Incorporating Newer Therapies and Strategies to Improve COPD Outcomes: A Practical Guide for Pharmacists. Learning Objectives.

Transcription

1 Incorporating Newer Therapies and Strategies to Improve COPD Outcomes: A Practical Guide for Pharmacists Learning Objectives Identify the risk factors for COPD and the clinical features that differentiate COPD from asthma Outline current guideline recommendations for the acute and long-term management of patients with COPD Summarize current evidence for available and emerging therapeutic options, such as long-acting β2 agonists and muscarinic antagonists, for the treatment of COPD Identify signs of treatment failure in patients with COPD and refer patients for appropriate clinical evaluation Demonstrate proper inhaler technique for various inhaler devices used to treat patients with COPD Patient Case Jeffrey is a 53-year-old male who presents to his healthcare practitioner with increased SOB over the past 2 weeks The patient has a family history of dyslipidemia Social history is positive for smoking (40 pack year history) Occupational history as a construction worker x 20 years Presently the patient is prescribed an albuterol inhaler PRN and simvastatin 20 mg daily Patient received both influenza and pneumococcal vaccine last month SOB = shortness of breath; PRN = as needed.

2 Patient Case (cont.) Over the past year, he has been frustrated with his breathing, believing his albuterol inhaler has not been working Over the past few weeks, his SOB has increased, requiring use of his albuterol inhaler up to 5x per day, with some relief He has required 3 hospital visits due to his breathing within the last 12 months His physical exam is unremarkable; however, during auscultation and percussion, a decrease in breath sounds is noted His physician is considering a diagnosis of COPD What Is COPD? Preventable and treatable disease Airflow limitations that are progressive Associated with chronic inflammatory response to the airways and lungs Due to noxious particles or gases Exacerbations and comorbidities contribute to overall severity in individualized patients Accessed February 2014 COPD Facts COPD is the third leading cause of death in the United States It affects more than 24 million Americans (nearly 8% of the population) at an annual estimated direct and indirect cost of 49.9 billion dollars Approximately 20% of diagnosed patients have not undergone spirometry and 63% with compromised lung function revealed by spirometry are not diagnosed with COPD Despite increased incidence, COPD remains under researched, underdiagnosed, and often untreated Hoyert DL et al. Natl Vital Stat Rep 2012;61:1-65. Global Initiative for Chronic Obstructive Lung Disease. files/gold_pocket_2013_mar27.pdf. Updated MMWR Morb Mortal Wkly Rep. 2012;61(46):

3 Risk Factors for COPD Occupational Gases Tobacco Smoke Environmental Gases Genetic Differentiate COPD vs Asthma COPD Rarely occurs before age 45 Current or former smokers History of exposure to risk factors Family history of COPD Chest radiographic changes Decreased DLco Airflow limitations only partially reversible Asthma Traditionally diagnosed in childhood Lack of smoking history Triggers (stress, specific allergens, etc.) will exacerbate the condition Airflow limitations are completely reversible DLco = Diffusing lung capacity of carbon monoxide. Chang J et al. J Intensive Care Med 2007;22: Inflammation in COPD Release Volatile Hydrocarbons Activates Respiratory Tract Macrophages Tobacco Smoke Release Result Airway and Parenchymal Damage Proteases Neutrophils Spurzem JR, et al. Sem in Resp Crit Care Med 2005;26:

4 Disease Progression COPD Exacerbations Expiratory flow limitations Air trapping Hyperinflation Breathlessness Deconditioning Inactivity Reduced exercise capacity Poor health-related quality of life Disability Disease progression Death Decramer M. Eur Respir Rev. 2006;15(99): Assessment of COPD COPD GOLD Guidelines First published in 2001 Complete revisions in 2006 and 2011 based on available research Most recent update was in early 2014 GOLD = Global Initiative for Chronic Obstructive Lung Disease. Accessed February 2014

