Drugs for asthma and COPD

Treatment Guidelines from The Medical Letter® Published by The Medical Letter, Inc • 145 Huguenot Street, New Rochelle, NY 10801 • A Nonprofit Pub lication IN THIS ISSUE (starts on next page) Drugs for Asthma and COPD p 75 Important Copyright Message The Medical Letter ® publications are protected b y US and inter national 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 ag ree to comply with US and inter national 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 11 (Issue 132) August 2013 (supercedes vol [Issue 99] November 2010 and vol 10 [Issue 114] February 2012) www.medicalletter.org Tables Treatment of Asthma Some FDA-Approved Drugs for Asthma Treatment of COPD Some FDA-Approved Drugs for COPD Page 76 Pages 78-79 Page 83 Page 84 Drugs for Asthma and COPD Related article(s) since publication ASTHMA Patients whose symptoms are mild and infrequent can use a short-acting bronchodilator as needed for relief of symptoms Patients with more frequent cough, wheeze, chest tightness or shortness of breath should begin treatment with a long-term controller medication Low daily doses of an inhaled corticosteroid suppress airway inflammation and reduce the risk of exacerbations For patients who remain symptomatic despite compliance with inhaled corticosteroid treatment and good inhalational technique, addition of a long-acting beta2-agonist is recommended Patients with more severe disease may need higher doses of inhaled corticosteroids Failure of pharmacologic treatment can often be attributed to lack of adherence to prescribed medications, uncontrolled co-morbid conditions such as allergic rhinitis, or continued exposure to tobacco smoke or other airborne pollutants, allergens or irritants INHALATION DEVICES — Metered-dose inhalers (MDIs) require coordination of inhalation with handactuation of the device Valved holding chambers (VHCs) or spacers help some patients, especially young children and the elderly, use MDIs effectively VHCs have one-way valves that prevent the patient from exhaling into the device, minimizing the need for coordinated actuation and inhalation Spacers are tubes or chambers placed between the canister and a face mask or mouthpiece, which also avoids the need to coordinate actuation and inhalation Both VHCs and spacers retain the larger particles emitted from the MDI, decreasing their deposition in the oropharynx and leading to a higher proportion of small respirable particles being inhaled Dry powder inhalers (DPIs), which are breathactuated and not require a propellant, can be used in patients who are capable of performing a rapid deep inhalation Delivery of inhaled medications through a nebulizer with a face mask or mouthpiece is less dependent on the patient’s coordination and cooperation, but more time-consuming, less efficient, and more costly than delivery through an MDI or DPI SHORT-ACTING BETA2-AGONISTS — Inhaled short-acting beta2-agonists (SABAs) 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 exercise-induced bronchoconstriction (EIB) In patients whose asthma is well controlled, SABAs should be needed infrequently (12 years old Treatment should be adjusted based on response All regimens include use of a SABA as needed The ideal dose of an ICS is the lo west dose that maintains asthma control The FDA recommends stopping a LABA once symptoms are controlled, but the recommendation is controversial (SJ Szefler and WW Busse J Allergy Clin Immunol 2012; 130:1256) In patients who remain uncontrolled despite agg ressive treatment with a high-dose ICS plus a LABA, or al glucocorticoids are sometimes added Addition of omalizumab can be considered in patients with allergic asthma Most of the beneficial effects of ICSs are achieved at relatively low doses The ideal dose for a given patient is the lowest dose that maintains asthma control; this dose may change seasonally and over time Current evidence suggests that, at usual doses, all ICSs are similar in efficacy; they are not interchangeable, however, on a per-microgram or per-puff basis because the dose varies with the drug, the formulation and the delivery device.7 Adverse Effects – Local adverse effects of ICSs may include oral candidiasis (thrush), dysphonia, and reflex cough and bronchospasm Their incidence can be reduced by use of a valved holding chamber (VHC) or a spacer, and by mouth-rinsing after inhalation Clinically relevant adverse effects on hypothalamic-pituitary-adrenal (HPA) axis function generally not occur with low- or medium-dose ICSs Regular administration of low- or medium-dose ICSs may reduce growth slightly during the first year of treatment, especially in prepubertal patients In the Childhood Asthma Management Study (CAMP), which used a medium dose of an ICS, mean adult height was 1.2 cm less with budesonide compared to placebo.8 Patients who require high-dose ICS treatment should be monitored for HPA axis suppression, changes in bone density, and development of cataracts or glaucoma ICSs not increase the risk of pneumonia in patients with asthma.9 Oral – Systemic glucocorticoids are the most effective drugs available for exacerbations of asthma incom- 76 pletely responsive to bronchodilators Even when an acute exacerbation responds to bronchodilators, addition of a short course of an oral glucocorticoid can decrease symptoms and may prevent a relapse For asthma exacerbations, daily systemic glucocorticoids are generally required for only 3-10 days, after which no tapering is needed Oral glucocorticoids should only rarely be used as longterm control medications and then only in that small minority of patients with very poorly controlled severe persistent asthma despite compliance with an optimal treatment regimen of medications and environmental control In this situation, an oral glucocorticoid should be given at the lowest effective dose, preferably on alternate mornings, in order to minimize toxicity LONG-ACTING BETA2-AGONISTS — Monotherapy with an inhaled long-acting beta2-agonist (LABA), such as salmeterol or formoterol, is not recommended If a LABA is required, it should be used in combination with an ICS, preferably in the same inhaler The combination inhalers salmeterol/fluticasone (Advair), formoterol/budesonide (Symbicort) and formoterol/mometasone (Dulera) are FDA-approved for use in patients with persistent asthma