Adult Asthma Clinical Practice Guideline Summary

Adult Asthma Clinical Practice Guideline Summary The following evidence-based guideline was developed to assist Primary Care physicians and other clinicians in the management of asthma in adults. It was adapted from the National Heart, Lung and Blood Institute Expert Panel Review 3 (NHLBI EPR-3). It was reviewed and re-approved in 2013. Key Points 1. An accurate diagnosis is essential to treatment. 2. Severity assessment determines initial therapy. 3. Degree of asthma control determines ongoing therapy. 4. Use a stepwise approach for initial and ongoing therapy. 5. Effective control includes managing special situations. 6. Managing exacerbations is an important part of care. Definition of Asthma Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role. In susceptible individuals, this inflammation causes recurrent episodes of coughing (particularly at night or early in the morning), wheezing, breathlessness, and chest tightness. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. Establishing the Diagnosis To establish a diagnosis of asthma, use a medical history, physical exam and spirometry to determine that: Episodic symptoms of airflow obstruction or airway hyperresponsiveness are present. Airflow obstruction is at least partially reversible, measured by spirometry. Reversibility is determined by an increase in FEV 1 of > 200 ml and 12% from baseline measure after inhalation of short-acting beta 2 -agonist (SABA). Some studies indicate that an increase of 10% of the predicted FEV 1 after inhalation of a SABA may have higher likelihood of separating patients who have asthma from those who have chronic obstructive pulmonary disease (COPD). Alternative diagnoses have been excluded (e.g., allergic rhinitis and sinusitis, congestive heart failure, pulmonary embolism, chronic obstructive pulmonary disease, drug-related cough, vocal cord dysfunction, and other pulmonary conditions). Indicators for a diagnosis of asthma include wheezing, cough, chest tightness, dyspnea, worsening of symptoms in the presence of environmental stimuli, and worsening of symptoms at night. Referral to an asthma specialist is recommended if signs and symptoms are atypical, if there are problems with a differential diagnosis, or if additional testing is indicated. Assessing Severity and Control After establishing the diagnosis, assessment of asthma severity, control and responsiveness to medication typically guide the choice of therapy (see Figure 1 and Tables 1 to 3). Severity: the intrinsic intensity of the disease process. Severity is most easily and directly measured in a patient who is not receiving long-term control therapy. Severity can also be measured, once asthma control is achieved, by the step of care (i.e., the amount of medication) required to maintain control. Control: the degree to which the manifestations of asthma are minimized by therapeutic intervention and the goals of therapy are met. Responsiveness: the ease with which asthma control is achieved by therapy. Asthma severity and asthma control include the domains of current impairment and future risk. Impairment: frequency and intensity of symptoms and functional limitations the patient is currently experiencing or has recently experienced. Risk: the likelihood of either asthma exacerbations, progressive decline in lung function, or risk of adverse effects from medication. Table 1: Components of Asthma Control Components of Control IMPAIRMENT RISK Symptoms Nighttime awakenings Interference with normal activity Short-acting beta 2 -agonist use for symptom control Lung function Validated questionnaires* Exacerbations requiring oral systemic corticosteroids Progressive loss of lung function Treatement-related adverse effects * Asthma Control Test (ACT). Derived from Figures 3-5b, 3-5c, Expert Panel Report 3; 75-77. For use within Kaiser Permanente only. 1 Last Reviewed/Revised: 4/2013

