Inhalers for Asthma in Adults and Children 6 Years and Older · (SABA) and short-acting muscarinic...

Version 1.3 November 2016

Medicines Management Programme

Inhalers for Asthma in Adults and

Children 6 Years and Older

Prescribing and Cost Guidance

Approved by Prof. Michael Barry, Clinical Lead, MMP.

Date approved Version 1 July 2014

Date updated Version 1.1 Jan 2015

Version 1.2 Oct 2015

Version 1.3 Nov 2016


Table of Contents

1.Background ................................................................................................................. 1

2. Purpose ...................................................................................................................... 2

3. Definitions .................................................................................................................. 2

4. Treatment of Asthma ................................................................................................. 2

4.1 Inhaler devices ..................................................................................................... 3

4.2 Stepwise approach to asthma treatment ............................................................ 8

4.3 Reviewing asthma treatment .............................................................................. 9

5. Inhaled therapies ....................................................................................................... 9

5.1 Short-acting beta2 agonists (SABA) .................................................................... 10

5.2 Short-acting muscarinic antagonists (SAMA) .................................................... 11

5.3 Inhaled corticosteroids (ICS) .............................................................................. 11

5.4 Long-acting beta2 agonists (LABA) ..................................................................... 13

5.5 Inhaled corticosteroids and long-acting beta2 agonists (ICS/LABA) .................. 14

5.6 Long-acting muscarinic antagonists (LAMA) ...................................................... 17

6. Spacer devices .......................................................................................................... 18

7. Summary .................................................................................................................. 19

8. References................................................................................................................ 21

9. Bibliography ............................................................................................................. 25

Appendix 1. Summary - Management of Asthma in Clinical Practice ......................... 26

Appendix 2. Asthma – Summary of Inhaler Costs ....................................................... 27

Appendix 3. New in this update ................................................................................... 28

Figures

Figure 1. Management of Asthma in Clinical Practice (adults and children ≥ 6 years)..8

Tables

Table 1: Different types of Dry Powder Inhalers currently available for treatment of asthma............................................................................................................................ 6

Table 2. Short-acting beta2 agonists (SABA) ................................................................ 10

Table 3. Short-acting muscarinic antagonists (SAMA) ................................................. 11

Table 4. Estimated Equipotent Doses of ICS for adults ............................................... 11

Table 5. Inhaled corticosteroids (ICS) .......................................................................... 12

Table 6. Long-acting beta2 agonists (LABA) ................................................................. 13

Table 7. Combination devices containing ICS/LABA .................................................... 15

Table 8: Long acting muscarinic antagonist (LAMA) .................................................... 18

Table 9. Spacer devices ................................................................................................ 18

Table 10. Device to aid MDI use .................................................................................. 18


List of Abbreviations

BA Breath actuated

BD ‘Bis die’ – twice daily

CFC Chlorofluorocarbon

CS Corticosteroid

DPI Dry powder inhaler

DPS Drugs Payment Scheme

GMS General Medical Service

HSE Health Service Executive

ICS Inhaled corticosteroids

IT Inhaler Technique

LABA Long-acting beta2 agonist

LAMA Long-acting muscarinic antagonist

LTRA Leukotriene receptor 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

SR Sustained release

This medicinal product is subject to additional monitoring.

Acknowledgements

The Medicines Management Programme (MMP) wishes to acknowledge the staff of

the National Medicines Information Centre (NMIC), in particular the editorial

committee; members of the Asthma Clinical Advisory Group; Prof. Pat Manning,

Clinical Lead, National Clinical Programme for Asthma and members of the Asthma

Clinical Programme for their input.

1

1. Background

Asthma describes a heterogeneous group of conditions that results in recurrent,

reversible airways obstruction and is characterised by recurrent episodes of

wheezing, breathlessness, chest tightness and coughing.1 While the clinical spectrum

of asthma varies significantly, inflammation is consistently found along the

respiratory tract and its effects are most pronounced in the medium-sized bronchi.2

In Ireland, asthma affects an estimated 450,000 people.3 While there is no

universally agreed method of classifying the condition, asthma severity at an

individual level is often classified according to the intensity of treatment needed to

achieve good control (Figure 1 [Page 8]).4

Inhalation is the preferred route of administration for asthma because it delivers

drugs directly to the airways, resulting in potent therapeutic effects with fewer

systemic side effects.4 There are currently over 50 licensed inhalers for the

treatment of asthma reimbursed by the Primary Care Reimbursement Service

(PCRS).5, 6 These drugs and devices represent a considerable cost to the health

system. Analyses of 2013 PCRS pharmacy claims data were performed to estimate

expenditure on inhalers used in obstructive airways disease. Patients under the age

of 40 years were included in analyses under the assumption that this age group

would largely represent asthma. Between the General Medical Services (GMS) and

Drugs Payment (DP) schemes, pharmacy claims for inhalers amounted to

expenditurei in excess of €16 million for this group.7 Combination inhalers

represented approximately 18% of inhaler prescriptions for asthma but accounted

for 50% of expenditure. In 2015 expenditure on inhalers for all age groups exceeded

€91.6 million on the GMS scheme.7

Inhaled drugs have been identified as a priority by the Medicines Management

Programme (MMP). The MMP undertook a review in July 2014 into available inhaler

i Expenditure estimates include ingredient cost, pharmacy fee, and tax, where applicable.

2

devices for the treatment of asthma and their associated costs, and to inform

prescribers of these costs via this Prescribing and Cost Guidance. This review has

been subsequently updated in January 2015, October 2015 and November 2016 to

take account of new products and price updates.

