The Medical Letter ® on Drugs and Therapeutics Volume 59 ISSUE ISSUE No 1433 1518 April 10, 2017 IN THIS ISSUE Drugs for COPD Volume 56 Important Copyright Message FORWARDING OR COPYING IS A VIOLATION OF U.S AND INTERNATIONAL COPYRIGHT LAWS The Medical Letter, Inc publications are protected by U.S 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 U.S 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 Published by The Medical Letter, Inc • A Nonprofit Organization 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 The Medical Letter ® on Drugs and Therapeutics Volume 59 April 10, 2017 Take CME Exams ISSUE ISSUE No 1433 1518 IN THIS ISSUE Drugs for COPD Volume 56 The main goals of treatment for chronic obstructive pulmonary disease (COPD) are to relieve symptoms, reduce the frequency and severity of exacerbations, and prevent disease progression Updated guidelines for treatment of COPD have been published in recent years.1,2 Some Recommendations for Treatment of COPD ▶ Patients with COPD should stop smoking; pharmacotherapy can be helpful, especially with varenicline (Chantix) ▶ Patients with occasional dyspnea can use inhaled shortacting bronchodilators as needed for acute symptom relief ▶ For patients who have moderate to severe dyspnea or TABLES IN THIS ISSUE Some Inhaled Bronchodilators for COPD p 58 Some Long-Acting Bronchodilator Inhalers: Ease of Use p 59 Some Inhaled Corticosteroids and Other Drugs for COPD p 60 Treatment of COPD p 61 Inhaled Short-Acting Bronchodilators for COPD online only Inhaled Long-Acting Bronchodilators for COPD online only Some Inhaled Corticosteroids for COPD online only Correct Use of Inhalers for COPD online only SMOKING CESSATION — Cigarette smoking is the primary cause of COPD in the US Smoking cessation offers health benefits at all stages of the disease and can slow the decline of lung function Counseling and pharmacotherapy can help patients stop smoking Varenicline (Chantix) appears to be the most effective drug for treatment of tobacco dependence Nicotine replacement therapy and bupropion (Zyban, and others) are also effective.3 Use of ≥2 medications has been more effective than monotherapy.4,5 SHORT-ACTING BRONCHODILATORS — For patients with occasional dyspnea, an inhaled short-acting bronchodilator can provide acute relief Short-acting drugs, which include inhaled beta2-agonists such as albuterol and the antimuscarinic (anticholinergic) ipratropium, can relieve symptoms and improve FEV1 (forced expiratory volume in one second) Shortacting beta2-agonists have a more rapid onset of action than ipratropium, but ipratropium has a longer duration of action (6-8 hrs vs ~4 hrs) Combining a short-acting beta2-agonist with ipratropium is more effective than either drug alone.6 The combination of ipratropium and albuterol is available in a single inhaler (see Table 1) ▶ ▶ ▶ ▶ ▶ symptoms, or who are at increased risk of exacerbations, regular treatment with an inhaled long-acting bronchodilator (an antimuscarinic or a beta2-agonist) can relieve symptoms, improve lung function, and reduce the frequency of exacerbations An inhaled long-acting beta2-agonist plus an inhaled longacting antimuscarinic can be used in patients with moderate to severe dyspnea or symptoms who are at increased risk for exacerbations and in those inadequately controlled on monotherapy Addition of an inhaled corticosteroid is recommended for patients with moderate to