Major drug classes commonly used in the treatment of asthma and asthma exacerbations include
Bronchodilators (beta-2 agonists, anticholinergics)
Corticosteroids
Leukotriene modifiers
Mast cell stabilizers
Methylxanthines
Immunomodulators
Drugs in these classes (see table Drug Treatment of Chronic Asthma) are inhaled, taken orally, or injected subcutaneously or intravenously; inhaled drugs come in aerosolized and powdered forms. Use of aerosolized forms with a spacer or holding chamber facilitates deposition of the drug in the airways rather than the pharynx; patients are advised to wash and dry their spacers after each use to prevent bacterial contamination. In addition, use of aerosolized forms requires coordination between actuation of the inhaler (drug delivery) and inhalation; powdered forms reduce the need for coordination, because drug is delivered only when the patient fully inhales with a good effort.
(See also Asthma and Treatment of Acute Asthma Exacerbations.)
Drug Treatment of Asthma*
Drug | Form | Dosage | Comments | |
|---|---|---|---|---|
Children | Adults | |||
Short-acting beta agonists | ||||
HFA: 90 mcg/puff | Same as adults | 2 puffs every 4–6 hours as needed and 2 puffs 15–30 minutes before exercise | It is not recommended for maintenance treatment. Regular use indicates diminishing asthma control and need for additional drug. MDI-DPI is as effective as nebulized therapy if patients can coordinate the inhalation maneuver using the spacer and holding chamber. | |
DPI: 90 mcg/puff | ≥ 4 years: Same as adults < 4 years: Not used | 2 puffs every 4–6 hours as needed and 2 puffs 15–30 minutes before exercise | ||
Nebulized solution: 5 mg/mL and 0.63, 1.25, and 2.5 mg/3 mL | < 5 years: 0.63–2.5 mg in 3 mL of saline every 4–6 hours as needed ≥ 5 years: 0.05 mg/kg in 3 mL saline every 4–6 hours as needed (minimum 1.25 mg, maximum 2.5 mg) | 1.25–5 mg in 3 mL saline every 4–6 hours as needed | ||
HFA: 45 mcg/puff | < 5 years: Not established ≥ 5 years: Same as adults | 2 puffs every 4–6 hours as needed | R | |
Nebulized solution: 0.31, 0.63, and 1.25 mg/3 mL and 1.25 mg/0.5 mL | < 5 years: 0.31–1.25 mg in 3 mL every 4–6 hours as needed 5–11 years: 0.31–0.63 mg every 8 hours as needed (maximum 0.63 mg every 8 hours) ≥ 12 years: Same as adults | 0.63–1.25 mg every 6–8 hours as needed | ||
Long-acting beta agonists (not to be used as monotherapy) | ||||
Nebulized solution: 15 mcg/2 mL | Not established | 15–25 mcg every 12 hours | R | |
Nebulized solution: 20 mcg/2 mL | Not established | 20 mcg every 12 hours | DPI form is no longer available. | |
HFA: 21 mcg/puff (not available in the US) | ≥ 12 years: Same as adults | 2 puffs every 12 hours; when taken before exercise, should be taken 30–60 minutes before exercise | Duration of action is 12 hours. One dose nightly is helpful for nocturnal asthma. | |
DPI: 50 mcg/puff | < 4 years: Not established ≥ 4 years: Same as adults | 1 puff every 12 hours and 30 minutes before exercise | ||
Ultra–long-acting beta agonists (not to be used as monotherapy) | ||||
Indacaterol | DPI: 75 mcg/puff | Not established | 1 puff once a day | — |
SMI: 2.5 mcg/puff | Not established | 2 puffs once a day | — | |
Vilanterol | DPI: 25 mcg/puff | Not established | 1 puff once a day | |
Anticholinergics | ||||
HFA: 17 mcg/puff | < 12 years: Not established ≥ 12 years: Same as adults | 2 puffs every 6 hours as needed (maximum 12 puffs/day) | It should not be used as first-line therapy. Regular use provides no clear benefit for long-term maintenance therapy but should be added for treatment of acute symptoms. | |
Nebulized solution: 500 mcg (0.02%, 2 mL) | < 12 years: Not established ≥ 12 years: Same as adults | 500 mcg every 6–8 hours as needed | ||
