The medical letter on drugs and therapeutics april 10 2017

The Medical Letter

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on Drugs and Therapeutics
Volume 59

ISSUE
ISSUE
No.

1433
1518

April 10, 2017

IN THIS ISSUE

Drugs for COPD

Volume 56

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The Medical Letter

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on Drugs and Therapeutics
Volume 59

April 10, 2017
Take CME Exams

ISSUE

ISSUE No.

1433
1518

IN THIS ISSUE

Drugs for COPD

Volume 56

The main goals of treatment for chronic obstructive
pulmonary disease (COPD) are to relieve symptoms,
reduce the frequency and severity of exacerbations,
and prevent disease progression. Updated guidelines for treatment of COPD have been published in
recent years.1,2

Some Recommendations for Treatment of COPD

▶ Patients with COPD should stop smoking; pharmacotherapy
can be helpful, especially with varenicline (Chantix).

▶ Patients with occasional dyspnea can use inhaled shortacting bronchodilators as needed for acute symptom relief.

▶ For patients who have moderate to severe dyspnea or

TABLES IN THIS ISSUE
Some Inhaled Bronchodilators for COPD.................................... p 58
Some Long-Acting Bronchodilator Inhalers: Ease of Use ......... p 59
Some Inhaled Corticosteroids and Other Drugs for COPD ........ p 60
Treatment of COPD ...................................................................... p 61
Inhaled Short-Acting Bronchodilators for COPD............. online only
Inhaled Long-Acting Bronchodilators for COPD ............. online only
Some Inhaled Corticosteroids for COPD.......................... online only
Correct Use of Inhalers for COPD ..................................... online only

SMOKING CESSATION — Cigarette smoking is the

primary cause of COPD in the US. Smoking cessation
offers health benefits at all stages of the disease and
can slow the decline of lung function. Counseling and
pharmacotherapy can help patients stop smoking.
Varenicline (Chantix) appears to be the most effective
drug for treatment of tobacco dependence. Nicotine
replacement therapy and bupropion (Zyban, and
others) are also effective.3 Use of ≥2 medications has
been more effective than monotherapy.4,5
SHORT-ACTING BRONCHODILATORS — For patients
with occasional dyspnea, an inhaled short-acting
bronchodilator can provide acute relief. Short-acting
drugs, which include inhaled beta2-agonists such as
albuterol and the antimuscarinic (anticholinergic)
ipratropium, can relieve symptoms and improve FEV1
(forced expiratory volume in one second). Shortacting beta2-agonists have a more rapid onset of
action than ipratropium, but ipratropium has a longer
duration of action (6-8 hrs vs ~4 hrs).
Combining a short-acting beta2-agonist with
ipratropium is more effective than either drug alone.6
The combination of ipratropium and albuterol is
available in a single inhaler (see Table 1).

▶

▶

▶
▶
▶

symptoms, or who are at increased risk of exacerbations,
regular treatment with an inhaled long-acting bronchodilator
(an antimuscarinic or a beta2-agonist) can relieve symptoms,
improve lung function, and reduce the frequency of
exacerbations.
An inhaled long-acting beta2-agonist plus an inhaled longacting antimuscarinic can be used in patients with moderate
to severe dyspnea or symptoms who are at increased risk
for exacerbations and in those inadequately controlled on
monotherapy.
Addition of an inhaled corticosteroid is recommended
for patients with moderate to severe COPD who
experience frequent exacerbations despite treatment with
bronchodilators.
All patients should be assessed for proper inhalation technique.
Oxygen therapy can improve survival in patients with
severe hypoxemia.
Pulmonary rehabilitation should be considered for all patients.

Regular use of an inhaled short-acting bronchodilator
is not recommended for treatment of COPD. Patients
on maintenance treatment for COPD should have
a short-acting bronchodilator available for use as
needed for acute relief.
INHALED LONG-ACTING BRONCHODILATORS —
Regular treatment with an inhaled long-acting
bronchodilator (either a beta2-agonist or an
antimuscarinic agent) is recommended for patients
who have moderate to severe dyspnea or symptoms
or who are at increased risk of exacerbations.

