Download COPD - HSE

Medicines Management Programme
Inhaled Medicines for Chronic
Obstructive Pulmonary Disease
(COPD)
Prescribing and Cost Guidance
Approved by
Date approved
Date updated
Prof. Michael Barry, Clinical Lead, MMP.
Version 1 July 2014
Version 1.1 Jan 2015
Version 1.2 Oct 2015
Version 1.3 Nov 2016
Version 1.3 November 2016
Table of Contents
1. Background ................................................................................................................ 1
2. Purpose ...................................................................................................................... 2
3. Definitions .................................................................................................................. 2
4. Treatment of COPD .................................................................................................... 3
4.1 Smoking cessation ................................................................................................ 3
4.2 Inhaled therapies for COPD ................................................................................. 3
4.3 Inhaler devices ................................................................................................. 4
4.3.1 Pressurised Metered Dose Inhalers (pMDI).................................................. 4
4.3.2 Breath Actuated Metered Dose Inhalers (BA MDI) ...................................... 5
4.3.3 Soft Mist Inhalers (SMI) ................................................................................ 5
4.3.4 Dry Powder Inhalers (DPI) ............................................................................. 5
5. Inhaled therapies ....................................................................................................... 9
5.1 Short-acting beta2 agonists (SABA) ...................................................................... 9
5.2 Short-acting muscarinic antagonists (SAMA) ...................................................... 9
5.3 Long-acting muscarinic antagonists (LAMA) ...................................................... 10
5.4 Long-acting beta2-agonists (LABA) ..................................................................... 10
5.5 Combined long-acting beta2 agonist and long-acting muscarinic antagonist
(LABA/LAMA) ........................................................................................................... 11
5.6 Inhaled corticosteroids (ICS) .............................................................................. 12
5.7 Combined inhaled corticosteroids and long-acting beta2 agonist (ICS/LABA) .. 13
6. Nebulised therapy .................................................................................................... 15
7. Summary .................................................................................................................. 16
8. References................................................................................................................ 18
Appendix 1. Summary - Inhaled therapies for stable COPD ........................................ 23
Appendix 2. Practice Points – Management of COPD ................................................. 24
Appendix 3. COPD- Summary of Inhaler Costs ............................................................ 25
Appendix 4. New in this update ................................................................................... 26
Tables
Table 1. Classification of severity of airflow limitation in COPD ................................... 1
Table 2. Classification according to risk of future exacerbations & symptoms............. 1
Table 3. Dry Powder Inhaler (DPI) devices currently on the market for COPD ............. 6
Table 4. Inhaled therapies for stable COPD ................................................................... 8
Table 5. Short-acting beta2 agonists (SABA) .................................................................. 9
Table 6. Short-acting muscarinic antagonists (SAMA) ................................................... 9
Table 7. Inhaled long-acting muscarinic antagonists (LAMA)...................................... 10
Table 8. Inhaled long-acting beta2 agonists (LABA) ..................................................... 11
Table 9. Combination LABA and LAMA ........................................................................ 12
Table 10. Inhaled corticosteroids................................................................................. 13
Table 11. Combination devices containing ICS/LABA .................................................. 14
Figures
Figure 1. Pressurised Metered Dose Inhaler (pMDI) ..................................................... 5
Version 1.3 November 2016
List of Abbreviations
BA
Breath-actuated
COPD Chronic obstructive pulmonary disease
DPI
Dry powder inhaler
FEV1
Forced expiratory volume in 1 second
FVC
Forced vital capacity
GMS
General Medical Service
GOLD Global Initiative for Chronic Obstructive Lung Disease
HSE
Health Service Executive
ICS
Inhaled corticosteroids
IT
Inhaler Technique
LABA Long-acting beta2 agonist
LAMA Long-acting muscarinic antagonist
MMP Medicines Management Programme
MDI
Metered dose inhaler
PCRS Primary Care Reimbursement Service
pMDI Pressurised metered dose inhaler
SABA Short-acting beta2 agonist
SAMA Short-acting muscarinic antagonist
SMI
Soft mist inhaler
This medicinal product is subject to additional monitoring.
Acknowledgements
The MMP wishes to acknowledge the staff of the National Medicines Information
Centre (NMIC), in particular the editorial committee, and Prof. Tim McDonnell, Clinical
Lead, National Clinical Programme for COPD for their input.
Version 1.3 November 2016
1. Background
Chronic obstructive pulmonary disease (COPD) is a preventable and treatable
condition characterised by chronic slowly progressive airway obstruction.1-3 COPD is
the preferred term for patients with airways obstruction who were previously
diagnosed with chronic bronchitis or emphysema.4 Other conditions now referred to
as COPD are chronic obstructive airways disease and chronic airway flow limitation.5
A clinical diagnosis of COPD should be considered for any patient > 35 years with risk
factors for COPD and symptoms that include dyspnoea, chronic cough or sputum
production.1, 4 The presence of a post-bronchodilator FEV1/FVC < 0.70 confirms the
presence of persistent airflow limitation of COPD.1, 4
The Global Initiative for Chronic Obstructive Lung Disease (GOLD) has classified COPD
into four categories according to severity of disease. Patients are also classified
according to their level of risk of future exacerbation and symptoms.1
Table 1. Classification of severity of airflow limitation in COPD
(based on post-bronchodilator FEV1)
In patients with FEV1/FVC < 0.70
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
Table 2. Classification according to risk of future exacerbations & symptoms
Patient
Characteristics
Spirometric
Exacerbations per
category
Classification
year
A
Low risk, less symptoms
GOLD 1-2
≤1
B
Low risk, more symptoms
GOLD 1-2
≤1
C
High risk, less symptoms
GOLD 3-4
≥2
D
High risk, more symptoms
GOLD 3-4
≥2
There are currently over 36 licensed inhalers for the treatment of COPD that are
reimbursed by the Primary Care Reimbursement Service (PCRS).6, 7 These drugs and
devices represent a considerable cost to the health service. Analyses of 2013 PCRS
pharmacy claims data were performed to estimate total expenditure on inhalers used
1
in obstructive airways disease. Patients over the age of 40 years were included in the
analyses under the assumption that this age group would largely represent COPD.
Between the General Medical Services (GMS) and Drugs Payment (DP) schemes,
pharmacy claims for inhalers for COPD amounted to expenditurei in excess of €90
million in 2013.8 Expenditure on inhalers used in obstructive airways disease for all
age groups exceeded €91.6 million on the GMS scheme alone in 2015. Of this €45.5
million (50%) was spent on inhalers containing a combination of inhaled corticosteroid
(ICS) and long-acting beta2 agonist (LABA).
2. Purpose
This document outlines, in general terms, the treatment of COPD, and provides
practice tips and pricing information on licensed, reimbursable inhalers for the
treatment of COPD. It was first published in July 2014, with subsequent updates in
January 2015, October 2015 and November 2016 to take account of new products and
price updates.
Prescribers should be cognisant of the costs associated with inhaled
therapies for COPD and where possible, should endeavour to prescribe
less expensive inhaled therapies for the management of COPD.
3. Definitions
For the purposes of this report the associated cost refers to the reimbursed cost of
the inhaler preparation as listed on the Health Service Executive (HSE) PCRS website
(www.pcrs.ie). Only licensed, reimbursable inhalers are included in this review. Where
two or more preparations of the same device are listed, the less expensive preparation
has been selected for the evaluation. The prices listed do not include mark-up or
dispensing fees that private/DPS patients may be charged. Costs are correct as of 1st
October 2016. For a full list of all reimbursed prices please refer to www.pcrs.ie (under
list of reimbursable items). Unless otherwise stated, the terms ‘actuation’ and ‘puff’
are considered interchangeable.
i
Expenditure estimates include ingredient cost, pharmacy fee, and tax, where applicable.
2
4. Treatment of COPD
4.1 Smoking cessation
Smoking cessation following a diagnosis of COPD is the intervention with the greatest
capacity to influence the natural history of the disease.1, 4, 9, 10 All patients should be
actively encouraged to quit smoking and appropriate support should be provided. For
more information on smoking cessation support services, visit www.quit.ie.
4.2 Inhaled therapies for COPD
None of the existing pharmacological agents has been shown to modify the long-term
decline in lung function associated with COPD, however, appropriate treatment can
reduce COPD symptoms, reduce the frequency and severity of exacerbations, and
improve health status and exercise tolerance.1
Inhalation is the preferred route of administration in stable COPD.1

