Download Chronic Obstructive Pulmonary Disease

Kathleen McNamara, PharmD
PGY1 Pharmacy Resident 2015-2016 NEIMEF & WHC
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Therapy Goals & Assessment
Non-pharmacologic & Pharmacologic Therapy
◦ Medications
◦ Mechanism of Action
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Adverse Effects
Pricing & Usual Dose
Summary
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Reduce symptoms
◦ Relieve symptoms
◦ Improve exercise tolerance
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Reduce Risk
◦ Prevent disease progression
◦ Prevent & treat exacerbations
◦ Reduce mortality
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
Cost of pre & post spirometry test at FPC: $141
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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
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Regular assessment of lung function
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Bronchodilators
◦ Beta₂-agonists
◦ Anticholinergics
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Inhaled & oral corticosteroids
Phosphodiesterase-4 (PDE-4) Inhibitor
Methylxanthine
Oxygen
Patient
Group
Recommended 1st
Choice
Alternative Choice
A
SA Anticholinergic PRN
OR
SABA PRN
(Grade 1A)
LA Anticholinergic
OR LABA
OR SABA & SA Antichoinergic
B
LA Anticholinergic
OR LABA
(Grade 1B)
LA Anticholinergic AND LABA
C
ICS + LABA
&/or LA Anticholinergic
LA Anticholinergic & LABA
OR LA Anticholinergic & PDE-4 inhibitor
OR LABA& PDE-4 inhibitor
ICS + LABA
&/or
LA Anticholinergic
(Bronchodilator Grade1B)
(ICS - Grade 2B)
ICS +LABA and LA Anticholinergic
OR ICS + LABA & PDE-4 inhibitor
OR LA Anticholinergic & LABA
OR LA anticholinergic & PDE-4 inhibitor
(Bronchodilator - Grade1B)
(ICS - Grade 2B)
D
SA= Short-acting
LA= Long-acting
ICS= Inhaled Corticosteroid
PDE-4= phosphodiesterase-4
Oxygen therapy
Supplemental
Therapy
Pulmonary rehab
Short-acting
inhaled
bronchodilator
for acute relief
of symptoms
Combination of inhaled corticosteroid, long-acting
β-agonist, and long-acting anticholinergic
Combination of anticholinergic
and β-agonist bronchodilator
Stepwise
Drug Therapy
Pneumococcal and annual influenza vaccination, smoking cessation
and regular assessment of lung function
Health Care Maintenance
Sutherland, 2004
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Mechanism of action: Bind to beta-2 receptors
causing relaxation of bronchial smooth muscle,
resulting in bronchodilation.
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Short-acting
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Long-acting
◦ Albuterol (ProAir, Ventolin, Proventil) T ½= 4-6 hours
◦ Levalbuterol (Xopenex) T ½= 4 hours
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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
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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
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Long-acting
◦ Tiotropium (Spiriva) T ½= 5-6 DAYS
◦ Aclidinium bromide (Tudorza) T ½=5-8 hours
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Do you choose between anticholinergic or β₂agonist?
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1-yr, randomized, double-blind, doubledummy , parallel-group trial
◦ 7,376 patients
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Tiotropium, as compared with salmeterol:
◦ increased time to 1st exacerbation
 187 vs. 145 days
 17% risk reduction (hazard ratio 0.83; 95% CI 0.770.90
◦ 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
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Review of 7 clinical studies
◦ >12,000 patients with COPD
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Spiriva has shown to be more effective at
reducing exacerbations compared with LABA
◦ OR=0.86; (95% CI 0.79-0.93)
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Symptom improvement & changes in lung
function were similar between the two groups
NO significant difference
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FEV
Quality of life
Overall all-cause hospitalizations
Mortality
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Mechanism of action: Anti-inflammatory,
exact mechanism is unknown
Fluticasone (Flovent)
Budesonide (Pulmicort Flexhaler)
Beclomethasone (QVAR)
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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
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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
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PDE-4 Inhibitor
Mechanism of action: increases cAMP levels,
leading to reduction in lung inflammation
◦ Roflumilast (Daliresp)
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Methylxanthine
Mechanism of action: true mechanism not
fully understood, bronchodilation through
smooth muscle relaxation and suppression of
airway stimuli.
◦ Theophylline
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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%
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Serevent:
◦ Musculoskeletal: pain 12%
◦ Neuro: headache 13-17%
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Arcapta
◦ Respiratory: cough 6-24%
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Atrovent
◦ Respiratory: bronchitis 10-23%, sinusitis 14%
◦ GI: xerostomia 4%
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Spiriva
◦ Respiratory: pharyngitis 10%, upper respiratory
infection 43% (w/ powder formulation)
◦ GI: xerostomia 4% (w/ respimat spray), 12-16% (w/
powder formulation)
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Flovent
◦ Respiratory: sinusitis 4-10%, throat irritation 322%, upper respiratory infection 14-21%
◦ Neuro: headache 2-16%
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Pulmicort
◦ Respiratory: respiratory tract infection 3-38%
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Methylprednisone
◦ Cardio: hypertension
◦ Immunologic: at risk for infection
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Daliresp
◦ Endocrine metabolic: decreased weight 7-20%
◦ GI: diarrhea 10%
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Theophylline
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Cardio: tachycardia, arrhythmia
GI: nausea/vomiting/diarrhea
Neuro: headache
Psychiatric: irritability/restlessness/insomnia
SA β-agonists
ProAir (albuterol)
Xopenex (levalbuterol)
Usual Dose
Price
2 inhalations q4-6h $59.17
prn
2 inhalations q4-6h $72.46
prn
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
SA Anticholinergic
Atrovent (ipratropium)
Usual Dose
2 inhalations q6h
prn
Price
$290.04
LA Anticholinergics
Spiriva (tiotropium)
18mcg inhaled daily $351.41
Tudorza (aclidinium
bromide)
400mcg BID
$313.70
Inhaled Corticosteroids
Usual Dose
Price
Flovent HFA (fluticasone)
1-2 inhalations BID $216.22
Pulmicort Flexhaler
(budesonide)
QVAR (beclomethasone)
1-2 inhalations BID $156.63
1-2 inhalations BID
$150.00
40-80mg daily in
1-2 divided doses
Usual
Dose
then
taper
$27.75
500mcg daily
$287.83 (#30)
300mg ER BID
$57.80 (#100)
Systemic Corticosteroids
methylprednisolone
Phosphodiesterase-4
Inhibitor
Daliresp (roflumilast
Methylxanthine
Theophylline 300mg ER
Price
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
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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.
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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.
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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
Thank you!