Long-acting antimuscarinic agents (LAMAs; also
called long-acting anticholinergics) may be more
effective than long-acting beta2-agonists (LABAs) in
preventing exacerbations in patients with moderate
to very severe COPD.7,8 In patients with less severe
COPD, there is no strong evidence supporting the use
of one over the other.9,10
57

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The Medical Letter

April 10, 2017

Vol. 59 (1518)

®

Table 1. Some Inhaled Bronchodilators for COPD
Drug

Some Available
Formulations

Delivery Device1

Usual
Adult Dosage

Cost2

17 mcg/inh

HFA MDI (200 inh/unit)

2 inh qid PRN

$332.70

200 mcg/mL soln

Nebulizer3

500 mcg qid PRN

90 mcg/inh

HFA MDI (605 or 200 inh/unit) 90-180 mcg q4-6h PRN

90 mcg/inh
0.63, 1.25, 2.5 mg/
3 mL soln

DPI (200 inh/unit)
Nebulizer3

90-180 mcg q4-6h PRN
1.25-5 mg q4-8h PRN

45 mcg/inh
0.31, 0.63, 1.25 mg/
3 mL soln

HFA MDI (80, 200 inh/unit)
Nebulizer3

90 mcg q4-6h PRN
0.63-1.25 mg tid PRN

68.20
855.00
439.90

344.907

Inhaled Short-Acting Antimuscarinic
Ipratropium – Atrovent HFA
(Boehringer Ingelheim)
generic – single-dose vials

18.104

Inhaled Short-Acting Beta2-Agonists
Albuterol – ProAir HFA (Teva)
Proventil HFA (Merck)
Ventolin HFA (GSK)
ProAir Respiclick (Teva)
generic

Levalbuterol –
Xopenex HFA (Sunovion)
Xopenex (Akorn)
generic

56.20
75.40
52.20
53.00
21.306

Inhaled Short-Acting Beta2-Agonist/Short-Acting Antimuscarinic Combination
Albuterol/ipratropium –
Combivent Respimat
(Boehringer Ingelheim)
generic

100 mcg/20 mcg/inh

ISI (120 inh/unit)

1 inh qid PRN

2.5 mg/0.5 mg/3 mL soln

Nebulizer3

2.5 mg/0.5 mg qid PRN

73.107

Inhaled Long-Acting Beta2-Agonists (LABAs)
Arformoterol – Brovana (Sunovion)

15 mcg/2 mL soln

Nebulizer3

15 mcg bid

871.20

Indacaterol – Arcapta Neohaler
(Sunovion)

75 mcg/cap

DPI (30 inh/unit)

1 inh once/d

213.60

Olodaterol – Striverdi Respimat
(Boehringer Ingelheim)

2.5 mcg/inh

ISI (60 inh/unit)

2 inh once/d

181.60

Salmeterol – Serevent Diskus (GSK)

50 mcg/blister

DPI (28, 60 inh/unit)

1 inh bid

351.60

Formoterol – Perforomist (Mylan)

20 mcg/2 mL soln

Nebulizer3

20 mcg bid

838.80

Inhaled Long-Acting Antimuscarinic Agents (LAMAs)8
Aclidinium – Tudorza Pressair
(AstraZeneca)

400 mcg/inh

DPI (30, 60 inh/unit)

1 inh bid

322.20

Glycopyrrolate – Seebri Neohaler
(Sunovion)

15.6 mcg/cap

DPI (6, 60 inh/unit)

1 inh bid

394.20

Tiotropium –
Spiriva Handihaler (Boehringer Ingelheim) 18 mcg/cap
Spiriva Respimat
2.5 mcg/inh

DPI (5, 30, 90 inh/unit)
ISI (60 inh/unit)

18 mcg9 once/d
2 inh once/d

368.20
368.20

Umeclidinium – Incruse Ellipta (GSK)

DPI (7, 30 inh/unit)

