Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma

FIGURE 17. USUAL DOSAGES FOR LONG-TERM CONTROL MEDICATIONS*

0–4 Years 5–11 Years ≥12 Years of Medication of Age of Age Age and Adults Potential Adverse Effects Comments (not all inclusive) Inhaled Corticosteroids (See Figure 18, “Estimated Comparative Daily Dosages for ICSs.”)

Oral Systemic Corticosteroids (Apply to all three corticosteriods.)

Methylprednisolone 0.25–2 mg/kg 0.25–2 mg/kg 7.5–60 mg daily ■ Short-term use: reversible ■ For long-term treatment of severe daily in single daily in single in a single dose abnormalities in glucose metabo- persistent asthma, administer single 2, 4, 8, 16, dose in a.m. or dose in a.m. or in a.m. or qod lism, increased appetite, fluid dose in a.m. either daily or on alternate 32 mg tablets qod as needed qod as needed as needed for retention, weight gain, mood days (alternate-day therapy may for control for control control alteration, hypertension, peptic produce less adrenal suppression). Prednisolone ulcer, and rarely aseptic necrosis. ■ Short courses or “bursts” are effective Short-course Short-course Short-course 5 mg tablets, ■ Long-term use: adrenal axis for establishing control when initiating “burst”: 1–2 “burst”: 1–2 “burst”: to 5 mg/5 cc, suppression, growth suppression, therapy or during a period of gradual mg/kg/day, maxi- mg/kg/day, maxi- achieve control, 15 mg/5 cc dermal thinning, hypertension, deterioration. mum 30 mg/day mum 60 mg/day 40–60 mg per diabetes, Cushing’s syndrome, ■ There is no evidence that tapering for 3–10 days for 3–10 days day as single or Prednisone cataracts, muscle weakness, the dose following improvement in 2 divided doses and—in rare instances symptom control and pulmonary function for 3–10 days 1, 2.5, 5, 10, 20, —impaired immune function. prevents relapse. 50 mg tablets; ■ Consideration should be given to ■ Children receiving the lower dose 5 mg/cc, coexisting conditions that could (1 mg/kg/day) experience fewer 5 mg/5 cc be worsened by systemic corti- behavioral side effects, and it appears costeroids, such as herpes virus to be equally efficacious. infections, varicella, tuberculosis, ■ For patients unable to tolerate the liquid hypertension, peptic ulcer, dia- preparations, dexamethasone syrup at betes mellitus, osteoporosis, and 0.4 mg/kg/day may be an alternative. Strongyloides Studies are limited, however, and the longer duration of activity increases the risk of adrenal suppression.

Inhaled Long-Acting Beta2-Agonists (LABAs) (Apply to both LABAs.)

Salmeterol ■ Should not be used for acute symptom relief or exacerbations. DPI 50 mcg/ NA 1 blister 1 blister ■ Tachycardia, skeletal muscle Use only with ICSs. blister q 12 hours q 12 hours tremor, hypokalemia, prolongation of QTc interval in overdose. ■ Decreased duration of protection against Formoterol ■ A diminished bronchoprotective EIB may occur with redgular use. DPI 12 mcg/ NA 1 capsule 1 capsule effect may occur within 1 week ■ Most children <4 years of age cannot single-use q 12 hours q 12 hours of chronic therapy. Clinical signif- provide sufficient inspiratory flow for capsule icance has not been established. adequate lung delivery. ■ Potential risk of uncommon, ■ Do not blow into inhaler after dose is severe, life-threatening or fatal activated. exacerbation; see text for addi- ■ Each capsule is for single use only; addi- tional discussion regarding safety tional doses should not be administered of LABAs. for at least 12 hours. ■ Capsules should be used only with the inhaler and should not be taken orally.