severe COPD who experience frequent exacerbations despite treatment with bronchodilators All patients should be assessed for proper inhalation technique Oxygen therapy can improve survival in patients with severe hypoxemia Pulmonary rehabilitation should be considered for all patients Regular use of an inhaled short-acting bronchodilator is not recommended for treatment of COPD Patients on maintenance treatment for COPD should have a short-acting bronchodilator available for use as needed for acute relief INHALED LONG-ACTING BRONCHODILATORS — Regular treatment with an inhaled long-acting bronchodilator (either a beta2-agonist or an antimuscarinic agent) is recommended for patients who have moderate to severe dyspnea or symptoms or who are at increased risk of exacerbations Long-acting antimuscarinic agents (LAMAs; also called long-acting anticholinergics) may be more effective than long-acting beta2-agonists (LABAs) in preventing exacerbations in patients with moderate to very severe COPD.7,8 In patients with less severe COPD, there is no strong evidence supporting the use of one over the other.9,10 57 Published by The Medical Letter, Inc • A Nonprofit Organization The Medical Letter April 10, 2017 Vol 59 (1518) ® Table Some Inhaled Bronchodilators for COPD Drug Some Available Formulations Delivery Device1 Usual Adult Dosage Cost2 17 mcg/inh HFA MDI (200 inh/unit) inh qid PRN $332.70 200 mcg/mL soln Nebulizer3 500 mcg qid PRN 90 mcg/inh HFA MDI (605 or 200 inh/unit) 90-180 mcg q4-6h PRN 90 mcg/inh 0.63, 1.25, 2.5 mg/ mL soln DPI (200 inh/unit) Nebulizer3 90-180 mcg q4-6h PRN 1.25-5 mg q4-8h PRN 45 mcg/inh 0.31, 0.63, 1.25 mg/ mL soln HFA MDI (80, 200 inh/unit) Nebulizer3 90 mcg q4-6h PRN 0.63-1.25 mg tid PRN 68.20 855.00 439.90 344.907 Inhaled Short-Acting Antimuscarinic Ipratropium – Atrovent HFA (Boehringer Ingelheim) generic – single-dose vials 18.104 Inhaled Short-Acting Beta2-Agonists Albuterol – ProAir HFA (Teva) Proventil HFA (Merck) Ventolin HFA (GSK) ProAir Respiclick (Teva) generic Levalbuterol – Xopenex HFA (Sunovion) Xopenex (Akorn) generic 56.20 75.40 52.20 53.00 21.306 Inhaled Short-Acting Beta2-Agonist/Short-Acting Antimuscarinic Combination Albuterol/ipratropium – Combivent Respimat (Boehringer Ingelheim) generic 100 mcg/20 mcg/inh ISI (120 inh/unit) inh qid PRN 2.5 mg/0.5 mg/3 mL soln Nebulizer3 2.5 mg/0.5 mg qid PRN 73.107 Inhaled Long-Acting Beta2-Agonists (LABAs) Arformoterol – Brovana (Sunovion) 15 mcg/2 mL soln Nebulizer3 15 mcg bid 871.20 Indacaterol – Arcapta Neohaler (Sunovion) 75 mcg/cap DPI (30 inh/unit) inh once/d 213.60 Olodaterol – Striverdi Respimat (Boehringer Ingelheim) 2.5 mcg/inh ISI (60 inh/unit) inh once/d 181.60 Salmeterol – Serevent Diskus (GSK) 50 mcg/blister DPI (28, 60 inh/unit) inh bid 351.60 Formoterol – Perforomist (Mylan) 20 mcg/2 mL soln Nebulizer3 20 mcg bid 838.80 Inhaled Long-Acting Antimuscarinic Agents (LAMAs)8 Aclidinium – Tudorza Pressair (AstraZeneca) 400 mcg/inh DPI (30, 60 inh/unit) inh bid 322.20 Glycopyrrolate – Seebri Neohaler (Sunovion) 15.6 mcg/cap DPI (6, 60 inh/unit) inh bid 394.20 Tiotropium – Spiriva Handihaler (Boehringer Ingelheim) 18 mcg/cap Spiriva Respimat 2.5 mcg/inh DPI (5, 30, 90 inh/unit) ISI (60 inh/unit) 18 mcg9 once/d inh once/d 368.20 368.20 Umeclidinium – Incruse Ellipta (GSK) DPI (7, 30 inh/unit) inh once/d 324.10 62.5 mcg/inh Inhaled Long-Acting Antimuscarinic Agents/Long-Acting Beta2-Agonist Combinations (LAMA/LABA Combinations) Glycopyrrolate/formoterol – Bevespi Aerosphere (AstraZeneca) mcg/4.8 mcg/inh HFA MDI (120 inh/unit) inh bid 334.60 Glycopyrrolate/indacaterol – Utibron Neohaler (Sunovion) 15.6 mcg/27.5 mcg/cap DPI (60 inh/unit) inh bid 340.20 Tiotropium/olodaterol – Stiolto Respimat (Boehringer Ingelheim) 2.5 mcg/2.5 mcg/inh ISI (60 inh/unit) inh once/d 340.90 Umeclidinium/vilanterol – Anoro Ellipta (GSK) 62.5 mcg/25 mcg/inh DPI (7, 30 inh/unit) inh once/d 340.90 DPI = dry powder inhaler; ER = extended-release; HFA = hydrofluoroalkane; inh = inhalation; ISI = inhalation spray inhaler; MDI = metered-dose inhaler All patients should be assessed for proper inhalation technique Approximate WAC for 30 days’ treatment at the lowest recommended adult dosage For short-acting beta2-agonists and Atrovent HFA, cost is for 200 inhalations WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly March 5, 2017 Reprinted with permission by First Databank, Inc All rights reserved ©2017 www.fdbhealth.com/policies/drug-pricing-policy Nebulized solutions may be used for very young, very old, and other patients unable to use handheld inhalers More time is required to administer the drug and the device may not be portable Nebulizers and nebulized drugs may be covered as durable medical equipment (DME) under Medicare part B Cost for 100 doses Only Ventolin HFA is available in an inhaler containing 60 inh/unit Cost for 100 2.5-mg doses Cost for 120 doses Also called inhaled long-acting anticholinergics Contents of one capsule; two inhalations of the powder are required to deliver the full dose 58 The Medical Letter ® LABAs can provide sustained bronchodilation for at least 12 hours They have been shown to improve lung function and quality of life, and to reduce the frequency of exacerbations in patients with COPD.11 Several inhaled LABAs are available alone or in fixeddose combinations with other agents for treatment of COPD in the US (see Tables and 3) Inhaled beta2-agonists can cause tachycardia, palpitations, prolongation of the QT interval, hypokalemia, skeletal muscle tremors and cramping, headache, insomnia, and increases in serum glucose concentrations Unstable angina and myocardial infarction have been reported Tolerance can develop with continued use All LABAs in the US include a boxed warning about an increased risk of asthma-related death; there is no evidence to date that patients with COPD are at risk Four inhaled LAMAs are available alone or in combination with other agents for the treatment of COPD (see Table 1) Tiotropium, the longest available and best studied LAMA, has been shown to improve lung function and reduce exacerbation and hospitalization rates, but it may not reduce the rate of lung function decline.12,13 The other three LAMAs are generally considered similar in safety and efficacy to tiotropium.14-16 Inhaled antimuscarinics have limited systemic absorption They commonly cause dry mouth Pharyngeal irritation, urinary retention, and increases in intraocular pressure may occur; antimuscarinic inhalers should be used with caution in patients with narrow-angle glaucoma and in those with symptomatic prostatic hypertrophy or bladder neck obstruction Long-Acting Bronchodilator Combinations – Combining a LAMA with a LABA can improve lung function and reduce symptoms, and may decrease exacerbation rates in patients with COPD Dual bronchodilator therapy is recommended