 times per day^

Legend:

• # 2.5 mg racemic albuterol base
• ^ For moderate asthma exacerbations, NAEPPEP recommends ipratropium/albuterol doses of 3 mL (ipratropium bromide 0.5mg/ albuterol base 2.5 mg) every 4-6 hours in the emergency setting. For severe asthma exacerbations, NAEPPEP recommends ipratropium/albuterol doses of 3 mL (ipratropium bromide 0.5mg/ albuterol base 2.5 mg) every 20 minutes for 3 doses, then as needed for up to 3 hours in the emergency setting¹²

Short-acting beta2-adrenergic bronchodilators are FDA-approved to manage bronchospasm episodes in pediatric patients with reversible obstructive airway disease^1-6. Racemic albuterol nebulized solution is FDA-approved to provide bronchospasm relief in children 2 years of age and older with reversible obstructive airway disease^1-5. Levalbuterol nebulized solutions are FDA-approved for use in the management and prevention of acute asthma exacerbations in children 6 years of age and older^1,2,6. Ipratropium is FDA-approved for use in children 12 years of age and older for management of bronchospasm associated with COPD^1,2,11. Recommended dosages are summarized in Tables 6 and 7. Patient profiles with dosages exceeding these recommendations will be reviewed.

Table 6. Maximum Recommended Nebulized Bronchodilator Pediatric Dosages: Short-Acting Sympathomimetics^1-6

Drug Name	Dosage Strength	Maximum Recommended Dosage
Racemic albuterol (generics)	0.63 mg/3 ml (0.021%) or 1.25 mg/3 ml (0.042%)	2-12 years of age: 1.25 mg 4 times daily (5 mg/day) +
Racemic albuterol (generics)	2.5 mg/3 ml (0.083%); 2.5 mg/ 0.5 ml (0.5%)	2-12 years of age: 2.5 mg 4 times daily (10 mg/day) *+
	2.5 mg/ 0.5 ml (0.5%)	Greater than 12 years of age: 2.5 mg 4 times daily (10 mg/day)+
Levalbuterol (Xopenex®, generics)	0.31 mg/3 ml; 0.63 mg/3 ml; 1.25 mg/3 ml; 1.25 mg/0.5 ml	6 years to 11 years of age: #   0.63 mg three times daily (every 6-8 hours) 12 years of age and older: ^  1.25 mg three times daily (every 6-8 hours)

Legend:

• * Children weighing less than15 kg who require less than 2.5 mg/dose should use the 0.5% albuterol inhalation solution instead of the 0.083% albuterol inhalation solution³
• + Manufacturers state that more frequent administration or higher doses not recommended; however, in patients 12 years or younger with severe asthma exacerbations, the National Asthma Education and Prevention Program Expert Panel (NAEPPEP) recommends racemic albuterol doses of 0.15 mg/kg (minimum dose 2.5 mg) for 3 doses then 0.15-0.3 mg/kg (up to 10 mg) every 1-4 hours as needed, or 0.5 mg/kg/hour by continuous nebulization. In patients greater than 12 years of age the NAEPPEP recommends 2.5-5 mg every 20 minutes for 3 doses, then 2.5-10 mg every 1-4 hours as needed, or 10-15 mg/hour by continuous nebulization¹²
• # For acute asthma exacerbations in children 12 years and younger, NAEPPEP recommends levalbuterol doses of 0.075 mg/kg (1.25 mg minimum) every 20 minutes x 3 doses, then 0.075—0.15 mg/kg (5 mg max) every 1—4 hours as needed¹²
• ^ For acute asthma exacerbations in children greater than 12 years, NAEPPEP recommends levalbuterol doses of 1.25-2.5 mg every 20 minutes for 3 doses, then 1.25-5 mg every 1-4 hours as needed¹²

Table 7. Maximum Recommended Nebulized Bronchodilator Pediatric Dosages: Short-Acting Anticholinergics^1,2,11

Drug Name	Dosage Strength	Maximum Recommended Dosage
Ipratropium (various generics)	500 mcg/2.5 ml (0.02%)	Greater than or equalt to 12 years of age: 500 mcg 4 times daily, every 6 hours apart

Nebulized long-acting beta2-adrenergic bronchodilators and long-acting anticholinergics as well as combination therapy with ipratropium and racemic albuterol are not indicated for use in pediatric patients as safety and efficacy of these agents in this patient population have not been established^1,2,7-10,14.