Key: DPI, dry powder inhaler; EIB, exercise-induced broncospasm; HFA, hydrofluoroalkane; ICS, inhaled corticosteroids; IgE, immunoglobulin E; MDI, metered-dose inhaler; NA, not available (either not approved, no data available, or safety and efficacy not established for this age group); SABA, short-acting beta2-agonist *Note: Dosages are provided for those products that have been approved by the U.S. Food and Drug Administration or have sufficient clinical trial safety and efficacy data in the appropriate age ranges to support their use.

46 Guidelines for the Diagnosis and Management of Asthma Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma

FIGURE 17. USUAL DOSAGES FOR LONG-TERM CONTROL MEDICATIONS* (continued)

0–4 Years 5–11 Years ≥12 Years of Medication of Age of Age Age and Adults Potential Adverse Effects Comments (not all inclusive) Combined Medication

Fluticasone/Salmeterol ■ See notes for ICS and LABA. ■ There have been no clinical trials in children <4 years of age. DPI ■ Most children <4 years of age cannot 100 mcg/50 mcg, NA 1 inhalation bid, 1 inhalation bid; provide sufficient inspiratory flow for 250 mcg/50 mcg, dose depends on dose depends on adequate lung delivery. or 500 mcg/ level of severity level of severity ■ Do not blow into inhaler after dose is 50 mcg or control or control activated. HFA ■ 100/50 DPI or 45/21 HFA for patients 45 mcg/21 mcg who have asthma not controlled on 115 mcg/21 mcg low- to medium-dose ICS 230 mcg/21 mcg ■ 250/50 DPI or 115/21 HFA for patients who have asthma not controlled on medium to high dose ICS.

Budesonide/ ■ See notes for ICS and LABA. ■ There have been no clinical trials in Formoterol children <4 years of age. ■ Currently approved for use in youths HFA MDI NA 2 puffs bid, dose 2 puffs bid; dose ≥12 years of age. Dose for children 80 mcg/4.5 mcg depends on level depends on level 5–12 years of age based on clinical 160mcg/4.5 mcg of severity or of severity or trials using DPI with slightly different control control delivery characteristics. ■ 80/4.5 for patients who have asthma not controlled on low- to medium-dose ICS. ■ 160/4.5 for patients who have asthma not controlled on medium- to high-dose ICS.

Cromolyn/Nedocromil

Cromolyn ■ Cough and irritation. ■ One dose of cromolyn before exercise ■ 15–20 percent of patients or allergen exposure provides effective MDI NA 2 puffs qid 2 puffs qid complain of an unpleasant taste prophylaxis for 1–2 hours. Not as 0.8 mg/puff from nedocromil. effective as inhaled beta2-agonists for EIB as SABA. Nebulizer 1 ampule qid 1 ampule qid 1 ampule qid ■ Safety is the primary advantage ■ 4- to 6-week trial of cromolyn or 20 mg/ampule NA <2 years of of these nedocromil may be needed to determine age maximum benefit. ■ Dose by MDI may be inadequate to Nedocromil affect hyperresponsiveness. ■ Once control is achieved, the frequency MDI NA <6 years of 2 puffs qid 2 puffs qid of dosing may be reduced. 1.75 mg/puff age

Managing Asthma Long Term 47 Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma FIGURE 17. USUAL DOSAGES FOR LONG-TERM CONTROL MEDICATIONS* (continued)

0–4 Years 5–11 Years ≥12 Years of Medication of Age of Age Age and Adults Potential Adverse Effects Comments (not all inclusive) Immunomodulators

Omalizumab ■ Pain and bruising of injection sites ■ Do not administer more than 150 mg (Anti IgE) in 5–20 percent of patients. per injection site. ■ Anaphylaxis has been reported in ■ Monitor patients following injections; be Subcutaneous NA NA 150–375 mg SC 0.2% of treated patients. prepared and equipped to identify and injection, 150 mg/ q 2–4 weeks, ■ Malignant neoplasms were treat anaphylaxis that may occur. 1.2 mL following depending on reported in 0.5 percent of patients ■ Whether patients will develop significant reconstitution with body weight and compared to 0.2 percent receiving antibody titers to the drug with 1.4 mL sterile pretreatment placebo; relationship to drug is long-term administration is unknown. water for injection serum IgE level unclear. Leukotriene Modifiers

