Kathleen McNamara, PharmD PGY1 Pharmacy Resident 2015-2016 NEIMEF & WHC.
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Transcript of Kathleen McNamara, PharmD PGY1 Pharmacy Resident 2015-2016 NEIMEF & WHC.
COPD (Chronic Obstructive Pulmonary Disease)
Kathleen McNamara, PharmDPGY1 Pharmacy Resident 2015-2016 NEIMEF & WHC
Therapy Goals & Assessment Non-pharmacologic & Pharmacologic
Therapy◦ Medications◦ Mechanism of Action
Adverse Effects Pricing & Usual Dose Summary
Overview
Reduce symptoms◦ Relieve symptoms◦ Improve exercise tolerance
Reduce Risk◦ Prevent disease progression◦ Prevent & treat exacerbations◦ Reduce mortality
Therapy Goals
Classification of Severity of Airflow Limitation in COPD
GOLD 1 Mild FEV₁ ≥ 80% predicted
GOLD 2 Moderate 50% ≤ FEV₁ < 80% predicted
GOLD 3 Severe 30% ≤ FEV₁ < 50% predicted
GOLD 4 Very Severe FEV₁ < 30% predicted
COPD Assessment
Cost of pre & post spirometry test at FPC: $141
Smoking cessation Immunizations
◦ Influenza Annually for all patients with COPD
◦ Pneumococcal All smokers & All patients < 65 years old with COPD Anyone > 65 years of age
Regular assessment of lung function
Non-Pharmacological Therapy
Bronchodilators◦ Beta₂-agonists◦ Anticholinergics
Inhaled & oral corticosteroids Phosphodiesterase-4 (PDE-4) Inhibitor Methylxanthine Oxygen
Pharmacologic Therapy
Patient Group
Recommended 1st Choice
Alternative Choice
A SA Anticholinergic PRNORSABA PRN (Grade 1A)
LA AnticholinergicOR LABAOR SABA & SA Antichoinergic
B LA Anticholinergic OR LABA (Grade 1B)
LA Anticholinergic AND LABA
C ICS + LABA&/or LA Anticholinergic (Bronchodilator - Grade1B) (ICS - Grade 2B)
LA Anticholinergic & LABAOR LA Anticholinergic & PDE-4 inhibitorOR LABA& PDE-4 inhibitor
D ICS + LABA&/orLA Anticholinergic(Bronchodilator Grade1B) (ICS - Grade 2B)
ICS +LABA and LA AnticholinergicOR ICS + LABA & PDE-4 inhibitorOR LA Anticholinergic & LABAOR LA anticholinergic & PDE-4 inhibitor
Pharmacologic Therapy for Stable COPD
SA= Short-acting ICS= Inhaled CorticosteroidLA= Long-acting PDE-4= phosphodiesterase-4
Oxygen therapy
Pulmonary rehabSupplemental Therapy
Stepwise Drug Therapy
Health Care Maintenance
Symptoms
Combination of inhaled corticosteroid, long-acting β-agonist, and long-acting anticholinergic
Combination of anticholinergic and β-agonist bronchodilator
Short-acting inhaled bronchodilator for acute relief of symptoms
Pneumococcal and annual influenza vaccination, smoking cessation and regular assessment of lung function
FEV1
Sutherland, 2004
Mechanism of action: Bind to beta-2 receptors causing relaxation of bronchial smooth muscle, resulting in bronchodilation.
Short-acting◦ Albuterol (ProAir, Ventolin, Proventil) T ½= 4-6 hours◦ Levalbuterol (Xopenex) T ½= 4 hours
Long-acting◦ Formoterol (Foradil) T ½= 10 hours ◦ Salmeterol (Serevent) T ½= 5.5 hours ◦ Arformoterol (Brovana) T ½= 26 hours ◦ Indacaterol (Arcapta) T ½= 40-56 hours
β₂-agonists
Mechanism of action: block the action of acetylcholine & decrease cGMP (cyclic guanosine monophosphate) in bronchial smooth muscle causing bronchodilation.
Short-acting◦ Ipratropium (Atrovent) T ½=1.5 hours
Long-acting◦ Tiotropium (Spiriva) T ½= 5-6 DAYS ◦ Aclidinium bromide (Tudorza) T ½=5-8 hours
Anticholinergics
Do you choose between anticholinergic or β₂-agonist?