1 inh once/d

324.10

62.5 mcg/inh

Inhaled Long-Acting Antimuscarinic Agents/Long-Acting Beta2-Agonist Combinations (LAMA/LABA Combinations)
Glycopyrrolate/formoterol –
Bevespi Aerosphere (AstraZeneca)

9 mcg/4.8 mcg/inh

HFA MDI (120 inh/unit)

2 inh bid

334.60

Glycopyrrolate/indacaterol –
Utibron Neohaler (Sunovion)

15.6 mcg/27.5 mcg/cap

DPI (60 inh/unit)

1 inh bid

340.20

Tiotropium/olodaterol –
Stiolto Respimat (Boehringer Ingelheim)

2.5 mcg/2.5 mcg/inh

ISI (60 inh/unit)

2 inh once/d

340.90

Umeclidinium/vilanterol –
Anoro Ellipta (GSK)

62.5 mcg/25 mcg/inh

DPI (7, 30 inh/unit)

1 inh once/d

340.90

DPI = dry powder inhaler; ER = extended-release; HFA = hydrofluoroalkane; inh = inhalation; ISI = inhalation spray inhaler; MDI = metered-dose inhaler
1. All patients should be assessed for proper inhalation technique.
2. Approximate WAC for 30 days’ treatment at the lowest recommended adult dosage. For short-acting beta2-agonists and Atrovent HFA, cost is for 200 inhalations. WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not
represent an actual transactional price. Source: AnalySource® Monthly. March 5, 2017. Reprinted with permission by First Databank, Inc. All rights reserved.

©2017. www.fdbhealth.com/policies/drug-pricing-policy.
3. Nebulized solutions may be used for very young, very old, and other patients unable to use handheld inhalers. More time is required to administer the drug
and the device may not be portable. Nebulizers and nebulized drugs may be covered as durable medical equipment (DME) under Medicare part B.
4. Cost for 100 doses.
5. Only Ventolin HFA is available in an inhaler containing 60 inh/unit.
6. Cost for 100 2.5-mg doses.
7. Cost for 120 doses.
8. Also called inhaled long-acting anticholinergics.
9. Contents of one capsule; two inhalations of the powder are required to deliver the full dose.

58


The Medical Letter

®

LABAs can provide sustained bronchodilation for at
least 12 hours. They have been shown to improve
lung function and quality of life, and to reduce the
frequency of exacerbations in patients with COPD.11
Several inhaled LABAs are available alone or in fixeddose combinations with other agents for treatment of
COPD in the US (see Tables 1 and 3).
Inhaled beta2-agonists can cause tachycardia, palpitations, prolongation of the QT interval, hypokalemia,
skeletal muscle tremors and cramping, headache,
insomnia, and increases in serum glucose concentrations.
Unstable angina and myocardial infarction have been
reported. Tolerance can develop with continued use.
All LABAs in the US include a boxed warning about an
increased risk of asthma-related death; there is no

evidence to date that patients with COPD are at risk.
Four inhaled LAMAs are available alone or in combination with other agents for the treatment of COPD (see
Table 1). Tiotropium, the longest available and best
studied LAMA, has been shown to improve lung function
and reduce exacerbation and hospitalization rates, but
it may not reduce the rate of lung function decline.12,13
The other three LAMAs are generally considered similar
in safety and efficacy to tiotropium.14-16
Inhaled antimuscarinics have limited systemic
absorption. They commonly cause dry mouth.
Pharyngeal irritation, urinary retention, and increases
in intraocular pressure may occur; antimuscarinic
inhalers should be used with caution in patients with
narrow-angle glaucoma and in those with symptomatic
prostatic hypertrophy or bladder neck obstruction.
Long-Acting
Bronchodilator
Combinations
–
Combining a LAMA with a LABA can improve lung
function and reduce symptoms, and may decrease
exacerbation rates in patients with COPD. Dual
bronchodilator therapy is recommended for patients
who have moderate to severe dyspnea or symptoms
and are at increased risk for exacerbations and for
those with persistent symptoms or exacerbations
despite use of a single long-acting bronchodilator.17,18
Four fixed-dose combinations of a LAMA and a LABA
have been approved by the FDA (see Table 1).
INHALED CORTICOSTEROIDS (ICSs) — ICSs do not slow

the progression of COPD or reduce mortality.19 They are
less effective than inhaled long-acting bronchodilators
for treatment of COPD and should not be used as
monotherapy. Use of an ICS in addition to a long-acting
bronchodilator can improve lung function and reduce
exacerbations.20 Addition of an ICS is recommended