Leukotriene Receptor Antagonists (LTRAs)

Montelukast ■ No specific adverse effects have ■ Montelukast exhibits a flat dose-response been identified. curve. Doses >10 mg will not produce 4 mg or 5 mg 4 mg qhs 5 mg qhs 10 mg qhs ■ Rare cases of Churg-Strauss a greater response in adults. chewable tablet (1–5 years of (6–14 years of have occurred, but the ■ No more efficacious than placebo in age) age) 4 mg granule association is unclear. infants ages 6–24 months. packets ■ As long-term therapy may attenuate exercise-induced bronchospasm in some 10 mg tablet patients, but less effective than ICS therapy.

Zafirlukast NA 10 mg bid 40 mg daily ■ Postmarketing surveillance has ■ For zafirlukast, administration with meals (7–11 years of (20 mg tablet reported cases of reversible decreases bioavailability; take at least 10 mg tablet age) bid) hepatitis and, rarely, irreversible 1 hour before or 2 hours after meals. 20 mg tablet hepatic failure resulting in death ■ Zarfirlukast is a microsomal P450 enzyme and liver transplantation. inhibitor that can inhibit the metabolism of warfarin. Doses of these drugs should be monitored accordingly. ■ Monitor hepatic enzymes (ALT). Warn patients to discontinue use if they experience signs and symptoms of liver dysfunction.

5-Lipoxygenase ■ Elevation of liver enzymes has ■ For zileuton, monitor hepatic enzymes (ALT). Inhibitor been reported. Limited case ■ Zileuton is a microsomal P450 enzyme reports of reversible hepatitis and inhibitor that can inhibit the metabolism Zileuton NA 2,400 mg daily NA hyperbilirubinemia. of warfarin and theophylline. Doses 600 mg tablet (give tablets qid) of these drugs should be monitored accordingly. Methylxanthines

Theophylline Starting dose Starting dose Starting dose ■ Dose-related acute toxicities ■ Adjust dosage to achieve serum 10 mg/kg/day; 10 mg/kg/day; 10 mg/kg/day up include tachycardia, nausea and concentration of 5–15 mcg/mL at steady Liquids, sustained- usual maximum: usual maximum: to 300 mg vomiting, tachyarrhythmias (SVT), state (at least 48 hours on same dosage). release tablets, ■ <1 year of 16 mg/kg/day maximum; usual central nervous system stimula- ■ Due to wide interpatient variability and capsules age: 0.2 (age maximum: tion, headache, seizures, in theophylline metabolic clearance, in weeks) + 5 800 mg/day hematemesis, hyperglycemia, routine serum theophylline level = mg/kg/day and hypokalemia. monitoring is essential. ■ Adverse effects at usual ■ Patients should be told to discontinue ■ ≥1 year therapeutic doses include if they experience toxicity. of age: insomnia, gastric upset, ■ Various factors (diet, food, febrile illness, 16 mg/kg/day aggravation of ulcer or reflux, age, smoking, and other medications) increase in hyperactivity in can affect serum concentrations. See some children, difficulty in EPR—3 Full Report 2007 and package urination in elderly males inserts for details. who have prostatism.

48 Guidelines for the Diagnosis and Management of Asthma Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma FIGURE 18. ESTIMATED COMPARATIVE DAILY DOSAGES FOR INHALED CORTICOSTEROIDS