for patients who have moderate to severe dyspnea or symptoms and are at increased risk for exacerbations and for those with persistent symptoms or exacerbations despite use of a single long-acting bronchodilator.17,18 Four fixed-dose combinations of a LAMA and a LABA have been approved by the FDA (see Table 1) INHALED CORTICOSTEROIDS (ICSs) — ICSs not slow the progression of COPD or reduce mortality.19 They are less effective than inhaled long-acting bronchodilators for treatment of COPD and should not be used as monotherapy Use of an ICS in addition to a long-acting bronchodilator can improve lung function and reduce exacerbations.20 Addition of an ICS is recommended Vol 59 (1518) April 10, 2017 Table Some Long-Acting Bronchodilator Inhalers: Ease of Use Aerosphere Inhaler Bevespi Aerosphere (glycopyrrolate/formoterol) ▶ Metered-dose inhaler; requires coordination of inhalation with hand-actuation; drug delivery is not dependent on strength of breath intake ▶ Easy to assemble; requires priming ▶ Indicator shows approximately how many doses are left ▶ Twice-daily dosing Ellipta Inhalers Anoro Ellipta (umeclidinium/vilanterol), Breo Ellipta (fluticasone furoate/vilanterol), Incruse Ellipta (umeclidinium) ▶ Dry powder inhaler; drug delivery to lungs is dependent upon ability to perform a rapid, deep inhalation ▶ No assembly or priming required ▶ Indicator shows how many doses are left ▶ Doses may be wasted if inhaler is opened/closed accidentally ▶ Once-daily dosing Respimat Inhalers Spiriva Respimat (tiotropium), Striverdi Respimat (olodaterol), Stiolto Respimat (tiotropium/olodaterol) ▶ Inhalation spray inhaler; drug delivery to lungs is not dependent on strength of breath intake ▶ Assembly may be difficult for some patients ▶ Indicator shows approximately how many doses are left ▶ Once-daily dosing Neohaler Inhalers Arcapta Neohaler (indacaterol), Seebri Neohaler (glycopyrrolate), Utibron Neohaler (glycopyrrolate/indacaterol) ▶ Dry powder inhaler; drug delivery to lungs is dependent upon ability to perform a rapid, deep inhalation ▶ Removal of the capsule from the foil pack and insertion of the capsule into the inhaler may be difficult for some patients ▶ Transparent capsules may be helpful in determining if the full dose was inhaled ▶ Once-daily dosing (Arcapta); twice-daily dosing (Utibron, Seebri) Pressair Inhaler Tudorza Pressair (aclidinium) ▶ Dry powder inhaler; drug delivery to lungs is dependent upon ability to perform a rapid, deep inhalation ▶ No assembly required ▶ Twice-daily dosing Handihaler Inhaler Spiriva Handihaler (tiotropium) ▶ Dry powder inhaler; drug delivery to lungs is dependent upon ability to perform a rapid, deep inhalation ▶ Inserting the capsules into the device may be difficult for some patients ▶ Once-daily dosing Diskus Inhalers Advair Diskus (fluticasone propionate/salmeterol), Serevent Diskus (salmeterol) ▶ Dry powder inhaler; drug delivery to lungs is dependent upon ability to perform a rapid, deep inhalation ▶ Indicator shows how many doses are left ▶ Twice-daily dosing for patients with moderate to very severe COPD who continue to have exacerbations while receiving longacting bronchodilators Various combinations of ICSs and LABAs are available (see Table 3) Adverse Effects – Local effects of ICSs on the mouth and pharynx include candidiasis and dysphonia 59 The Medical Letter April 10, 2017 Vol 59 (1518) ® Table Some Inhaled Corticosteroids and