5 Combined Assessment of COPD Three components determine severity of disease Symptom assessment CAT mmrc COPD Control Questionnaire (CCQ) Spirometry to assess degree of airflow limitations Risk of exacerbations CAT = COPD assessment test; mmrc = modified Medical Research Council. Global Initiative for Chronic Obstructive Lung Disease Accessed March 6, CAT Eight questions; 5-point scale 0 = least severe; 5 = most severe Cough Phlegm (mucus) Chest tightness Breathless walking up a hill or 1 flight of stairs Activity limitations Confident to leave home Sleep Energy Assessment Minimum score: 0 Maximum score: 40 Accessed February 2014 mmrc Questionnaire Severity Score Level of Breathlessness None 0 Only breathlessness with strenuous exercise Mild 1 Short of breath hurrying or walking up a hill Moderate 2 Walks slower than age group or has to stop for breath when walking on the level at own pace Severe 3 Stops for breath after walking 100 meters or a few minutes on the level Very Severe 4 Breathless when dressing\undressing or too breathless to leave the house mmrc = modified Medical Research Council. Doherty DE, et al. J Fam Pract. 2006;55(11):S1-S8.

6 Assessment of COPD Symptoms CAT <10 less symptoms/low risk or less symptoms high risk >10 more symptoms/low risk or more symptoms/high risk mmrc breathlessness scale 0-1 less symptoms/low risk or less symptoms high risk >2 more symptoms/low risk or more symptoms/high risk Exacerbations Airflow limitations (spirometry) Accessed February 2014 Combined Assessment of COPD Risk GOLD Classification of Airflow Limitations C High risk Less Symptoms A Low risk Less Symptoms D High risk More Symptoms B Low risk More Symptoms mmrc 0 1 mmrc >2 CAT <10 CAT >10 Symptoms (mmrc or CAT score) >2 1 0 Exacerbation History Risk Accessed February 2014 Classification of Severity of Airflow Limitations in COPD (Based on Postbronchodilator FEV 1 ) in Patients With FEV 1 /FVC < 0.70 Classification Severity FEV 1 GOLD 1 Mild FEV 1 80% predicted GOLD 2 Moderate 50% FEV 1 < 80% predicted GOLD 3 Severe 30% FEV 1 < 50% predicted GOLD 4 Very Severe FEV 1 < 30% predicted FEV 1 = forced expiratory volume (in 1 second); FVC = forced vital capacity. Accessed February 2014.

7 Performing Spirometry Accessed March 6, Koegelenberg CFN, et al. South African Medical Journal. 2012;103(1): index.php/samj/article/view/6197/4720. Accessed March 6, Combined Assessment of COPD (cont.) Patient A B C D Characteristics Low risk Low symptoms Low risk More symptoms High risk Less symptoms High risk More symptoms Spirometry Classification Exacerbations per Year mmrc CAT GOLD <10 GOLD GOLD <10 GOLD Accessed February Clinical Case Remember Jeffrey? Spirometry and COPD assessment are performed on Jeffrey by the pharmacist with the following results: FEV 1 = 41% CAT = 15 Oxygen saturation (SaO2)= 95% History of 3 exacerbations in 12 months Combined assessment: Category D

8 Strategies for Risk Reduction in Patients with COPD Avoidance of risk factors Smoking cessation Reduction of indoor pollution Reduction of occupational exposure Regular physical activity Influenza and pneumococcal vaccinations GOLD = Global Initiative for Chronic Obstructive Lung Disease. Accessed February 2014 Patient Group Pharmacologic Therapy for Stable COPD (Long-term Management) Recommended First Choice A SA ACH PRN SA beta 2 agonist PRN B LA ACH LA beta 2 agonist C ICS + LA beta 2 agonist LA ACH D ICS + LA beta 2 agonist LA ACH Combo of both above Alternative Choice LA ACH LA beta 2 agonist SA beta 2 agonist and SA ACH Other Options Theophylline LA ACH + LA beta 2 agonist SA beta 2 agonist PRN SA ACH PRN Combo of 2 above Theophylline LA ACH + LA beta 2 agonist Either above with PDE-4 inhibitor ICS + LA beta 2 agonist + LA ACH ICS + LA beta 2 agonist + PDE- 4 inhibitor LA ACH + LA beta 2 agonist LA ACH + PDE-4 inhibitor SA ACH PRN SA beta 2 agonist PRN Combo of 2 above Theophylline SA beta 2 agonist SA ACH Combo of 2 above Carbocysteine Theophylline SA = short acting; PRN = as needed; ACH = anticholinergic; LA = long acting; ICS = inhaled corticosteroid; PDE 4 = phosphodiesterase 4. Therapy for COPD Exacerbations (Acute Management) Supplemental oxygen Bronchodilators Short-acting inhaled beta 2 -agonists with or without short-acting anticholinergics Systemic corticosteroids Antibiotics in patient with: Increased dyspnea, sputum volume, and sputum purulence Increased sputum purulence and one other cardinal symptom Mechanical ventilation GOLD = Global Initiative for Chronic Obstructive Lung Disease. Accessed February 2014