Low Daily Dose Medium Daily Dose High Daily Dose ≥12 Years ≥12 Years ≥12 Years Child 0–4 Child 5–11 of Age and Child 0–4 Child 5–11 of Age and Child 0–4 Child 5–11 of Age and Drug Years of Age Years of Age Adults Years of Age Years of Age Adults Years of Age Years of Age Adults Beclomethasone HFA 40 or 80 mcg/puff NA 80–160 mcg 80–240 mcg NA >160–320 mcg >240–480 mcg NA >320 mcg >480 mcg Budesonide DPI 90, 180, or 200 NA 180–400 mcg 180–600 mcg NA >400–800 mcg >600– NA >800 mcg >1,200 mcg mcg/inhalation 1,200 mcg Budesonide Inhaled Inhalation suspension 0.25–0.5 mg 0.5 mg NA >0.5–1.0 mg 1.0 mg NA >1.0 mg 2.0 mg NA for nebulization Flunisolide 250 mcg/puff NA 500–750 mcg 500–1,000 mcg NA 1,000– >1,000– NA >1,250 mcg >2,000 mcg 1,250 mcg 2,000 mcg Flunisolide HFA 80 mcg/puff NA 160 mcg 320 mcg NA 320 mcg >320–640 mcg NA ≥640 mcg >640 mcg Fluticasone HFA/MDI: 44, 110, or 176 mcg 88–176 mcg 88–264 mcg >176–352 mcg >176–352 mcg >264–440 mcg >352 mcg >352 mcg >440 mcg 220 mcg/puff DPI: 50, 100, or NA 100–200 mcg 100–300 mcg NA >200–400 mcg >300–500 mcg NA >400 mcg >500 mcg 250 mcg/inhalation Mometasone DPI 200 mcg/inhalation NA NA 200 mcg NA NA 400 mcg NA NA >400 mcg Triamcinolone acetonide 75 mcg/puff NA 300–600 mcg 300–750 mcg NA >600–900 mcg >750– NA >900 mcg >1,500 mcg 1,500 mcg Key: DPI, dry power inhaler; HFA, hydrofluoroalkane; MDI, metered-dose inhaler; NA, not available (either not approved, no data available, or safety and efficacy not established for this age group)

Therapeutic Issues:

■ The most important determinant of appropriate dosing is the clinician’s judgment of the patient’s response to therapy. The clinician must monitor the patient’s response on several clinical parameters and adjust the dose accordingly. Once control of asthma is achieved, the dose should be carefully titrated to the minimum dose required to maintain control.

■ Preparations are not interchangeable on a mcg or per puff basis. This figure presents estimated comparable daily doses. See EPR—3 Full Report 2007 for full discussion.

■ Some doses may be outside package labeling, especially in the high-dose range. Budesonide nebulizer suspension is the only inhaled corticosteroid (ICS) with FDA-approved labeling for children <4 years of age.

■ For children <4 years of age: The safety and efficacy of ICSs in children <1 year has not been established. Children <4 years of age generally require delivery of ICS (budesonide and fluticasone HFA) through a face mask that should fit snugly over nose and mouth and avoid nebulizing in the eyes. Wash face after each treatment to prevent local corticos- teroid side effects. For budesonide, the dose may be administered 1–3 times daily. Budesonide suspension is compatible with albuterol, ipratropium, and levalbuterol nebulizer solutions in the same nebulizer. Use only jet nebulizers, as ultrasonic nebulizers are ineffective for suspensions. For fluticasone HFA, the dose should be divided 2 times daily; the low dose for children <4 years of age is higher than for children 5–11 years of age due to lower dose delivered with face mask and data on efficacy in young children.

Potential Adverse Effects of Inhaled Corticosteroids:

■ Cough, dysphonia, oral thrush (candidiasis).

■ Spacer or valved holding chamber with non-breath-actuated MDIs and mouthwashing and spitting after inhalation decrease local side effects.

■ A number of the ICSs, including fluticasone, budesonide, and mometasone, are metabolized in the gastrointestinal tract and liver by CYP 3A4 isoenzymes. Potent inhibitors of CYP 3A4, such as ritonavir and ketoconazole, have the potential for increasing systemic concentrations of these ICSs by increasing oral availability and decreasing systemic clearance. Some cases of clinically significant Cushing syndrome and secondary adrenal insufficiency have been reported.