Comparison of Agents
1-yr, randomized, double-blind, double-dummy , parallel-group trial ◦ 7,376 patients
Tiotropium, as compared with salmeterol:◦ increased time to 1st exacerbation
187 vs. 145 days 17% risk reduction (hazard ratio 0.83; 95% CI 0.77-
0.90◦ Increased time to 1st severe exacerbation
Hazard ratio 0.72; 95% CI 0.61-0.85◦ Reduced annual # severe exacerbations
0.09 vs 0.13, rate ratio 0.73; 95% CI 0.66-0.82
Tiotropium vs Salmeterol for Prevention of Exacerbations of COPD
Review of 7 clinical studies ◦ >12,000 patients with COPD
Spiriva has shown to be more effective at reducing exacerbations compared with LABA◦ OR=0.86; (95% CI 0.79-0.93)
Symptom improvement & changes in lung function were similar between the two groups
NO significant difference◦ FEV◦ Quality of life◦ Overall all-cause hospitalizations ◦ Mortality
Tiotropium vs. long-acting β-agonists for stable chronic obstructive pulmonary disease
Mechanism of action: Anti-inflammatory, exact mechanism is unknown
Fluticasone (Flovent) Budesonide (Pulmicort Flexhaler) Beclomethasone (QVAR)
Inhaled Corticosteroids
12-month, double-blind, parallel-group study 2485 patients with history COPD exacerbation Methods
◦ All participants received triple therapy of Spiriva, Serevent & Flovent x 6 week run-in period
◦ Then randomized to continue triple therapy or withdrawal Flovent in 3 steps over 12 weeks
Primary end point: time to first moderate or severe COPD exacerbation
Results ◦ Compared with continued glucocorticoid use, withdrawal
met noninferiority criteria with respect to the first moderate or severe exacerbation
Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD
PDE-4 Inhibitor Mechanism of action: increases cAMP levels,
leading to reduction in lung inflammation◦ Roflumilast (Daliresp)
Methylxanthine Mechanism of action: true mechanism not
fully understood, bronchodilation through smooth muscle relaxation and suppression of airway stimuli. ◦ Theophylline
Phosphodiesterase-4 Inhibitor & Methylxanthine
Adverse effects
General◦ Respiratory: 5% or more: bronchitis, cough, sore
throat, rhinitis 5-16%, upper respiratory infection 5-21%
◦ GI: nausea 10%, pharyngitis 14%◦ Neuro: feeling nervous 7%, tremor 5-7%
Serevent: ◦ Musculoskeletal: pain 12%◦ Neuro: headache 13-17%
Arcapta◦ Respiratory: cough 6-24%
Beta-agonists Adverse Effects
Atrovent◦ Respiratory: bronchitis 10-23%, sinusitis 14%◦ GI: xerostomia 4%
Spiriva◦ Respiratory: pharyngitis 10%, upper respiratory
infection 43% (w/ powder formulation)◦ GI: xerostomia 4% (w/ respimat spray), 12-16%
(w/ powder formulation)
Adverse Effects with Anticholinergic Medications
Flovent◦ Respiratory: sinusitis 4-10%, throat irritation 3-
22%, upper respiratory infection 14-21%◦ Neuro: headache 2-16%
Pulmicort◦ Respiratory: respiratory tract infection 3-38%
Methylprednisone ◦ Cardio: hypertension◦ Immunologic: at risk for infection
Steroid Adverse Effects
Daliresp◦ Endocrine metabolic: decreased weight 7-20%◦ GI: diarrhea 10%
Theophylline◦ Cardio: tachycardia, arrhythmia◦ GI: nausea/vomiting/diarrhea◦ Neuro: headache◦ Psychiatric: irritability/restlessness/insomnia
Adverse Effects with Alternative Treatment
Pricing $$$
What is the approximate cash price cost to a patient for ProAir? (Without insurance)
SA β-agonists Usual Dose Price
ProAir (albuterol) 2 inhalations q4-6h prn
$59.17
Xopenex (levalbuterol) 2 inhalations q4-6h prn
$72.46
LA β-agonists
Foradil (formoterol) 12mcg inhaled BID $137.78
Serevent (salmeterol) 50mcg inhaled BID $312.73
Brovana (arformoterol) 15mcg inhaled BID $755.26
Arcapta (indacaterol) 75mcg inhaled daily
$225.83
Beta-agonists
How much would you estimate Spiriva to cost a patient without insurance?
SA Anticholinergic Usual Dose Price
Atrovent (ipratropium) 2 inhalations q6h prn
$290.04
LA Anticholinergics
Spiriva (tiotropium) 18mcg inhaled daily
$351.41
Tudorza (aclidinium bromide)
400mcg BID $313.70
Anticholinergics
Inhaled Corticosteroids Usual Dose Price
Flovent HFA (fluticasone)
1-2 inhalations BID $216.22
Pulmicort Flexhaler (budesonide)
1-2 inhalations BID $156.63
QVAR (beclomethasone) 1-2 inhalations BID $150.00
Systemic Corticosteroids
methylprednisolone 40-80mg daily in 1-2 divided doses then taper
$27.75
Steroids & Alternative Treatments
Phosphodiesterase-4 Inhibitor
Usual Dose Price
Daliresp (roflumilast 500mcg daily $287.83 (#30)Methylxanthine Theophylline 300mg ER 300mg ER BID $57.80 (#100)
Combination Products Usual Dose Price
Combivent (albuterol/ipratropium)
1 inhalation QID $329.44
Advair 100/50 (salmeterol/fluticasone)
1 inhalation BID $278.46
Symbicort 160 (formoterol/budesonide)
2 inhalations BID $306.35
Stiolto Respimat(tiotropium/olodaterol)
2 inhalations QD $ 340.00
Breo Ellipta(fluticasone/vilanterol)
1 inhalation QD $320.00
Combination Products
Generally NOT indicated for majority of patients with COPD.
BUT, some antibiotics (macrolides) may have anti-inflammatory effects in addition to antibiotic effect.◦ May be appropriate for continued, frequent
exacerbations despite optimal therapy with bronchodilators and anti-inflammatory agents.
Chronic Antibiotic Therapy
Summary
Chong J, Karner C, Poole P. Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease (Review). The Cochrane Collection. Published by John Wiley & Sons, Ltd.
Global Strategy for the Diagnosis, Management, and Prevention of COPD. Scientific information and recommendations for COPD programs. Updated 2015.
Magnussen, Disse, Rodriguez-Roisin, et al. Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD. NEJM 371;14. 2 October, 2014.
Micromedex Drug Index
References
Questions?Thank you!