Vol. 59 (1518)

April 10, 2017

Table 2. Some Long-Acting Bronchodilator Inhalers:
Ease of Use
Aerosphere Inhaler
Bevespi Aerosphere (glycopyrrolate/formoterol)
▶ Metered-dose inhaler; requires coordination of inhalation with
hand-actuation; drug delivery is not dependent on strength of
breath intake
▶ Easy to assemble; requires priming
▶ Indicator shows approximately how many doses are left
▶ Twice-daily dosing
Ellipta Inhalers
Anoro Ellipta (umeclidinium/vilanterol), Breo Ellipta (fluticasone
furoate/vilanterol), Incruse Ellipta (umeclidinium)
▶ Dry powder inhaler; drug delivery to lungs is dependent upon
ability to perform a rapid, deep inhalation
▶ No assembly or priming required
▶ Indicator shows how many doses are left
▶ Doses may be wasted if inhaler is opened/closed accidentally
▶ Once-daily dosing

Respimat Inhalers
Spiriva Respimat (tiotropium), Striverdi Respimat (olodaterol),
Stiolto Respimat (tiotropium/olodaterol)
▶ Inhalation spray inhaler; drug delivery to lungs is not dependent
on strength of breath intake
▶ Assembly may be difficult for some patients
▶ Indicator shows approximately how many doses are left
▶ Once-daily dosing
Neohaler Inhalers
Arcapta Neohaler (indacaterol), Seebri Neohaler (glycopyrrolate),
Utibron Neohaler (glycopyrrolate/indacaterol)
▶ Dry powder inhaler; drug delivery to lungs is dependent upon
ability to perform a rapid, deep inhalation
▶ Removal of the capsule from the foil pack and insertion of the
capsule into the inhaler may be difficult for some patients
▶ Transparent capsules may be helpful in determining if the full
dose was inhaled
▶ Once-daily dosing (Arcapta); twice-daily dosing (Utibron, Seebri)
Pressair Inhaler
Tudorza Pressair (aclidinium)
▶ Dry powder inhaler; drug delivery to lungs is dependent upon
ability to perform a rapid, deep inhalation
▶ No assembly required
▶ Twice-daily dosing
Handihaler Inhaler
Spiriva Handihaler (tiotropium)
▶ Dry powder inhaler; drug delivery to lungs is dependent upon
ability to perform a rapid, deep inhalation
▶ Inserting the capsules into the device may be difficult for some
patients

▶ Once-daily dosing
Diskus Inhalers
Advair Diskus (fluticasone propionate/salmeterol), Serevent
Diskus (salmeterol)
▶ Dry powder inhaler; drug delivery to lungs is dependent upon
ability to perform a rapid, deep inhalation
▶ Indicator shows how many doses are left
▶ Twice-daily dosing

for patients with moderate to very severe COPD who
continue to have exacerbations while receiving longacting bronchodilators. Various combinations of ICSs
and LABAs are available (see Table 3).
Adverse Effects – Local effects of ICSs on the mouth
and pharynx include candidiasis and dysphonia.
59


The Medical Letter

April 10, 2017

Vol. 59 (1518)

®

Table 3. Some Inhaled Corticosteroids and Other Drugs for COPD
Drug

Some Available
Formulations

Delivery Device1

Usual
Adult Dosage

Cost2

Inhaled Corticosteroids (ICSs)3
Beclomethasone dipropionate –
QVAR (Teva)

40, 80 mcg/inh

HFA MDI (120 inh/unit)

40-320 mcg bid

$156.70

Budesonide4 – Pulmicort Flexhaler
(AstraZeneca)