■ In high doses, systemic effects may occur, although studies are not conclusive, and clinical significance of these effects has not been established (e.g., adrenal suppression, osteoporosis, skin thinning, and easy bruising). In low-to-medium doses, suppression of growth velocity has been observed in children, but this effect may be transient, and the clinical significance has not been established.

Managing Asthma Long Term 49 Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma

FIGURE 19. USUAL DOSAGES FOR QUICK-RELIEF MEDICATIONS*

<5 Years 5–11 Years ≥12 Years of Medication of Age of Age Age and Adults Potential Adverse Effects Comments (not all inclusive)

Inhaled Short-Acting Beta2-Agonists Dose applies Dose applies Dose applies to Albuterol. to to all four Apply to all four (SABAs) Albuters/and SABAs Levalbuterol. MDI

Albuterol CFC 1–2 puffs 1–2 puffs 2 puffs ■ Tachycardia, skeletal muscle ■ Drugs of choice for acute bronchospasm. 5 minutes before 5 minutes before 5 minutes before tremor, hypokalemia, ■ Differences in potencies exist, but all 90 mcg/puff, exercise exercise exercise increased lactic acid, products are essentially comparable on a 200 puffs/canister headache, hyperglycemia. puff per puff basis. Inhaled route, in general, ■ An increasing use or lack of expected effect Albuterol HFA 2 puffs every 2 puffs every 2 puffs every causes few systemic indicates diminished control of asthma. 4–6 hours, as 4–6 hours, as 4–6 hours, as 90 mcg/puff, adverse effects. Patients ■ Not recommended for long-term daily treat- needed for needed for needed for 200 puffs/canister with preexisting cardiovas- ment. Regular use exceeding 2 days/week symptoms symptoms symptoms cular disease, especially the for symptom control (not prevention of EIB) elderly, may have adverse indicates the need for additional long-term Levalbuterol HFA NA <4 years of cardiovascular reactions control therapy. age 45 mcg/puff, with inhaled therapy. ■ May double usual dose for mild exacerbations. 200 puffs/canister ■ For levalbuterol, prime the inhaler by releasing 4 actuations prior to use. Pirbuterol CFC NA NA ■ For HFA: periodically clean HFA actuator, as Autohaler drug may plug orifice. ■ For autohaler: children <4 years of age 200 mcg/puff, may not generate sufficient inspiratory flow 400 puffs/canister to activate an auto-inhaler. ■ Nonselective agents (i.e., epinephrine, isoproterenol, metaproterenol) are not recom- mended due to their potential for excessive cardiac stimulation, especially in high doses.

Nebulizer solution ■ May mix with cromolyn solution, budesonide inhalant suspension, or ipratropium solution Albuterol for nebulization. May double dose for severe 0.63 mg/3 mL 0.63–2.5 mg in 1.25–5 mg in 1.25–5 mg in (Same as with MDI) exacerbations. 1.25 mg/3 mL 3 cc of saline 3 cc of saline 3 cc of saline 2.5 mg/3 mL q 4–6 hours, as q 4–8 hours, as q 4–8 hours, as ■ Does not have FDA-approved labeling for 5 mg/mL (0.5%) needed needed needed children <6 years of age. ■ Compatible with budesonide inhalant Levalbuterol suspension. The product is a sterile-filled (R-albuterol) preservative-free unit dose vial. 0.31 mg/3 mL 0.31–1.25 mg 0.31–0.63 mg, 0.63 mg– (Same as with MDI) 0.63 mg/3 mL in 3 cc q 8 hours, 1.25 mg 1.25 mg/0.5 mL q 4–6 hours, as as needed for q 8 hours, 1.25 mg/3 mL needed for symp- symptoms as needed for toms symptoms

Key: CFC, chlorofluorocarbon; ED, emergency department; EIB, exercise-induced bronchospasm; HFA, hydrofluoroalkane; IM, intramuscular; MDI, metered-dose inhaler; NA, not available (either not approved, no data available, or safety and efficacy not established for this age group); PEF, peak expiratory flor; SABA, short-acting beta2-agonist *Dosages are provided for those products that have been approved by the U.S. Food and Drug Administration (FDA) or have sufficient clinical trial safety and efficacy data in the appropriate age ranges to support their use.