Initial and Ongoing Therapy Medications for asthma are categorized into two general classes: long-term control medication (inhaled corticosteroids) and quick-relief medication. Selection of medications includes consideration of the general mechanisms and role of the medication in therapy, delivery devices, and safety. Long-term control medications are used daily to achieve and maintain control of persistent asthma. The most effective are those that attenuate the underlying inflammation characteristic of asthma. Quick-relief medications are used to treat acute symptoms and exacerbations. A stepwise approach to therapy is recommended. See Tables 2 to 4 for therapy recommendations based on a step-wise approach. The goal of asthma therapy is to maintain long-term control of asthma with the least amount of medication, thereby exposing the patient to the least risk for adverse effects from pharmacologic therapy. Accordingly, once therapy is initiated and the level of asthma control is assessed, changes can be made to therapy according to this stepwise approach. This includes step-down therapy, as well. For patients classified with intermittent asthma, treatment with short-acting bronchodilators on an as-needed basis is recommended. For patients classified with persistent asthma, treatment with the lowest-step therapy that will control symptoms is recommended. Inhaled corticosteroids (ICS) are the preferred longterm control therapy. In general, ICS s are well tolerated and safe at the recommended dosages. The addition of LABA (salmeterol or formoterol) to the treatment of patients who require more than low-dose ICS alone to control asthma improves lung function, decreases symptoms, and reduces exacerbations and use of SABA for quick relief in most patients to a greater extent than doubling the dose of ICS s. Instruct patients in the use of inhaled medications, and review patients technique at every patient visit. The Asthama Guideline Development Team (GDT) strongly endorses the following 2010 FDA statements: Use of a long-acting beta-agonist (LABA) alone without use of a long-term asthma control medication is contraindicated in the treatment of asthma. LABAs should not be used in patients whose asthma is adequately controlled on low-or medium-dose inhaled corticosteroid (ICS). LABAs should only be used as additional therapy for patients with asthma who are currently taking but are not adequately controlled on a long-term asthma control medication, such as an ICS. Once asthma control is achieved and maintained, patients should be assessed at regular intervals and step down therapy should begin (e.g., discontinue LABA), if possible without loss of asthma control, and the patient should continue to be treated with a longterm asthma control medication, such as an ICS. Additionally the GDT recommends: Use forced combination products such as fluticasone /salmeterol (Advair), budesonide/formoterol (Symbicort), and mometasone/formoterol (Dulera) when prescribing LABAs for all age groups to ensure medication adherence. Consider referring patients of all ages who require LABAs to Allergy or Pulmonology for initial and ongoing evaluation. Immunotherapy Consider subcutaneous allergen immunotherapy for patients who have persistent asthma when there is clear evidence of a relationship between symptoms and exposure to an allergen to which the patient is sensitive. Evidence is strongest for use of subcutaneous immunotherapy for single allergens, particularly house dust mites, animal dander, and pollen. If use of allergen immunotherapy is elected, it should be administered only in a physician s office where facilities and trained personnel are available to treat any life-threatening reaction that can, but rarely does, occur. For use within Kaiser Permanente only. 2 Last Reviewed/Revised: 4/2013

Comorbid Conditions Identify and treat comorbid conditions that may impede asthma management. If these conditions are treated appropriately, asthma control may improve. Comorbid conditions may include: Allergic Bronchopulmonary Aspergillosis Gastroesophageal Reflux Obese or overweight patients Obstructive Sleep Apnea Rhinitis or sinusitis Stress and depression Managing Special Situations INTRODUCTION Patients who have asthma may encounter situations that will require adjustments to their asthma management to keep their asthma under control. Special situations described in this section include: Exercise-Induced Bronchospasm (EIB), Surgery, and Pregnancy. EXERCISE-INDUCED BRONCHOSPASM (EIB) Anticipate EIB in all asthma patients, especially those with a history of cough, shortness of breath, chest pain or tightness, wheezing, or endurance problems during exercise. An exercise challenge, in which a 15% decrease in PEF or FEV 1 (measured before and after exercise at 5-minute intervals for 20 to 30 minutes), will establish the diagnosis. An important dimension of adequate asthma control is the patient s ability to participate in any activity without experiencing asthma symptoms. Recommended treatments for EIB include: Long-term control therapy, if appropriate. Frequent or severe EIB may indicate the need to initiate or step up long-term control medication. Pretreatment before exercise: Inhaled beta 2 -agonists will prevent EIB