9 Signs of Treatment Failure Increased cough and sputum production Worsening dyspnea Increased fatigue Activity limitations Sleep disturbances Increased need for bronchodilators Does the patient have COPD? Clinical referral Clinical Evaluation Referral Pulmonary Confirm diagnosis Pulmonary function testing (spirometry, DL CO ) Chest radiograph Gastroenterology Gastroesophageal reflux Cardiology Heart Failure DL CO Diffusing lung capacity of carbon monoxide Prevention of COPD Exacerbation Smoking cessation Influenza and pneumococcal vaccine Knowledge of treatment therapy including proper inhaler technique Early pulmonary rehabilitation after hospitalization Maintain physical activity with anxiety, depression and social problem discussion Pharmacotherapy Accessed February 2014.

10 Efficacy of Various Chronic COPD Therapies in Reducing the Risk for Exacerbations Treatments Long-acting Placebo beta agonist Long-acting anticholinergic Inhaled corticosteroids 0.77 ( ) 0.71 ( ) 0.78 ( ) Long-acting beta agonist 0.91 ( ) 1.00 ( ) Long-acting anticholinergics 1.10 ( Inhaled corticosteroids 0.72 Long-acting ( ) beta agonist Odds Ratio inhaled corticosteroids Puhan MA, et al. BMC Med. 2009;7: ( ) 1.02 ( ) 0.93 ( ) Indications for Hospital Assessment or Admission Marked increase in intensity of symptoms Severe underlying COPD Onset of new physical signs Failure of an exacerbation to respond to initial medical management Presence of serious comorbidities Frequent exacerbations Older age Insufficient home support Accessed February Current and Emerging Therapeutic Options for COPD