Other Drugs for COPD Drug Some Available Formulations Delivery Device1 Usual Adult Dosage Cost2 Inhaled Corticosteroids (ICSs)3 Beclomethasone dipropionate – QVAR (Teva) 40, 80 mcg/inh HFA MDI (120 inh/unit) 40-320 mcg bid $156.70 Budesonide4 – Pulmicort Flexhaler (AstraZeneca) 90, 180 mcg/inh DPI (60, 120 inh/unit) 180-720 mcg bid 216.50 Ciclesonide – Alvesco (Sunovion) 80, 160 mcg/inh HFA MDI (60 inh/unit) 80-320 mcg bid 228.90 Flunisolide – Aerospan HFA (Meda) 80 mcg/inh HFA MDI (60, 120 inh/unit) 160-320 mcg bid 196.10 Fluticasone furoate – Arnuity Ellipta (GSK) 100, 200 mcg/inh DPI (14, 30 inh/unit) 100-200 mcg once/d 159.00 Fluticasone propionate – Flovent Diskus (GSK) Flovent HFA ArmonAir Respiclick (Teva) 50, 100, 250 mcg/blister 44, 110, 220 mcg/inh 55, 113, 232 mcg/inh DPI (28, 60 inh/unit) HFA MDI (120 inh/unit) DPI (60 inh/unit) 100-1000 mcg bid 88-880 mcg bid 55-232 mcg bid 171.40 171.40 N.A 100, 200 mcg/inh 110, 220 mcg/inh HFA MDI (120 inh/unit) DPI (30, 60, 120 inh/unit) 200-400 mcg bid 220-880 mcg once/d in evening or 220 mcg bid 178.80 179.00 Mometasone furoate – Asmanex HFA (Merck) Asmanex Twisthaler (Merck) Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combinations (ICS/LABA Combinations) Fluticasone propionate/salmeterol – Advair Diskus5 (GSK) 100, 250, 500 mcg/50 mcg/ DPI (28, 60 inh/unit) blister 45, 115, 230 mcg/21 mcg/inh HFA MDI (60, 120 inh/unit) 55, 113, 232 mcg/14 mcg/inh DPI (60 inh/unit) 250/50 mcg bid 361.40 inh bid inh bid 290.90 N.A Fluticasone furoate/vilanterol – Breo Ellipta6 (GSK) 100, 200 mcg/25 mcg/inh DPI (14, 30 inh/unit) inh once/d 321.70 Budesonide/formoterol – Symbicort7 (AstraZeneca) 80, 160 mcg/4.5 mcg/inh HFA MDI (60, 120 inh/unit) inh bid 308.70 500 mcg tabs none 500 mcg PO once/d 199.00 100, 200, 300, 400, 450, 600 mg ER tabs; 80 mg/15 mL soln 80 mg/15 mL soln none 300-600 mg PO once/d or divided bid Advair HFA3 AirDuo Respiclick3 (Teva) Phosphodiesterase-4 (PDE4) Inhibitor Roflumilast – Daliresp (AstraZeneca) Methylxanthine Theophylline8,9 – generic Elixophyllin (Nostrum Labs) Theo-24 (Auxilium) Theochron (Caraco) 100, 200, 300, 400 mg ER caps 100, 200, 300 mg ER tabs 15.90 300-600 mg/d PO 1261.30 divided tid-qid 300-600 mg PO once/d10 86.50 300-600 mg PO once/d 15.10 DPI = dry powder inhaler; ER = extended-release; HFA = hydrofluoroalkane; inh = inhalation; ISI = inhalation spray inhaler; MDI = metered-dose inhaler; NA = cost not available All patients should be assessed for proper inhalation technique Approximate WAC for 30 days’ treatment at the lowest usual adult dosage WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price Source: AnalySource® Monthly March 5, 2017 Reprinted with permission by First Databank, Inc All rights reserved ©2017 www.fdbhealth.com/policies/drug-pricing-policy Not FDA-approved for treatment of COPD Inhaled corticosteroid monotherapy is not recommended for treatment of COPD Budesonide is also available as a suspension for nebulization (Pulmicort Respules, and generics) that is FDA-approved only for treatment of asthma in children 1-8 years old Only the 250/50 mcg dose is FDA-approved for use in COPD Only the 100/25 mcg dose is FDA-approved for use in COPD Only the 160/4.5 mcg dose is FDA-approved for use in COPD Extended-release formulations may not be interchangeable Periodic monitoring is recommended to maintain peak serum concentrations between and 12 mcg/mL 10 Theo-24 should not be taken