Airway smooth muscle relaxation leading to bronchodilatation is achieved mainly
by beta2-agonists and muscarinic antagonists.11

Regular treatment with long-acting inhaled bronchodilators is more effective and
convenient than treatment with short-acting bronchodilators.12

Combination
bronchodilator
therapy
may
increase
the
degree
of
bronchodilatation with fewer associated side effects.1, 13, 14, 15

Regular treatment with inhaled corticosteroids (ICS) is only appropriate for
patients with an FEV1<50% predicted and repeated exacerbations (i.e. three
exacerbations in the last three years).12

ICS monotherapy is not recommended in the long-term treatment of COPD,
however, combinations containing a long-acting beta2-antagonist (LABA) and ICS
are recommended in patients at high risk of exacerbations.1
3
4.3 Inhaler devices
The selection of a suitable inhaler device is crucial in the management of COPD.
Currently available inhaler devices for the treatment of COPD are pressurised metered
dose inhalers (pMDI), breath-actuated metered dose inhalers (BA MDI), breath
actuated dry powder inhalers (DPI) and soft mist inhalers (SMI).16
Poor inhaler technique (IT) is a common cause of suboptimal COPD management.17
Successful use of a given drug/device combination requires that patients are
continually instructed on its use and inhaler technique should be assessed
regularly.16 NICE guidance on the management of COPD recommends that inhalers
should only be prescribed after patients have received training in the use of the
device and have demonstrated satisfactory technique.4 This guidance also states that
patients should have their ability to use an inhaler device regularly assessed by a
competent healthcare professional. Videos to guide patients on appropriate inhaler
technique are available on the COPD Support Ireland website www.copd.ie
4.3.1 Pressurised Metered Dose Inhalers (pMDI)

