Palliative Medicine Matters - Hospice Pharmacia

Palliative Medicine Matters
Vol. 5, No. 2 • SPRING 2012
Choice of Inhaler Device in Advanced COPD:
A Review and Critique for the Palliative Care Clinician
Kevin T. Bain, PharmD, MPH, BCPS, CGP, CPH, FASCP, CCA
For patients with chronic obstructive pulmonary disease (COPD),
inhalation is the preferred route for administering respiratory
medications for both acute and maintenance treatment. 1 Although
COPD treatment guidelines acknowledge that inhalation is the
preferred route of administration, 2-4 these same guidelines hardly
address the choice of inhaler device for administering respiratory
medications, especially for patients with advanced COPD. 1,3
Furthermore, literature reviews on this subject matter suggest that,
when used with proper administration technique, there are not
significant differences between inhaler devices in terms of efficacy and
safety. 1,4-6 However, factors besides efficacy and safety affect the choice
of inhaler device for patients with COPD. 1 The purpose of this article
is to review and critique the inhaler devices currently available for the
treatment of COPD and to extract from it the factors that are of key
importance in choosing the most appropriate inhaler device for the
patient with advanced COPD.
What are the available respiratory medications for the
treatment of COPD?
The classes of respiratory medications available for the treatment of
COPD are shown in Table 1. These medications are very briefly
summarized below. They have been reviewed in more detail
elsewhere. 1,2
Bronchodilators are the mainstay of treatment of all stages of COPD. 1,2
The principal bronchodilators available and most commonly used
in patients with COPD are anticholinergics, β 2
-agonists, and
methylxanthines; however, methylxanthines are not available for
inhalation. 1,2 Bronchodilators are used alone or in combination for
short-term (acute) treatment of exacerbations and for long-term
(maintenance) treatment of symptoms. 2
While inhaled corticosteroids are the mainstay of treatment of asthma,
their role in the treatment of COPD is limited to specific indications. 2
The addition of an inhaled corticosteroid to maintenance treatment
with one or more long-acting bronchodilators is most commonly
used in patients with severe (Stage III) to very severe (Stage IV)
COPD, namely those with a forced expiratory volume in one second
(FEV 1
) < 50% predicted and frequent exacerbations. 2
Table 1. Respiratory Medications Commercially Available in the United States 1,3,7
MEDICATION
CLASS
INHALER DEVICE
pMDI BA-pMDI DPI Nebulizer
SAAC Ipratropium (Atrovent ® HFA) None None Ipratropium (Atrovent ® )
LAAC None None Tiotropium (Spiriva ® ) None
Albuterol (Ventolin ® HFA)
Albuterol (AccuNeb ® )
SABA Levalbuterol (Xopenex ® HFA) Pirbuterol (Maxair ® )
None
Levalbuterol (Xopenex ® )
Metaproterenol
Formoterol (Foradil ® ) Arformoterol (Brovana ® )
LABA None None
Indacaterol (Arcapta ® ) Formoterol (Perforomist ® )
Salmeterol (Serevent ® )
SABA + SAAC Albuterol-ipratropium (Combivent ® ) None None Albuterol-ipratropium (DuoNeb ® )
Beclomethasone (QVAR ® )
Budesonide (Pulmicort ® ) Budesonide (Pulmicort Respules ® )
ICS
Ciclesonide (Alvesco ® ) None
Fluticasone (Flovent ® )
Fluticasone (Flovent ® HFA) Mometasone (Asmanex ® )
Budesonide-formoterol (Symbicort ® )
Fluticasone-salmeterol (Advair ® )
ICS + LABA
Fluticasone-salmeterol (Advair ® HFA)
None
None
Mometasone-formoterol (Dulera ® )
Methylxanthines None None None None
BA-pMDI = breath-actuated pressurized metered-dose inhaler; DPI = dry powder inhaler; ICS = inhaled corticosteroid; LAAC = long-acting anticholinergic;
LABA = long-acting β 2
-agonist; pMDI = pressurized metered-dose inhaler; SAAC = short-acting anticholinergic; SABA = short-acting β 2
-agonist.
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What are the available types of inhaler devices for the
treatment of COPD?