SMI: 1.25 mcg/puff | < 6 years: Not established ≥ 6 years: Same as adults | 2 puffs once a day (max 2 puffs/day) | ||
DPI: 18 mcg/capsule | Not established | 18 mcg (1 capsule) once a day | ||
Corticosteroids (inhaled) | ||||
HFA: 40–80 mcg/puff | < 4 years: Not established 4–11 years: 1 puff every 12 hours (usual maximum 80 mcg twice a day) ≥ 12 years: Same as adults | 1–2 puffs every 12 hours (usual maximum 320 mcg twice a day) | Doses depend on severity and range from 1–2 puffs to whatever dose is needed to control asthma. All may have systemic effects when used long term. Maximum threshold is that above which hypothalamic- pituitary-adrenal suppression is produced. If higher doses are necessary for asthma control, specialist consultation is recommended. | |
DPI: 90 or 180 mcg/puff | < 6 years: Not recommended ≥ 6 years: Initial dose of 180 mcg twice a day (maximum 360 mcg twice a day) | Initial dose of 360 mcg twice a day (maximum 720 mcg twice a day) | ||
Nebulized solution: 0.25, 0.5, or 1.0 mg (each in 2 mL solution) | 1–8 years only: If previously taking bronchodilators alone, initial dose of 0.5 mg once a day or 0.25 mg twice a day (maximum 0.5 mg/day) If previously taking inhaled corticosteroids, initial dose of 0.5 mg once a day or 0.25 mg twice a day If previously taking oral corticosteroids, initial dose of 0.5 mg twice a day or 1 mg once a day (maximum 1 mg/day) | Not indicated for adults | ||
HFA: 80 or 160 mcg/puff | ≤ 5 years: 160 mcg daily 6–11 years: Low dose 80 mcg once a day, medium dose > 80 to 160 mcg once a day, high dose > 160 mcg once a day ≥ 12 years: Same as adult | If previously taking bronchodilators alone, initial dose of 80 mcg twice a day (maximum 320 mcg twice a day) If previously taking inhaled corticosteroids, initial dose of 80 mcg twice a day (maximum 640 mcg twice a day) If previously taking oral corticosteroids, initial dose of 320 mcg twice a day (maximum 640 mcg twice a day) | ||
HFA: 80 mcg/puff | < 5 years: Not established 5–11 years: 1 puff twice a day (maximum 2 puffs twice a day [320 mcg/day]) ≥ 12 years: Same as adults | 2 puffs twice a day (maximum 4 puffs twice a day [640 mcg/day]) | ||
HFA: 44, 110, or 220 mcg/puffs | 0--4 years: 50 mcg/day 5–11 years: usually 44–220 mcg total daily dose ≥ 12 years: Same as adults | If previously taking bronchodilators alone, initial dose of 88 mcg twice a day (maximum 440 mcg twice a day) If previously taking inhaled corticosteroids, initial dose of 88–220 mcg twice a day (maximum 440 mcg twice a day) If previously taking oral corticosteroids, initial dose of 440–880 mcg twice a day (maximum 880 mcg twice a day) | ||
DPI: 50, 100, or 250 mcg/puff | 0–4 years: not established 5–11 years: usually 50–200 mcg total daily dose (usual maximum 100 mcg twice a day) ≥ 12 years: Same as adults | If previously taking bronchodilators alone, initial dose of 100 mcg twice a day (maximum 500 mcg twice a day) If previously taking inhaled corticosteroids, initial dose of 100–250 mcg twice a day (maximum 500 mcg twice a day) If previously taking oral corticosteroids, initial dose of 500–1000 mcg twice a day (maximum 1000 mcg twice a day) | ||
DPI: 50, 100, or 200 mcg/puff | 0–4 years: Not established 5–11 years: 1 puff (50 mcg) once a day ≥ 12 years: Same as adults | If previously taking bronchodilators alone, initial dose of 100 mcg once a day (maximum 200 mcg/day) If previously taking inhaled corticosteroids, initial dose of 100-200 mcg once a day (maximum 200 mcg/day) | ||