that is not well-controlled on an ICS alone The addition of a LABA improves lung function, decreases symptoms and exacerbations, and reduces rescue use of shortacting beta2-agonists.10,11 LABAs are not indicated for relief of acute bronchospasm Adverse Effects – LABAs, especially if used in higher-than-recommended doses, can cause tremor, hypokalemia, tachycardia and other cardiac effects Tolerance (some loss of efficacy) can occur with daily use of a LABA.3 An FDA meta-analysis found that use of a LABA was associated with an increased risk of asthma-related hospitalization, intubation and death These results prompted the FDA to recommend that LABAs be discontinued once asthma is controlled A secondary analysis of the original meta-analysis did not find a significant increase in risk in a subset of patients who were assigned to use an ICS with a LABA.12 A meta-analysis of clinical trials in asthma patients controlled with a combination of an ICS and a LABA found that discontinuation of LABA therapy was associated with worsening asthma control.13 The manufacturers of LABAs are conducting post-marketing trials to assess the safety of a LABA-ICS combination compared to that of an ICS alone.14 LEUKOTRIENE MODIFIERS — Montelukast and zafirlukast are less effective alternatives to low-dose ICS treatment for patients who are unable or unwilling Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 Drugs for Asthma and COPD to use an ICS.15 Leukotriene modifiers are also generally less effective than an inhaled LABA as add-on therapy for patients not well controlled on an ICS alone Like LABAs, leukotriene modifiers are not recommended for treatment of acute asthma symptoms Adverse Effects – Montelukast is considered safe for long-term use Both zafirlukast and (especially) zileuton have been reported to cause life-threatening hepatic injury; liver function tests should be monitored and patients should be advised to discontinue the medication immediately if abdominal pain, nausea, jaundice, itching or lethargy occur Rarely, Churg-Strauss vasculitis has been reported with montelukast and zafirlukast; in most cases, this was probably a consequence of corticosteroid withdrawal rather than a direct effect of the drug.15 ANTICHOLINERGICS — Ipratropium bromide is an inhaled short-acting anticholinergic bronchodilator FDA-approved only to treat chronic obstructive pulmonary disease (COPD) It has been used off-label in asthma as an alternative reliever medication in patients who cannot take a SABA or in combination with a SABA for treatment of acute bronchoconstriction Tiotropium bromide, an inhaled long-acting anticholinergic bronchodilator, is also approved only for use in COPD (see Table 4) In patients with asthma uncontrolled on an ICS, addition of tiotropium has been as effective as adding a LABA in improving lung function and symptoms.16 Addition of tiotropium to combination treatment with an ICS and a LABA improved lung function in patients with poorly controlled severe asthma and increased the time to the first severe exacerbation.17,18 Adverse Effects – Anticholinergics can cause dry mouth, pharyngeal irritation, increased intraocular pressure and urinary retention, but inhaled ipratropium and tiotropium have limited systemic bioavailability They should be used with caution in patients with glaucoma, symptomatic prostatic hypertrophy, or bladder neck obstruction THEOPHYLLINE — Theophylline, taken alone or concurrently with an ICS, is now used infrequently for persistent asthma Monitoring serum theophylline concentrations is recommended to maintain peak levels between and 15 mcg/mL Adverse Effects – Theophylline can cause nausea, vomiting, nervousness, headache and insomnia At high serum concentrations, hypokalemia, hyperglycemia, tachycardia, cardiac arrhythmias, tremor, neuromuscular irritability, seizures and death can occur Theophylline is metabolized in the liver, mainly by CYP1A2 and CYP3A4 Many other drugs used concomitantly can interact with theophylline, either by increasing its metabolism and decreasing its serum concentrations and efficacy, or by decreasing its metabolism, leading to higher concentrations and toxicity Clearance of theophylline is reduced in elderly patients and those with liver disease or heart failure ANTI-IgE ANTIBODY — Omalizumab (Xolair) is a recombinant humanized monoclonal antibody that prevents IgE from binding to mast cells and basophils, thereby preventing release of 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 welldocumented specific sensitization to a perennial airborne allergen, such as mold, pollen or animal dander Subcutaneous injection of omalizumab every or weeks reduces asthma exacerbations and has a modest ICS-sparing effect In adults and adolescents, omalizumab added to standard treatment improved symptoms and reduced exacerbations.19,20 When added to standard treatment in children with allergic asthma, omalizumab improved asthma control, decreased exacerbations and reduced maintenance ICS doses.21 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 The labeling of omalizumab includes a boxed warning regarding the risk of anaphylaxis Consensus analyses of post-marketing data have reported a 0.09% rate of anaphylaxis in asthma patients receiving omalizumab injections They should be administered in a healthcare setting by providers prepared to manage potentially life-threatening anaphylaxis Patients should be kept under observation for hours after the first three omalizumab injections, and for 30 minutes after subsequent injections Some cases of anaphylaxis due to omalizumab have had an onset of symptoms more than hours post-injection Patients receiving omalizumab should be instructed on how to recognize anaphylaxis and advised to self-inject epinephrine promptly if it occurs.22 IMMUNOTHERAPY — In selected patients with allergic asthma, specific immunotherapy (subcutaneous injections and [off label] sublingual tablets) may provide long-lasting benefits in reducing asthma symptoms and the need for medications.23 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 may lead to modest improve- Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 77 Drugs for Asthma and COPD Table Some FDA-Approved Drugs for Asthma Some Available Formulations Drug Adult Dosage Pediatric Dosage HFA MDI (602 or 200 inh/unit) 90 