50 Guidelines for the Diagnosis and Management of Asthma Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma

FIGURE 19. USUAL DOSAGES FOR QUICK-RELIEF MEDICATIONS* (continued)

<5 Years 5–11 Years ≥12 Years of Medication of Age of Age Age and Adults Potential Adverse Effects Comments (not all inclusive) Anticholinergics Ipratropium HFA MDI

17 mcg/puff, NA NA 2–3 puffs ■ Drying of mouth and ■ Multiple doses in the emergency department 200 puffs/canister q 6 hours respiratory secretions, (not hospital) setting provide additive benefit increased wheezing in to SABA. Nebulizer solution some individuals, blurred ■ Treatment of choice for bronchospasm due 0.25 mg/mL NA NA 0.25 mg vision if sprayed in eyes. to beta-blocker medication. (0.025%) q 6 hours If used in the ED, produces ■ Does not block EIB. less cardiac stimulation ■ Reverses only cholinergically mediated Ipratropium with than SABAs. bronchospasm; does not modify reaction albuterol to antigen. MDI ■ May be an alternative for patients who do not tolerate SABA. 18 mcg/puff of NA NA 2–3 puffs ■ Has not proven to be efficacious as ipratropium q 6 hours long-term control therapy for asthma. bromide and 90 mcg/puff of albuterol 200 puffs/canister Nebulizer solution ■ Contains EDTA to prevent discoloration of 0.5 mg/3 mL NA NA 3 mL the solution. This additive does not induce ipratropium q 4–6 hours bromide and bronchospasm. 2.5 mg/3 mL albuterol

Systemic Corticosteroids

Dosages apply to first three corticosteroids. (Applies to the first three corticosteroids.) Methylprednisolone ■ Short courses or “bursts” are effective for 2, 4, 6, 8, 16, Short course Short course Short course ■ Short-term use: reversible establishing control when initiating therapy 32 mg tablets “burst:” “burst”: “burst”: abnormalities in glucose or during a period of gradual deterioration. 1–2 mg/kg/ 40–60 mg/day 40–60 mg/day metabolism, increased Action may begin within an hour. Prednisolone day, maximum as single or as single or appetite, fluid retention, ■ The burst should be continued until patient 60 mg/day, for 2 divided doses 2 divided doses weight gain, facial flushing, achieves 80 percent PEF personal best or 5 mg tablets, 3–10 days for 3–10 days for 3–10 days mood alteration, hyperten- symptoms resolve. This usually requires 5 mg/5 cc, sion, peptic ulcer, and 3–10 days but may require longer. There is 15 mg/5 cc rarely aseptic necrosis. no evidence that tapering the dose following ■ Consideration should be improvement prevents relapse in asthma Prednisone given to coexisting condi- exacerbations. 1, 2.5, 5, 10, 20, tions that could be wors- ■ Other systemic corticosteroids such as 50 mg tablets; ened by systemic corticos- hydrocortisone and dexamethasone given 5 mg/cc, teroids, such as herpes in equipotent daily doses are likely to be as 5 mg/5 cc virus infections, varicella, effective as prednisolone. tuberculosis, hypertension, peptic ulcer, diabetes mellitus, osteoporosis, and Strongyloides.