11 Current Inhaled Medications for COPD Medication Brand Usual Starting Dose Duration β 2 -Agonists Short-acting Albuterol ProAir, Proventil, Ventolin 2 puffs q 4-6 hrs PRN 4-6 h Levalbuterol Xopenex HFA 2 puffs q 4-6 hrs PRN 4-6 h Pirbuterol Maxair Autohaler 2 puffs q 4-6 hrs PRN 5 h Long-acting Formoterol Foradil Aerolizer, 1 inhaled capsule bid 12+ h Perforomist, Brovana Indacaterol Arcapta Neohaler 1 inhaled capsule daily 24+ h Salmeterol Serevent Diskus 1 puff bid 12+ h Olodaterol Respimat 2 puffs once daily 24 + h HFA = hydrofluoroalkane. Accessed April 3, Cazzola M, et al. Drugs Today. 2011;106: Accessed April 3, PL Detail-Document, Inhalers for COPD. Pharmacist s Letter/Prescriber s Letter. August Current Inhaled Medications for COPD Cont d Medication Brand Usual Starting Dose Duration Anticholinergics Short-acting Ipratropium bromide Atrovent 2 puffs qid 6-8 h Long-acting Aclidinum Tudorza Pressair 1 puff bid 24+ h Tiotropium bromide Spiriva Handihaler 1 inhaled capsule 24+ h daily Umeclidinium Incruse Ellipta 1 inhalation daily 24 h Combination Bronchodilators Albuterol/ipratropium Combivent 2 puffs q 4-6 hrs PRN 4-6 h Umeclidinum/Vilanterol Anoro Ellipta 1 puff daily 24 h Accessed April 3, Salmon M, et al. J Pharmacol Exp Ther. 2013;345(2): Slack RJ, et al. J Pharmacol Exp Ther. 2013;344(1): PL Detail-Document, Inhalers for COPD. Pharmacist s Letter/Prescriber s Letter. August Current Inhaled Medications for COPD Cont d Medication Brand Usual Starting Dose Duration Inhaled Corticosteroids Budesonide Pulmicort Flexhaler 1-2 puffs bid 12 h Fluticasone Flovent HFA 1-2 puffs bid 12 h Beclomethasone QVAR 1-2 puffs bid 12 h Combination Inhalers Formoterol/Budesonide Symbicort 2 puffs bid 12 h Fluticasone/Salmeterol Advair Diskus 1 puff bid Advair HFA 2 puffs bid 12 h Fluticasone/Vilanterol Breo Ellipta 1 puff daily 24 h HFA = hydrofluoroalkane; PDE4 = phosphodiesterase 4. PL Detail-Document, Inhalers for COPD. Pharmacist s Letter/Prescriber s Letter. August Accessed April 3, Slack RJ, et al. J Pharmacol Exp Ther. 2013;344(1):

12 Current Oral Medications for COPD Medication Brand Usual Starting Dose Duration Corticosteroids Methylprednisolone 4-48mg/day depending on h disease and response Prednisolone 5-60mg/day depending on h disease and response Prednisone 5-60mg/day depending on h disease and response PDE4 Inhibitor Roflumilast Daliresp One 500 mcg tablet daily 17+ h HFA = hydrofluoroalkane; PDE4 = phosphodiesterase 4. Using Oral Corticosteroids: a toolbox. Pharmacist s Letter/Prescriber s Letter. 2010;26(5): Accessed April 3, Roflumilast PDE4 inhibitor ( camp and inflammation) Reduce the risk of COPD exacerbations in severe COPD associated with chronic bronchitis and history of exacerbation Change in FEV ml 14.9% % reduction in COPD exacerbations Adverse effects Psychiatric (5.9%) including suicidal ideations; Moderate weight loss (7.5%); Diarrhea (9.5%); nausea (4.7%); headache (4.4%) Drug interactions (CYP3A4) Contraindicated with moderate/severe hepatic disease Pregnancy category C Reid DJ, et al. Ann Pharmacother. 2012;46: Indacaterol Maleate LABA that stimulates formation of camp which activates protein kinase-a resulting in bronchodilation Efficacy Decreased COPD exacerbations, need for rescue inhaler, and improved exercise tolerance Adverse effects Cough / muscle spasms / headache / tremor Contraindicated for acute episodes of COPD or asthma and hypersensitivity to milk proteins Drug interactions: Steroids and diuretics hypokalemia; MAO and tricyclic antidepressants QT interval LABA = long acting beta agonist Slaton RM, et al. P&T 2012;37:86-98.