Pressurised Metered Dose Inhalers (pMDIs) consist of a pressurized canister
inside a plastic case with a mouthpiece attached. pMDIs use a propellant to push
the medication out of the inhaler and the dose is taken by simultaneous
inhalation by the individual. Examples include: Salamol® CFC-free inhaler
(salbutamol 100mcg) and Atrovent® CFC-free inhaler (ipratropium). A spacer
device, e.g. Volumatic® should be used where coordinating pMDI actuation and
inhalation is problematic.17, 18
4
Figure 1. Pressurised Metered Dose Inhaler (pMDI)
4.3.2 Breath Actuated Metered Dose Inhalers (BA MDI)
These inhalers automatically release a spray of medication when the person begins
to inhale. They usually look similar to pMDI but do not require coordination of
actuating the device and inhaling. An example is: Salamol® Easi-breath CFC-free
inhaler (salbutamol 100mcg).
4.3.3 Soft Mist Inhalers (SMI)
There are currently two soft mist inhalers (SMI) licensed for use in COPD, Spiriva®
Respimat (containing the long acting muscarinic antagonist tiotropium) and
Striverdi® Respimat (containing the long acting beta2 agonist olodaterol). Two
actuations once daily are required for both respimat inhalers.
4.3.4 Dry Powder Inhalers (DPI)
DPIs may be preferred in COPD as the particle deposition tends to be more central
with the fixed airflow limitation and lower inspiratory flow rate in COPD.1 There are
over 20 DPIs licensed for the treatment of COPD with 10 different device types. The
different DPI devices are listed in table 3. DPIs contain ICS, LAMA and LABA therapies
alone and combination therapies of LABA/LAMA and ICS/LABA.
5
Table 3. Dry Powder Inhaler (DPI) devices currently on the market for COPD
Device
Image
Individual product examples
Category
Notes
Aerolizer
Foradil® (formoterol fumarate)
LABA
Load the inhaler device each time with capsule prior to inhalation
AirFluSal
Forspiro®
(fluticasone propionate/salmeterol)
ICS/LABA
Pre-loaded in foil blister pack
Visual screen to view if powder fully inhaled
Onbrez® (indacaterol)
Seebri® (glycopyrronium)
Ultibro® (indacaterol/glycopyrronium)
LABA
LAMA
LABA/LAMA
Load the inhaler device each time with capsule prior to inhalation
Serevent® (salmeterol)
Flixotide® (fluticasone propionate)
Seretide® (fluticasone propionate/salmeterol)
Bufomix® (budesonide/formoterol)
LABA
ICS
ICS/LABA
ICS/LABA
Pre-loaded inhaler device
Incruse® (umeclidinium bromide)
Anoro® (vilanterol/umeclidinium)
Relvar® (fluticasone furoate/vilanterol)
Eklira®(aclidinium bromide)
Brimica® (aclidinium bromide/formoterol
fumarate)
Spiriva® (tiotropium)
LAMA
LABA/LAMA
ICS/LABA
LAMA
LAMA/LABA
Pre-loaded inhaler device
Device has a 6 week expiry from date of first use
DuoResp Spiromax® (budesonide/formoterol)
ICS/LABA
Use within 6 months of removing from the foil wrapping
Bricanyl® (terbutaline)
Oxis® (formoterol) 12mcg and 6mcg
Pulmicort® (budesonide)
Symbicort® (budesonide/formoterol)
SABA
LABA
ICS
ICS/LABA
Pre-loaded inhaler device
Breezhaler
Diskus
Easyhaler
Ellipta
Genuair
Handihaler
Spiromax
Turbohaler
LAMA
6
Pre-loaded inhaler device
Pre-loaded inhaler device
To be used within 60 (Brimica) or 90 (Eklira) days of opening the
pouch
Load the inhaler device each time with capsule prior to inhalation
Visual area to view capsule
Practice tip: Inhaler Devices
A patient’s ability to use inhalers correctly is crucial when prescribing an
inhaler device:
 DPIs may be preferred in COPD as the particle deposition tends to be more
central with the fixed airflow limitation and lower inspiratory flow rate in
COPD.1
 Some COPD patients may have difficulty using a DPI, which often involves
loading the dose or priming the device, and a pMDI, breath-actuated MDI
or SMI may be considered. A spacer device, e.g. Volumatic®, may be useful
where coordinating pMDI actuation and inhalation is problematic.17, 18
Table 4 outlines the recommended inhaled treatments for COPD according to severity
of disease and risk of exacerbations.1 For convenience, an inhaler(s) within each
therapeutic drug class is suggested, generally on the basis of cost. As detailed in
section 3, only licensed, reimbursed inhalers are included. Full pricing information for
all currently licensed, reimbursed inhalers for the treatment of COPD is available in
section 5 of this Prescribing and Cost Guidance.
Prescribing Tip: Black Triangle