for more than 80% of patients. SABA used shortly before exercise may be helpful for 2 to 3 hours. LABA can be protective up to 12 hours, but there is some shortening of the duration of protection when LABA is used on a daily basis. Frequent or chronic use of LABA as pretreatment for EIB is discouraged, as it may disguise poorly controlled persistent asthma. LTRAs, with an onset of action generally hours after administration, can attenuate EIB in up to 50% of patients. A warm-up period before exercise may reduce the degree of EIB. A mask or scarf over the mouth may attenuate cold-induced EIB. SURGERY AND ASTHMA Patients who have asthma are at risk for specific complications during and after surgery. These complications include acute bronchoconstriction triggered by intubation, hypoxemia and possible hypercapnia, impaired effectiveness of cough, atelectasis, and respiratory infection, latex, and even some anesthetic agents. The likelihood of these complications depends on the severity of the patient s airway hyperresponsiveness, airflow obstruction, mucus hypersecretions, latex sensitivity, and history of prior surgeries, because the latter is a risk factor for both latex and anesthetic agent sensitivities. PREGNANCY AND ASTHMA Maintaining adequate control of asthma during pregnancy is important for the health and well-being of both the mother and her baby. Maternal asthma increases the risk of perinatal mortality, preeclampsia, preterm birth, and low-birth-weight infants. More severe asthma is associated with increased risks, while better-controlled asthma is associated with decreased risks. It is safer for pregnant women who have asthma to be treated with asthma medications than to have asthma symptoms and exacerbations. Monitoring and making appropriate adjustments in therapy may be required to maintain lung function and, hence, blood oxygenation that ensures oxygen supply to the fetus. Pregnant women with asthma should be treated the same as non-pregnant asthmatics except for the following specifications: Budesonide is the preferred inhaled corticosteroid (the only category B corticosteroid). If there is concern about losing asthma control by switching inhaled corticosteroids and a patient s asthma is already well controlled on a different inhaled corticosteroid, there is no need to change to budesonide. Albuterol is the preferred short-acting beta-agonist. There is little experience with leukotriene modifiers in pregnancy. Of these, zileuton is not recommended for use in pregnancy; and zafirlukast and montelukast should only be used for otherwise recalcitrant asthma that has responded to these medications prior to pregnancy. For pregnant women discharged after hospitalization for an acute exacerbation of their asthma, an inhaled corticosteroid, as needed inhaled short-acting betaagonist, and an oral corticosteroid are recommended. For use within Kaiser Permanente only. 3 Last Reviewed/Revised: 4/2013

Managing Exacerbations Severe exacerbations can be life threatening and can occur in patients at any level of asthma severity; i.e., intermittent, or mild, moderate, or severe persistent asthma (see Figure 2, 3). Patients at high risk of asthma-related death require special attention particularly intensive education, monitoring, and care. Such patients should be advised to seek medical care early during an exacerbation. Risk factors for asthma-related death include: Previous severe exacerbation (e.g., intubation or ICU admission for asthma). Two or more hospitalizations or > 3 ED visits in the past year. Use of > 2 canisters of SABA per month. Difficulty perceiving airway obstruction or the severity of worsening asthma. Low socioeconomic status or inner-city residence. Illicit drug use. Major psychosocial problems or psychiatric disease. Comorbidities, such as cardiovascular disease or other chronic lung disease. HOME MANAGEMENT Early treatment by the patient at home is the best strategy for managing asthma exacerbations. Instruct patients on the following: Use a written asthma action plan that notes when and how to treat signs of an exacerbation. A peak flow-based plan may be particularly useful for patients who have difficulty perceiving airflow obstruction or have a history of severe exacerbations. Recognize early indicators of an exacerbation, including worsening PEF. Adjust their medications by increasing SABA and, in some cases, adding a short course of oral systemic corticosteroids. Doubling the dose of ICS s is not effective. Remove or withdraw from allergens or irritants in the environment that may contribute to the