2. Purpose

This document outlines, in general terms, the treatment of asthma in adults and

children aged 6 years and over, and provides practice tips and pricing information on

licensed, reimbursable inhalers for the treatment of asthma.

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.

Only licensed, reimbursable inhalers are included in this review. Where two or more

preparations of the same device are listed the least expensive preparation has been

selected for the evaluation. Costs are correct as of October 2016. For a full list of the

reimbursed prices please refer to www.pcrs.ie (under list of reimbursable items).

Unless otherwise stated, the terms ‘actuation’ and ‘puff’ are considered

interchangeable.

4. Treatment of Asthma

The goals of asthma treatment are: 3, 4, 8

1. maintain control of symptoms

2. maintain normal activity including exercise

3. maintain pulmonary function as close to normal as possible

4. prevent asthma exacerbations and asthma-related mortality

Numerous inhaled drugs, used alone and in combination, are available for the

treatment of chronic asthma. Bronchodilators such as short-acting beta2 agonists

http://www.pcrs.ie/

3

(SABA) and short-acting muscarinic antagonists (SAMA) produce rapid

bronchodilatation and relief from symptoms of asthma.9 Inhaled corticosteroids (ICS)

act as preventer (‘maintenance’) therapies in chronic asthma and are given with and

without inhaled bronchodilators.10, 11

A number of inhalers containing a combination of ICS and long-acting beta2 agonist

(LABA) are available; these are indicated where dual therapy is necessary.12-23

4.1 Inhaler devices

Available inhaler devices for asthma comprise pressurised metered dose inhalers

(pMDI), dry powder inhalers (DPI) and breath-actuated metered dose inhalers (BA

MDI). A soft mist inhaler (SMI) was also recently licensed for use in asthma in adults

(Spiriva® Respimat, licensed in Ireland September 2014). The dosage and type of

inhaler device should be individualised for each patient and titrated to achieve

maximum control of symptoms; different age groups may require different inhaler

devices for effective therapy.2, 4

Patients must be educated on how to use their specific device(s) and inhaler technique

(IT) should be assessed regularly.8 Evidence shows that patients’ competence in self-

administration of inhaled medications is improved by educational interventions, and

repeated training in correct inhaler use improves asthma symptoms, quality of life,

lung function, and reduces the use of reliever medications as well as emergency

hospital admissions.24 Videos to guide patients on appropriate IT and checklists for

healthcare professionals are available on the asthma society website on

www.asthma.ie.

A patient’s ability to handle inhalers correctly is a crucial issue when choosing the most

appropriate inhaler device. Incorrect or inadequate use of inhalers and medication

remains the most common reason for failure to achieve control.3 Adherence to

therapy is likely to be influenced by the patient’s attitude and experience in using the

device. If a patient feels his/her treatment is not working, adherence is likely to be

poor and consequently, treatment efficacy may be reduced.24

http://www.asthma.ie/

4

Most patients can be taught to use a pMDI effectively but some patients, particularly

the elderly and children, may have difficulty using them.9 While there are variations in

individuals’ preferences for and ability to use different inhaler devices, a pMDI has

been found to be as effective as other types of hand-held inhalers for the delivery of

ICS and SABA.25-29 Inhaler technique (IT) can have a considerable effect on the amount

of drug delivered to the lungs.30 Poor IT in the delivery of ICS has been shown to be

strongly associated with asthma instability.31 Spacer devices are useful because they

remove the need to coordinate actuation with inhalation and should be considered

for use with pMDIs (see section 6).9

DPIs are useful for those who are unwilling or unable to use a pMDI. However,

inspiratory flow rate must be sufficient to allow dry powder transformation into an

emitted dose appropriate for lung deposition. Therefore, DPIs may be less suitable in

some cases. If there are concerns about a patient having significant hyperinflation,

DPIs should be used with some caution. Also, similar to other controller medications,

DPIs should not be initiated in those experiencing a severe asthma exacerbation.32

Breath-actuated metered dose inhalers (BA MDIs) are suitable for adults and older

children provided they can use the device effectively.9 BA MDIs are similar in

appearance to pMDIs but do not require press-and-breathe coordination.33

Practice tip

Prescribe the same inhaler device for each drug (i.e. either a pMDI or

DPI) for reliever and maintenance therapy.

This removes the need to train the patient on using multiple device types,

and avoids confusion.

Switching between device types can result in incorrect dosing, adverse

effects and drug wastage.

Inhaler technique checklists are available on www.asthma.ie to assist

patient training and review.

http://www.asthma.ie/

5

Practice points: Pressurised Metered Dose Inhalers (pMDI)

Where the inspiratory flow rate is too rapid, an increase in

oropharyngeal drug deposition may occur – training in inhaler

technique or the use of a spacer device may help.

Loss of Prime: If a pMDI has not been used in a few days, the first

actuation may be sub-optimal. Advise the patient to perform a ‘test’

actuation while pointing the inhaler away from himself/herself.

Shake the pMDI before use to ensure even distribution of drug and

accurate dosing.

Practice points: Dry Powder Inhalers (DPI)

A number of different DPI inhalers are available and patients must be

instructed on how to use each individual device e.g. how to prime the

dose (load the capsule/blister etc.) See Table 1 for different types of

DPI inhalers

Where a patient’s inspiratory flow rate is insufficient, e.g. some

elderly patients, a DPI may not be suitable.

Incorrect use can result in high oropharyngeal drug deposition.

Exhaling into the device can reduce its functioning – the dose may be

blown out of the chamber or the humid air can cause agglomeration of

the dry powder.

Holding a DPI at the incorrect orientation prior to inhalation may cause

the dose to fall out of the dosing chamber.

Some patients may have difficulty co-

ordinating actuation with inhalation –

training in inhaler technique or the use

of a spacer device may help.