Many of the newly available treatments for COPD carry the black triangle symbol.
These products are subject to additional monitoring and healthcare professionals
are asked to report any suspected adverse reactions to the HPRA.
Refer to the summary of costs to see all products subject to this alert (appendix 3).
7
Table 4. Inhaled therapies for stable COPD
GOLD guideline 1
patient category
1st choice treatment categories
(product example*)
Alternative treatment
GOLD 1-2
Category A
Short-acting beta2 agonist (SABA)
Long-acting muscarinic
antagonist (LAMA)
Mild – moderate COPD
with a low risk of
exacerbations &
less symptoms.
FEV1 ≥ 80%
predicted
GOLD 1-2
Category B
Mild – moderate COPD
with a low risk of
exacerbations &
more symptoms.
E.g. salbutamol 100 μg PRN
(Gerivent®, Salamol®,
Salbul®, Ventolin®)
or
Short-acting
(SAMA)
LAMA
Severe-very severe
COPD with a high risk of
exacerbations &
less symptoms.
E.g. glycopyrronium 44μg
once daily (Seebri®
breezhaler)
LABA
E.g. budesonide/
formoterol 320/9 μg BD
(Bufomix® Easyhaler 320/9)
or
E.g. umeclidinium/
vilanterol once daily
(Anoro® Ellipta
55/22µg)
LAMA + LABA
or
LAMA +
PDE-4 inhibitor ‡
or
E.g. glycopyrronium 44μg
once daily (Seebri®
breezhaler)
ICS + LABA
LABA +
PDE-4 inhibitor ‡
ICS + LABA + LAMA
E.g. budesonide/
formoterol 320/9 μg BD
(Bufomix® Easyhaler 320/9)
and/or
or
ICS + LABA + PDE-4
inhibitor ‡
or
LAMA + LABA
LAMA
FEV1 < 30%
predicted
LAMA + LABA
E.g. olodaterol 2.5µg
(Striverdi®) once daily (two
puffs) or salmeterol 50µg
BD (Serevent® DIskus)
Inhaled corticosteroid (ICS) + LABA
30% ≤ FEV1 < 50%
predicted
Severe-very severe
COPD with a high risk of
exacerbations &
more symptoms.
SABA + SAMA
or
LAMA
GOLD 3-4
Category D
Long-acting beta2 agonist
(LABA)
antagonist or
E.g. ipratropium 20 μg PRN
(Atrovent®)
50% ≤ FEV1 < 80%
predicted
GOLD 3-4
Category C
muscarinic
or
E.g. glycopyrronium 44μg
once daily (Seebri®
breezhaler)
or
LAMA +
PDE-4 inhibitor ‡
* Examples listed are for illustrative purposes only. For full list of inhalers in each category please refer to appendix 3
This medicinal product is subject to additional monitoring by the European Medicines Agency. This will allow quick
identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
‡ Phosphodiesterase-4 inhibitor (roflumilast). This is an oral therapy and is not reimbursed by the HSE.
8
5. Inhaled therapies
5.1 Short-acting beta2 agonists (SABA)
GOLD 1-2; Category A
Table 5 details the costs associated with salbutamol and terbutaline inhaler
preparations for COPD. Typical usage would be eight actuations per day for salbutamol
and four actuations per day for terbutaline. 17, 19, 20
Table 5. Short-acting beta2 agonists (SABA)
Drug and device
Device
type
Strength
Doses
per
device
Cost per
device €
Cost per
actuation
€
Salbutamol
Salamol ® CFC-free inhaler
pMDI
100mcg
200
2.96
0.01
Salbutamol® CFC-free inhaler pMDI
100mcg
200
3.00
0.02
Gerivent ® CFC-free inhaler
pMDI
100mcg
200
2.95
0.01
Ventamol® CFC-free inhaler
pMDI
100mcg
200
2.95
0.01
Salbul® Inhalation Suspension pMDI
100mcg
200
3.01
0.02
Ventolin® Evohaler
pMDI
100mcg
200
3.20
0.02
Salamol® Easi-breathe CFCBA MDI 100mcg
200
7.95
0.04
free inhaler
Novolizer® Salbutamol
BA MDI 100mcg
200
8.90
0.04
Ventolin® Diskus
DPI
200mcg
60
4.48
0.07
Terbutaline
Bricanyl® Turbohaler
DPI
500mcg
100
5.94
0.06
BA: breath-actuated; pMDI: pressurised metered-dose inhaler; DPI: dry powder inhaler
5.2 Short-acting muscarinic antagonists (SAMA)
GOLD 1-2; Category A
Table 6 details the approximate costs associated with the only available ipratropium
inhaler for COPD, Atrovent®. Typical usage would be approximately eight actuations
per day. 17,21
Table 6. Short-acting muscarinic antagonists (SAMA)
Drug and device
Device
Strength
Doses per Cost per
device
device €
Ipratropium
Atrovent® CFC-free
pMDI
20mcg
200
2.67
inhaler
pMDI: pressurised metered-dose inhaler
9
Cost per
actuation €
0.01
5.3 Long-acting muscarinic antagonists (LAMA)
GOLD 1-2; Category B and GOLD 3-4; Category C-D
Table 7 details the costs associated with aclidinium, glycopyrronium, tiotropium and
umeclidinium inhaler devices for COPD. Typical usage is one actuation twice daily for
Eklira Genuair® (aclidinium), one actuation per day for Seebri® (glycopyrronium),
Spiriva® (tiotropium) Handihaler and Incruse® Ellipta (umeclidinium), and two
actuations once daily for Spiriva® (tiotropium) Respimat. 17, 22-26
Table 7. Inhaled long-acting muscarinic antagonists (LAMA)
Device Labelled
Doses
type
Strength
per
Cost per
Drug and device
(dose
device device
delivered)
€
Aclidinium bromide
Eklira Genuair®
DPI
322 μg
60
34.08
Glycopyrronium
Seebri®
DPI
44μg
30
34.00
breezhaler
Tiotropium
Spiriva® Handihaler DPI
18 μg
30
37.72
Spiriva® Respimat
SMI
2.5 μg
Umeclidinium
Incruse® Ellipta
DPI
55 μg
DPI: dry powder inhaler; SMI: Soft Mist Inhaler
Cost per actuation
€
0.57 (1.14 per day)
1.13 (per day)
1.26 (per day)
60
37.38
0.62 (x2 for one
medicinal dose, 1.25 per
day)
30
34.75
1.16 (per day)
5.4 Long-acting beta2-agonists (LABA)
GOLD 1-2; Category B
Table 8 details the costs associated with the LABAs formoterol, indacaterol, olodaterol
and salmeterol for COPD. Cost per actuation is listed and is not indicative of cost per
day as products may require one or two actuations per day or up to four actuations
per day depending on the drug and device (refer to individual SmPCs for licensed doses
and frequencies). Typical usage may be two - four actuations per day for formoterol
10
and salmeterol (depending on the device strength), two puffs from the Respimat
inhaler once daily for olodaterol and one actuation per day for indacaterol.17, 27-34
Table 8. Inhaled long-acting beta2 agonists (LABA)
Device Strength Doses
Drugs and device
type
per
device
Formoterol
Foradil® Aerolizer
DPI
12 μg
60
Oxis® Turbohaler
DPI
12 μg
60
Oxis® Turbohaler
DPI
6 μg
60
Indacaterol
Onbrez® Breezhaler
DPI
150 μg
30
Onbrez® Breezhaler
DPI
300 μg
30
Olodaterol
Striverdi Respimat®
SMI
2.5 μg
60
Salmeterol
Salmeterol Neolab®
pMDI
25 µg
120
Serevent® Evohaler
pMDI
25 μg
120
Serevent® Diskus
DPI
50 μg
60
Cost per
device €
Cost per
actuation €
23.09
20.11
16.55
0.38
0.34
0.28
31.89
34.15
1.06
1.14
28.68
0.48 (x 2)
26.37
0.22
28.57
0.24
25.49
0.42
DPI: Dry Powder Inhaler; SMI: Soft Mist Inhaler; pMDI: pressurised Metered Dose Inhaler
5.5 Combined long-acting beta2 agonist and long-acting muscarinic antagonist
(LABA/LAMA)
GOLD 1-2; Category B and GOLD 3-4; Category C
Table 9 outlines the cost associated with combination LABA/LAMA inhalers. Ultibro®
Breezhaler contains a combination of indacaterol and glycopyrronium and Anoro®
Ellipta contains a combination of vilanterol and umeclidinium. Both of these are
administered once daily.17, 35, 36 Brimica® Genuair contains a combination of aclidinium
bromide and formoterol and is administered twice daily.37 Spiolto® respimat contains
a combination of tiotropium and olodaterol and is administered as two puffs once
daily at the same time each day.38
11
Table 9. Combination LABA and LAMA
Drugs and device
Device
type
Indacaterol/Glycopyrronium
Ultibro® Breezehaler
DPI
Vilanterol/Umeclidinium
Anoro® Ellipta
DPI
Aclidinium/formoterol
Brimica® Genuair
DPI
Tiotropium/olodaterol
Spiolto® Respimat
SMI
Strength
Doses per
device
Cost
per
device
€
Cost per actuation
€
85/43µg
30
54.03
1.80 (once daily)
55/22µg
30
43.15
1.44 (once daily)
340/12µg
60
45.36
0.76 (twice daily,
cost per day 1.52)
2.5/2.5µg
60 puffs
(30
medicinal
doses)
45.36
0.76 (two
actuations daily,
cost per day 1.52)
DPI: Dry Powder Inhaler; SMI: Soft Mist Inhaler
Prescribing Tip
If a patient requires both a LAMA and a LABA as inhaled therapy for
symptom control, consider a combination treatment which may assist in:

Promoting compliance (due to less inhaled treatments required)

Reduced cost of dual therapy

Reduced confusion in use of different devices
When a LABA/LAMA combination is indicated for COPD,
Think….
ANORO® Ellipta 55/22µg (vilanterol/umeclidinium)
once daily
5.6 Inhaled corticosteroids (ICS)
GOLD 3-4; Category C-D; in combination with LABA.
Table 10 outlines the cost associated with ICS. Cost per actuation is listed and is not
indicative of cost per day as doses vary between products and patient needs (refer to
individual SmPCs for licensed doses and frequencies). Typical usage can be 2-4
actuations per day, depending on the inhaler device and strength.17, 39-41
12
Table 10. Inhaled corticosteroids
Drug and device
Budesonide
Pulmicort® Turbohaler
Fluticasone propionate
Flixotide® Diskus
Flixotide® Evohaler
Device
type
Strength
Doses per
device
Cost per
device €
Cost per
actuation €
DPI
400 μg
50
13.41
0.27
DPI
pMDI
500 μg
250 μg
60
120
30.84
32.82
0.51
0.27
Practice tip
ICS monotherapy is not indicated in the long-term management of COPD. Those with
severe and very severe airflow limitation or frequent exacerbations that are not
adequately controlled by LABA may benefit from ICS but a combination device of ICS and
LABA is preferred (e.g. Bufomix® 320/9μg). Regular ICS therapy does not modify the longterm decline in FEV1 or mortality in patients with COPD.1
Treatment with ICS, alone or in combination with a LABA, is associated with an
increased risk of non-fatal pneumonia.1, 42
5.7 Combined inhaled corticosteroids and long-acting beta2 agonist (ICS/LABA)
GOLD 3-4; Category C-D
An inhaler containing a combination of ICS and LABA may be indicated in more severe
COPD, particularly where patients are at high risk of exacerbations.1 Table 11 details
the available combination inhalers and their associated costs.17, 43-51 Typical usage is
twice daily but Relvar® is once daily dosing.
Notably, Seretide® Evohaler and Relvar® Ellipta 184/22 μg strength DPI are not
licensed in the treatment of COPD.52,53
13
Table 11. Combination devices containing ICS/LABA
Drug and device
Device Strength
type
μg
EQUIVALENT
DOSES
EQUIVALENT
DOSES
EQUIVALENT
DOSES
Doses
per
device
Budesonide/Formoterol (micrograms)
Bufomix®
DPI
160/4.5
120
Easyhaler (DPI)*
DuoResp®
BA
160/4.5
120
Spiromax
MDI
Symbicort®
DPI
200/6
120
Turbohaler
Bufomix®
DPI
320/9
60
Easyhaler (DPI)*
DuoResp®
BA
320/9
60
Spiromax
MDI
Symbicort®
DPI
400/12
60
Turbohaler*
Fluticasone propionate/Salmeterol (micrograms)
AirFluSal®
DPI
500/50
60
Forspiro
Seretide® Diskus
DPI
500/50
60
Fluticasone furoate/Vilanterol (micrograms)
Relvar® Ellipta
DPI
92/22
30
Cost
per
device
€
Cost per
Cost
actuation per day
‡
€
31.86
0.27
1.06
37.58
0.31
1.25
40.85
0.34
1.36
31.86
0.53
1.06
36.85
0.61
1.22
38.98
0.65
1.30
41.41
0.69
1.38
45.12
0.75
1.50
34.45
1.15
1.15
* Bufomix® Easyhaler and Symbicort® Turbohaler fixed-dose combination of budesonide and
formoterol have been shown to be bioequivalent with regard to total systemic exposure and exposure
via the lungs.43,
‡ Cost per day for standard daily doses i.e. “one inhalation twice daily” for devices with 60 doses, “one
inhalation once daily” for devices with 30 doses and “two inhalations twice daily” for devices with 120
doses. Where there are two strengths of the same brand of inhaler the strength which provides the
correct dose in the least number of inhalations should be chosen.
Practice tip
The quantity of LABA per actuation differs between Seretide® Evohaler
and Seretide® Diskus. Seretide® Evohaler is not licensed for treatment of
COPD.
One puff per dose only of Seretide® Diskus should be prescribed. More
than one puff per dose of Seretide® Diskus is not licensed. Prescribing
Seretide® 500/50 Diskus two puffs twice daily, rather than the
recommended one puff twice daily, leads to excessive dosing, an
increased risk of adverse effects, and drug wastage.
14
Practice Point
ICS/LABA combination products cost the state over €50 million per year.
New therapies with equivalent efficacy offer the opportunity to save money
for both patients and the state without compromising on safety and efficacy.
Bufomix® 320/9μg is dose equivalent to Symbicort® 400/12μg but is 18% less
expensive.
AirFluSal® Forspiro 500/50μg is dose equivalent to Seretide® Diskus
500/50μg but is 9% less expensive.
Prescribing Tip
When an ICS/LABA combination is indicated for COPD,
Think….
BUFOMIX® 320/9μg (budesonide/formoterol)
twice daily
6. Nebulised therapy
The preferred route of drug administration in COPD is inhalation. However, in some
instances, e.g. physical disability or cognitive impairment, the use of a nebuliser may
be appropriate.54 Nonetheless, nebuliser loading and operation requires manipulative
skill, and if lack of such skill is responsible for inadequate technique with inhaler
devices it is likely that this may also be the case with a nebuliser.4 One of the primary
advantages of nebulizers in COPD is the minimal coordination and effort required
during inhalation compared to pMDIs and DPIs.55 A further advantage of using
nebulisers is their ability to aerosolise high doses of drugs that are not readily
attainable using DPIs or pMDIs.56
15
During an exacerbation of COPD, bronchodilator therapy can also be administered via
nebuliser if necessary and oxygen given if appropriate. Short-acting bronchodilators
available in solutions for nebulisation are salbutamol (SABA) and ipratropium (SAMA);
a solution containing these two drugs in combination is also available. Regular use of
high dose bronchodilator therapy via a nebuliser may cause significant side effects,
e.g. tachycardia, tremor.54
The role of nebulised or inhaled corticosteroids for the treatment of chronic COPD and
during an exacerbation is less clear. Use is associated with an increased risk of nonfatal pneumonia 1, 4, 42 and prescribers should be mindful of this risk and exercise due