DPI: 110 or 220 mcg/puff | < 4 years: Not established 4–11 years: 110 mcg once a day in the evening ≥ 12 years: Same as adults | If previously taking bronchodilators alone or inhaled corticosteroids, initial dose of 220 mcg once a day in the evening (maximum 220 mcg twice a day or 440 mcg once a day in the evening) If previously taking oral corticosteroids, initial dose of 440 mcg twice a day (maximum 880 mcg twice a day) | ||
HFA: 50, 100, or 200 mcg/puff | < 12 years: Not established ≥ 12 years: Same as adults | If previously taking bronchodilators alone, initial dose of 220 mcg (delivering 200 mcg) once or twice a day (maximum 440 mcg/day) If previously taking inhaled corticosteroids, initial dose of 110–220 mcg (delivering 100 or 200 mcg) twice a day (maximum 800 mcg/day) If previously taking oral corticosteroids, initial dose of 440 mcg (delivering 400 mcg) twice a day (maximum 800 mcg/day) | ||
Systemic corticosteroids (oral) | ||||
Tablets: 2, 4, 8, 16, or 32 mg | 0–11 years: Short-course burst: 1–2 mg/kg once a day (maximum 60 mg) for 3–10 days ≥ 12 years: Same as adults | 7.5–60 mg once a day in the morning or every other day in the morning Short-course burst: 40–60 mg once a day (or 20–30 mg twice a day) for 3–10 days | Maintenance doses should be given in a single dose in the morning every day or every other day as needed for control. Some evidence suggests clinical effectiveness increases with no increase in adrenal suppression when dose is given at 3 PM. Short-course burst doses are effective for establishing control when initiating therapy or during a period of gradual deterioration. The burst should be continued until PEF = 80% of personal best or symptoms resolve, possibly requiring > 3–10 days of therapy. | |
Tablets: 5 mg Solution: 5 mg/5 mL or 15 mg/5 mL | ||||
Tablets: 1, 2.5, 5, 10, 20, or 50 mg Solution: 5 mg/mL or 5 mg/5 mL | ||||
Combination drugs | ||||
Not established | 1 puff qid (maximum 6 puffs/day) | |||
3-mL vial via nebulization 4 times a day for ambulatory rescue therapy (maximum 6 doses/24 hours) | — | |||
< 4 years: Not established 4–11 years: 1 puff (100/50) twice a day ≥ 12 years: Same as adults | 1 puff twice a day | The 250/50 dose is indicated for asthma not controlled by low-to-medium doses of inhaled corticosteroids. The 500/50 dose is indicated for asthma not controlled by medium-to-high doses of inhaled corticosteroids. | ||
< 12 years: Not established ≥ 12 years: Same as adults | 2 puffs twice a day | — | ||
< ≥ 12 years: 2 puffs twice a day and as needed Maximum total daily maintenance and rescue of 8 puffs (36 mcg) | 2 puffs twice a day and as needed Maximum total daily maintenance and rescue of 12 puffs (54 mcg). | The 80/4.5 dose is indicated for asthma not controlled by low-to-medium doses of inhaled corticosteroids. The 160/4.5 dose is indicated for asthma not controlled by medium-to-high doses of inhaled corticosteroids. | ||
< 5 years: 2 puffs twice a day as needed and do not exceed this dose for maintenance therapy ≥ 5 years: 2 puffs twice a day and as needed Maximum total daily maintenance and rescue of 8 puffs (36 mcg) | 2 puffs twice a day and as needed Maximum total daily maintenance and rescue of 12 puffs (54 mcg) | The 100/5 dose is recommended for asthma not controlled by low-to-medium–dose inhaled corticosteroids. The 200/5 dose is recommended for asthma not controlled by high-dose inhaled corticosteroids. | ||
Not established | 1 puff once/day | Recommended starting dose is based on asthma severity. | ||
Mast cell stabilizers | ||||
Nebulized solution: 20 mg/ampule | < 2 years: Not established ≥ 2 years: Same as adults | 1 ampule 3 or 4 times a day | One dose provides effective prophylaxis for 1–2 hours. | |
Leukotriene modifiers | ||||
