Drugs for asthma

Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 1000 Main Street, New Rochelle, NY 10801 • A Nonprofit Publication IN THIS ISSUE (starts on next page) Drugs for Asthma p 11 Important Copyright Message The Medical Letter® publications are protected by US and international copyright laws Forwarding, copying or any distribution of this material is prohibited Sharing a password with a non-subscriber or otherwise making the contents of this site available to third parties is strictly prohibited By accessing and reading the attached content I agree to comply with US and international copyright laws and these terms and conditions of The Medical Letter, Inc For further information click: Subscriptions, Site Licenses, Reprints or call customer service at: 800-211-2769 FORWARDING OR COPYING IS A VIOLATION OF US AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter publications are protected by US and international copyright laws Forwarding, copying or any other distribution of this material is strictly prohibited For further information call: 800-211-2769 Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Publication Volume 10 (Issue 114) February 2012 www.medicalletter.org Tables Treatment of Asthma Drugs for Asthma Page 13 Pages 14-15 Drugs for Asthma RECOMMENDATIONS: Use of a short-acting bronchodilator as needed for relief of symptoms may be sufficient for asthma patients whose symptoms are infrequent, mild and transient In patients with more frequent or more severe cough, wheeze, chest tightness or shortness of breath, regular use of a controller medication is recommended Low daily doses of an inhaled corticosteroid suppress airway inflammation and reduce the risk of exacerbations Higher inhaled corticosteroid doses may be needed in patients with more severe disease In patients who remain symptomatic despite compliance with inhaled corticosteroid treatment and good inhalational technique, addition of a long-acting beta-2 agonist is recommended In patients >12 years old with uncontrolled allergic asthma, omalizumab can be added For patients of any age with allergic asthma, allergen immunotherapy may provide longlasting benefits Failure of pharmacologic treatment can usually be attributed to lack of adherence to prescribed medications, uncontrolled co-morbid conditions, or continued exposure to tobacco smoke or other airborne pollutants, allergens or irritants INHALATION DEVICES Inhalation is the preferred route of delivery for most asthma drugs Chlorofluorocarbons (CFCs), which have ozone-depleting properties, are being phased out as propellants in metered-dose inhalers Non-chlorinated hydrofluoroalkane (HFA) propellants, which not deplete the ozone layer, are being used instead Metered-dose inhalers (MDIs) require coordination of inhalation with hand-actuation of the device Valved holding chambers (VHCs) or spacers can help young children or elderly patients use MDIs effectively VHCs have one-way valves that prevent the patient from exhaling into the device, eliminating the need for coordinated actuation and inhalation Spacers are open tubes placed on the mouthpiece of an MDI Both VHCs and spacers retain the large particles emitted from the MDI, preventing their deposition in the oropharynx and leading to a higher proportion of small respirable particles being inhaled Dry powder inhalers (DPIs), which are breathactuated, can be used in patients who are capable of performing a rapid deep inhalation Delivery of inhaled asthma medications through a nebulizer with a face mask or mouthpiece is less dependent on the patient’s coordination and cooperation, but more time-consuming than delivery through an MDI or DPI SHORT-ACTING BETA-2 AGONISTS Inhaled short-acting beta-2 agonists (SABAs), such as albuterol, are used for rapid relief of asthma symptoms Their onset of action occurs within minutes; their peak effect occurs within 30-60 minutes and they have a duration of action of 4-6 hours.1 SABAs not decrease the inflammation of the airways that occurs in asthma They should only be used as needed for relief of symptoms or for prevention of exerciseinduced bronchoconstriction (EIB) In patients whose asthma is under control, SABAs should be needed infrequently (12 years old Treatment should be adjusted based on response The