caution.
7. Summary
The treatment of COPD requires careful evaluation of the individual patient. The
choice of inhaled therapy should be made according to a number of criteria, including
severity of COPD, risk of exacerbation, cost and patient preference.
Inhalers for COPD represent the largest proportion of inhaler expenditure, accounting
for approximately €90 million of an overall expenditure of €107 million in 2013 (GMS
and DP schemes). In 2015 total expenditure for inhalers used in obstructive airways
disease on the GMS scheme alone cost the HSE €91.6 million. Approximately 50%
(€45.5 million) of this expenditure was on devices containing a combination of ICS and
LABA, corresponding to an average of approximately 65,500 prescriptions and over
€3.8million in expenditure per month.
In the category of ICS/LABA there are now a number of devices that offer a cost saving
to both patients and the state and the MMP recommends consideration of these when
prescribing in this category.
Bufomix® 320/9μg is dose equivalent to Symbicort® 400/12 μg but is 18% less
expensive while AirFluSal 500/50μg is 9% less expensive than Seretide® Diskus
500/50μg which are dose equivalent.
16
There is significant variation between individual inhaled drugs and inhaler devices for
the treatment of COPD in terms of cost, with reimbursement costs ranging from €0.10
to €1.80 per day. For private/DPS patients on inhaled therapies for COPD, these costs
may be significantly higher. Prescribers should be mindful of variations in cost when
prescribing inhaled therapies for the treatment of COPD and should endeavour to
prescribe the least expensive inhaler device that is appropriate for a particular patient,
in line with international best practice. Prescribers should pay close attention to the
dosing recommendations of inhalers for COPD, bearing in mind that inappropriate
dosing may lead to adverse effects and drug wastage. This is of particular concern with
combination inhaler devices where the LABA-to-ICS ratio may differ between inhaler
devices.
This document contains information regarding the acquisition costs of available
inhaled drugs and inhaler devices as of 1st October 2016 and provides a useful tool for
prescribers for selecting cost-effective inhaler options for their patients with COPD.
17
8. References
1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global
Initiative for Chronic Obstructive Lung Disease (GOLD) 2016 Available from:
http://www.goldcopd.org/.
2. Health Service Executive, National COPD programme. Accessed at www.hse.ie on
10/07/2015.
3. Crinion S et al. COPD exacerbations – a comparison of Irish data with European
data from the ERS COPD audit. Irish Medical Journal 2013; 106(9); 268-272.
4. NICE clinical guideline 101: Chronic obstructive pulmonary disease – management
of chronic obstructive pulmonary disease in adults in primary and secondary care
(partial update), June 2010. Accessed at www.nice.org.uk on 3/4/2014.
5. O’Farrell A, De La Harpe D, Johnson H, Bennet K. Trends in COPD mortality in inpatient admissions in men and women: evidence of convergence. Irish Medical
Journal 2011; 104(8):245-248.
6. Health Products Regulatory Authority (HPRA) Human Medicines Listing. Accessed
at www.hpra.ie on 23/07/2015.
7. Reimbursable drugs listing.
Primary Care Reimbursement Service (PCRS).
Accessed at www.pcrs.ie on 1/10/2016.
8. Medicines Management Programme (MMP). Internal analyses, 07/2014 and
10/2016. On file.
9. Ejiofor S, Turner A. Expert Review: Pharmacotherapies for COPD. Clinical Medicine
Insights: Circulatory, Respiratory and Pulmonary Medicine 2013; 7:17-34.
10. Tonnesen P. Smoking cessation and COPD. European Respiratory Review 2013;
22(127):37-43.
11. Tashkin DP, Ferguson GT. Combination bronchodilator therapy in the
management of chronic obstructive pulmonary disease. Respiratory Research
2013; 14(49).
12. Management of Chronic Obstructive Pulmonary Disease in General Practice. Irish
College of General Practitioners. 2009.
13. Rossi A, Polese G. Indacaterol: A comprehensive review. International Journal of
COPD 2013; 8:353-363.
18
14. Karner C, Cates CL. Long-acting beta2-agonist in addition to tiotropium versus
either tiotropium or long-acting beta2-agonist alone for chronic obstructive
pulmonary disease. Cochrane Database of Systematic Reviews 2012, Issue 4. Art.
No.: CD009889. DOI: 10.1002/14651858.CD008989.pub2.
15. Appleton S, Jones T, Poole P, Lasserson TJ, Adams R, Smith B, Muhammed J.
Ipratropium bromide versus long-acting beta2-agonists for stable chronic
obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2006,
Issue 3. Art. No.: CD006101. DOI: 10.1002/14651858.CD006101.
16. Fink JB et al. Inhaler devices for patients with COPD. COPD: Journal of Chronic
Obstructive Pulmonary Disease 2013; 10(4):523-535.
17. Joint Formulary Committee. British National Formulary May 2014 (online) London:
BMJ Group and Pharmaceutical Press
<http://www.medicinescomplete.com>
[Accessed on 20/5/2014].
18. Chronic Obstructive Pulmonary Disease. Therapeutics Bulletin 2013; 19(4).
National Medicines Information Centre. Accessed at www.nmic.ie on 3/4/2014.
19. Ventolin® evohaler SmPC. Last revised 05/2015. Accessed at www.hpra.ie on
10/07/2015.
20. Bricanyl® Turbohaler SmPC. Last revised 05/2015. Accessed at www.hpra.ie on
10/07/2015.
21. Atrovent® inhaler SmPC. Last revised 02/2015. Accessed at www.hpra.ie on
10/07/2015.
22. Seebri® SmPC. Last revised 05/2015. Accessed at www.medicines.ie on
10/07/2015.
23. Spiriva® (Handihaler®) SmPC. Last revised 12/2014. Accessed at www.medicines.ie
on 10/07/2015.
24. Spiriva® Respimat. Last revised 01/2015. Accessed at www.medicines.ie on
10/07/2015.
25. Incruse® Ellipta 55micrograms SmPC. Last revised 23/04/2015. Accessed at
www.medicines.ie 10/07/2015.