Tablets, chewable tablets, and granules: 4, 5, or 10 mg | 12 mo–5 years: 4 mg orally once a day in the evening 6–14 years: 5 mg orally once a day in the evening ≥ 15 years: Same as adults | 10 mg orally once a day in the evening Exercise-induced asthma: 10 mg orally 2 hours before exercise | ||
Tablet: 10 or 20 mg | < 5 years: Not established 5–11 years: 10 mg orally twice a day ≥ 12 years: Same as adults | 20 mg orally in the evening | It must be taken 1 hour before or 2 hours after meals. | |
Tablet, immediate-release: 600 mg | < 12 years: Not established ≥ 12 years: Same as adults | 600 mg orally 4 times a day | Dosing may limit adherence. | |
Extended-release: 1200 mg | < 12 years: Not established ≥ 12 years: Same as adults | 1200 mg orally twice a day within 1 hour after morning and evening meals | ||
Methylxanthines | ||||
Capsule, extended-release: 100, 200, 300, and 400 mg Elixir: 80 mg/15 mL Tablet, extended-release: 100, 200, 400, 450, or 600 mg | Initial dose of 10 mg/kg/day up to 600 mg/day, then adjusted to achieve a serum concentration of 5–15 mcg/mL at steady state | Initial dose of 10 mg/kg/day up to 600 mg/day, then adjusted to achieve a serum concentration of 5–15 mcg/mL at steady state | The wide variability in metabolic clearance, drug interactions, and potential for adverse effects mandate routine serum level monitoring. Availability of safer alternatives has led to declining use of this drug. Safety may be better with a target level < 10 mcg/mL. | |
Immunomodulators | ||||
Subcutaneous injection: 30 mg/mL | < 12 years: Not established > 12 years: Same as adults | 30 mg subcutaneously every 4 weeks for 3 doses then every 8 weeks thereafter | ||
Subcutaneous injection: 300 mg/2mL or 200 mg/1.14 mL | < 6- years: Not established 6–11 years: Refer to specialist for dose adjustment ≥ 12 years: Same as adults | 400 mg subcutaneously once then 200 mg every 2 weeks or 600 mg subcutaneously once then 300 mg every 2 weeks | The initial dose should be given as two injections. | |
Subcutaneous injection: 100 mg | < 6 years: Not established 6–12 years: Refer to specialist for dose adjustment ≥ 12 years: Same as adults | 100 mg subcutaneously once every 4 weeks | — | |
Subcutaneous injection: 150 mg/1.2 mL | < 12 years: 75–375 mg subcutaneously every 2–4 weeks, depending on body weight and pretreatment serum IgE level ≥ 12 years: Same as adults | 150–375 mg subcutaneously every 2–4 weeks, depending on body weight and pretreatment serum IgE level | Maximum dose per injection site is 150 mg. | |
Intravenous: 100 mg/10 mL | Not established | 3 mg/kg IV once every 4 weeks | — | |
* All ages unless specified differently. | ||||
DPI = dry-powder inhaler; HFA = hydrofluoroalkane; MDI = metered-dose inhaler; SMI = soft mist inhaler; PEF = peak expiratory flow. | ||||
Adapted from the National Heart, Lung, and Blood Institute: Expert Panel Report 3, Guidelines for the diagnosis and management of asthma—full report 2007. August 28, 2007. Available at www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf. | ||||
Beta agonists
Beta2-adrenergic receptor agonists and beta agonists relax bronchial smooth muscle, decrease mast cell degranulation and histamine release, inhibit microvascular leakage into the airways, and increase mucociliary clearance. Beta-2 agonist preparations may be short-acting, long-acting, or ultra–long-acting (see tables Drug Treatment of Chronic Asthma and Drug Treatment of Asthma Exacerbations).
Short-actinghypokalemiaR
Long-acting
Ultra-long-acting beta agonists (eg, indacaterol) are active for up to 24 hours and as with long-acting beta agonists are used for moderate to severe asthma, and should never be used as a monotherapy. They interact synergistically with inhaled corticosteroids and permit lower dosing of corticosteroids.