ideal dose of an ICS is the lowest dose that maintains asthma control The FDA recommends stopping a LABA once symptoms are controlled In patients who remain uncontrolled despite aggressive treatment with a high-dose ICS plus a LABA, oral glucocorticoids are sometimes added Addition of omalizumab can be considered in patients with allergic asthma inflammatory mediators after allergen exposure It is FDA-approved for use in patients >12 years old with moderate to severe persistent asthma not well controlled on an ICS who have well-documented specific sensitization to a perennial airborne allergen, such as mold or animal dander Subcutaneous injection of omalizumab every or weeks reduces asthma exacerbations and has a modest ICS-sparing effect In adults and adolescents, when added to standard treatment, omalizumab improved symptoms and reduced exacerbations.16,17 When added to standard treatment in children with allergic asthma, omalizumab improved asthma control, decreased exacerbations and reduced maintenance ICS doses.18 Use of omalizumab does not preclude simultaneous use of allergen immunotherapy Adverse Effects – Injection-site pain and bruising occur in up to 20% of patients Anaphylaxis has occurred, but the incidence is extremely low (0.2% of patients) A national task force monitoring these rare cases of anaphylaxis continues to advise keeping patients under observation for hours after the first three omalizumab injections, and for 30 minutes after subsequent injections Additionally, patients receiving omalizumab should be instructed on how to Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 114) • February 2012 13 Drugs for Asthma Table Drugs for Asthma Some Available Formulations Drug Inhaled Beta-2 Agonists, Short-Acting Albuterol – generic Solution for nebulization1 single-dose vials 0.63, 1.25, 2.5mg/3mL multi-dose vials 100 mg/20 mL AccuNeb (Dey) single-dose vials ProAir HFA (Teva) Proventil HFA (Schering) Ventolin HFA (GSK) Levalbuterol – generic Xopenex (Sepracor) Xopenex HFA (Sepracor) Pirbuterol2 – Maxair Autohaler (Medicis) Inhaled Corticosteroids Beclomethasone dipropionate – QVAR (Teva) Budesonide – Pulmicort Flexhaler (AstraZeneca) Pulmicort Turbuhaler Solution for nebulization1 0.63, 1.25 mg/3 mL HFA MDI (200 inh/unit) 90 mcg/inhalation Adult Dosage Pediatric Dosage 1.25-5 mg q4-8h PRN 2-4 yrs: 0.63-2.5 mg q4-6h PRN 5-11 yrs: 1.25-5 mg q4-8h PRN 2-12 yrs: 0.63 or 1.25 mg tid-qid PRN >4 yrs: 90-180 mcg q4-6h PRN 90-180 mcg q4-6h PRN Solution for nebulization1 0.31, 0.63, 1.25 mg/3 mL 0.63-1.25 mg tid q6-8h PRN HFA MDI (80, 200 inh/unit) 45 mcg/inh Breath-actuated CFC MDI (80, 400 inh/unit) 200 mcg/inh 90 mcg q4-6h PRN 200-400 mcg q4-6h PRN HFA MDI (100 inh/unit) 40, 80 mcg/inhalation DPI (60, 120 inh/unit) 90, 180 mcg/inhalation DPI (200 inh/unit) 200 mcg/inhalation Susp for nebulization4 0.25, 0.5 mg/2mL 40-320 mcg bid3 5-11 yrs: 40-80 mcg bid3 360-720 mcg bid 6-17 yrs: 180-360 mcg bid 200-800 mcg bid3 >6 yrs: 200-400 mcg bid3 generic – single-dose vials Pulmicort Respules (AstraZeneca) single-dose ampules 0.25, 0.5mg, 1mg/2mL Ciclesonide – Alvesco HFA MDI (60 inh/unit) (Nycomed) 80, 160 mcg/inhalation Flunisolide – Aerospan HFA HFA MDI (60, 120 inh/unit) (Forest) 80 mcg/inhalation Fluticasone propionate – Flovent Diskus (GSK) DPI (60 inh/unit) 50, 100, 250 mcg/blister Flovent HFA (GSK) HFA MDI (120 inh/unit) 44, 110, 220 mcg/inhalation Mometasone furoate – Asmanex Twisthaler DPI (30, 60, 120 inh/unit) (Schering-Plough) 110, 220 mcg/inhalation Oral Glucocorticoids Methylprednisolone – generic 4, 8, 16, 32 mg tabs Medrol (Pfizer) Prednisolone – generic 5, 15 mg/5 mL syrup Prelone (Teva) 15 mg/5 mL syrup Orapred (Shionogi) 15 mg/5 mL PO solution Orapred ODT 10, 15, 30 mg disintegrating tabs Pediapred (UCB) mg/5mL PO solution Prednisone – generic 1, 2.5, 5, 10, 20, 50 mg tabs; mg/5 mL PO solution —— 6-11 yrs: 0.31-0.63 mg tid q6-8h PRN >12 yrs: 0.63- 1.25 mg tid q6-8h PRN >4 yrs: 90 mcg q4-6h PRN >12 yrs: 200-400 mcg q4-6h PRN 1-8 yrs: 0.25-0.5 mg once/d or bid or mg once/d3 80-320 mcg bid3 >12 yrs: 80-320 mcg bid3 160-320 mcg bid3 6-11 yrs: 80-160 mcg bid3 100-1000 mcg bid3 4-11 yrs: 50-100 mcg bid3 88-880 mcg bid3 4-11 yrs: 88 mcg bid 220-440 mcg 1x/day in evening or 220 mcg bid 4-11 yrs: 110 mcg 1x/d in evening 5-60 mg