exacerbation. Monitor response to treatment and promptly communicate with the clinician about any serious deterioration in symptoms or PEF or about decreased responsiveness to SABA treatment, including decreased duration of effect. The following home management techniques are not recommended because no studies demonstrate their effectiveness and they may delay patients from obtaining necessary care: drinking large volumes of liquids; breathing warm, moist air; or using overthe-counter products, such as antihistamines or cold remedies. Pursed-lip and other forms of breathing may help to maintain calm, but these methods do not improve lung function. Asthma Self-Management & Education Ongoing patient education, including components of clinician follow-up, monitoring, reinforcement, and adherence strategies is recommended for improving asthma control. Continuing education for providers is recommended for improving asthma control. Written action plans (peak flow and/or symptom based) as part of an overall effort to educate patients in self-management are recommended, especially for patients who are not controlled on long-term controller medication and patients with a history of severe exacerbations. The goal of the action plan is to provide information on the timing and method of increasing treatment, the duration and when and how to seek medical help. For use within Kaiser Permanente only. 4 Last Reviewed/Revised: 4/2013

Figure 1: SUMMARY OF RECOMMENDED KEY CLINICAL ACTIVITIES FOR THE DIAGNOSIS AND MANAGEMENT OF ASTHMA CLINICAL ISSUE MANAGING ASTHMA LONG TERM KEY CLINICAL ACTIVITIES FOUR COMPONENTS OF CARE ASSESSMENT AND MONITORING EDUCATION ACTION STEPS GOAL OF ASTHMA THERAPY IS ASTHMA CONTROL: Reduce impairment (prevent chronic symptoms, require infrequent use of short-acting beta 2 - agonist (SABA), maintain (near) normal lung function and normal activity levels). Reduce risk (prevent exacerbations, minimize need for emergency care or hospitalization, prevent loss of lung function, or for children, prevent reduced lung growth, have minimal or no adverse effects of therapy). Assess asthma severity to initiate therapy. Assess asthma control to monitor and adjust therapy. Schedule follow-up care. Provide selfmanagement education. Develop a written asthma action plan in partnership with patient. Integrate education into all points of care where health professionals interact with patients. Use severity classification chart, assessing both domains of impairment and risk, to determine initial treatment. Use asthma control chart, assessing both domains of impairment and risk, to determine if therapy should be maintained or adjusted (step up if necessary, step down if possible). Use multiple measures of impairment and risk: different measures assess different manifestations of asthma; they may not correlate with each other; and they may respond differently to therapy. Obtain lung function measures by spirometry at least every 1 to 2 years, more frequently for not-well-controlled asthma. Asthma is highly variable over time, and periodic monitoring is essential. In general, consider scheduling patients at 2- to 6-week intervals while gaining control; at 1 to 6 month intervals, depending on step of care required or duration of control, to monitor if sufficient control is maintained; at 3-month intervals if a step down in therapy is anticipated. Assess asthma control, medication technique, written asthma action plan, patient adherence and concerns at every visit. Teach and reinforce: Self-monitoring to assess level of asthma control and signs of worsening asthma (either symptom or peak flow monitoring shows similar benefits for most patients). Peak flow monitoring may be particularly helpful for patients who have difficulty perceiving symptoms, a history of severe exacerbations, or moderate or severe asthma. Using written asthma action plan (review differences between long-term control and quick-relief medication). Taking medication correctly (inhaler technique and use of devices). Avoiding environmental factors that worsen asthma. Tailor education to literacy level of patient. Appreciate the potential role of a patient s cultural beliefs and practices in asthma management. Agree on treatment goals and address patient concerns. Provide instructions for (1) daily management (long-term control medication, if appropriate, and environmental control measures) and (2) managing worsening asthma (how to adjust medication, and know when to seek medical care). Involve all members of the health care team in providing/reinforcing education, including physicians, nurses, pharmacists, respiratory therapists, and asthma educators. Encourage education at all points of care: clinics (offering separate self-management education programs as well as incorporating education into every patient visit), Emergency Departments and hospitals, pharmacies, schools and other community settings, and patients homes. Use a variety of educational strategies and methods. Source: 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. Accessed August 29, 2007. For use within Kaiser Permanente only. 5 Last Reviewed/Revised: 4/2013