mcg/inhalation 90-180 mcg q4-6h PRN >4 yrs: 90-180 mcg q4-6h PRN Solution for nebulization3 0.63, 1.25, 2.5mg/3mL 100 mg/20 mL 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 Cost1 Inhaled Beta2-Agonists, Short-Acting Albuterol – ProAir HFA (Teva) Proventil HFA (Merck) Ventolin HFA (GSK) generic single-dose vials multi-dose vials AccuNeb (Dey) single-dose vials Levalbuterol – Xopenex HFA (Sunovion) Xopenex (Sunovion) generic Pirbuterol5 – Maxair Autohaler (Valeant) Solution for nebulization3 0.63, 1.25 mg/3 mL —— HFA MDI (80, 200 inh/unit) 45 mcg/inhalation Solution for nebulization3 0.31, 0.63, 1.25 mg/3 mL 90 mcg q4-6h PRN 0.63-1.25 mg tid q6-8h PRN Breath-actuated CFC MDI (80, 400 inh/unit) 200 mcg/inh $45.00 52.00 40.00 24.004 6.004 180.004 >4 yrs: 90 mcg q4-6h PRN 48.00 621.00 536.00 200-400 mcg q4-6h PRN 6-11 yrs: 0.31-0.63 mg tid q6-8h PRN >12 yrs: 0.63- 1.25 mg tid q6-8h PRN >12 yrs: 200-400 mcg q4-6h PRN 40-320 mcg bid6 5-11 yrs: 40-80 mcg bid6 120.00 180-720 mcg bid 6-17 yrs: 180-360 mcg bid 161.00 308.008 80-320 mcg bid6 1-8 yrs: 0.25 mg bid or 0.5 mg once/day or bid or mg once/day6 >12 yrs: 80-320 mcg bid6 220.008 174.00 160-320 mcg bid6 6-11 yrs: 80-160 mcg bid6 N.A 100-1000 mcg bid6 4-11 yrs: 50-100 mcg bid6 121.00 88-880 mcg bid6 4-11 yrs: 88 mcg bid 121.00 220-880 mcg once/day in evening or 220 mcg bid 4-11 yrs: 110 mcg 1x/d in evening 142.00 409.00 Inhaled Corticosteroids Beclomethasone dipropionate – QVAR (Teva) HFA MDI (100 or 120 inh/unit) 40, 80 mcg/inhalation Budesonide – Pulmicort Flexhaler DPI (60, 120 inh/unit) (AstraZeneca) 90, 180 mcg/inhalation Pulmicort Respules (AstraZeneca) Suspension for nebulization7 single-dose ampules 0.25, 0.5 mg, mg/2mL generic – single-dose vials 0.25, 0.5 mg/2mL Ciclesonide – Alvesco HFA MDI (60 inh/unit) (Sunovion) 80, 160 mcg/inhalation Flunisolide – Aerospan HFA HFA MDI (60, 120 inh/unit) (Acton) 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) (Merck) 110, 220 mcg/inhalation —— CFC = Chlorofluorocarbon; DPI = Dry powder inhaler; HFA = Hydrofluoroalkane; MDI = Metered-dose inhaler; inh = inhalation; N.A = Not yet available Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended adult dosage For SABAs, cost is for 100 doses $ource® Monthly (Selected from FDB MedKnowledge™) July 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Only Ventolin HFA is available as 60 inhalations/unit Nebulized solutions may be used for very young, very old and other patients unable to use pressurized aerosols More time is required to administer the drug and the device may not be portable Cost of 100 2.5-mg doses (gener ics) or 1.25-mg doses (AccuNeb) CFC-containing MDIs will not be mar keted 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 Cost based on the lowest recommended pediatric dosage ments in exacerbation rates.24 Patients undergo fiberoptic 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 TREATMENT FAILURE — Failure of pharmacologic treatment can usually be attributed to lack of adherence to prescribed medications, uncontrolled comorbid conditions, or continued exposure to tobacco 78 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 ophthalmic nonselective beta-adrenergic blockers, such as propranolol (Inderal, and others) or timolol, can decrease the bronchodilating effect of both endogenous and exogenous beta2-agonists in patients with asthma Patients with moderate or severe asthma may benefit from meeting with trained asthma educators to have Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 Drugs for Asthma and COPD Table Some FDA-Approved Drugs for Asthma (continued) Some Available Formulations Drug Adult Dosage Pediatric Dosage Cost1 Oral Glucocorticoids Methylprednisolone – generic Medrol (Pfizer) Prednisolone – generic Prelone (Adamis) Orapred (Shionogi) Orapred ODT Pediapred (UCB) Prednisone – generic mg tabs 2, 4, 8, 16, 32 mg tabs mg/5mL solution, 15 mg/5 mL syrup, solution 15 mg/5 mL syrup 15 mg/5 mL solution 10, 15, 30 mg disintegrating tabs mg/5 mL solution 1, 2.5, 5, 10, 20, 50 mg tabs; mg/5 mL solution 7.5-60 mg once/day or every other day or 40-60 mg once/day or divided bid x 3-10 days for an acute exacerbation Inhaled Beta2-Agonists, Long-Acting8 Salmeterol – Serevent Diskus DPI (60 inh/unit) 50 mcg bid (GSK) 50 mcg/blister DPI (60 inh/unit) 12 mcg bid Formoterol – Foradil Aerolizer (Merck) 12 mcg/capsule Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combinations Fluticasone propionate/salmeterol – Advair Diskus (GSK) DPI (60 inh/unit) inhalation bid 100, 250, 500 mcg/ 50 mcg per blister9 Advair HFA (GSK) HFA MDI (60, 120 inh/unit) inhalations bid 45, 115, 230 mcg/ 21 mcg per inhalation Budesonide/formoterol – Symbicort (AstraZeneca) HFA MDI (60, 120 inh/unit) inhalations bid 80, 160 mcg/4.5 mcg per inhalation Mometasone/formoterol – Dulera (Merck) HFA MDI (60, 120 inh/unit) inhalations bid 100, 200 mcg/5 mcg per inhalation Leukotriene Modifiers10 Montelukast – generic 10 mg tabs, 4, mg chew tabs, 10 mg PO once/day Singulair (Merck) mg oral granules Zafirlukast – generic Accolate (AstraZeneca) Zileuton – Zyflo (Cornerstone) extended-release Zyflo CR Anti-IgE Antibody Omalizumab – Xolair (Genentech) Theophylline13 generic Theo-24 (Actient) Theochron (Caraco) 10 11 12 13 14 15 10, 20 mg tabs 20 mg PO bid 600 mg tabs $34.00 0-11 yrs: 0.25-2 mg/kg 31.00 once/day or every other day 4.00 max 60 mg/day) or 14.00 1-2 mg/kg/d divided bid 79.00 x 3-10 days (max 60 mg/d) 103.00 for an acute exacerbation 52.00 2.00 >4 yrs: 50 mcg bid 190.00 >5 yrs: 12 mcg bid 183.00 4-11 yrs: inhalation (100/50 mcg) bid >12 yrs: inhalation bid >12 yrs: inhalations bid 215.00 215.00 >12 yrs: inhalations bid 206.00 >12 yrs: inhalations bid 224.00 >1 yr: or mg PO once/day11 25.00 166.00 600 mg PO qid 5-11 yrs: 10 mg PO bid >12 yrs: 20 mg PO bid >12 yrs: 600 mg PO qid 80.00 114.00 1500.00 600 mg ER tabs 1200 mg PO bid >12 yrs: 1200 mg PO bid 1500.00 Powder for injection 150 mg/5 mL vial 150-300 mg SC q4wks >12 yrs: 150-300 mg q4wks or 225-375 mg SC q2wks 12 or 225-375 mg q2wks 12 100, 200, 300, 400, 450, 600 mg ER tabs; 80 mg/15mL oral elixir 100, 200, 300, 400 mg ER caps 100, 200, 300 mg ER tabs 300-600 mg/once day or divided bid 10 mg/kg/d 14 (max 300 mg/day) 300-600 mg once/day15 300-600 mg once/day 747.00 8.00 68.00 15.00 Use of a long-acting beta 2-agonist (LABA) alone without concomitant