once/d or every other day or 40-60 mg once/d or divided bid x 3-10 days for an acute exacerbation 0-11 yrs: 0.25-2 mg/kg once/d or every other day (max 60 mg/d) or 1-2 mg/kg x 3-10 days (max 60 mg/d) for an acute exacerbation CFC = Chlorofluorocarbon; DPI = Dry powder inhaler; HFA = Hydrofluoroalkane; MDI = Metered-dose inhaler Nebulized solutions may be more convenient for very young, very old and other patients unable to use pressurized aerosols More time is required to administer the drug, however, and the device is usually not portable CFC-containing MDIs will not be marketed after December 2013 Dose is based on prior asthma therapy See package insert for specific dosing instructions Only approved for use in children 1-8 years old 14 Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 114) • February 2012 Drugs for Asthma Table Drugs for Asthma (continued) Some Available Formulations Drug Adult Dosage Pediatric Dosage 50 mcg bid >4 yrs: 50 mcg bid 12 mcg bid >5 yrs: 12 mcg bid inhalation bid inhalations bid 4-11 yrs: inhalation (100/50 mcg) bid >12 yrs: inhalation bid >12 yrs: inhalations bid inhalations bid >12 yrs: inhalations bid inhalations bid >12 yrs: inhalations bid 10 mg tabs, 4, mg chew tabs, mg oral granules 10 mg PO once/d >1 yr: or mg PO once/day8 10, 20 mg tabs 20 mg PO bid 600 mg tabs 600 mg PO qid 5-11 yrs: 10 mg PO bid >12 yrs: 20 mg PO bid >12 yrs: 600 mg PO qid 600 mg ER tabs 1200 mg PO bid >12 yrs: 1200 mg PO bid Solution for nebulization1 250 mcg/mL HFA MDI (200 inh/unit) 17 mcg/inhalation DPI (5, 30, 90 inh/unit) 18 mcg/capsule 500 mcg qid PRN —— inhalations qid PRN —— 18 mcg once/d —— Inhaled Beta-2 Agonists, Long-Acting5 Salmeterol – Serevent Diskus DPI (60 inh/unit) (GSK) 50 mcg/blister Formoterol – Foradil Aerolizer DPI (60 inh/unit) (Merck) 12 mcg/capsule Inhaled Corticosteroid/Long-Acting Beta-2 Agonist Combinations Fluticasone/salmeterol – Advair Diskus (GSK) DPI (60 inh/unit) 100, 250, 500 mcg/ 50 mcg per blister6 Advair HFA (GSK) HFA MDI (60, 120 inh/unit) 45, 115, 230 mcg/ 21 mcg per inhalation Budesonide/formoterol – Symbicort HFA (AstraZeneca) HFA MDI (60, 120 inh/unit) 80, 160 mcg/4.5 mcg per inhalation Mometasone/formoterol – Dulera (Merck) HFA MDI (120 inh/unit) 100, 200 mcg/5 mcg per inhalation Leukotriene Modifiers7 Montelukast – Singulair (Merck) Zafirlukast – generic Accolate (AstraZeneca) Zileuton – Zyflo (Cornerstone) extended-release Zyflo CR Anticholinergics9 Ipatropium – generic Atrovent HFA (Boehringer Ingelheim) Tiotropium – Spiriva HandiHaler (Boehringer Ingelheim) Anti-IgE Antibody Omalizumab – Xolair (Genentech) Powder for injection 150 mg/5 mL vial Theophylline generic Theo-24 (UCB Pharma) Uniphyl (Purdue) 100, 125, 200, 300 mg ER caps;100, 200, 300, 400, 450, 600 mg ER tabs; 80 mg/15mL oral elixir11 100, 200, 300, 400 mg ER caps11 400, 600mg ER tabs11 150-300 mg SC q4wks >12 yrs: 150-300 mg q4wks or 225-375 mg SC q2wks10 or 225-375 mg q2wks10 300-600 mg/once day or divided bid 10 mg/kg/d12 300-600 mg once/day 400-600 mg once/day Use of a long-acting beta-2 agonist (LABA) alone without concomitant use of a long-term asthma controller medication is contraindicated in the treatment of asthma Only the 100 mcg/50 mcg formulation is approved for use in children Montelukast is taken once daily in the evening, with or without food Montelukast granules must be taken within 15 minutes of opening the packet Zafirlukast is taken hour before or hours after a meal Zileuton is taken within one hour after morning and evening meals Montelukast is approved for prevention of exercise-induced bronchoconstriction only in patients >15 years Dosage for 12-23 months: one packet of 4-mg oral granules; for 2-5 yrs: 4-mg chewable tab once/d or one packet of mg oral granules; for 6-14 yrs: 5-mg chewable tab once/d Not FDA-approved for asthma 10 Dose depends on the patient’s body weight and total serum IgE level See package insert for specific dosing instructions 11 Extended-release formulations may not be interchangeable If Theo-24 is taken 1 year old; in infants 0.2 x (age in weeks) + = dose in mg/kg/day Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 114) • February 2012 15 Drugs for Asthma recognize anaphylaxis and told to self-inject epinephrine promptly if it occurs.19 of a short course of an oral