6

Table 1: Different types of Dry Powder Inhalers currently available for treatment of asthma

Inhaler device

Image Individual products 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

Diskus

Serevent® Diskus (salmeterol) Flixotide Diskus® (fluticasone propionate) Seretide Diskus® (fluticasone propionate/salmeterol)

LABA ICS ICS/LABA

Pre-loaded inhaler device

Easyhaler

Bufomix® (budesonide/formoterol)

ICS/LABA Pre-loaded inhaler device

Ellipta

Relvar® (fluticasone furoate/vilanterol)

ICS/LABA Pre-loaded inhaler device Device has a 6 week expiry from date of first use

Novolizer

Budesonide ICS Cartridge is loaded to device. Shelf life of 6 months from first opening

Spiromax

DuoResp Spiromax® (budesonide/formoterol)

ICS/LABA Use within 6 months of removing from the foil wrapping.

Turbohaler

Bricanyl® (terbutaline) Oxis® (formoterol) Pulmicort® (budesonide) Symbicort® (budesonide/formoterol)

SABA LABA ICS ICS/LABA

Pre-loaded inhaler device

Twisthaler

Asmanex®(mometasone) ICS Pre-loaded inhaler device

7

Inhaler of Choice

The dosage and type of inhaler device should be individualised for each patient, taking into

account the patient’s ability to use the device and his/her preferences, among other factors.

However, pMDIs appear to be equally as effective as other types of inhaler device for the delivery

of SABA and ICS. With appropriate training, most patients can be taught to use a pMDI effectively.

A spacer device should be used for younger children or those with difficulty co-ordinating

actuation and inhalation with a pMDI.

pMDIs for SABA and ICS delivery are generally

the least expensive inhaler devices and

consequently, should be considered first line for

the treatment of asthma.

8

4.2 Stepwise approach to asthma treatment

A stepwise approach to the introduction of asthma medications is recommended, as outlined in Figure 1.

Each patient should start therapy at the step most appropriate to his/her symptoms and move up or down the treatment ladder

according to symptoms.9 At each step, a reliever medication, e.g. salbutamol pMDI, should be provided for quick relief of

symptoms.

Figure 1. Management of Asthma in Clinical Practice (adults and children ≥ 6 years) 4, 8

Step 1 Inhaled SABA (as required)

Step 2 Add ICS (Dose titrated to severity of disease)

Step 3 Add LABA or increase ICS - continue LABA if good response or if no response stop LABA and add oral LTRA*/ sustained-release (SR) theophylline† to ICS

Step 4 Consider increasing ICS to maximum dose with LABA (if response to LABA observed). Stop LABA if no benefit. Consider addition of LTRA/ SR theophylline† or tiotropium (respimat®)‡

Step 5 Maintain high dose ICS Add daily low dose oral corticosteroid (CS); Add tiotropium (respimat®) ‡ (Refer to specialist care)

Mild intermittent asthma

Regular controller therapy

Initial add-on therapy Persistent poor control Continuous/ frequent use of CS

Increasing severity of symptoms

*LTRA: Leukotriene receptor antagonist

‡ Tiotropium (Respimat® soft mist inhaler) is indicated as add-on therapy in ADULTS ONLY with a history of exacerbations

† For children 6-11 years, theophylline is not recommended and preferred step 3 is medium dose ICS

9

4.3 Reviewing asthma treatment

Review treatment every 3 months.

If control has been achieved, a stepwise reduction may be possible.

Reduce the dose of ICS slowly (consider reduction every 3 months, decreasing

the dose by up to 25-50% each time).8, 9

5. Inhaled therapies

Patient and age-specific dosing information is not discussed in this document. Please

consult relevant guidance and the current SmPC for specific information relating to

dosing in special populations, e.g. children.

Suggested Treatment Reductions

Inhaled Corticosteroids

Beclometasone pMDI (Beclazone®) 250 μg BD → 200 μg BD → 100 μg BD*

Budesonide DPI (Pulmicort®) 400 μg BD → 200 μg BD → 100 μg BD*

* Where control is achieved with a low-dose ICS alone, in most patients dosing frequency may be reduced to once daily.3 (μg = micrograms)

Combination Inhalers

Fluticasone propionate/Salmeterol (Seretide®) → Reduce dose* → Fluticasone

(Flixotide®)

Budesonide/Formoterol (Bufomix®) →Reduce dose* → Budesonide (Pulmicort®)

* Begin by reducing the dose of ICS by approx. 50% while continuing the LABA (e.g. change from Seretide® 500/50 Diskus [one puff BD] to Seretide® 250/50 Diskus [one puff BD]). If control is maintained, reduce the ICS dose further (e.g. to Seretide® 100/50 Diskus) until a low dose is reached. The LABA may then be stopped and the patient maintained on an ICS.3

Switching advice

When stepping down treatment ensure the patient is maintained on the same device

type (i.e. pMDI or DPI). Avoid switching between devices unless necessary.

10

5.1 Short-acting beta2 agonists (SABA)

Salbutamol and terbutaline are SABAs indicated for the relief of bronchospasm

associated with asthma.9 Salbutamol is available as a pMDI, a BA MDI and a DPI.5

Terbutaline is available as a DPI only.5

Depending on the drug and inhaler device specified, the cost of SABA treatment for

the relief of asthma symptoms varies. Table 2 lists the associated costs of SABA inhaler

devices. Typical dosage would be four actuations per day.34-35

Table 2. Short-acting beta2 agonists (SABA)

*BA: breath-actuated; pMDI: pressurised metered-dose inhaler; DPI: dry powder inhaler

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 CFC-free inhaler

BA MDI 100mcg 200 7.95 0.04

Novolizer® Salbutamol BA DPI 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

Indicated in all steps of asthma treatment.