13 Tiotropium Bromide M1 and M3 selective long-acting muscarinic antagonist Indicated for long-term maintenance treatment and reducing exacerbations in COPD Most widely prescribed agent in COPD 2013 Cochrane Review - tiotropium vs. placebo 22 studies involving 23,309 patients Improved FEV 1 and mean quality of life; significantly reduced exacerbations; fewer hospitalizations due to exacerbations Adverse effects Dry mouth / worsening of narrow-angle glaucoma / paradoxical bronchospasm / worsening of urinary retention Food and Drug Administration. Drugs@FDA. drugsatfda/index.cfm. Accessed March 6, Karner C, et al. Cochrane Database Syst Rev. 2013;6: Aclidinium Bromide Long-acting anticholinergic that inhibits the M3 receptor at the smooth muscle leading to bronchodilation Efficacy Improved peak FEV1 and FEV1 at 24 weeks (100 to > 200ml vs placebo) Improved health status and dyspnea Adverse effects Paradoxical bronchoconstriction, worsening of narrow-angle glaucoma and urinary retention Contraindications none Limit use with other anticholinergic agents Food and Drug Administration. Drugs@FDA. drugsatfda/index.cfm. Accessed March 6, Jones PW, et al. Eur Respir J. 2012;40: Umeclidinium Bromide Long-acting anticholinergic that inhibits the M3 receptor at the smooth muscle leading to bronchodilation Efficacy Mean peak FEV1 at day 1 and day 168 (126ml and 130ml vs placebo) Improved health status and dyspnea Adverse effects Paradoxical bronchoconstriction, worsening of narrow-angle glaucoma and urinary retention Contraindicated for severe hypersensitivity to milk proteins No identifiable drug interactions Food and Drug Administration. Drugs@FDA. /index.cfm. Accessed October 2, 2014.

14 Umeclidinium Bromide/Vilanterol Combination anticholinergic/long-acting beta 2 - agonist indicated for once daily maintenance treatment of COPD Efficacy Improved peak FEV1 and FEV1 on day 1 and 24 weeks 167 ml and 224ml vs placebo Lower transition dyspnea score; lower risk of exacerbation; decreased need for rescue inhaler Adverse effects Paradoxical bronchospasm / pulse, blood pressure, ECG changes / worsening of narrow-angle glaucoma and urinary retention Inhibitor of cytochrome 450 3A4 Food and Drug Administration. Drugs@FDA. Feldman GJ et al. Ther Adv Respir Dis 2013;7(6): Fluticasone Furoate/Vilanterol Combination inhaled corticosteroid and long-acting beta agonist indicated for maintenance of COPD Efficacy Improved FEV 1 at 24 weeks >130 ml vs. placebo Decreased COPD exacerbations and well tolerated Adverse effects Infections (bronchitis, sinusitis) / headache and back pain Inhibitor of cytochrome P450 3A4 Food and Drug Administration. Drugs@FDA. drugsatfda/index.cfm. Accessed March 6, April 17, 2013 Meeting of the Pulmonary-Allergy Drugs Advisory Committee. Drugs/Pulmonary-AllergyDrugsAdvisoryCommittee/ucm htm. Accessed March 6, Olodaterol LABA that stimulates formation of camp which activates protein kinase-a resulting in bronchodilation Indicated for COPD including both chronic bronchitis and/or emphysema Efficacy Improved FEV1 at weeks 12, 24 and 48 5 mcg improved FEV1 from ml vs placebo Adverse effects Nasopharyngitis (11.3%), upper respiratory tract infections (8.2%), bronchitis (4.7%) Drug interactions: Steroids and diuretics hypokalemia; MAO and tricyclic antidepressants QT interval Two actuations (2.5 mcg/actuation = 5 mcg) dose once daily via Respimat delivery system Food and Drug Administration. Drugs@FDA. Accessed August 5, 2014

15 Changes in Existing Medications Albuterol/ipratropium was discontinued in 2013 Re-launched Key Features: 120 doses (20 mcg ipratropium/100 mcg albuterol per dose) 1 inhalation 4 times daily Dose indicator (red zone = 7 days of drug remaining) No shaking or spacer required Inhaler locks when there is no more medicine remaining Food and Drug Administration. Drugs@FDA. drugsatfda/index.cfm. Accessed March 5, Changes in Existing Medications Pharmacists must re-educate themselves and patients about how to use the new albuterol/ipratropium inhaler Intricate priming and delivery system If inhaler not used in 3 days, abbreviated priming required or complete priming if not used in 21 days Moderately more expensive than former albuterol/ipratropium metered-dose inhaler Food and Drug Administration. Drugs@FDA. drugsatfda/index.cfm. Accessed March 5, Respiratory Delivery Devices and Proper Inhaler Technique