90, 180 mcg/inh

DPI (60, 120 inh/unit)

180-720 mcg bid

216.50

Ciclesonide – Alvesco (Sunovion)

80, 160 mcg/inh

HFA MDI (60 inh/unit)

80-320 mcg bid

228.90

Flunisolide – Aerospan HFA (Meda)

80 mcg/inh

HFA MDI (60, 120 inh/unit)

160-320 mcg bid

196.10

Fluticasone furoate –
Arnuity Ellipta (GSK)

100, 200 mcg/inh

DPI (14, 30 inh/unit)

100-200 mcg once/d

159.00

Fluticasone propionate –
Flovent Diskus (GSK)
Flovent HFA
ArmonAir Respiclick (Teva)

50, 100, 250 mcg/blister
44, 110, 220 mcg/inh
55, 113, 232 mcg/inh

DPI (28, 60 inh/unit)
HFA MDI (120 inh/unit)
DPI (60 inh/unit)

100-1000 mcg bid
88-880 mcg bid
55-232 mcg bid

171.40
171.40
N.A.

100, 200 mcg/inh
110, 220 mcg/inh

HFA MDI (120 inh/unit)
DPI (30, 60, 120 inh/unit)

200-400 mcg bid

220-880 mcg once/d in
evening or 220 mcg bid

178.80
179.00

Mometasone furoate –
Asmanex HFA (Merck)
Asmanex Twisthaler
(Merck)

Inhaled Corticosteroid/Long-Acting Beta2-Agonist Combinations (ICS/LABA Combinations)
Fluticasone propionate/salmeterol –
Advair Diskus5 (GSK)

100, 250, 500 mcg/50 mcg/
DPI (28, 60 inh/unit)
blister
45, 115, 230 mcg/21 mcg/inh HFA MDI (60, 120 inh/unit)
55, 113, 232 mcg/14 mcg/inh DPI (60 inh/unit)

250/50 mcg bid

361.40

2 inh bid
1 inh bid

290.90
N.A

Fluticasone furoate/vilanterol –
Breo Ellipta6 (GSK)

100, 200 mcg/25 mcg/inh

DPI (14, 30 inh/unit)

1 inh once/d

321.70

Budesonide/formoterol –
Symbicort7 (AstraZeneca)

80, 160 mcg/4.5 mcg/inh

HFA MDI (60, 120 inh/unit)

2 inh bid

308.70

500 mcg tabs

none

500 mcg PO once/d

199.00

100, 200, 300, 400, 450,
600 mg ER tabs;
80 mg/15 mL soln
80 mg/15 mL soln

none

300-600 mg PO once/d
or divided bid

Advair HFA3
AirDuo Respiclick3 (Teva)

Phosphodiesterase-4 (PDE4) Inhibitor
Roflumilast – Daliresp (AstraZeneca)
Methylxanthine
Theophylline8,9 – generic
Elixophyllin (Nostrum Labs)
Theo-24 (Auxilium)
Theochron (Caraco)

100, 200, 300, 400 mg
ER caps
100, 200, 300 mg ER tabs

15.90

300-600 mg/d PO
1261.30

divided tid-qid
300-600 mg PO once/d10
86.50
300-600 mg PO once/d

15.10

DPI = dry powder inhaler; ER = extended-release; HFA = hydrofluoroalkane; inh = inhalation; ISI = inhalation spray inhaler; MDI = metered-dose inhaler; NA = cost
not available
1. All patients should be assessed for proper inhalation technique.
2. Approximate WAC for 30 days’ treatment at the lowest usual adult dosage. WAC = wholesaler acquisition cost or manufacturer’s published price to wholesalers; WAC represents a published catalogue or list price and may not represent an actual transactional price. Source: AnalySource® Monthly. March 5, 2017.
Reprinted with permission by First Databank, Inc. All rights reserved. ©2017. www.fdbhealth.com/policies/drug-pricing-policy.
3. Not FDA-approved for treatment of COPD. Inhaled corticosteroid monotherapy is not recommended for treatment of COPD.
4. Budesonide is also available as a suspension for nebulization (Pulmicort Respules, and generics) that is FDA-approved only for treatment of asthma in
children 1-8 years old.
5. Only the 250/50 mcg dose is FDA-approved for use in COPD.
6. Only the 100/25 mcg dose is FDA-approved for use in COPD.
7. Only the 160/4.5 mcg dose is FDA-approved for use in COPD.
8. Extended-release formulations may not be interchangeable.
9. Periodic monitoring is recommended to maintain peak serum concentrations between 8 and 12 mcg/mL.
10. Theo-24 should not be taken <1 hr before a high-fat content meal; the entire 24-hour dose can be released in a 4-hour period, resulting in toxicity.