Practice tip

Where a patient requires two puffs of SABA twice a week or more, a regular

inhaled corticosteroid (ICS) is indicated.

11

5.2 Short-acting muscarinic antagonists (SAMA)

Ipratropium is a SAMA and can provide short-term relief in chronic asthma, but SABAs

(e.g. salbutamol) act more quickly and are preferred.4 Table 3 details the costs

associated with the only available ipratropium inhaler for asthma, Atrovent®. Typical

usage would be four actuations per day.36

Table 3. Short-acting muscarinic antagonists (SAMA)



Cost per device €


Ipratropium

Atrovent® pMDI 20mcg 200 2.67 0.01

pMDI: pressurised metered-dose inhaler

5.3 Inhaled corticosteroids (ICS)

Inhaled corticosteroids (ICS) with and without inhaled beta2-agonists are the mainstay

of treatment in chronic asthma.2, 4 Numerous ICSs are available, both as single-agent

inhaler devices and in combination with LABAs (Section 5.5).

Table 4. Estimated Equipotent Doses of ICS for adults3

Drug Low daily dose (micrograms)

Medium daily dose (micrograms)

High daily dose (micrograms)

Beclometasone dipropionate e.g. Beclazone® CFC-free pMDI

200-500 >500-1000 >1000

Budesonide e.g. Pulmicort® Turbohaler (DPI)

200-600 >600-1000 >1000

Ciclesonide e.g. Alvesco® (pMDI)

80-160 >160-300 >320

Fluticasone propionate e.g. Flixotide® (pMDI/DPI)

100-250 >250-500 >500

Mometasone furoate e.g. Asmanex® Twisthaler (DPI)

200-400 >400-800 >800

pMDI: pressurised metered-dose inhaler; DPI: dry powder inhaler

Table 5 lists the individual ICSs and their associated costs.37-46 Cost per actuation is

listed and is not indicative of cost per day as products may require one or two puffs

Indicated from step 2 of asthma treatment.

Indicated for bronchospasm and acute asthmatic episodes.

12

once or twice daily depending on the inhaler used and patient needs (refer to

individual SmPCs for licensed doses and frequencies).

Table 5. Inhaled corticosteroids (ICS) Drug and device Device

type Strength Doses per

device Cost per device €


Beclometasone

Beclazone® CFC-free inhaler pMDI 50mcg 200 5.36 0.03

Beclazone Easi-breathe® CFC-free inhaler BA MDI 50mcg 200 5.58 0.03

Becotide® Evohaler pMDI 50mcg 200 3.05 0.02

QVAR® Inhaler* (aerosol) pMDI 50mcg 200 10.86 0.05

QVAR® Autohaler* pMDI 50mcg 200 10.86 0.05




QVAR® Inhaler* (aerosol) pMDI 100mcg 200 23.24 0.12

QVAR® Autohaler* pMDI 100mcg 200 23.24 0.12






Budesonide

Pulmicort® Turbohaler DPI 100mcg 200 16.24 0.08


Novolizer® Budesonide device plus cartridges

DPI 200mcg 100 20.00 0.20


Novolizer® Budesonide device ( +cartridges) DPI 400mcg 50 20.00 0.40

Ciclesonide

Alvesco® pMDI 80mcg 60 17.73 0.30

Alvesco® pMDI 160mcg 60 21.60 0.36

Fluticasone propionate

Flixotide® Evohaler pMDI 50mcg 120 8.85 0.07

Flixotide® Diskus DPI 50mcg 60 5.64 0.09








Mometasone

Asmanex® Twisthaler DPI 200mcg 60 20.58 0.34




* The recommended total daily dose of beclometasone dipropionate extrafine aerosol from Qvar is lower

than that for current beclometasone dipropionate CFC product and should be adjusted to the individual patient.39, 40

Beclometasone is the least expensive ICS and is preferred by the MMP on the basis of cost. Beclometasone

should be considered first when prescribing an ICS, particularly if intending to prescribe a pMDI.

13

5.4 Long-acting beta2 agonists (LABA)

Formoterol and salmeterol should be used only in patients who regularly use an ICS.9

Salmeterol should not be used for the relief of an asthma attack; it has a slower onset

of action than salbutamol or terbutaline. The UK Committee for the Safety of

Medicines (CSM) has warned that LABAs should be added only if regular use of

standard-dose inhaled corticosteroids has failed to control asthma adequately.9 LABAs

should not be initiated in patients with rapidly deteriorating asthma and should be

introduced at a low dose. The effect should be properly monitored before considering

a dose increase.9

Table 6 details the available LABAs and their associated costs.47-51

Table 6. Long-acting beta2 agonists (LABA)



Cost per device €


Formoterol

Oxis® Turbohaler DPI 6mcg 60 16.55 0.28

Oxis® Turbohaler DPI 12mcg 60 20.11 0.34

Foradil® Aerolizer DPI 12mcg 60 23.09 0.38

Salmeterol

Salmeterol Neolab® pMDI 25mcg 120 26.37 0.22

Serevent® Evohaler pMDI 25mcg 120 28.57 0.24

Serevent® Diskus DPI 50mcg 60 25.49 0.42


Always use in combination with ICS.

Practice tip

There is no role for LABA monotherapy in the treatment of asthma. There

has been an increase in asthma deaths reported with excessive use of

inhaled beta-agonists without inhaled steroids. 50

14

5.5 Inhaled corticosteroids and long-acting beta2 agonists (ICS/LABA)

Combination therapy with an ICS and LABA is indicated where symptom control

remains suboptimal despite regular use of an ICS with ‘as required’ SABA.2,3 However

if there is no response to the addition of LABA therapy, treatment with LABA should

be discontinued and other treatment options should be considered.