16 Types of Inhaler Devices Nebulizers (jet, ultrasonic, vibrating mesh) Conventional pressure metered dose inhaler (pmdi) Albuterol Breath-activated pmdi Autohaler Dry powder inhaler Diskus Aerolizer HandiHaler Diskhaler Incorrect Inhaler Technique 28-68% of patients do not use MDIs or DPIs correctly Even with optimal use of any aerosol delivery system, lung deposition may range from 10-15% of the total medication dose Worsening pulmonary symptoms may not always indicate disease progression but may indicate inability to use inhaler device optimally Instructing patient in the essential steps in drug delivery with device and observe patient demonstrating are key factors for patient success American Association for Respiratory Care Guide to Aerosol Delivery Devices. Accessed April 9, 2014 Common Errors with Inhalers Unfamiliar with device Failure to hold breath for sufficient time after drug delivery Multiple actuations without waiting or shaking in between doses Incorrect position of inhaler Failure to breathe deeply and with enough force to deliver medication (dry power inhalers) Excess moisture from humidity or breathing into device Exhaling into device American Association for Respiratory Care Guide to Aerosol Delivery Devices. Accessed April 9, 2014

17 Errors with Specific Inhaler Devices pmdi Failure to shake and prime the device Failure to coordinate pmdi depression (actuation) on inhalation pmdi with spacer Build up of electrostatic charge, damaged or sticky valves Delay between actuation and inhalation Dry-powder inhalers Failure to pierce or open drug package Exhaling through the mouthpiece Not inhaling forcefully enough American Association for Respiratory Care Guide to Aerosol Delivery Devices. Accessed April 9, 2014 Tips for Correct Inhaler Technique Review device instructions and practice with placebo device Demonstrate assembly and correct use of device to patient using a checklist Provide the patient written instructions on how to use the device and include written plan for the use of medication Have patient practice using the device while being observed by clinician Review patient use of device at each return visit Review patients understanding of the inhaled medication at each return visit (when to use, purpose of drug, prescribed frequency) If poor management of airway disease occurs suspect incorrect use or non-adherence American Association for Respiratory Care Guide to Aerosol Delivery Devices. Accessed April 9, 2014 Respiratory Delivery Devices HandiHaler (tiotropium bromide inhalation powder) Device Use: 1. Dust cap 2. Mouthpiece 3. Base 4. Green piercing button 5. Center chamber Food and Drug Administration. Drugs@FDA. drugsatfda/index.cfm. Accessed March 5, 2014.

18 Respiratory Delivery Device Arcapta Neohaler (indacaterol inhalation powder) Device Use: Food and Drug Administration. drugsatfda/index.cfm. Accessed March 5, Respiratory Delivery Device Tudorza Pressair (aclidinium bromide inhalation powder) Device Use: Food and Drug Administration. drugsatfda/index.cfm. Accessed March 5, Respiratory Delivery Device Breo Ellipta (fluticasone furoate/vilanterol) Device Use: Food and Drug Administration. drugsatfda/index.cfm. Accessed March 5, 2014.

19 Respiratory Delivery Device Respimat Soft Mist TM Inhaler Turn the transparent base until in clicks Insert mouthpiece into mouth and while taking deep breath, press the dose-release button, and continue to breathe. Hold breath for 10 seconds or as long as comfortable and then breathe out slowly Food and Drug Administration. drugsatfda/index.cfm. Accessed March 5, Potential Roles for Pharmacists in Assisting Patients With COPD Advising and assisting with tobacco cessation Recommending and administering vaccines Monitoring and educating to improve adherence and correct inhaler technique Ensuring optimal pharmacotherapy to meet goals Providing medication therapy management services Performing spirometry testing American Pharmacists Association Foundation. J Am Pharm Assoc. 2011;51(2): Cawley MJ, et al. J Am Pharm Assoc. 2013;53(3): Summary for COPD Management Renewed interest including the addition of new pharmacologic treatments Pharmacotherapy can control symptoms, reduce exacerbations, and improve quality of life Many options available; however, combination therapy benefit is unclear Opportunities for pharmacists to assist patients and physicians at all levels of COPD