glucocorticoid Doubling the dose of an ICS is not effective and quadrupling the dose is only marginally effective.24 IMMUNOTHERAPY In selected patients with allergic asthma, specific immunotherapy (“allergy shots”) may provide longlasting benefits in reducing asthma symptoms and the need for medications.20 BRONCHIAL THERMOPLASTY Approved by the FDA in 2010 for use in adults with severe persistent asthma not well controlled on an ICS and a LABA, bronchial thermoplasty has been shown to modestly improve lung function and asthma symptoms.21 Patients undergo fiber optic bronchoscopy on separate occasions weeks apart During the procedure, the walls of the central airways are treated with radiofrequency energy that is converted to heat (target tissue temperature 65°C), resulting in ablation of airway smooth muscle Adverse effects, mainly worsening of asthma, are common in the weeks immediately following bronchial thermoplasty A long-term study found that lung function appears to remain stable for at least years following the procedure.22 TREATMENT FAILURE Failure of pharmacologic treatment can usually be attributed to lack of adherence to prescribed medications, uncontrolled co-morbid conditions or continued exposure to tobacco smoke and other airborne pollutants, allergens or irritants Smoking and exposure to second-hand smoke can cause airway hyperresponsiveness and decrease the effectiveness of ICSs Some patients with asthma may concurrently be taking aspirin or other NSAIDs that can cause asthma symptoms Oral or topical nonselective beta-adrenergic blockers, such as propranolol (Inderal, and others) or timolol, can precipitate bronchospasm in patients with asthma and decrease the bronchodilating effect of beta2 agonists Patients with moderate or severe asthma may benefit from meeting with trained asthma educators to have their inhaler technique checked and develop a personalized asthma management plan.23 MANAGING EXACERBATIONS Intensifying treatment at home when symptoms begin can prevent exacerbations from becoming severe Selfmanagement of asthma exacerbations, guided by a written asthma action plan, generally calls for increased doses of a SABA and, sometimes, initiation 16 Treatment of acute asthma in the urgent care setting or emergency department generally involves supplemental oxygen to relieve hypoxemia and a SABA (sometimes in combination with ipratropium), usually administered by face mask and nebulizer In moderate or severe exacerbations, an oral or intravenous glucocorticoid is added to reduce airway inflammation Severe asthma exacerbations unresponsive to these measures may respond to intravenous magnesium sulphate, especially in children, or to inhalation of heliox (typically a mixture of helium 79% and oxygen 21%) to decrease airflow resistance and improve delivery of aerosolized medications.25 EXERCISE-INDUCED BRONCHOCONSTRICTION Exercise-induced bronchoconstriction (EIB) may be the only manifestation of asthma in patients with mild disease EIB may also be a transient phenomenon in non-asthmatic athletes.26 SABAs used just before exercise will prevent EIB for 2-3 hours after inhalation in most patients LABAs prevent EIB for up to 12 hours, but if they are taken regularly, the protection may wane and not last throughout the day Montelukast decreases EIB in up to 50% of patients within hours after administration; the protection may last for up to 24 hours and does not wane with repeated use In some patients, EIB occurs because of poorly-controlled persistent asthma; in these patients, daily anti-inflammatory medications should be started or increased in dosage.3 ASTHMA IN PREGNANCY Maternal asthma increases the risk of pregnancy-related complications including pre-eclampsia, perinatal mortality, preterm birth and low birth weight.27 Albuterol is the preferred SABA for use in pregnancy ICSs (budesonide is the best studied) are the preferred long-term controller medications in pregnancy; they not appear to cross the placenta or have any effects on fetal adrenal function and are therefore unlikely to have adverse effects on fetal growth and development.27,28 The safety of low-to-moderate doses of ICSs has been confirmed in a cohort study of 13,280 pregnancies; the incidence of major congenital malformations was increased with use of higher