Systemic absorption of ICSs has been associated
with skin bruising, cataracts, reduced bone mineral
density, and an increased risk of fractures. Use of ICSs
in patients with COPD is associated with an increased
risk of pneumonia.21
ICS Withdrawal – In one study, 2485 patients with
COPD on triple therapy with tiotropium, salmeterol,
and fluticasone propionate were randomized to

either continue triple therapy or taper the ICS over
60

12 weeks. The time to the first moderate or severe
exacerbation within 12 months was similar in both
groups, but a statistically significant decrease in
trough FEV1 occurred in the corticosteroid taper
group; the clinical significance is unclear.22 A posthoc analysis found that the risk of exacerbation was
higher in the corticosteroid taper group compared
to the continuation group in patients who had blood
eosinophil levels ≥300 cells/mcL at baseline.23


The Medical Letter

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Vol. 59 (1518)

April 10, 2017

LABA/LAMA vs ICS/LABA — In patients who are at
increased risk of exacerbations, the combination of a
LABA and a LAMA appears to be more effective than
an ICS/LABA combination in reducing exacerbations.24
In a 52-week study comparing the combination of
glycopyrronium and indacaterol with fluticasone and
salmeterol, patients who received the LAMA/LABA
combination had 11% fewer exacerbations and a longer
time to the first exacerbation than those receiving the ICS/

LABA combination. The rates of mortality and adverse
effects were similar between the two treatments.25

Table 4. Treatment of COPD1-3

TRIPLE-THERAPY REGIMENS — Some studies have
found that adding a LAMA to a LABA/ICS regimen
can reduce exacerbations and improve lung function,
symptoms, and quality of life.26-29 Whether adding an
ICS to a LABA/LAMA combination provides similar
benefits remains to be established.

Occasional Dyspnea or Few Symptoms; ≥1 exacerbation5

THEOPHYLLINE — Theophylline can be tried in
patients with persistent symptoms despite treatment
with inhaled triple-therapy. Its primary mechanism of
action is bronchodilation; at low concentrations, it may
have anti-inflammatory effects.30 Theophylline has
a narrow therapeutic index; monitoring is warranted
periodically to maintain peak serum concentrations
between 8 and 12 mcg/mL.
Adverse Effects – Dose-related adverse effects of
theophylline include nausea, nervousness, headache,
and insomnia. Vomiting, hypokalemia, hyperglycemia,
tachycardia, cardiac arrhythmias, tremors, neuromuscular irritability, and seizures can occur at
supratherapeutic serum concentrations. Theophylline
is metabolized hepatically, primarily by CYP1A2 and
CYP3A4; any drug that inhibits or induces these enzymes can affect theophylline serum concentrations.31
ROFLUMILAST — Roflumilast (Daliresp) is an oral

phosphodiesterase-4 (PDE4) inhibitor approved for
use in patients with severe COPD associated with
chronic bronchitis and a history of exacerbations. It
reduces inflammation by increasing intracellular levels
of cAMP; it does not cause bronchodilation.32 Oncedaily treatment can modestly improve lung function
and reduce the frequency of exacerbations, but it does
not appear to improve symptoms or quality of life.33,34
Common adverse effects include nausea and diarrhea.
Significant weight loss and changes in mood and
behavior have been reported.
AZITHROMYCIN — Macrolide antibiotics have antiinflammatory effects. Once-daily or three times a
week off-label use of azithromycin (Zithromax, and