26. Eklira Genuair® 322 microgram SmPC. Last revised 27/04/2015. Accessed at
www.medicines.ie 07/08/2015
19
27. Foradil® Aerolizer SmPC. Last revised 03/2014. Accessed at www.hpra.ie on
10/07/2015.
28. Oxis® 6 microgram Turbohaler SmPC. Last revised 03/2015. Accessed at
www.hpra.ie on 10/07/2015.
29. Oxis® 12 microgram Turbohaler SmPC. Last revised 03/2015. Accessed at
www.hpra.ie on 10/07/2015.
30. Onbrez® 150 microgram Breezehaler SmPC. Last revised 12/2014. Accessed at
www.medicines.ie on 10/07/2015.
31. Striverdi® Respimat 2.5microgram SmPC. Last revised 01/07/2014. Accessed at
www.medicines.ie on 05/12/2014
32. Salmeterol Neolab® 25 microgram SmPc. Last revised March 2016. Accessed at
www.medicines.ie on 5/10/16.
33. Serevent® 25 microgram Evohaler SmPC, last revised 08/2014. Accessed at
www.hpra.ie on 10/07/2015.
34. Serevent® Diskus SmPC. Last revised 05/2015. Accessed at www.hpra.ie on
10/07/2015.
35. Ultibro® SmPC. Last revised 01/2015. Accessed at www.medicines.ie on
21/07/2015.
36. Anoro Ellipta 55micrograms/22micrograms SmPC. Last revised 16/05/2014.
Accessed at www.medicines.ie on 05/12/2014.
37. Brimica® Genuair 340/12micrograms SmPC. Date of first authorisation November
2014. Last revised February 2015. Accessed on 14/07/2015 on www.medicines.ie
38. Spiolto® Respimat 2.5microgram/2.5microgram inhalation solution SmPC. Date
of first authorisation: 06/2015. Accessed at www.medicines.ie on 02/10/2015.
39. Pulmicort® 400 microgram Turbohaler SmPC. Last revised 10/2014. Accessed at
www.medicines.ie on 10/07/2015.
40. Flixotide® 250 microgram Evohaler. Last revised 02/2015. Accessed at
www.medicines.ie on 10/07/2015.
41. Flixotide® 500 microgram Diskus. Last revised 02/2015. Accessed at
www.medicines.ie on 10/07/2015.
20
42. Kew KM, Seniukovich A. Inhaled steroids and risk of pneumonia for chronic
obstructive pulmonary disease. Cochrane Database of Systematic Reviews 2014,
Issue 3. Art. No.: CD010115. DOI: 10.1002/14651858.CD010115.pub
43. Bufomix® Easyhaler 160/4.5 microgram SmPC. Last revised 03/2016. Accessed at
www.hpra.ie on 5/10/2016.
44. DuoResp® 160/4.5 microgram SmPC. Last revised 18/7/16. Accessed at
www.hpra.ie on 5/10/16
45. Symbicort® 200/6 microgram SmPC. Last revised 7/2014. Accessed at www.hpra.ie
on 5/10/16.
46. Bufomix® Easyhaler 320/9 microgram SmPC, Last revised 03/2015. Accessed at
www.hpra.ie on 10/07/2015.
47. DuoResp® 320/9 microgram SmPC. Last revised 18/7/16. Accessed at www.hpra.ie
on 5/10/16
48. Symbicort® 400/12 microgram SmPC. Last revised 10/2014. Accessed at
www.hpra.ie on 10/07/2015.
49. AirFluSal® Forspiro® 500/50 microgram SmPC. Last revised 11/2014. Accessed at
www.hpra.ie on 10/07/2015
50. Seretide® 500 microgram Diskus SmPC. Last revised 01/2015. Accessed at
www.hpra.ie on 10/07/2015.
51. Relvar Ellipta® 92/22 micrograms SmPC. Last revised 12/2015. Accessed at
www.medicines.ie on 5/10/16.
52. Seretide® Evohaler SmPC. Last revised 04/2015. Accessed at www.medicines.ie on
10/07/2015.
53. Relvar Ellipta® 184/22 micrograms SmPC. Last revised 06/2015. Accessed at
www.medicines.ie on 10/07/2015.
54. National Clinical Guideline Centre (2010). Chronic obstructive pulmonary disease:
Management of Chronic Obstructive Pulmonary Disease in Adults in Primary and
Secondary Care. London: National Clinical Guideline Centre. Accessed at
www.nice.org.uk on 11/6/2014.
55. Dhand R et al. The role of nebulized therapy in the management of COPD: Evidence
and Recommendations. COPD: Journal of Chronic Obstructive Pulmonary Disease
2012; 9(1): 58-72.
21
56. Laube BL et al. What the pulmonary specialist should know about the new
inhalation therapies: ERS/IASM taskforce report. European Respiratory Journal
2011; 37:1308-1331.
22
Appendix 1. Summary - Inhaled therapies for stable COPD
GOLD guideline 1
patient category
1st choice treatment categories
(product example*)
Alternative treatment
GOLD 1-2
Category A
Short-acting beta2 agonist (SABA)
Long-acting muscarinic
antagonist (LAMA)
Mild – moderate COPD
with a low risk of
exacerbations &
less symptoms.
FEV1 ≥ 80%
predicted
GOLD 1-2
Category B
Mild – moderate COPD
with a low risk of
exacerbations &
more symptoms.
E.g. salbutamol 100 μg PRN
(Gerivent®, Salamol®,
Salbul®, Ventolin®)
or
Short-acting
(SAMA)
LAMA
Severe-very severe
COPD with a high risk of
exacerbations &
less symptoms.
E.g. glycopyrronium 44μg
once daily (Seebri®
breezhaler)
LABA
E.g. budesonide/
formoterol 320/9 μg BD
(Bufomix® Easyhaler 320/9)
or
E.g. umeclidinium/
vilanterol once daily
(Anoro® Ellipta
55/22µg)
LAMA + LABA
or
LAMA +
PDE-4 inhibitor ‡
or
E.g. glycopyrronium 44μg
once daily (Seebri®
breezhaler)
ICS + LABA
LABA +
PDE-4 inhibitor ‡
ICS + LABA + LAMA
E.g. budesonide/
formoterol 320/9 μg BD
(Bufomix® Easyhaler 320/9)
and/or
or
ICS + LABA + PDE-4
inhibitor ‡
or
LAMA + LABA
LAMA
FEV1 < 30%
predicted
LAMA + LABA
E.g. olodaterol 2.5µg
(Striverdi®) once daily (two
puffs) or salmeterol 50µg
BD (Serevent® DIskus)
Inhaled corticosteroid (ICS) + LABA
30% ≤ FEV1 < 50%
predicted
Severe-very severe
COPD with a high risk of
exacerbations &
more symptoms.
SABA + SAMA
or
LAMA
GOLD 3-4
Category D
Long-acting beta2 agonist
(LABA)
antagonist or
E.g. ipratropium 20 μg PRN
(Atrovent®)
50% ≤ FEV1 < 80%
predicted
GOLD 3-4
Category C
muscarinic
or
E.g. glycopyrronium 44μg
once daily (Seebri®
breezhaler)
or
LAMA +
PDE-4 inhibitor ‡
* Examples listed are for illustrative purposes only. For full list of inhalers in each category please refer to appendix 3
†This medicinal product is subject to additional monitoring by the European Medicines Agency. This will allow quick
identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions.
‡ Phosphodiesterase-4 inhibitor (roflumilast). This is an oral therapy and is not reimbursed by the HSE.
23
Appendix 2. Practice Points – Management of COPD
Practice Points – Management of COPD