ICS doses (>1000 mcg/day beclomethasone equivalent) during the first trimester.29 LABAs and montelukast appear to be safe in pregnancy.30 Teratogenicity in animals has been reported with zileuton Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 114) • February 2012 Drugs for Asthma ASTHMA IN CHILDREN For children with mild intermittent asthma, a SABA should be used as needed For mild, moderate or severe persistent asthma, ICSs are the preferred longterm treatment for control of symptoms; ICSs not, however, alter the underlying severity or progression of the disease In young children, a SABA or an ICS may best be delivered through a metered-dose inhaler with a valved holding chamber and face mask or mouthpiece, or through a nebulizer Dry powder inhalers are not suitable for use in young children, who cannot reliably inhale rapidly or deeply enough to use them effectively Nebulized budesonide is FDA-approved for use in children as young as one year of age ICSs given in low doses for years are generally safe for use in children, but linear growth should be monitored Low- or medium-dose ICSs administered regularly may reduce growth velocity slightly during the first year of treatment, but final adult height does not appear to be affected.7 Montelukast can be used as the controller in children whose parents prefer not to use an ICS It may also be used instead of a LABA as an add-on to an ICS, but it is generally less effective cologic treatment of both asthma and rhinitis improves asthma outcomes.35 Patients with concomitant allergic rhinitis and allergic asthma may benefit from specific immunotherapy with standardized allergens.20 GERD – Patients with poorly controlled asthma have a higher prevalence of GERD, but no cause-and-effect relationship has been demonstrated In asthma patients who have concomitant GERD symptoms, treatment with a proton pump inhibitor may slightly improve pulmonary function and asthma-related quality of life.36 In asthma patients with asymptomatic GERD, treatment with a proton pump inhibitor does not improve asthma control.37 Obesity – Obesity has been associated with asthma persistence and severity.4 Overweight and obese asthmatic patients may have a diminished response to ICSs.38 Weight loss may improve lung function and responsiveness to treatment Bariatric surgery has been reported to improve asthma control and airway hyperresponsiveness in overweight adults.39 ASTHMA IN THE ELDERLY Asthma in the elderly is often associated with co-morbidities, such as cardiovascular disease, diabetes, dementia, depression and frailty, and with polypharmacy Elderly asthmatic patients are more likely to have fixed airway obstruction with features that overlap COPD The elderly have more adverse effects from ICSs, including skin bruising, cataracts, increased intraocular pressure, hyperglycemia and accelerated loss of bone mass They may have both a reduced response to beta-adrenergic bronchodilators, especially if concomitantly taking a beta blocker, and an increased incidence of tachycardia, arrhythmias and tremors In these patients, tiotropium can be a useful bronchodilator Some older patients have difficulty inhaling any medication from a metered-dose or drypowder inhaler and may require a nebulizer.31-33 10 11 12 ASTHMA AND CO-MORBID DISEASES 13 Asthma is often associated with other co-morbid conditions including allergic rhinitis, gastroesophageal reflux disease (GERD), obesity, sinusitis, depression and anxiety Such co-morbidities can make asthma more difficult to treat.34 Allergic Rhinitis – Up to 95% of patients with asthma also suffer from persistent rhinitis Concurrent pharma- 14 15 16 17 CH Fanta Asthma N Engl J Med 2009; 360:1002 PM O’Byrne Therapeutic strategies to reduce asthma exacerbations J Allergy Clin Immunol 2011; 128:257 JM Weiler et al Pathogenesis, prevalence, diagnosis, and management of exercise-induced bronchoconstriction: a practice parameter Ann Allergy Asthma Immunol 2010; 105 (6 suppl):S1 National Heart, Lung and Blood Institute National Asthma Education and Prevention Program (NAEPP) Expert Panel Report (EPR) Guidelines for the diagnosis and management of asthma Full Report 2007 Available at www.nhlbi.nih.gov/guidelines/asthma/index.htm Accessed January 18, 2012 RC Strunk et al Long-term budesonide or