In general, a single inhaler device containing a combination of ICS and LABA is

preferred. The use of a combination inhaler will ensure that the LABA is not taken

without inhaled corticosteroid and may also improve inhaler adherence.8 Table 7

details the available combination inhalers and their associated costs. For convenience,

these inhalers have been categorised according to inhaler strength and inhalers of

equivalent strength are highlighted. Please refer to individual SPCs for full dosing

information. 12-23

Of note, both Symbicort Turbohaler (200mcg/6mcg and 400mcg/6mcg) and Bufomix

Easyhaler (160mcg/4.5mcg and 320mcg/9mcg) are licensed for use in adults and

adolescents aged 12-17 years while DuoResp Spiromax (160mcg/4.5mcg and

320mcg/9mcg) is indicated in adults 18 years of age and older only.13, 14, 15 ,17 ,18

Symbicort Turbohaler (100mcg/6mcg) and Bufomix Easyhaler (80mcg/4.5mcg) are

licensed from age 6 and older. 12,16


15

Table 7. Combination devices containing ICS/LABA Drug and preparations Strength Doses per device Cost per

device € Cost per actuation €

Budesonide/Formoterol

EQUIVALENT DOSES

Bufomix® Easyhaler (DPI)* 80mcg/4.5mcg 120 31.86 0.27

Symbicort® Turbohaler (DPI) 100mcg/6mcg 120 38.97 0.32

EQUIVALENT

DOSES

Bufomix® Easyhaler (DPI)* 160mcg/4.5mcg 120 31.86 0.27

DuoResp® Spiromax (DPI) ‡ 160mcg/4.5mcg 120 37.58 0.31

Symbicort® Turbohaler (DPI)* 200mcg/6mcg 120 40.85 0.34

EQUIVALENT

DOSES

Bufomix® Easyhaler (DPI)* 320mcg/9mcg 60 31.86 0.53

DuoResp® Spiromax (DPI) ‡ 320mcg/9mcg 60 36.85 0.61

Symbicort® Turbohaler (DPI)* 400mcg/12mcg 60 38.98 0.65

Fluticasone propionate/Formoterol

Flutiform® (pMDI) 50mcg/5mcg 120 26.43 0.22



Fluticasone propionate/Salmeterol

Seretide® Evohaler (pMDI) 50mcg/25mcg 120 25.06 0.21

Seretide® Diskus (DPI) 100mcg/50mcg 60 25.50 0.43



EQUIVALENT DOSES

AirFluSal® Forspiro® (DPI) 250mcg/50mcg 60 31.67 0.53


EQUIVALENT DOSES

AirFluSal® Forspiro® (DPI) 500mcg/50mcg 60 41.41 0.69


Fluticasone furoate**/Vilanterol

Relvar® Ellipta (DPI) 92mcg/22mcg 30† 34.45 1.15

Relvar® Ellipta (DPI) 184mcg/22mcg 30† 39.95 1.33

* 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.48 Bufomix® 160mcg/4.5mcg is equivalent to Symbicort®200mcg/6mcg and Bufomix® 320mcg/9mcg is equivalent to Symbicort® 400mcg/12mcg. These strengths are not recommended for children under 12 years of age.13,14,17,18 Bufomix® 80mcg/4.5mcg is equivalent to Symbicort® 100mcg/6mcg, this strength is suitable from age 6.12,16

** Fluticasone furoate (FF) 100mcg once daily is approximately equivalent to fluticasone propionate (FP) 250mcg twice daily and FF 200mcg once daily is approximately equivalent to FP 500mcg twice daily for asthma treatment.21 ‡ Indicated in adults 18 years of age and older only (not indicated for use in children, 12 years an younger or adolescents up to 17 years15

† Once daily administration21

16

Combination inhalers containing an ICS and LABA are generally not indicated for the

relief of the acute symptoms of asthma (‘reliever therapy’). However some inhalers

are now licensed as maintenance and reliever therapy for asthma in adults (i.e. over

18 years). Bufomix® 80/4.5 and 160/4.5 microgram Easyhalers and Symbicort® 100/6

and 200/6 microgram Turbohalers and DuoResp Spiromax 160/4.5 are licensed as

maintenance and reliever therapy for asthma in adults .12,13, 15-17 This approach has

been shown to result in reductions in exacerbations and improvement in asthma

control at relatively low doses.3 However, these inhaler devices are approximately six

to seven times more expensive per actuation than the SABA ‘reliever therapy’

terbutaline DPI (Bricanyl® Turbohaler) and are not licensed for use in this way for those

under 18 years.

Where a patient is accustomed to using a DPI for the maintenance

treatment of asthma (either as ICS monotherapy or combined ICS/LABA),

a short acting beta 2 agonist is preferred by the MMP for reliever therapy

on the basis of cost i.e. DPI Bricanyl® Turbohaler (terbutaline) or breath

actuated devices such as Salamol® (salbutamol) Easi-Breathe or Novolizer®

(salbutamol) DPI.

Practice tip: Seretide® Diskus

The quantity of LABA per actuation differs between Seretide® Evohaler and

Seretide® Diskus. While two puffs twice daily of Seretide® Evohaler is generally

indicated, only one puff of Seretide® Diskus should be prescribed twice daily.

More than one puff per dose of Seretide® Diskus is not licensed.