use of a long-ter m asthma controller medication is contr aindicated 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 mor ning and evening meals Montelukast is approved for prevention of exercise-induced bronchoconstriction in patients >6 years old 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 4-mg oral granules; for 6-14 yrs: 5-mg chewable tab once/d Dose depends on the patient’s body weight and total serum IgE level See package insert for specific dosing instructions Extended-release formulations may not be interchangeable Starting dose Usual maximum is 16 mg/kg/day (max 600 mg/day) in children >1 year old; in infants 0.2 x (age in w eeks) + = dose in mg/kg/da y If Theo-24 is taken 1000 mcg/day beclomethasone equivalent) during the first trimester in women with more severe or uncontrolled asthma, but not with low-to-moderate doses of ICSs.31 Another cohort study of the offspring of women who used an ICS during pregnancy found an increased risk of endocrine and metabolic disturbances after a follow-up of 6.1 years.32 LABAs and montelukast appear to be safe during pregnancy.33,34 Teratogenicity in animals has been reported with zileuton Allergen immunotherapy (without dose escalation) and omalizumab can be continued in pregnancy ASTHMA IN CHILDREN — For children with intermittent asthma, a SABA should be used as needed For mild, moderate or severe persistent asthma, ICSs are the preferred long-term treatment for control of symptoms 80 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 FDAapproved 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 slightly during the first year of treatment; in one study, mean adult height was 1.2 cm less with budesonide than with placebo.8 In another study, high-dose intermittent budesonide therapy was as efficacious as low-dose daily budesonide in reducing the need for a course of oral corticosteroids in preschool children with recurrent wheezing.35 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 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.36-38 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 beta2adrenergic bronchodilators, especially if concomitantly taking a beta blocker, and an increased incidence of tachycardia, arrhythmias and tremors In these patients, tiotropium (off-label) may be a useful bronchodilator Some older patients have difficulty inhaling any medication from a metered-dose or dry-powder inhaler and may require a nebulizer ASTHMA AND CO-MORBID DISEASES — 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.39 Allergic Rhinitis – Up to 95% of patients with asthma also suffer from persistent rhinitis Concurrent pharmacologic treatment of both asthma and rhinitis improves Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 Drugs for Asthma and COPD asthma outcomes.40 Patients with concomitant allergic rhinitis and allergic asthma may benefit from specific immunotherapy with standardized allergens.23 GERD – Patients with poorly controlled asthma have a higher prevalence of GERD, but a cause-and-effect relationship has not been demonstrated In adult asthma patients who have concomitant GERD symptoms, treatment with a proton pump inhibitor has been reported to improve pulmonary function and asthmarelated quality of life.41 In adult asthma patients with asymptomatic GERD, treatment with a proton pump inhibitor did not improve asthma control.42 A randomized controlled trial in children with poorly controlled asthma without symptoms of GERD found that lansoprazole did not improve lung function or reduce symptoms, but did increase the risk of adverse effects.43 Obesity – Obesity has been associated with asthma persistence and severity.4 Overweight and obese asthmatic patients may have a diminished response to ICSs.44 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.45 10 11 12 13 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 JP Parsons et al An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction Am J Respir Crit Care Med 2013; 187:1016 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 June 13, 2013 MA Rank et al The risk of asthma exacerbation after stopping low-dose inhaled corticosteroids: a systematic review and meta-analysis of randomized controlled trials J Allergy Clin Immunol 2013; 131:724 WJ Calhoun et al Comparison of physician-, biomarker-, and symptombased strategies for adjustment of inhaled corticosteroid therapy in adults with asthma: the BASALT randomized controlled trial JAMA 2012; 308:987 HW Kelly Comparison of inhaled corticosteroids: an update Ann Pharmacother 2009; 43:519 HW Kelly et al Effect of inhaled glucocorticoids in childhood on adult height N Engl J Med 2012; 367:904 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 JL Brozek et al Long-acting beta2 agonist step-off in patients with controlled asthma Arch Intern Med 2012; 172:1365 BA Chowdhury et al Assessing the safety of adding LABAs to inhaled corticosteroids for treating asthma N Engl J Med 2011; 364:2473 D Price et al Leukotriene antagonists as first-line or add-on asthmacontroller therapy N Engl J Med 2011; 364:1695 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 18 HA Kerstjens et al Tiotropium in asthma poorly controlled with standard combination therapy N Engl J Med 2012; 367:1198 19 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 20 NA Hanania et al Omalizumab in severe allergic asthma inadequately controlled with standard therapy: a randomized trial Ann Intern Med 2011; 154:573 21 WW Busse et al Randomized trial of omalizumab (anti-IgE) for asthma in inner-city children N Engl J Med 2011; 364:1005 22 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 23 MA Calderón et al Allergen-specific immunotherapy for respiratory allergies: from meta-analysis to registration and beyond J Allergy Clin Immunol 2011; 127:30 24 Bronchial thermoplasty for asthma Med Lett Dugs Ther 2010; 52:65 25 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 26 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 27 SC Lazarus Emergency treatment of asthma N Engl J Med 2010; 363:755 28 V Bougault et al Airway hyperresponsiveness in elite swimmers: is it a transient phenomenon? J Allergy Clin Immunol 2011; 127:892 29 M Schatz and MP Dombrowski Asthma in pregnancy N Engl J Med 2009; 360:1862 30 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 31 