There are three major types of inhaler devices available for the
treatment of COPD: the metered-dose inhaler (MDI), the dry
powder inhaler (DPI), and the nebulizer (Table 1). 1,3,7 Each of these
inhaler devices has their own advantages and disadvantages (Table
2). While the availability of several different types of inhaler devices
permits treatment to be tailored to the individual patient with
COPD, at the same time, it also makes it more difficult to make the
correct choice for the individual patient. 1
In the United States, the MDI is a popular and commonly used
inhaler device for administering respiratory medications to patients
with COPD. The MDI is convenient and portable and it is the least
costly inhaler device. 1,3,7 However, the pressurized MDI requires
perfect coordination between hand actuation of the device and
inhalation, a requirement that eludes many patients with COPD. 1,3,7
Adding a spacer device, such as EasiVent®, to the pressurized MDI
or using a breath-actuated pressurized MDI, such as the Autohaler®,
helps to lessen the problem of hand-inhalation coordination and also
improves medication delivery to the lungs, but it also increases the
cost of the inhaler device-respiratory medication combination. 1,3,7
Another way to lessen the hand-inhalation coordination problem with
the pressurized MDI is by using a DPI. 1,7 Besides being as convenient
and portable as a pressurized MDI (without a spacer device), the
DPI is also breath-actuated, only releasing the medication when
the patient inhales forcefully enough through the inhaler device. 1
However, some patients, particularly those with advanced COPD,
are unable to generate sufficient inspiratory flow to adequately deliver
the medication to the lungs. 1 Notwithstanding this disadvantage,
some of the DPIs available provide the patient with sensory feedback
mechanisms to assure the patient that the medication has been
properly administered and adequately delivered to the lungs. 1
The nebulizer is a popular inhaler device amongst patients with
COPD, and it is commonly used during acute treatment of
exacerbations. 1 The nebulizer is relatively easy for the patient to
use, only requiring tidal mouth breathing. 1 However, the nebulizer
requires more time for administering respiratory medications and is
more expensive (as a device) than the MDI or DPI. 1 Additionally, the
nebulizer is somewhat less effective than its counterparts in terms of
medication delivery to the lungs. 1 This problem, though, can usually
be solved by administering higher doses of respiratory medications.
Table 2. Advantages and Disadvantages of Inhaler Devices
Available in the United States 1,3,7
INHALER DEVICE ADVANTAGE DISADVANTAGE
pMDI (without a spacer
device)
pMDI (with a spacer
device)
BA-pMDI (without a
spacer device) *
DPI †
Jet Nebulizer
Ultrasonic and vibrating
mesh nebulizer
BA-pMDI = breath-actuated pressurized metered-dose inhaler; DPI = dry powder
inhaler; pMDI = pressurized metered-dose inhaler.
*An example is the Autohaler® (Maxair®).
†Examples include the Aerolizer® (Foradil®), Diskus® (Advair®, Flovent®, Serevent®),
Flexhaler (Pulmicort®), HandiHaler® (Spiriva®), Neohaler (Arcapta), and
Twishaler® (Asmanex®).
- Requires less time for administration
(about 1 minute)
- Compact and portable
- No medication preparation required
- Least costly
- Can be used with mechanical
ventilation
- Requires less time for administration
(about 1 minute)
- No medication preparation required
- Administration technique and
patient timing are less critical because
of reservoir effect
- Less oropharyngeal medication
deposition
- Less costly than nebulizer (but more
than pMDI alone)
- Requires less time for administration
(about 1 minute)
- Compact and portable
- No medication preparation required
- Patient timing is less critical because
of breath actuation
- Less costly than nebulizer (but more
than pMDI)
- Requires less time for administration
(< 1 minute)
- Compact and portable (there is no
need to use a spacer device)
- Patient timing is less critical because
of breath actuation
- Less costly than nebulizer (but more
than pMDI)
- Portable (but may require power
adaptor for use)
- No breath hold or adequate
inspiratory flow rate is required
- Administration technique and
patient timing are less important
- Can be used with mechanical
ventilation
- Portable (often battery powered,
allowing it to be used easliy in transit)
- No breath hold or adequate
inspiratory flow rate is required
- Administration technique and
patient timing are less important
- Proper administration technique and
patient timing are essential
- Requires breath hold
- More oropharyngeal medication
deposition
- Less compact and portable
- With the exception of anti-static
spacers, plastic spacers can accumulate
electrostatic charges that impair
mediation delivery, therefore, they must
be cleaned regularly and allowed to
air dry
- Bacterial contamination and build-up
of medication residue in the holding
chamber are possible, therefore, the
spacer must be cleaned regularly
- Proper administration technique is still
required (patient timing is less important)
- Requires breath hold
- More oropharyngeal medication
deposition
- Limited availability in the United States
- Cannot be used with mechanical
ventilation
- Single-dose devices require medication
preparation and may be mistaken for oral
medications
- Proper administration technique is still
required (patient timing is less important)
- An adequite inspiratory flow rate is
required
- Requires breath hold
- More oropharyngeal medication
deposition
- Humididty from exhaling can cause
clumping of the powder, decreasing
medication delivery on subsequent
inhalation
- Cannot be used with mechanical
ventilation
- Requires more time for administration
(about 10 to 15 minutes)
- Medication preparation is required
- Most require a wall outlet for use
- Bacterial contamination of the reservoir
is possible, therefore, it must be cleaned
regularly
- More costly (but often insurance
coverage will limit patient cost)
- Requires more time for administration
(about 5 to 10 minutes)
- Medication preparation is required
- Bacterial contamination of the reservoir
is possible, therefore, it must be cleaned
regularly
- Most costly (often not covered by
insurance)
What are the recommendations for choosing an inhaler
device for the treatment of COPD?
While the choice of respiratory medication is reasonably
straightforward for the majority of patients with COPD, the choice
of inhaler device is less clear. In most cases, there is no evidence-
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ased rationale for choosing one inhaler device over another, but
certain factors affect choice for the individual patient. 3 Factors
affecting the choice of inhaler device for patients with COPD are
listed in Box 1. These factors are discussed in more detail below,
along with some recommendations for choosing an inhaler device.