17

5.6 Long-acting muscarinic antagonists (LAMA)

The SMI long-acting muscarinic antagonist (LAMA) Spiriva® Respimat (tiotropium) is

licensed as of September 2014 as an add-on maintenance bronchodilator treatment

in adult patients with asthma who are currently treated with the maintenance

combination of inhaled corticosteroids (≥800 micrograms budesonide/day or

equivalent) and long-acting beta2 agonists and who experienced one or more severe

exacerbations in the previous year.53 This therapy is not licensed for children less

than 18 years. The cost is outlined in table 8.

Indicated from step 4 of asthma treatment (adults only).

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. However,

it is important when considering a switch that inhaler technique is checked to

ensure adherence to therapy.

Bufomix® 80/4.5µg, 160/4.5μg and 320/9μg are dose equivalent to Symbicort®

100/6µg, 200/6μg and 400/12μg respectively but are 18-22% less expensive.

AirFluSal® 250/50μg and 500/50μg are dose equivalent to Seretide® Diskus

250/50μg and 500/50μg but are 9% less expensive.

Prescribing Tip

When an ICS/LABA combination is indicated for asthma,

Think….

BUFOMIX® 80/4.5µg, 160/4.5μg or 320/9μg

(budesonide/formoterol)

twice daily

18

Table 8: Long acting muscarinic antagonist (LAMA) Drug and device Device

type Strength Doses per

device Cost per device €


Tiotropium

Spiriva Respimat SMI 2.5mcg 60 37.38 0.62 (x2) SMI: Soft mist inhaler

6. Spacer devices

Spacer devices remove the need for co-ordination between actuation of a pMDI and

inhalation.9 The spacer device reduces the velocity of the aerosol and subsequent

impaction on the oropharynx, and allows more time for evaporation of the propellant

so that a larger proportion of the particles can be inhaled and deposited in the lungs.9

Spacer devices are particularly useful for patients with poor inhalation technique, for

children, and for patients prone to candidiasis with ICS.9 Spacer devices help to reduce

systemic absorption of ICS, and are particularly useful for those requiring high doses

of ICS.4 The larger spacers with a one-way valve (i.e. Volumatic®) are considered most

effective.9 Table 9 outlines some of the spacer devices available on the Irish market.

Table 9. Spacer devices Spacer Device Category of patient Compatibility Reimbursed Comment

Aerochamber® Plus Small mask (orange) Medium mask (yellow) Large mask (blue)

12-18 months 18 months - 5 years >5 years

All pMDIs No

Available on www.asthma.ie

Aerochamber® AC Girlz mouthpiece (pink) Boyz mouthpiece (green)

>5 years >5 years

All pMDIs No Available on www.asthma.ie

Babyhaler® Infants and toddlers

Becotide®, Flixotide®, Ventolin® evohalers

Yes (€15.62)6

Available on www.asthma.ie

Volumatic® >5 years Becotide®, Flixotide®, Seretide®, Serevent®, Ventolin® evohalers

Yes (€3.34)6 Paediatric mask available*

* May result in additional cost Note: This list is not exhaustive (see also www.asthma.ie)

Table 10. Device to aid MDI use Device Compatibility Reimbursed Comment

Haleraid® Becotide®, Flixotide®, Seretide®, Serevent®, Ventolin® evohalers

No For use when strength in hands reduced. Devices available for 120- & 200-dose inhalers

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7. Summary

Inhaled therapies represent the cornerstone of asthma treatment. Selection of an

appropriate drug and inhaler device is crucial to achieving optimum asthma control.

Inhaled therapies should be tailored to the needs of the individual patient and their

suitability and effectiveness should be reassessed regularly, i.e. every 3 months.

In 2013, the HSE spent in excess of €107 million on inhalers for obstructive airways

diseases (GMS and DP schemes), of which approximately €16 million was attributed

to the treatment of patients with asthma. Inhalers for the treatment of chronic

obstructive pulmonary disease (COPD) account for the larger proportion of inhaler

expenditure. In 2015 the expenditure on the GMS scheme alone for inhalers used in

the treatment of obstructive airways disease was over €91.6 million.

50% of all expenditure on inhalers in 2015 was on devices containing a combination

of ICS and LABA. These inhalers account for over 65,500 GMS prescriptions per month,

costing the HSE approximately €3.8 million per month in 2015.

In the category of ICS/LABA there are now a number of dry powder inhaler (DPI)

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® 80/4.5µg, 160/4.5μg and 320/9μg are dose equivalent to Symbicort®

100/6µg, 200/6μg and 400/12μg respectively but are 18-22% less expensive.

AirFluSal 250/50μg and 500/50μg are dose equivalent to Seretide® Diskus 250/50μg

and 500/50μg but are 9% less expensive.

There is significant variation between inhaled drugs and individual inhaler devices in

terms of cost. For private/DPS patients on inhaled therapies for asthma, these costs

may be significantly higher. Prescribers should be mindful of these variations in cost

when prescribing inhaled therapies for the treatment of asthma and should

20

endeavour to prescribe the least expensive inhaler device that is appropriate and

suitable for a particular patient.

This document contains information regarding the reimbursement costs of available

inhaled drugs and inhaler devices and provides a useful tool for prescribers for

selecting cost-effective inhaler options for their patients.

For up to date reimbursement prices please refer to www.pcrs.ie. All prices contained

in this guide are subject to change but are current for products licensed in Ireland and

available on the PCRS website on October 2016.

http://www.pcrs.ie/

21

8. References

1. Martinez F, Vercelli D. Asthma. Lancet 2013; 382:1360-72

2. Global Strategy for Asthma Management and Prevention, Global Initiative for

Asthma (GINA) 2016. Available from: http://www.ginasthma.org/. Accessed on

14th September 2016.