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 32 M Tegethoff et al Inhaled glucocorticoids during pregnancy and offspring pediatric diseases: a national cohort study Am J Respir Crit Care Med 2012; 185:557 33 LN Bakhireva et al Safety of leukotriene receptor antagonists in pregnancy J Allergy Clin Immunol 2007; 119:618 34 B Cossette et al Impact of maternal use of asthma-controller therapy on perinatal outcomes Thorax 2013; 68:724 35 RS Zeiger et al Daily or intermittent budesonide in preschool children with recurrent wheezing N Engl J Med 2011; 365:1990 36 PG Gibson et al Asthma in older adults Lancet 2010; 376:803 37 CE Reed Asthma in the elderly: diagnosis and management J Allergy Clin Immunol 2010; 126:681 38 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 39 M Cazzola et al Asthma and comorbid medical illness Eur Respir J 2011; 38:42 40 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 41 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 42 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 43 JT Holbrook et al Lansoprazole for children with poorly controlled asthma JAMA 2012; 307:373 44 E Forno et al Decreased response to inhaled steroids in overweight and obese asthmatic children J Allergy Clin Immunol 2011; 127:741 45 AE Dixon et al Effects of obesity and bariatric surgery on airway hyperresponsiveness, asthma control, and inflammation J Allergy Clin Immunol 2011; 128:508 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 81 Drugs for Asthma and COPD CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) Patients with COPD should stop smoking; pharmacotherapy may be helpful, especially with varenicline (Chantix) Patients with mild, intermittent symptoms can be treated with inhaled short-acting bronchodilators for symptom relief When symptoms become more severe or persistent, inhaled long-acting bronchodilators may be helpful Regular use of long-acting bronchodilators may reduce the frequency of acute exacerbations Combinations of a beta2-agonist with an anticholinergic can be used for patients inadequately controlled with a single agent For patients with severe COPD who experience frequent exacerbations, addition of an inhaled corticosteroid (triple therapy) is recommended For patients with severe hypoxemia, oxygen therapy can improve survival Guidelines for treatment of COPD have been published or updated in recent years.46,47 SMOKING CESSATION — Cigarette smoking is the primary cause of COPD 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 quit Effective medications include varenicline (Chantix), nicotine replacement therapies, and bupropion (Zyban, and others).48 Varenicline offers a unique mechanism of action as a partial nicotinic receptor agonist, but the current labeling includes precautions regarding possible neuropsychiatric and cardiac side effects.49 Combining smoking cessation therapies may offer additional benefit.50 SHORT-ACTING BRONCHODILATORS — For patients with intermittent symptoms, therapy with an inhaled short-acting bronchodilator is recommended for acute relief Typically, these patients have mild airflow obstruction and symptoms are usually associated with exertion Short-acting agents, which include inhaled beta2-agonists such as albuterol (see Table 2) and the anticholinergic ipratropium (see Table 4), improve forced expiratory volume in one second (FEV1) and can relieve symptoms Short-acting beta2-agonists have a more rapid onset than ipratropium With chronic use, short-acting beta2-agonists have a duration of action of less than hours, while ipratropium may continue to act for hours (MDI) or for as long as hours (nebulized) Combination Therapy – Combining a beta2-agonist with ipratropium has an additive effect for acute relief The combination of ipratropium and albuterol has been more effective than either drug alone and is available 82 in a single inhaler In general, combining bronchodilators from different drug classes produces additional therapeutic effects at lower doses, which may help to minimize dose-related adverse effects Adverse Effects – Beta2-agonists can cause tachycardia, skeletal muscle tremors and cramping, headache, palpitations, prolongation of the QT interval, insomnia, hypokalemia, and increases in serum glucose They should be used with caution in patients with cardiovascular disease; unstable angina and myocardial infarction have been reported Tolerance can occur with continued use Ipratropium is a quaternary ammonium anticholinergic agent with limited systemic absorption Its most common adverse effect is dry mouth Pharyngeal irritation, urinary retention and increases in intraocular pressure may occur Anticholinergics should be used with caution in patients with glaucoma and in those with symptomatic prostatic hypertrophy or bladder neck obstruction LONG-ACTING BRONCHODILATORS — For patients with evidence of moderate to severe airflow obstruction and chronic symptoms, regular treatment with a long-acting bronchodilator is recommended Choices include an inhaled long-acting beta2-agonist or an anticholinergic agent (see Table 4) Long-acting beta2-agonists are intended to provide sustained bronchodilation for at least 12 hours They have been shown to improve lung function and quality of life and to lower exacerbation rates in patients with COPD.51 Indacaterol (Arcapta Neohaler) is a new long-acting beta2-agonist that is administered once daily.52 All long-acting beta2-agonist products in the US include a boxed warning about an increased risk of asthmarelated deaths; there is no evidence to date that patients with COPD are at risk The adverse effects of long-acting beta2-agonists are similar to those of the short-acting agents Tolerance to the therapeutic effects of long-acting beta2-agonists can occur with continued use Two long-acting anticholinergics are available in the US Tiotropium has a long duration of action that permits once-daily dosing, and there is no evidence of tolerance to its therapeutic effects The UPLIFT trial enrolled 5993 patients with COPD and randomized them to either tiotropium or placebo, in addition to their usual medications, for years Tiotropium improved lung function, and reduced the rates of exacerbation and hospitalization, compared to placebo, but did not significantly reduce the rate of decline in FEV1 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 Drugs