Figure 2: CLASSIFYING SEVERITY OF ASTHMA EXACERBATIONS IN THE URGENT OR EMERGENCY CARE SETTING Note: Patients are instructed to use quick-relief medications if symptoms occur or if PEF drops below 80% predicted or personal best. If PEF is 50% to 79%, the patient should monitor response to quick-relief medication carefully and consider contacting a clinician. If PEF is below 50%, immediate medical care is usually required. In the urgent or emergency care setting, the following parameters describe the severity and likely clinical course of an exacerbation. MILD MODERATE SYMPTOMS AND SIGNS Dyspnea only with activity (assess tachypnea in young children) Dyspnea interferes with or limits usual activity INITIAL PEF (OR FEV 1 ) PEF 70% predicted or personal best PEF 40% to 69% predicted or personal best Usually cared for at home CLINICAL COURSE Prompt relief with inhaled SABA Possible short course of oral systemic corticosteroids Usually requires office or ED visit Relief from frequent inhaled SABA Oral systemic corticosteroids; some symptoms last for 1 to 2 days after treatment is begun SEVERE Dyspnea at rest; interferes with conversation PEF < 40% predicted or personal best Usually requires ED visit and likely hospitalization Partial relief from frequent inhaled SABA Oral systemic corticosteroids; some symptoms last for > 3 days after treatment is begun Adjunctive therapies are helpful SUBSET: LIFE THREATENING Too dyspnoeic to speak; perspiring PEF < 25% predicted or personal best Requires ED/hospitalization; possible ICU Minimal or no relief from frequent inhaled SABA Intravenous corticosteroids Adjunctive therapies are helpful KEY: ED, emergency department; FEV 1, forced expiratory volume in 1 second; ICU, intensive care unit; PEF, peak expiratory flow; SABA, short-acting beta 2 -agonist For use within Kaiser Permanente only. 6 Last Reviewed/Revised: 4/2013

FIGURE 3: MANAGEMENT OF ASTHMA EXACERBATIONS: EMERGENCY DEPARTMENT AND HOSPITAL-BASED CARE For use within Kaiser Permanente only. 7 Last Reviewed/Revised: 4/2013

Table 2: CLASSIFYING ASTHMA SEVERITY AND INITIATING THERAPY IN ADULTS COMPONENTS OF SEVERITY Impairment Normal FEV 1 /FVC: 8-19 yr 85% 20-39 yr 80% 40-59 yr 75% 60-80 yr 70% Risk Symptoms Nighttime awakenings Short-acting beta 2 -agonist use for symptom control (not prevention of EIB) Interference with normal activity Lung Function FEV 1 FEV 1 /FVC Exacerbations requiring oral systemic corticosteroids Recommended Step for Initiating Therapy INTERMITTENT 2 days/week 2x/month 2 days/week PERSISTENT MILD MODERATE SEVERE > 2 days/week but not daily 3-4x/month > 2 days/week but not daily Daily > 1x/week but not nightly Daily Thoughout the day Often 7x/week Several times per day None Minor limitation Some limitation Extremely limited Normal FEV 1 between exacerbations > 80% Normal 0-1/year 2x/year > 80% Normal 60% - 80% Reduced 5% < 60% Reduced > 5% Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients in any severity class. Step 1 Step 2 Step 3 Step 4 or 5 Re-evaluate control in 2 to 6 weeks and adjust therapy accordingly. Table 3: ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN ADULTS COMPONENTS OF CONTROL Impairment Normal FEV 1 /FVC: 8-19 yr 85% 20-39 yr 80% 40-59 yr 75% 60-80 yr 70% Risk CLASSIFICATION OF ASTHMA CONTROL WELL-CONTROLLED NOT WELL-CONTROLLED VERY POORLY CONTROLLED Symptoms 2 days/week > 2 days/week but not daily Throughout the day Nighttime awakenings SABA Use for symptoms Interference with normal activity 2x/month 1-3x/week 4x/week 2 days/week > 2 days/week Several times per day None Some limitation Extremely limited FEV 1 or peak flow > 80% 60% to 80% < 60% ACT Questionnaire 20 16 to 19 15 Exacerbations requiring oral steroids Progressive loss of lung function Treatment-related adverse effects Recommended Action for Treatment 0 to1/year 2/year Evaluation requires long-term follow-up care. Intensity of medication side effects does not correlate to specific levels of control, but should be considered in the overall assessment of risk. Maintain current step. Regular follow-up every 1 to 6 months. Consider step down if well-controlled for 3 months. Step up 1 step. Re-evaluate in 2 to 6 weeks. Consider oral steroids. Step up 1 to 2 steps. Re-evaluate in 2 weeks. Source for both tables: 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. Accessed August 29, 2007. For use within Kaiser Permanente only. 8 Last Reviewed/Revised: 4/2013