Box 1. Factors Affecting Choice of Inhaler Device 1,3,4
– Availability (of the inhaler device-respiratory
medication combination)
– Preference (of the prescriber and the patient)
– Administration technique
– Cost
Availability
Although there are numerous respiratory medications available
for the treatment of COPD, not all are available in each inhaler
device (Table 1 and Table 2). For example, in the United States, the
long-acting anticholinergic tiotropium is only available in a DPI
whereas the short-acting anticholinergic ipratropium is available
in both a pressurized MDI and a nebulizer. Ipratropium is also
available in combination with the short-acting β 2
-agonist albuterol
in both a pressurized MDI and a nebulizer. Such availability may
be particularly useful in the treatment of patients with advanced
COPD because more often than not they use multiple respiratory
medications simultaneously. As a general recommendation,
when a respiratory medication is available in both a MDI and a
nebulizer (e.g., ipratropium, albuterol, levalbuterol) and the patient
demonstrates proper administration technique, a MDI (without
a spacer device) should be chosen because of its convenience,
portability, and lower cost compared with a nebulizer. 3
Preference
Prescriber preference, which is sometimes based on the clinical
situation, often affects choice of inhaler device. For example, using
a nebulizer during acute treatment of exacerbations is preferred
by many prescribers. Although bronchodilators have equivalent
efficacy when administered by nebulizer or MDI with spacer device
during acute treatment of exacerbations, 4 many prescribers regard
a nebulizer as more convenient than other inhaler devices because
these inhaler devices do not require hand-inhalation coordination or
breath hold. 1,3,8
Differences in patient preference for a specific inhaler device have
also been observed. 1,9,10 For example, although using a nebulizer
requires more administration time and is more costly compared
with using a MDI or DPI, using a nebulizer is preferred by many
patients with COPD, including and perhaps especially those with
advanced COPD. 1 One reason for this is that administration of
respiratory medication by nebulizer is rather easy, only requiring
tidal mouth breathing. Another reason for this is that patients are
impressed by the fact that a nebulizer delivers a visible cloud of
respiratory medication and that these inhaler devices are used in the
hospital setting. 1,8 As a general recommendation, the patient should
be involved in the choice of the inhaler device, mainly because
failure to consider patient preference may translate into poor
adherence to treatment, improper administration technique, and
ultimately decreased control of disease. 1,10,11
Administration Technique
With the exception of nebulizers, all inhaler devices require a degree
of hand-inhalation coordination and most require a breath hold
to obtain good delivery of respiratory medications to the lungs. 12
Unfortunately, improper administration technique, especially
incorrect hand-inhalation coordination and breath hold with a MDI
or DPI, is a common problem in patients with COPD, occurring
in a substantial proportion (close to 50%) of the population. 7,9,13-16
Improper administration technique can result in poor delivery of
respiratory medications to the lungs, increased use of respiratory
medications and cost associated with such use, and decreased
control of disease. 10 This is clearly one of the major factors affecting
choice of inhaler device in advanced COPD.
It is essential to appropriately demonstrate and instruct patients
on proper administration technique and to frequently reevaluate
their ability to handle inhaler devices and use them properly. 2,3
A nebulizer is recommended for patients with COPD who are
judged incapable of proper administration technique using either
a MDI or DPI. 1,17 Taking into account that COPD is a disease
that predominantly affects patients of advanced age and the effect
that ageing has on the cognitive and physical abilities (i.e., learning
capacity, inspiratory flow, manual dexterity, and visual acuity)
of the patient, 1,12,13 it is reasonable to surmise that a substantial
majority of patients with advanced COPD are incapable of proper
administration technique using either a MDI or DPI. Therefore,
based on this factor alone, a nebulizer may be the recommended
choice of inhaler device for most patients with advanced COPD.
Cost
While reimbursement is certainly an important factor affecting
the ability and willingness of patients with COPD to pay the
cost of their prescribed inhalation treatment, it is not the only
cost-contributing factor affecting the choice of inhaler device. For
example, although a nebulizer is more costly than a MDI or DPI
and some nebulizers are not covered or only partially covered by
insurance, as previously discussed, many patients prefer to use
a nebulizer and many others, especially patients with advanced
COPD, are incapable of properly using inhaler devices other than
a nebulizer. Therefore, when choosing an inhaler device for the
treatment of COPD, consideration should be given to the fact
that the most costly inhaler device is the one a patient does not or
cannot use. 1
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What is the take-away message?
Many different inhaler devices are available for administering respiratory medications for patients with advanced COPD. As a consequence,
the palliative care clinician may have some difficulty choosing the most appropriate inhaler device for an individual patient. In the absence of
clinically-relevant differences in efficacy and safety, the palliative care clinician needs to consider other factors affecting the choice of inhaler
device. These factors include availability, preference, administration technique, and cost. Considering all of these factors together, a nebulizer may
be the most appropriate inhaler device for the majority of patients with advanced COPD.
References
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Respir J. 2010;19(1):10-20.
2. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (Updated
2010). Available at: www.goldcopd.org. Accessed February 15, 2012.
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