for Asthma and COPD during the study period.53,54 Tiotropium is generally well tolerated and appears to be safe.55 Adverse effects are similar to those of ipratropium.56 Aclidinium (Tudorza Pressair) is a newer long-acting anticholinergic for treatment of COPD.57 Twice-daily inhaled therapy reduces symptoms and improves lung function in patients with moderate to severe COPD58,59; direct comparisons with tiotropium, which is dosed once daily, are lacking, but the new device may be easier to use.60 Choice of a Long-Acting Bronchodilator – The choice of a long-acting bronchodilator lies between a long-acting beta2-agonist and a long-acting anticholinergic There is no strong evidence supporting the use of either one over the other One population-based retrospective cohort study in >40,000 elderly patients found that initial use of a long-acting beta2-agonist was associated with lower mortality than initial use of long-acting anticholinergics.61 A 1-year trial in more than 7000 subjects with moderate to very severe COPD found that use of tiotropium, compared to salmeterol, resulted in a longer time to an exacerbation, a reduction in the risk of an exacerbation, and a decrease in overall exacerbation frequency.62 An accompanying editorial cautioned that these results did not apply to patients with milder disease and also indicated that therapy with indacaterol, a newer long-acting beta2-agonist, in doses of 150 and 300 mcg provided benefits similar to those of tiotropium in other trials.63 How the FDAapproved dosage of 75 mcg once daily compares to approved doses of other inhaled bronchodilators remains to be established A nested case-control analysis of a retrospective cohort study in 191,000 patients concluded that both inhaled long-acting beta2-agonists and long-acting anticholinergics were associated with an increased risk of adverse cardiovascular events, including a hospitalization or emergency department visit.64 When patients are not adequately controlled with a single long-acting bronchodilator, combining a long-acting anticholinergic with a long-acting beta2-agonist may be helpful.65 THEOPHYLLINE — Slow-release theophylline can be used as an oral alternative or in addition to inhaled bronchodilators (see Table 2) Its primary mechanism of action is bronchodilation Because of significant inter- and intra-patient variability in theophylline clearance, dosing requirements vary The drug has a narrow therapeutic index; monitoring is warranted periodically to maintain peak serum concentrations between and 15 mcg/mL for treatment of COPD Table Treatment of COPD1 Patient Group Group A3 Preferred Alternatives Group B4 Preferred Alternatives Group C5 Preferred Alternatives Group D6 Preferred Alternatives Recommended Regimen2 Short-acting anticholinergic as needed or SABA as needed Long-acting anticholinergic or LABA or SABA + short-acting anticholinergic Long-acting anticholinergic or LABA Long-acting anticholinergic + LABA ICS + LABA or Long-acting anticholinergic Long-acting anticholinergic + LABA or ICS or PDE4 inhibitor + Long-acting anticholinergic or LABA ICS + LABA and/or long-acting anticholinergic ICS + LABA + long-acting anticholinergic or ICS + LABA + PDE4 inhibitor or Long-acting anticholinergic + LABA or Long-acting anticholinergic + PDE4 inhibitor SABA = inhaled short-acting beta2-agonist; LABA = inhaled long-acting beta2-agonist; ICS = inhaled corticosteroid; PDE4 inhibitor = phosphodiesterase-4 inhibitor Adapted from global strategy for the diagnosis, management, and prevention of chronic obstr uctive pulmonary disease: GOLD executive summary Updated 2013 Available at www.goldcopd.com Accessed July 15, 2013 Short-acting anticholinergics and shor t-acting beta2-agonists can be added to any regimen for acute relief Theophylline may be used as an oral alternative or in addition to inhaled bronchodilators Group A = few symptoms and low risk of exacerbations Group B = more significant symptoms, but low risk of exacerbations Group C = few symptoms, but high risk of exacerbations Group D = many symptoms and high risk of exacerbations Adverse Effects – At theophylline serum concentrations >12-15 mcg/mL, nausea, nervousness, headache and insomnia occur with increasing frequency in patients with COPD Vomiting, hypokalemia, hyperglycemia, tachycardia, cardiac arrhythmias, tremors, neuromuscular irritability and seizures can also occur at higher serum concentrations Theophylline is metabolized in the liver, primarily by CYP1A2 and CYP3A4 Any drug that inhibits or induces these enzymes can affect theophylline metabolism.66 Clearance of theophylline is reduced in the elderly and in patients with liver disease or heart failure CORTICOSTEROIDS — Inhaled corticosteroid monotherapy is not approved for use in COPD Various combinations of inhaled corticosteroids and long-acting beta2-agonists are available as listed in Table The most recent addition to these options is a combination of fluticasone furoate and vilanterol (Breo Ellipta), the Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 83 Drugs for Asthma and COPD Table Some FDA-Approved Drugs for COPD Drug Some Formulations Delivery Device Usual Adult Dosage Cost1 17 mcg/inhalation HFA MDI (200 inh/unit) Nebulizer inhalations qid PRN $215.002 Inhaled Short-Acting Anticholinergic Ipratropium Atrovent HFA (Boehringer Ingelheim) generic – single-dose vials 200 mcg/mL soln 500 mcg qid PRN 18.002 Inhaled Short-Acting Beta2-Agonist/Short-Acting Anticholinergic Combination Albuterol/ipratropium Combivent (Boehringer Ingelheim) Combivent Respimat (Boehringer Ingelheim) DuoNeb (Dey) generic Inhaled Long-Acting Beta2-Agonists 90 mcg/18 mcg/ inhalation 100 mcg/20 mcg/ inhalation 2.5 mg/0.5 mg /3 mL soln CFC MDI (200 inh/unit) MDI (120 inh/unit) Nebulizer inhalations qid PRN 216.002 inhalation qid PRN 240.004 2.5 mg/0.5 mg qid PRN 270.004 91.004 Indacaterol – Arcapta Neohaler (Novartis) Salmeterol – Serevent Diskus (GSK) Formoterol – Foradil Aerolizer (Merck) Perforomist (Dey) Arformoterol – Brovana (Sunovion) Inhaled Long-Acting Anticholinergics 75 50 12 20 15 DPI (30 inh/unit) DPI (60 inh/unit) DPI (60 inh/unit) Nebulizer Nebulizer 75 50 12 20 15 mcg once/day mcg bid mcg bid mcg bid mcg bid 173.00 190.00 183.00 472.00 457.00 Tiotropium – Spiriva HandiHaler (Boehringer Ingelheim) Aclidinium – Tudorza Pressair (Forest) 18 