The safety of regular long-term use of beta agonists has been confirmed by multiple randomized, controlled trials and meta-analyses, including a large international safety study that was followed by removal of a black box warning by the Food and Drug Administration (1). Because the safety and efficacy of long-acting beta agonists have been demonstrated only when used in combination with an inhaled corticosteroid, all long-acting and ultra-long beta agonists should be used only in combination with an inhaled corticosteroid for patients whose condition is not adequately controlled with other asthma controllers (eg, low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants additional maintenance therapies. Daily use or diminishing effects of short-acting beta agonists or use of ≥ 1 canister per month suggests inadequate control and the need to begin or intensify other therapies.
Anticholinergics (antimuscarinics)
Corticosteroids
Corticosteroids inhibit airway inflammation, reverse beta-receptor down-regulation, and inhibit cytokine production and adhesion protein activation. They block the late response (but not the early response) to inhaled allergens. Routes of administration include oral, IV, and inhaled. In acute asthma exacerbations, early use of systemic corticosteroids often aborts the exacerbation, decreases the need for hospitalization, prevents relapse, and speeds recovery. Oral and IV routes are equally effective.
Inhaled corticosteroids have no role in acute exacerbations but are indicated for long-term suppression, control, and reversal of inflammation and symptoms. They substantially reduce the need for maintenance oral corticosteroid therapy. Adverse local effects of inhaled corticosteroids include dysphonia and oral candidiasis, which can be prevented or minimized by having the patient use a spacer, gargle with water after corticosteroid inhalation, or both. Systemic effects are all dose related, can occur with oral or inhaled forms, and when due to inhaled forms, occur mainly with doses > 800 mcg/day. They include suppression of the adrenal-pituitary axis, osteoporosis, cataracts, skin atrophy, hyperphagia, and easy bruisability. Whether inhaled corticosteroids suppress growth in children is unclear. Most children treated with inhaled corticosteroids eventually reach their predicted adult height. Latent tuberculosis may be reactivated by systemic corticosteroid use.
Mast cell stabilizers
Mast cell stabilizers inhibit histamine release from mast cells, reduce airway hyperresponsiveness, and block the early and late responses to allergens. They are given by inhalation prophylactically to patients with exercise-induced or allergen-induced asthma. They are ineffective once symptoms have occurred. They are the safest of all antiasthmatic drugs but the least effective.
Leukotriene modifiers
Methylxanthines
Methylxanthines relax bronchial smooth muscle (probably by inhibiting phosphodiesterase) and may improve myocardial and diaphragmatic contractility through unknown mechanisms. Methylxanthines appear to inhibit intracellular release of calcium, decrease microvascular leakage into the airway mucosa, and inhibit the late response to allergens. They decrease the infiltration of eosinophils into bronchial mucosa and of T cells into epithelium.
gastroesophageal reflux (by reducing lower esophageal sphincter pressure).
Immunomodulators
9
9
Clinicians who give any of these immunomodulators should be prepared to identify and treat anaphylaxis or allergic hypersensitivity reactionsherpes zoster infection; therefore, zoster vaccination is recommend prior to initiation of therapy unless contraindicated.
Pearls & Pitfalls
Other drugs
Other drugs are used in asthma treatment uncommonly and in specific circumstances. Magnesium is often used in the emergency department, but it is not recommended in the management of chronic asthma.
Immunotherapy may be indicated when symptoms are triggered by allergy, as suggested by history and confirmed by allergy testing. Immunotherapy is generally more effective in children than adults. If symptoms are not significantly relieved after 24 months, then therapy is stopped. If symptoms are relieved, therapy should continue for ≥ 3 years, although the optimum duration is unknown.
Treatment reference
1. US Food and Drug Administration: FDA Drug Safety Communication: FDA review finds no significant increase in risk of serious asthma outcomes with long-acting beta agonists (LABAs) used in combination with inhaled corticosteroids (ICS).April 15, 2011. Updated December 20, 2017. Accessed January 21, 2022.