Occasional Dyspnea or Few Symptoms; ≤1 exacerbation4
Inhaled ipratropium as needed
or Inhaled short-acting beta2-agonist
as needed
or LAMA
or LABA
Moderate to Severe Dyspnea or Symptoms; ≤1 exacerbation4
Initial

LAMA
or LABA

Persistent or
Severe Symptoms
Initial

LAMA + LABA

LAMA (preferred)
or LABA

Further
Exacerbations

LAMA + LABA (preferred)
or LABA + ICS

Moderate to Severe Dyspnea or Symptoms; ≥1 exacerbation5
Initial
Further
Exacerbations

LABA + LAMA
ICS + LABA + LAMA
or ICS + LABA6
or ICS + LABA + LAMA + roflumilast7
or ICS + LABA + LAMA + azithromycin8

ICS = inhaled corticosteroid; LABA = inhaled long-acting beta2-agonist;
LAMA = inhaled long-acting antimuscarinic agent
1. Adapted from the Global Strategy for the Diagnosis, Management, and
Prevention of COPD, Global Initiative for Chronic Obstructive Pulmonary
Disease (GOLD) 2017. Available at: . Accessed March
30, 2017. Dyspnea and symptoms should be assessed using mMRC
(Modified British Medical Research Council) and CAT (COPD Assessment
Test), respectively.
2. Short-acting anticholinergics and beta2-agonists can be added to any

regimen for acute relief.
3. Theophylline may be used if other long-acting bronchodilators are unavailable or unaffordable.
4. Exacerbation that did not lead to hospital admission.
5. ≥1 exacerbation leading to hospital admission or ≥2 exacerbations.
6. An ICS/LABA combination may be considered a first choice for patients with
asthma/COPD overlap or high blood eosinophil levels.
7. In patients with FEV1 <50% predicted and chronic bronchitis.
8. Or another macrolide. Consider use in former smokers.

generics) has been shown to reduce the risk of an
exacerbation over one year and improve quality of life
in patients with COPD at increased risk of exacerbation,
but use of the drug has been associated with hearing
loss and development of antimicrobial resistance.35,36
Efficacy and safety data beyond one year of use are
not available.
OXYGEN THERAPY — For patients with severe
hypoxemia, use of long-term supplemental oxygen
therapy has been shown to increase survival and may
improve quality of life.37 In a recent study, long-term
oxygen therapy did not lead to reduced mortality or
longer time to first hospitalization in patients with mild
to moderate hypoxemia.38
PULMONARY REHABILITATION — The benefits of
pulmonary rehabilitation programs for patients with
COPD are well established. Pulmonary rehabilitation
can improve dyspnea, functional capacity, and quality
of life, and reduce the number of hospitalizations.39 ■
61

The Medical Letter

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1. GOLD 2017 global strategy for the diagnosis, management and
prevention of COPD. Available at www.goldcopd.org. Accessed
March 30, 2017.
2. 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
European Respiratory Society. Ann Intern Med 2011; 155:179.
3. Drugs for tobacco dependence. Med Lett Drugs Ther 2016;
58:27.
4. CF Koegelenberg et al. Efficacy of varenicline combined with
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5. JO Ebbert et al. Combination varenicline and bupropion SR for
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6. J Nichols. Combination inhaled bronchodilator therapy in the
management of chronic obstructive pulmonary disease. Pharmacotherapy 2007; 27:447.
7. C Vogelmeier et al. Tiotropium versus salmeterol for the prevention of exacerbations of COPD. N Engl J Med 2011; 364:
1093.
8. ML Decramer et al. Once-daily indacaterol versus tiotropium
for patients with severe chronic obstructive pulmonary disease
(INVIGORATE): a randomised, blinded, parallel-group study.
Lancet Respir Med 2013; 1:524.
9. 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.
10. JA Wedzicha. Choice of bronchodilator therapy for patients
with COPD. N Engl J Med 2011; 364: 1167.
11. KM Kew et al. Long-acting beta2-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2013;
10:CD010177.
12. DP Tashkin et al. A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 2008; 359:1543.
13. M Decramer et. al. Effect of tiotropium on outcomes in patients
with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet 2009; 374:1171.
14. Aclidinium bromide (Tudorza Pressair) for COPD. Med Lett
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15. Seebri Neohaler and Utibron Neohaler for COPD. Med Lett
Drugs Ther 2016; 58:39.
16. Umeclidinium (Incruse Ellipta) for COPD. Med Lett Drugs Ther
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17. T van der Molen and M Cazzola. Beyond lung function in COPD
management: effectiveness of LABA/LAMA combination therapy on patient-centred outcomes. Prim Care Respir J 2012;
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22. H Magnussen et al. Withdrawal of inhaled glucocorticoids and