nedocromil treatment, once discontinued, does not alter the course of mild to moderate asthma in children and adolescents J Pediatr 2009; 154:682 HW Kelly Comparison of inhaled corticosteroids: an update Ann Pharmacother 2009; 43:519 S Pedersen Clinical safety of inhaled corticosteroids for asthma in children: an update of long-term trials Drug Saf 2006; 29:599 PM O’Byrne et al Risks of pneumonia in patients with asthma taking inhaled corticosteroids Am J Respir Crit Care Med 2011; 183:589 E Bateman et al Meta-analysis: effects of adding salmeterol to inhaled corticosteroids on serious asthma-related events Ann Intern Med 2008; 149:33 RF Lemanske, Jr et al Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids N Engl J Med 2010; 362:975 AW McMahon et al Age and risks of FDA-approved long-acting ßadrenergic receptor agonists Pediatrics 2011; 128:e1147 BA Chowdhury et al Assessing the safety of adding LABAs to inhaled corticosteroids for treating asthma N Engl J Med 2011; 364:2473 PM O’Byrne et al Efficacy of leukotriene receptor antagonists and synthesis inhibitors in asthma J Allergy Clin Immunol 2009; 124:397 SP Peters et al Tiotropium bromide step-up therapy for adults with uncontrolled asthma N Engl J Med 2010; 363:1715 HA Kerstjens et al Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial J Allergy Clin Immunol 2011; 128:308 GJ Rodrigo et al Efficacy and safety of subcutaneous omalizumab vs placebo as add-on therapy to corticosteroids for children and adults with asthma: a systematic review Chest 2011; 139:28 NA Hanania et al Omalizumab in severe allergic asthma inadequately Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 114) • February 2012 17 Drugs for Asthma 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 controlled with standard therapy: a randomized trial Ann Intern Med 2011; 154:573 WW Busse et al Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children N Engl J Med 2011; 364:1005 L Cox et al American Academy of Allergy, Asthma & Immunology/American College of Allergy, Asthma & Immunology Omalizumab-Associated Anaphylaxis Joint Task Force follow-up report J Allergy Clin Immunol 2011; 128:210 MA Calderón et al Allergen-specific immunotherapy for respiratory allergies: from meta-analysis to registration and beyond J Allergy Clin Immunol 2011; 127:30 Bronchial thermoplasty for asthma Med Lett Dugs Ther 2010; 52:65 NC Thomson et al Long-term (5 year) safety of bronchial thermoplasty: Asthma Intervention Research (AIR) trial BMC Pulm Med 2011; 11:8 FM Ducharme et al Written action plan in pediatric emergency room improves asthma prescribing, adherence, and control Am J Respir Crit Care Med 2011; 183:195 J Oborne et al Quadrupling the dose of inhaled corticosteroid to prevent asthma exacerbations: a randomized, double-blind, placebo-controlled, parallel-group clinical trial Am J Respir Crit Care Med 2009; 180:598 SC Lazarus Emergency treatment of asthma N Engl J Med 2010; 363:755 V Bougault et al Airway hyperresponsiveness in elite swimmers: is it a transient phenomenon? J Allergy Clin Immunol 2011; 127:892 M Schatz and MP Dombrowski Asthma in pregnancy N Engl J Med 2009; 360:1862 NA Hodyl et al Fetal glucocorticoid-regulated pathways are not affected by inhaled corticosteroid use for asthma during pregnancy Am J Respir Crit Care Med 2011; 183:716 L Blais et al High doses of inhaled corticosteroids during the first trimester of pregnancy and congenital malformations J Allergy Clin Immunol 2009; 124:1229 LN Bakhireva et al Safety of leukotriene receptor antagonists in pregnancy J Allergy Clin Immunol 2007; 119:618 PG Gibson et al Asthma in older adults Lancet 2010; 376:803 CE Reed Asthma in the elderly: diagnosis and management J Allergy Clin Immunol 2010; 126:681 NA Hanania et al Asthma in the elderly: Current understanding and future research needs—a report of a National Institute on Aging (NIA) workshop J Allergy Clin Immunol 2011; 128:S4 M Cazzola et al Asthma and comorbid medical illness Eur Respir J 2011; 38:42 J Bousquet et al Allergic rhinitis and its impact on asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen) Allergy 2008; 63 Suppl 86:8 TO Kiljander et al Effect of esomeprazole 40 mg once or twice daily on asthma: a randomized, placebo-controlled study Am J Respir Crit Care Med 2010; 181:1042 American