Regular treatment with long-acting inhaled bronchodilators is more effective and convenient than treatment with short-acting
bronchodilators.

Combination bronchodilator therapy (long-acting beta2 agonist + long-acting muscarinic agonist [LABA + LAMA]) may increase the degree
of bronchodilatation with fewer associated side effects.

Inhaled corticosteroid (ICS) monotherapy is not recommended in the long-term treatment of COPD, however, combinations containing a
LABA and ICS may be appropriate in patients at high risk of exacerbations. ICS use is associated with a higher risk of pneumonia.

A patient’s ability to use an inhaler correctly is crucial when prescribing an inhaler device:
 DPIs may be preferred in COPD as the particle deposition tends to be more central with the fixed airflow limitation and lower inspiratory
flow rates in COPD.
 Some COPD patients may have difficulty using a DPI, which often involves loading the dose, and a pMDI, breath-actuated MDI or soft
mist inhaler may be considered. A spacer device, e.g. Volumatic®, may be useful when coordinating actuation and inhalation is a
problem.

Nebulised bronchodilator therapy may be necessary where patients are unable to ambulate or during exacerbations. There is a limited role,
however, for nebulised corticosteroids in the management of chronic COPD and during exacerbations. Use of nebulised corticosteroids is
associated with an increased risk of non-fatal pneumonia and prescribers should exercise due caution.
24
Appendix 3. COPD- Summary of Inhaler Costs
Costs listed reflect the reimbursed price. Private/DPS patients pay significantly more than the reimbursed price.
This medicinal product is subject to additional monitoring by the European Medicines Agency. This will allow quick
identification of new safety information.
BA MDI – Breath-actuated metered dose inhaler, pMDI – Pressurised metered dose inhaler, DPI – Dry powder inhaler, SMI – Soft
mist inhaler, µg = microgram
- 25 -
Medicines Management Programme
Version 1.3 November 2016
Appendix 4. New in this update- version 1.3

GOLD categories have been updated to 2016 guidelines.

Where examples of inhalers are included in each category the most cost effective inhaler
in that category is given.

Costs have been updated to October 2016 prices.

Recommendation to use Anoro® when LABA/LAMA combination is indicated.
- 26 -