exacerbations of COPD. N Engl J Med 2014; 371:1285.

62

Vol. 59 (1518)

April 10, 2017

23. H Watz et al. Blood eosinophil count and exacerbations in severe chronic obstructive pulmonary disease after withdrawal
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32. Roflumilast (Daliresp) for COPD. Med Lett Drugs Ther 2011;
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Online Only Tables
Inhaled Short-Acting Bronchodilators for COPD
/>Inhaled Long-Acting Bronchodilators for COPD
/>Some Inhaled Corticosteroids for COPD
/>Correct Use of Inhalers for COPD
/>

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Issue 1518 Questions
(Correspond to questions #71-80 in Comprehensive Exam #76, available July 2017)
6. Which of the following LAMA-containing inhalers would be
best for an 80-year-old woman who has difficulty taking deep
breaths?
a. Incruse Ellipta
b. Spiriva Respimat
c. Seebri Neohaler
d. Tudorza Pressair

Drugs for COPD
1. Which of the following is the most effective treatment for

tobacco dependence?
a. e-cigarettes
b. nicotine replacement therapy
c. bupropion
d. varenicline
2. A 50-year-old woman with COPD experiences occasional
dyspnea during exercise. She does not have a history of
asthma. Which of the following should you recommend?
a. an inhaled corticosteroid used daily
b. an inhaled LABA/LAMA combination used once daily
c. inhaled ipratropium used four times daily
d. an inhaled short-acting beta2-agonist used as needed
3. In patients with COPD, inhaled LABAs have been shown to:
a. improve lung function
b. reduce exacerbations
c. improve quality of life
d. all of the above
4. A 62-year-old woman with a history of mild COPD now is
experiencing worsening dyspnea during usual activity. She
has never been hospitalized for an exacerbation and has not
been taking chronic therapy for COPD. Which of the following
treatments would be most appropriate for this patient?
a. an inhaled short-acting bronchodilator as needed
b. an inhaled LAMA
c. an inhaled LABA/LAMA combination
d. an inhaled ICS/LABA combination
5. Adverse effects of inhaled antimuscarinics include:
a. dry mouth
b. QT prolongation
c. muscle tremors

d. all of the above

7. A 70-year-old man with severe COPD has been experiencing
frequent exacerbations while taking a LABA/LAMA
combination. The best choice for management of this patient
would be to:
a. discontinue the LAMA
b. add an oral corticosteroid
c. add an inhaled corticosteroid
d. begin oxygen therapy
8. For treatment of COPD, peak serum concentrations of
theophylline should be:
a. <6 mcg/mL
b. between 8-12 mcg/mL
c. between 15-20 mcg/mL
d. >20 mcg/mL
9. Roflumilast:
a. reduces exacerbations
b. improves quality of life
c. is a bronchodilator
d. all of the above
10. Which of the following statements about the use of
azithromycin in COPD is true?
a. it can reduce exacerbations
b. hearing loss has occurred
c. data on its use beyond 1 year are lacking
d. all of the above

ACPE UPN: Per Issue Exam: 0379-0000-17-518-H01-P; Release: April 10, 2017, Expire: April 10, 2018
Comprehensive Exam 76: 0379-0000-17-076-H01-P; Release: July 2017, Expire: July 2018

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