Lung Association Asthma Clinical Research Centers et al Efficacy of esomeprazole for treatment of poorly controlled asthma N Engl J Med 2009; 360:1487 E Forno et al Decreased response to inhaled steroids in overweight and obese asthmatic children J Allergy Clin Immunol 2011; 127:741 AE Dixon et al Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation J Allergy Clin Immunol 2011; 128:508 Mobile App Now Available Download The Medical Letter’s free App for the iPhone, iPad and Android through your device’s App store BlackBerry coming soon For more information: medicalletter.org/apps or scan the code below Treatment Guidelines ® from The Medical Letter EDITOR IN CHIEF: Mark Abramowicz, M.D EXECUTIVE EDITOR: Gianna Zuccotti, M.D., M.P.H., F.A.C.P., Harvard Medical School EDITOR: Jean-Marie Pflomm, Pharm.D ASSISTANT EDITORS, DRUG INFORMATION: Susan M Daron, Pharm.D., Corinne E Zanone, Pharm.D CONSULTING EDITORS: Brinda M Shah, Pharm.D., F Peter Swanson, M.D CONTRIBUTING EDITORS: Carl W Bazil, M.D., Ph.D., Columbia University College of Physicians and Surgeons Vanessa K Dalton, M.D., M.P.H., University of Michigan Medical School Eric J Epstein, M.D., Albert Einstein College of Medicine Jules Hirsch, M.D., Rockefeller University David N Juurlink, BPhm, M.D., PhD, Sunnybrook Health Sciences Centre Richard B Kim, M.D., University of Western Ontario Hans Meinertz, M.D., University Hospital, Copenhagen Sandip K Mukherjee, M.D., F.A.C.C., Yale School of Medicine Dan M Roden, M.D., Vanderbilt University School of Medicine F Estelle R Simons, M.D., University of Manitoba Jordan W Smoller, M.D., Sc.D., Harvard Medical 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members residing in Canada are eligible to receive Mainpro-M2 credits due to a reciprocal agreement with the American Academy of Family Physicians Treatment Guidelines CME activities are eligible for either Section or Section (when creating a personal learning project) in the Maintenance of Certification Program of the Royal College of Physicians and Surgeons of Canada (RCPSC) MISSION: The mission of The Medical Letter's Continuing Medical Education Program is to support the professional development of healthcare professionals including physicians, nurse practitioners, pharmacists and physician assistants by providing independent, unbiased drug information and prescribing recommendations that are free of industry influence The program content includes current information and unbiased reviews of FDA-approved and off-label uses of drugs, their mechanisms of action, clinical trials, dosage and administration, adverse effects and drug interactions The Medical Letter delivers educational content in the form of self-study material The expected outcome of the CME Program is to increase the participant’s ability to know, or apply knowledge into practice after assimilating, information presented in materials contained in Treatment Guidelines The Medical Letter will strive to continually improve the CME program through periodic assessment of the program and activities The Medical Letter aims to be a leader in supporting the professional development of healthcare professionals through Core Competencies by providing continuing medical education that is unbiased and free of industry influence The Medical Letter is supported solely by subscription fees and accepts no advertising, grants or donations GOAL: Through this program, The Medical Letter expects to provide the healthcare community with unbiased, reliable and timely educational content that they will use to make independent and informed therapeutic choices in their practice LEARNING OBJECTIVES: The objective of this activity is to meet the need of healthcare professionals for unbiased, reliable and timely information on treatment of major diseases The Medical Letter expects to provide the healthcare community with educational content that they will use to make independent and informed therapeutic choices in their practice Participants will be able to select and prescribe, or confirm the appropriateness of the prescribed usage of the drugs and other therapeutic modalities discussed in Treatment Guidelines with specific attention to clinical evidence of effectiveness, adverse effects and patient management Upon completion of this activity, the