Managing Asthma Long Term 51 Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma

FIGURE 19. USUAL DOSAGES FOR QUICK-RELIEF MEDICATIONS* (continued)

<5 Years 5–11 Years ≥12 Years of Medication of Age of Age Age and Adults Potential Adverse Effects Comments (not all inclusive) Systemic Corticosteroids (continued) Repository injection 7.5 mg/kg IM 240 mg IM once 240 mg IM once ■ May be used in place of a short burst of (Methylprednisolone once oral steroids in patients who are vomiting or acetate) if adherence is a problem. 40 mg/mL 80 mg/mL

52 Guidelines for the Diagnosis and Management of Asthma Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma

FIGURE 22. DOSAGES OF DRUGS FOR ASTHMA EXACERBATIONS

Dosage Medication Child Dose* Adult Dose Comments (not all inclusive)

Inhaled Short-Acting Beta2-Agonists (SABA)

Albuterol 0.15 mg/kg (minimum dose 2.5–5 mg every 20 minutes Only selective beta2 agonists are recommended. Nebulizer solution 2.5 mg) every 20 minutes for for 3 doses, then 2.5–10 mg For optimal delivery, dilute aerosols to minimum of (0.63 mg/3 mL, 3 doses then 0.15–0.3 mg/kg up to every 1–4 hours as 3 mL at gas flow of 6–8 L/min. Use large volume 1.25 mg/3 mL, 10 mg every 1–4 hours as needed, or needed, or 10–15 mg/hour nebulizers for continuous administration. May mix 2.5 mg/3 mL, 0.5 mg/kg/hour by continuous continuously. with ipratropium nebulizer solution. 5.0 mg/mL) nebulization. MDI 4–8 puffs every 20 minutes for 3 doses, 4–8 puffs every 20 minutes In mild-to-moderate exacerbations, MDI plus VHC is (90 mcg/puff) then every 1–4 hours inhalation maneu- up to 4 hours, then every as effective as nebulized therapy with appropriate ver as needed. Use VHC; add mask in 1–4 hours as needed. administration technique and coaching by trained children <4 years. personnel. Bitolterol Has not been studied in severe asthma exacerbations. Nebulizer solution See albuterol dose; thought to be half as See albuterol dose. Do not mix with other drugs. (2 mg/mL) potent as albuterol on mg basis. MDI See albuterol MDI dose. See albuterol MDI dose. Has not been studied in severe asthma exacerbations. (370 mcg/puff) Levalbuterol (R-albuterol) Nebulizer solution 0.075 mg/kg (minimum dose 1.25 mg) 1.25–2.5 mg every Levalbuterol administered in one-half the mg dose of (0.63 mg/3 mL, every 20 minutes for 3 doses, then 20 minutes for 3 doses, albuterol provides comparable efficacy and safety. 1.25 mg/0.5 mL 0.075–0.15 mg/kg up to 5 mg every then 1.25–5 mg every Has not been evaluated by continuous nebulization. 1.25 mg/3 mL) 1–4 hours as needed. 1–4 hours as needed. MDI See albuterol MDI dose See albuterol MDI dose. (45 mcg/puff)

Pirbuterol See albuterol MDI dose; thought to be See albuterol MDI dose. Has not been studied in severe asthma exacerbations MDI half as potent as albuterol on a mg basis. (200 mcg/puff)

Systemic (Injected) Beta2-Agonists Epinephrine 0.01 mg/kg up to 0.3–0.5 mg every 0.3–0.5 mg every No proven advantage of systemic therapy over aerosol. 1:1,000 (1 mg/mL) 20 minutes for 3 doses sq. 20 minutes for 3 doses sq. Terbutaline 0.01 mg/kg every 20 minutes for 0.25 mg every 20 minutes No proven advantage of systemic therapy over aerosol. (1 mg/mL) 3 doses then every 2–6 hours as for 3 doses sq. needed sq.

Anticholinergics

Ipratropium bromide 0.25–5 mg every 20 minutes for 0.5 mg every 20 minutes for May mix in same nebulizer with albuterol. Should not Nebulizer solution 3 doses, then as needed 3 doses, then as needed be used as first-line therapy; should be added to (0.25 mg/mL) SABA therapy for severe exacerbations. The addition of ipratropium has not been shown to provide further benefit once the patient is hospitalized. MDI 4–8 puffs every 20 minutes as 8 puffs every 20 minutes as Should use with VHC and face mask for children (18 mcg/puff) needed up to 3 hours needed up to 3 hours <4 years. Studies have examined ipratropium bromide MDI for up to 3 hours.