mcg/capsule DPI (30, 90 inh/unit) 18 mcg once/day 260.00 400 mcg/inhalation DPI (60 inh/unit) 400 mcg bid 218.00 DPI (60 inh/unit) 250/50 mcg bid 268.00 DPI (30 inh/unit) 100/25 mcg once/day MDI (120 inh/unit) 320/9 mcg bid 236.00 none 500 mcg once/day 199.00 mcg/capsule mcg/blister mcg/capsule mcg/2 mL soln mcg/2 mL soln Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combinations Fluticasone propionate/salmeterol – Advair Diskus5 (GSK) Fluticasone furoate/vilanterol – Breo Ellipta (GSK) Budesonide/formoterol – Symbicort (Astra Zeneca) 100, 250, 500 mcg/ 50 mcg/blister 100 mcg/25 mcg/ blister 80, 160 mcg/ 4.5 mcg/inhalation N.A Phosphodiesterase-4 Inhibitor Roflumilast – Daliresp (Forest) 500 mcg oral tablet HFA = hydrofluoroalkane; MDI = metered-dose inhaler; CFC = chlorofluorocarbon; DPI = dry powder inhaler; inh = inhalation; N.A = not available Approximate wholesale acquisition cost (WAC) for 30 days’ treatment at the lowest recommended adult dosage $ource® Monthly (Selected from FDB MedKnowledge™) July 5, 2013 Reprinted with permission by FDB, Inc All rights reserved ©2013 www.fdbhealth.com/policies/drug-pricing-policy Actual retail prices may be higher Cost for 100 doses The manufacturer is discontinuing Combivent in July 2013 Cost for 120 doses Only the 250/50 mcg dose is FDA-approved for use in COPD Only the 160/4.5 mcg dose is FDA-approved for use in COPD first long-acting beta2-agonist/inhaled cortocosteroid combination to be approved for once-daily use in patients with COPD.67 No fixed-dose combinations of an inhaled corticosteroid with a long-acting anticholinergic are available some patients The results of several large studies indicate that inhaled corticosteroids not slow the progression of COPD or reduce mortality.69 Longterm treatment with oral corticosteroids is not recommended in COPD In patients with severe COPD (FEV1 1500 patients with COPD found that azithromycin 250 mg daily reduced the risk of an exacerbation over one year and improved quality of life.78 Hearing loss, prolongation of the QT interval and development of antimicrobial resistance will probably limit its long-term use OXYGEN THERAPY — For patients with severe hypoxemia, use of long-term supplemental oxygen therapy has been shown to increase survival and can improve quality of life.79 Oxygen therapy may also increase exercise capacity in patients with mild or moderate hypoxemia, but its long-term benefits in such patients are unclear.80 and severity of exacerbations, which have a significant effect on the course of the disease When exacerbations occur, treatment includes intensified use of short-acting bronchodilators, short-term therapy with systemic corticosteroids, and usually a course of antimicrobial therapy Short-acting beta2-agonists are generally used first Use of systemic corticosteroids can shorten recovery time and improve lung function; guidelines recommend prednisone doses of 30-40 mg daily for 10-14 days.2 A recent trial found days of oral prednisone 40 mg/day non-inferior to 14 days.83 The use of ventilatory support and supplemental oxygen therapy has been shown to reduce the morbidity and mortality associated with acute exacerbations 46 47 48 49 50 51 52 53 54 55 56 57 58 59 IMMUNIZATIONS — Patients with COPD should receive an influenza vaccine and a pneumococcal vaccine to reduce the risk of infection and complications from these pathogens.81 PULMONARY REHABILITATION — The benefits of pulmonary rehabilitation programs are well established for patients with COPD Pulmonary rehabilitation can reduce dyspnea and improve functional capacity and quality of life, as well as reduce the number of hospitalizations.82 60 61 62 63 64 65 ACUTE EXACERBATIONS — A major focus of chronic treatment of COPD is to reduce the frequency 66 A Qaseem et al Diagnosis and management of stable chronic obstructive pulmonary disease: a clinical practice guideline update from the American College of Physicians, American College of Chest Physicians, American Thoracic Society, and the European Respiratory Society Ann Intern Med 2011; 155:179 Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary Updated 2013 Available at www.goldcopd.com Accessed July 17, 2013 Drugs for tobacco dependence Treat Guidel Med Lett 2008; 6:61 RS McIntyre Varenicline and suicidality: a new era in medication safety surveillance Expert Opin Drug Saf 2008; 7:511 R Strassmann et al Smoking cessation interventions in COPD: a network meta-analysis of randomised trials Eur Respir J 2009; 34:634 GJ Rodrigo et al Safety of long-acting ß-agonists in stable COPD A systematic review Chest 2008; 133:1079 Indacaterol (Arcapta Neohaler) for COPD Med Lett Drugs Ther 2012; 54:33 DP Tashkin et al A 4-year trial of tiotropium in chronic obstructive pulmonary disease N Engl J Med 2008; 359:1543 M Decramer et al Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomized controlled trial Lancet 2009; 374:1171 TM Michele The safety of tiotropium – the FDA’s conclusions N Engl J Med 2010; 363:1097 Tiotropium (Spiriva) for COPD Med Lett Drugs Ther 2004; 46:41 JE Frampton Aclidinium in chronic obstructive pulmonary disease Drugs 2012; 72: 1999 EM Kerwin et al Efficacy and safety of a 12-week treatment with twice-daily aclidinium bromide in COPD patients (ACCORD COPD I) COPD 2012; 9:90 PW Jones et al Efficacy and safety of twice-daily aclidinium bromide in COPD patients: the ATTAIN study Eur Respir J 2012; 40:830 Aclidinium bromide (Tudorza Pressair) for COPD Med Lett Drugs Ther 2012; 54:99 A Gershon et al Comparison of inhaled long-acting ß-agonist and anticholinergic effectiveness in older patients with chronic obstructive pulmonary disease A cohort study Ann Intern Med 2011; 154; 583 C Vogelmeier et al Tiotropium versus salmeterol for the prevention of exacerbations of COPD N Engl J Med 2011; 364: 1093 JA Wedzicha Choice of bronchodilator therapy for patients with COPD N Engl J Med 2011; 364: 1167 A Gershon et al Cardiovascular safety of inhaled long-acting bronchodilators in individuals with chronic obstructive pulmonary disease JAMA Intern Med 2013; 173:1175 DP Tashkin et al Formoterol and tiotropium compared with tiotropium alone for treatment of COPD COPD 2009; 6:17 Inhibitors and inducers of CYP enzymes and P-glycoprotein Med Lett Drugs Ther 2013; 55:e44 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 85 Drugs for