participant will be able to: Explain the current approach to the management of asthma Discuss the pharmacologic options available for treatment of asthma and compare them based on their efficacy, dosage and administration, potential adverse effects and drug interactions Determine the most appropriate therapy given the clinical presentation of an individual 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Call us at 800-211-2769 or 914-235-0500 or e-mail us at: custserv@medicalletter.org Questions start on next page Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 114) • February 2012 DO NOT FAX OR MAIL THIS EXAM To take this exam, go to: medicalletter.org/cme Issue 114 Questions Inhaled corticosteroids have been shown to be more effective than which of the following in clinical trials? a long-acting beta-2 agonists b leukotriene modifiers c theophylline d all of the above Issue 114 Failure of pharmacologic asthma treatment can usually be attributed to: a lack of adherence b uncontrolled co-morbid conditions c exposure to smoke d all of the above Issue 114 Montelukast is less likely than zafirlukast or zileuton to: a be effective b be safe in pregnancy c cause hepatotoxicity d prevent exercise-induced asthma Issue 114 Inhaled corticosteroids: a can cause dysphonia b are only effective in high doses c are effective even after they are discontinued d significantly affect adult height when used chronically in children Issue 114 A 25-year-old woman with asthma has been taking a low dose of an inhaled corticosteroid for months She has had some improvement in her asthma symptoms but still requires use of an inhaled short-acting beta-2 agonist about days per week You decide to add an inhaled long-acting beta-2 agonist to her regimen Addition of salmeterol or formoterol in patients with persistent asthma not well controlled on low-dose inhaled corticosteroids: a improves lung function b decreases symptoms c reduces rescue use of short-acting beta-2 agonists d all of the above Issue 114 Inhaled long-acting beta-2 agonists: a should not be used with an inhaled corticosteroid b are contraindicated in patients with allergic asthma c have been associated with an increased risk of asthmarelated death d are the first-line treatment for patients with mild asthma Issue 114 Omalizumab: a is indicated only for allergic asthma b is given subcutaneously c has caused anaphylaxis d all of the above Issue 114 10 Which of the following statements about inhaled anticholinergics is true? a Both ipratropium and tiotropium are FDA-approved for use in patients with COPD b Ipratropium is used off-label as an alternate reliever medication in asthma patients intolerant to short-acting beta-2 agonist therapy c Tiotropium was as effective as a long-acting beta-2 agonist in patients with asthma not controlled on an inhaled corticosteroid in one study d all of the above Issue 114 Which of the following may be sufficient for asthma that is mild and intermittent? a an oral corticosteroid b omalizumab c an inhaled short-acting beta-2 agonist d an inhaled long-acting beta-2 agonist Issue 114 11 Which of the following is the least safe for use during pregnancy? a albuterol b zileuton c salmeterol d montelukast Issue 114 Inhaled short-acting beta-2 agonists: a reduce airway inflammation b can prevent exercise-induced bronchoconstriction c should be taken twice a day d have a 12-hour duration of action 12 Peak theophylline concentrations should be: a 5-10 mcg/mL b 10-15 mcg/mL c 15-20 mcg/mL d above 20 mcg/mL Issue 114 Issue 114 ACPE UPN: 379-0000-12-114-H01-P; Release: January 2012, Expire: January 2013 Treatment Guidelines from The Medical Letter • Vol 10 ( Issue 114) • February 2012 ... Treatment of Asthma Drugs for Asthma Page 13 Pages 14-15 Drugs for Asthma RECOMMENDATIONS: Use of a short-acting bronchodilator as needed for relief of symptoms may be sufficient for asthma patients... Issue 114) • February 2012 13 Drugs for Asthma Table Drugs for Asthma Some Available Formulations Drug Inhaled Beta-2 Agonists, Short-Acting Albuterol – generic Solution for nebulization1 single-dose... 114) • February 2012 Drugs for Asthma ASTHMA IN CHILDREN For children with mild intermittent asthma, a SABA should be used as needed For mild, moderate or severe persistent asthma, ICSs are the