56 Guidelines for the Diagnosis and Management of Asthma Excerpt from Summary Report 2007, Guidelines for the Diagnosis and Management of Asthma, National Asthma Education and Prevention Program, Expert Panel Report 3, Pages 46-52, 56-57. www.nhlbi.nih.gov/guidelines/asthma

FIGURE 22. DOSAGES OF DRUGS FOR ASTHMA EXACERBATIONS (continued)

Dosage Medication Child Dose* Adult Dose Comments (not all inclusive) Anticholinergics (continued)

Ipratropium with albuterol 1.5 mL every 20 minutes for 3 doses, 3 mL every 20 minutes for 3 May be used for up to 3 hours in the initial Nebulizer solution then as needed doses, then as needed management of severe exacerbations. The addition (Each 3 mL vial of ipratropium to albuterol has not been shown to contains 0.5 mg provide further benefit once the patient is hospitalized. ipratropium bromide and 2.5 mg albuterol.) MDI 4–8 puffs every 20 minutes as needed up 8 puffs every 20 minutes as Should use with VHC and face mask for children (Each puff contains to 3 hours needed up to 3 hours <4 years. 18 mcg ipratropium bromide and 90 mcg of albuterol.) Systemic Corticosteroids (Apply to all three corticosteriods.)

Prednisone 1 mg/kg in 2 divided doses (maximum = 40–80 mg/day in 1 or 2 For outpatient “burst,” use 40–60 mg in single or 60 mg/day) until PEF is 70 percent of divided doses until PEF 2 divided doses for total of 5–10 days in adults Methylprednisolone predicted or personal best reaches 70 percent of (children: 1–2 mg/ kg/day maximum 60 mg/day for Prednisolone predicted or personal best 3–10 days).

* Children ≤ 12 years of age Key: ED, emergency department; MDI, metered-dose inhaler; PEF, peak expiratory flow, VHC, valved holding chamber Notes: • There is no known advantage for higher doses of corticosteroids in severe asthma exacerbations, nor is there any advantage for intravenous administration over oral therapy provided gastrointestinal transit time or absorption is not impaired. • The total course of systemic corticosteroids for an asthma exacerbation requiring an ED visit of hospitalization may last from 3 to 10 days. For corticosteroid courses of less than 1 week, there is no need to taper the dose. For slightly longer courses (e.g., up to 10 days), there probably is no need to taper, especially if patients are concurrently taking ICSs. • ICSs can be started at any point in the treatment of an asthma exacerbation.

• No single measure is best for assessing severity or • Repeated lung function measures (FEV1 or predicting hospital admission. PEF) at 1 hour and beyond are the strongest single predictor of hospitalization. Such • Lung function measures (FEV or PEF) may be 1 measures may not be helpful, or easily obtained, useful for children ≥5 years of age, but these during severe exacerbations. measures may not be obtainable during an exacerbation. • Pulse oximetry is indicated for patients who are in severe distress, have FEV or PEF <40 percent • Pulse oximetry may be useful for assessing the 1 predicted, or are unable to perform lung initial severity; a repeated measure of pulse function measures. Only repeat assessments oximetry of <92–94 percent after 1 hour is after initial treatment, not a single assessment predictive of the need for hospitalization. upon admission, are useful for predicting the • Signs and symptoms scores may be helpful. need for hospitalization. Children who have signs and symptoms after 1–2 • Signs and symptoms scores at 1 hour after hours of initial treatment and who continue to initial treatments improve the ability to predict meet the criteria for a moderate or severe need for hospitalization. The presence of exacerbation have a >84 percent chance of drowsiness is a useful predictor of impending requiring hospitalization. respiratory failure and is reason to consider — For adults: immediate transfer to a facility equipped to offer ventilatory support.

Managing Exacerbations 57