Table 4: STEPWISE APPROACH FOR MANAGING ASTHMA ADULTS Quick Relief Medication for All Patients: SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20 minute intervals as needed. Short course of systemic oral corticosteroids may be needed. Use of SABA > 2 days a week for symptom control (but not prevention of EIB) indicates inadequate control and the need to step up treatment. INTERMITTENT ASTHMA PERSISTENT ASTHMA: DAILY MEDICATION CONSULT WITH ASTHMA SPECIALIST IF STEP 4 CARE OR HIGHER IS REQUIRED. CONSIDER CONSULTATION AT STEP 3. Step 6 CONSIDER CONSULTATION AT STEP 3. Step 1 SABA PRN Step 2 Low-dose ICS Alternative: Cromolyn, LTRA, Nedocromil, or Theophylline Step 3 Low-dose ICS plus LABA OR Combination therapy with Low-dose ICS OR Low-Dose ICS plus LTRA OR Theophylline or Medium Dose ICS Step 4 Combination therapy with Medium-dose ICS Alternative: Medium-dose ICS plus either LTRA, Theophylline, or Zileuton Step 5 Combination therapy with Medium-dose ICS AND Consider Omailzumab for patients who have allergies Combination therapy with Medium-dose ICS plus oral corticosteroid AND Consider Omailzumab for patients who have allergies Alternative: Low-dose ICS plus either LTRA, Theophylline, or Zileuton Patient Education and Environmental Control at Each Step Source: 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. Accessed August 29, 2007. For use within Kaiser Permanente only. 9 Last Reviewed/Revised: 4/2013

TABLE 5: Estimated Comparative Daily Dosages for ICS (NHLBI) Drug Low Daily Dose Medium Daily Dose High Daily Dose Beclomethasone HFA, 40 or 80 mcg/puff 80-240 mcg >240-480 mcg >480 mcg Budesonide DPI. (FG) 180 mcg/inhalation 180-600 mcg >600-1,200 mcg >1,200 mcg Flunisolide, (NF) 80 mcg/puff 320 mcg >320-640 mcg >640 mcg Fluticasone HFA, 44, 110, or 220 mcg/puff 88-264 mcg >264-440 mcg >440 mcg Mometasone, (FG) 110, 220 mcg/inhalation 220 mcg 440 mcg >440 mcg Ciclesonide MDI, (NF) 80 and 160 mcg 80-160 mcg >160-320 mcg >320 mcg 110 & 220 mcg/puff strengths of Fluticasone HFA are Non-Formulary. FG = Formulary with Guidelines; NF = Non-Formulary Table 6: Usual Dosages for Quick-Relief Medications (NHLBI) Medication Adult Dose Potential Adverse Effects Comments Albuterol 90 mcg/puff, 200 puffs/canister Nebulizer solution 2.5 mg/3 ml (0.083%) Levalbuterol HFA NF 45 mcg/puff, 200 puffs/canister Nebulizer solution 0.31 mg/3 ml, 0.63 mg/3 ml 1.25 mg/3 ml Pirbuterol CFC 200 mcg/puff, 400 puffs/canister Ipratropium 17 mcg/puff, 200 puffs/canister Nebulizer solution 500 mg/ml 2.5 ml Ipratropium with albuterol 18 mcg/puff of ipratropium & 90 mcg/puff of albuterol 200 puffs/canister 2 puffs every 4 to 6 hours, as needed for symptoms 2.5 mg 3 to 4 times daily as needed 2 puffs every 4 to 6 hours, as needed for symptoms 0.63 to 1.25 mg every 3 to 4 times daily as needed 2 puffs every 4 to 6 hours, as needed for symptoms 2 puffs 3 to 4 times daily as needed for symptoms 500 mg every 6 hours as needed for symptoms 2 puffs 3 to 4 times daily as needed for symptoms Inhaled Short-Acting Beta 2 -Agonists Tachycardia, skeletal muscle tremor, hypokalemia, increased lactic acid, headache, hyperglycemia. Inhaled route, in general, causes few systemic adverse effects. Patients with preexisting cardiovascular disease, especially the elderly, may have adverse cardiovascular reactions with inhaled therapy. Anticholinergics Drying of mouth and respiratory secretions, increased wheezing in some individuals, blurred vision if sprayed in eyes. NF = Non-Formulary; Non-Formulary, on commercial formulary in some regions. Drugs of choice for acute bronchospasm. Differences in potencies exist, but all products are essentially comparable on a per puff basis. An increasing use or lack of expected effect indicates diminished control of asthma. Not recommended for long-term daily treatment. Regular use exceeding 2 days/week for symptom control (not prevention of EIB) indicates the need for additional long-term control therapy. May double usual dose for mild exacerbations. For HFA: periodically clean HFA actuator, as drug may plug orifice. If used in the ED, produces less cardiac stimulation than SABAs. Treatment of choice for bronchospasm due to beta-blocker medication. Does not block EIB. Reverses only cholinergically mediated bronchospasm; does not modify reaction to antigen. May be an alternative for patients who do not tolerate SABA. Has not proven to be efficacious as long-term control therapy for asthma. For use within Kaiser Permanente only. 10 Last Reviewed/Revised: 4/2013