Asthma and COPD 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 FJ Martinez et al Fluticasone furoate/vilanterol (100/25; 200/25 μg) improves lung function in COPD: a randomised trial Respir Med 2013; 107:550 PM Calverley et al Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease N Eng J Med 2007; 356:775 IA Yang et al Inhaled corticosteroids for stable chronic obstructive pulmonary disease Cochrane Database Syst Rev 2007; (2): CD002991 Safety of inhaled corticosteroids in chronic obstructive pulmonary disease (COPD) Med Lett Drugs Ther 2010; 52:41 T Welte et al Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease Am J Respir Crit Care Med 2009; 180:741 D Singh et al Superiority of “triple” therapy with salmeterol/fluticasone proprionate and tiotropium bromide versus individual components in moderate to severe COPD Thorax 2008; 63:592 NA Hanania et al Benefits of adding fluticasone propionate/salmeterol to tiotropium in moderate to severe COPD Respir Med 2012; 106:91 TA Lee et al Outcomes associated with tiotropium use in patients with chronic obstructive pulmonary disease Arch Intern Med 2009; 169:1403 JM Michalski et al PDE4: a novel target in the treatment of chronic obstructive pulmonary disease Clin Pharmacol Ther 2012; 91:134 Roflumilast (Daliresp) for COPD Med Lett Drugs Ther 2011; 53:59 PM Calverley et al Roflumilast in symptomatic chronic obstructive pulmonary disease: two ransomised clinical trials Lancet 2009; 374:685 RK Albert et al Azithromycin for prevention of exacerbations of COPD N Engl J Med 2011; 365:689 JK Stoller et al Oxygen therapy for patients with COPD: current evidence and the long-term oxygen treatment trial CHEST 2010; 138:179 MB Drummond and RA Wise Oxygen therapy in COPD: What we know? Am J Respir Crit Care Med 2007; 176:321 Adult immunizations Treat Guidel Med Lett 2011; 9:75 R Casaburi and R ZuWallack Pulmonary rehabilitation for management of chronic obstructive pulmonary disease N Engl J Med 2009; 360:1329 JD Leuppi et al Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease JAMA 2013; 309:2223 Coming Soon in Treatment Guidelines: Drugs for Sexually Transmitted Infections – Sept 2013 Drugs for Parkinson’s Disease – Oct 2013 Follow us on Twitter @MedicalLetter 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 Z Morrison, 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 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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 program, the participant will be able to: Explain the current approach to the management of asthma and COPD Discuss the pharmacologic options available for treatment of asthma and COPD and compare them based on their efficacy, dosage and administration, potential adverse effects and drug interactions Determine the most appropriate therapy given the 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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 11 ( Issue 132) • August 2013 DO NOT FAX OR MAIL THIS EXAM To take CME exams and earn credit, go to: medicalletter.org/CMEstatus Issue 132 Questions The most effective long-term medications for control of persistent asthma are: a short-acting beta2-agonists b inhaled corticosteroids c long-acting beta2-agonists d oral glucocorticoids Effective options to help patients stop smoking include: a varenicline b counseling c nicotine replacement therapies d all of the above In the Childhood Asthma Management Study, budesonide, compared to placebo, reduced mean adult height by: a 0.3 cm b 1.2 cm c 2.1 cm d 3.2 cm Short-acting beta2-agonists: a have an additive effect when used in combination with ipratropium b are used on a regular basis at high doses for treatment of COPD c have a duration of action of greater than hours d cannot be administered via a nebulizer Long-acting beta2-agonists should not be used: a as monotherapy b in combination with an inhaled corticosteroid c in patients with allergic asthma d all of the above Adverse effects of inhaled anticholinergics include: a dry mouth b urinary retention c increased intraocular pressure d all of the above A 31-year-old man with persistent asthma has read about leukotriene modifiers in advertisements on the internet He asks your opinion about adding one of them to his current regimen You could tell him that: a none of them are recommended for treatment of acute asthma symptoms b montelukast is considered safe for long-term use c zileuton can cause life-threatening liver injury d all of the above 10 In patients with COPD, long-acting beta2-agonists have been shown to: a increase the risk of death b improve lung function and quality of life c be superior to inhaled anticholinergics d cause oral candidiasis Omalizumab is a recombinant monoclonal antibody directed against: a interleukin b interleukin 13 c IgE d none of the above The preferred controller medications for pregnant patients with asthma are: a inhaled corticosteroids b long-acting beta2-agonists c leukotriene modifiers d any of the above 11 A 65-year-old man with severe COPD has been experiencing frequent exacerbations while taking a combination of a long-acting anticholinergic and a long-acting beta2-agonist The best choice for management of this patient would be to: a discontinue the long-acting anticholinergic b add omalizumab c add an inhaled corticosteroid d add daily azithromycin 12 Theophylline: a can be used as an oral alternative for, or in addition to, inhaled bronchodilators b has a narrow therapeutic index and requires monitoring of serum concentrations c is metabolized by CYP enzymes and has many drug interactions d all of the above ACPE UPN: 0379-0000-13-132-H01-P; Release: July 2013, Expire: July 2014 Treatment Guidelines from The Medical Letter • Vol 11 ( Issue 132) • August 2013 ... November 2010 and vol 10 [Issue 114] February 2012) www.medicalletter.org Tables Treatment of Asthma Some FDA-Approved Drugs for Asthma Treatment of COPD Some FDA-Approved Drugs for COPD Page 76... Medical Letter • Vol 11 ( Issue 132) • August 2013 77 Drugs for Asthma and COPD Table Some FDA-Approved Drugs for Asthma Some Available Formulations Drug Adult Dosage Pediatric Dosage HFA MDI... Medical Letter • Vol 11 ( Issue 132) • August 2013 Drugs for Asthma and COPD Table Some FDA-Approved Drugs for Asthma (continued) Some Available Formulations Drug Adult Dosage Pediatric Dosage Cost1