3. Asthma Control in General Practice. Quality in Practice Committee, Irish College of

General Practitioners, Second Edition 2013. Accessed at

http://www.icgp.ie/go/library/icgp_publications on 26th August 2015.

4. Pocket Guide for Asthma Management and Prevention (for adults and children

older than 5 years): A pocket guide for physicians and nurses. Updated 2016.

Accessed at:

http://www.ginasthma.org/local/uploads/files/GINA_Pocket_2015.pdf on 14th

September 2016.

5. Health Products Regulatory Agency (HPRA) - Human medicines listing. Accessed at

www.hpra.ie on 14th September 2016.

6. HSE Primary Care Reimbursement Service (PCRS). Reimbursable items listing.

Accessed at www.pcrs.ie on 14th September 2016.

7. Medicines Management Programme (MMP) internal analyses, July 2014 and

October 2016. On file.

8. British Guideline on the Management of Asthma: Quick Reference Guide. The

British Thoracic Society/ Scottish Intercollegiate Guidelines Network. (Revised

2014). Accessed at https://www.brit-thoracic.org.uk/document-library/clinical-

information/asthma/btssign-asthma-guideline-quick-reference-guide-2014/

on 12th August 2015.

9. Joint Formulary Committee. British National Formulary May 2014 (online) London:

BMJ Group and Pharmaceutical Press <http://www.medicinescomplete.com>

[Accessed on 20th May 2014].

10. National Medicines Information Centre. Therapeutics Bulletin: Management of

Asthma (Part 1) 2013; 19:5. Accessed at www.nmic.ie on 10th March 2013.

11. National Medicines Information Centre. Therapeutics Bulletin: Management of

Asthma (Part 2) 2013; 19:6. Accessed at www.nmic.ie on 10th March 2013.

http://www.ginasthma.org/

http://www.icgp.ie/go/library/icgp_publications

http://www.ginasthma.org/local/uploads/files/GINA_Pocket_2015.pdf

http://www.hpra.ie/

http://www.pcrs.ie/

https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-quick-reference-guide-2014/

https://www.brit-thoracic.org.uk/document-library/clinical-information/asthma/btssign-asthma-guideline-quick-reference-guide-2014/

http://www.nmic.ie/

http://www.nmic.ie/

22

12. Bufomix® Easyhaler 80/4.5 microgram Summary of Product Characteristics, last

revised 4/8/16. Accessed at www.medicines.ie on 14th September 2016.

13. Bufomix® Easyhaler 160/4.5 microgram Summary of Product Characteristics, last


14. Bufomix® Easyhaler 320/9 microgram Summary of Product Characteristics, last


15. DuoResp® Spiromax Summary of Product Characteristics, last revised 28th April

2014. Accessed at www.ema.europa.eu on 19/08/2015.

16. Symbicort® Turbohaler 100/6 micrograms Summary of Product Characteristics,

last revised September 2014. Accessed at www.medicines.ie on 12th August 2015.


last revised July 2014. Accessed at www.medicines.ie on 12th August 2015.


last revised October 2014. Accessed at www.medicines.ie on 12th August 2015.

19. Seretide® Diskus Summary of Product Characteristics, last revised July 2015.

Accessed at www.medicines.ie on 12th August 2015.

20. Seretide® Evohaler Summary of Product Characteristics, last revised July 2015.


21. Relvar Ellipta® 92/22 micrograms Summary of Product Characteristics, last revised

June 2015. Accessed at www.medicines.ie on 12th August 2015.

22. Relvar Ellipta® 184/44 micrograms Summary of Product Characteristics, last

revised June 2015. Accessed at www.medicines.ie on 12th August 2015.

23. Flutiform® Summary of Product Characteristics, last revised August 2013.


24. Lavorini F, Usmani OS. Correct inhalation technique is critical in achieving good

asthma control. Primary Care Respiratory Journal 2013; 22(4): 385-386.

25. Brocklebank D et al. Comparison of the effectiveness of inhaler devices in asthma

and chronic obstructive airways disease: a systematic review of the literature.

Health Technology Assessment 2001; 5:1-149. Accessed at http://www.hta.ac.uk

on 5th June 2014.

http://www.medicines.ie/



http://www.ema.europa.eu/









http://www.hta.ac.uk/

23

26. Wright J, Brocklebank D and Ram, F. Inhaler devices for the treatment of asthma

and chronic obstructive airways disease (COPD). Quality and Safety in Health Care

2002; 11:376-382.

27. Dolovich MB et al. Device selection and outcomes of aerosol therapy: Evidence-

based guidelines: American College of Chest Physicians/American College of

Asthma, Allergy, and Immunology. Chest 2005; 127:335-371.

28. Ram FSF, Brocklebank DDM, White J, Wright JJ, Jones P. Pressurised metered dose

inhalers versus all other hand-held inhaler devices to deliver beta-2 agonist

bronchodilators for non-acute asthma. Cochrane Database of Systematic Reviews

2002, Issue 2. Art. No.: CD002158. DOI: 10.1002/14651858.CD002158.

29. Ram FS, Wright J, Brocklebank D & White JE. Systematic review of clinical

effectiveness of pressurised metered dose inhalers versus other hand held inhaler

devices for delivering beta2 agonists bronchodilators in asthma. BMJ 2001;

323:901-905.

30. Cochrane MG et al. Inhaled corticosteroids for asthma therapy: patient

compliance, devices and inhalation technique. Chest 2000; 117:542-550.

31. Giraud V, Roche N. Misuse of corticosteroid metered-dose inhaler is associated

with decreased asthma stability. European Respiratory Journal 2002; 19:246-251.

32. Haughney J et al. Choosing inhaler devices for people with asthma: current

knowledge and outstanding research needs. Respiratory Medicine 2010;

104:1237-1245.