Table 7: Usual Dosages for Long-Term Controller Medications (NHLBI) MEDICATION / DOSAGE FORM ADULT DOSE COMMENTS Methylprednisolone 2, 4, 8, 16, 32 mg tablets Prednisolone 5 mg tablets, 5 mg/5 ml, 15 mg/5 ml Prednisone 1, 2.5, 5, 10, 20, 50 mg tablets; 5 mg/5 ml* 7.5 to 60 mg po daily in a single dose in a.m. or qod as needed for control. Short-course burst to achieve control, 40 to 60 mg po per day as single dose or 2 divided doses for 3 to 10 days Systemic Corticosteriods For long-term treatment of severe persistent asthma, administer single dose in a.m. either daily or on alternate days (alternate-day therapy may produce less adrenal suppression). Short courses or bursts are effective for establishing control when initiating therapy or during a period of gradual deterioration. There is no evidence that tapering the dose following improvement in symptom control and pulmonary function prevents relapse. For patients unable to tolerate the liquid preparations, dexamethasone syrup at 0.4 mg/kg/day may be an alternative. Studies are limited, however, and the longer duration of activity increases the risk of adrenal suppression. Long-Acting Inhaled Beta-Agonists (Should not be used for acute relief or exacerbations. Use with corticosteroids.) Salmeterol (FG) DPI 50 mcg/dose 50 mcg INH q 12 hours For both Salmeterol and Formoterol Should not be used for acute symptom relief or exacerbations. Use only with ICS s. Consider prescribing Advair. Formoterol (NF) DPI 12 mcg/single-use capsule Combined Medication Fluticasone / Salmeterol (FG) DPI 100/50, 250/50, or 500/50 MDI 45/21, 115/21, 230/21 (NF) Budesonide / Formoterol (NF) MDI 80/4.5 or 160/4.5 Mometasone / Formoterol (NF) MDI 100/5, 200/5 Leukotriene Modifiers Montelukast (NF) 4 mg or 5 mg chewable tablet, 4 mg granule packet, 10 mg tablet Zafirlukast (NF) 10 or 20 mg tablet Zileuton (NF) 600 mg tablet Methylxanthines Theophylline Liquids, sustained-release tablets, and capsules 12 mcg INH q 12 hours 1 inhalation bid; dose depends on severity of asthma 2 puffs bid 2 puffs bid; dose depends on severity of asthma 2 puffs bid; dose depends on severity of asthma Decreased duration of protection against EIB may occur with regular use. Do not blow into inhaler after dose is activated. For Formoterol only Each capsule is for single use only; additional doses should not be administered for at least 12 hours. Capsules should be used only with the inhaler and should not be taken orally. Do not blow into inhaler after dose is activated. 100/50 DPI for patients who have asthma not controlled on low- to medium-dose ICS. 250/50 DPI for patients who have asthma not controlled on medium- to highdose ICS. 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. 100/5 for patients who have asthma not controlled on low- to medium-dosed ICS. 200/5 for patients who have asthma not controlled on high-dosed ICS. 10 mg qhs Montelukast exhibits a flat dose-response curve. Doses > 10 mg will not produce a greater response. As long-term therapy may attenuate exercise-induced bronchospasm in some patients, but less effective than ICS therapy. 20 mg po bid For zafirlukast, administration with meals decreases bioavailability; take at least 1 hour before or 2 hours after meals. Zarfirlukast is a microsomal P450 enzyme 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. 1200 mg po bid Monitor hepatic enzymes (ALT). Starting dose 10 mg/kg/day, up to 300 mg max; usual max 800 mg/day Zileuton is a microsomal P450 enzyme inhibitor that can inhibit the metabolism of warfarin and theophylline. Doses of these drugs should be monitored accordingly. Adjust dosage to achieve serum concentration of 5 to 15 mcg/ml at steady state (at least 48 hours on same dosage). Due to wide interpatient variability in theophylline metabolic clearance, routine serum theophylline level monitoring is essential. Patients should be told to discontinue if they experience toxicity. Various factors (diet, food, febrile illness, age, smoking, and other medications) can affect serum concentrations. See EPR 3 Full Report 2007 and package inserts for details. NF = Non-Formulary; FG = Formulary with Guidelines Commercial: Non-Formulary with Restrictions and Guidelines, Medicare Part D: Formulary For use within Kaiser Permanente only. 11 Last Reviewed/Revised: 4/2013