33. Price D et al. Improvement of asthma control with a breath-actuated pressurised

metered dose inhaler (BAI): a prescribing claims study of 5556 patients using a

traditional pressurised metered dose inhaler (MDI) or a breath-actuated device.

Respiratory Medicine 2003; 97:12-19.

34. Ventolin® Evohaler Summary of Product Characteristics, last revised July 2015.


35. Bricanyl® Turbohaler Summary of Product Characteristics, last revised May 2015.


36. Atrovent ® Inhaler Summary of Product Characteristics, last revised February 2015.





24

37. Beclazone® Easi-breathe Summary of Product Characteristics, last revised June

2011. Accessed at www.hpra.ie on 14th July 2014.

38. Becotide® Evohaler Summary of Product Characteristics, last revised July 2015.


39. Qvar® Aerosol (actuation pressurised inhalation solution) Summary of Product

Characteristics, last revised February 2014. Accessed at www.hpra.ie on 12th

August 2015.

40. QVAR Autohaler Summary of Product Characteristics, last revised February 2014.

Accessed at www.hpra.ie on 19th August 2015.

41. Pulmicort® Turbohaler 200 micrograms Summary of Product Characteristics, last

revised 16th May 2013. Accessed at www.medicines.ie on 27th May 2014.

42. Novoliser Budesonide 200 micrograms inhaler Summary of Product

Characteristics, last revised October 2013. Accessed at www.medicines.ie on 12th

August 2015.

43. Alvesco® 160 micrograms Summary of Product Characteristics, last revised March

2015. Accessed at www.medicines.ie on 12th August 2015.

44. Flixotide® Evohaler Summary of Product Characteristics, last revised July 2015.


45. Flixotide® Diskus Summary of Product Characteristics, last revised July 2015.


46. Asmanex® Twisthaler Summary of Product Characteristics, last revised October

2014. Accessed at www.medicines.ie on 12th August 2015.

47. Foradil® Summary of Product Characteristics, last revised July 2015. Accessed at

www.medicines.ie on 12th August 2015.

48. Oxis Turbohaler 6 and 12 micrograms Summary of Product Characteristics, last

revised March 2015. Accessed at www.medicines.ie on 13th August 2015.

49. Serevent® Diskus Summary of Product Characteristics, last revised July 2015.


50. Serevent® Evohaler Summary of Product Characteristics, last revised July 2015.


http://www.hpra.ie/


http://www.hpra.ie/

http://www.hpra.ie/











25

51. Salmeterol Neolab® Summary of Product Characteristic, last revised November

2012. Accessed on www.hpra.ie on 13th August 2015.

52. Salpeter SR, Wall AJ, Buckley NS. Long-acting Beta-agonists with and without

Inhaled Corticosteroids and Catastrophic Asthma Events. The American Journal of

Medicine (2010) 123: 322-328

53. Spiriva® Respimat Summary of Product Characteristics, last revised January 2015.


9. Bibliography

1. Honohan J, Manning P. Asthma control in general practice. Irish College of General

Practitioners in collaboration with the Asthma Society of Ireland, 2008.

2. Frequently-Asked Questions in Asthma: Clinician’s Desk Reference. Eds: G Douglas

and K Elward. Publishers: Manson Publishing Ltd, UK 2011. pps 157-162.

3. Ventolin® Diskus Summary of Product Characteristics, last revised August 2013.

Accessed at www.medicines.ie on 12th March 2014.

http://www.hpra.ie/



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Appendix 1. Summary - Management of Asthma in Clinical Practice

Each patient should start therapy at the step most appropriate to his/her symptoms and move up and down the treatment ladder according to symptoms.

Review treatment every three months; if control has been achieved, a stepwise reduction may be possible (Section 4.3).

Step 1 Inhaled short-acting beta2 agonist (SABA) as required

Mild intermittent asthma

Step 2 Add inhaled corticosteroid (ICS) Titrate dose to severity of disease

Regular controller therapy

Step 3 Add long-acting beta2 agonist (LABA) or increase ICS Continue LABA if good response or if no response to LABA, stop LABA and add LTRA*/sustained release (SR) theophylline † to ICS

Initial add-on therapy

Step 4 Consider increasing ICS to maximum dose with LABA (if response to LABA observed) Stop LABA if no benefit. Consider addition of LTRA/SR theophylline † or tiotropium (respimat®)‡

Persistent poor control

Step 5 Maintain high dose ICS ± daily low dose oral corticosteroid (CS); Consider adding tiotropium (respimat®)

(Specialist care)

Continuous/ frequent use of CS

Increasing severity of symptoms

Practice Points Where a patient requires two puffs of SABA twice weekly, a regular inhaled corticosteroid is indicated.

A patient’s ability to use an inhaler correctly is crucial when prescribing an inhaler device: Most patients can be taught to use a pressurised metered dose inhaler (pMDI). A spacer device should be used when a patient has difficulty using a pMDI or a breath-actuated MDI may be useful. Dry powder inhalers (DPIs) are useful for those unable to use a pMDI. However, inspiratory flow rate must be sufficient to enable

lung deposition.

Patients must be trained on how to use their device; inhaler technique should be assessed regularly (checklists for inhaler technique review are available on www.asthma.ie)

It is good practice to use one inhaler device type per patient, i.e. pMDI or DPI for both reliever and maintenance therapy. This avoids the need to train the patient in more than one device type and reduces confusion. Having more than one device type in use or switching between devices can lead to incorrect dosing, adverse effects and drug wastage.

Seretide® Diskus is not licensed at a dose of two puffs twice daily; the correct dose is one puff twice daily.

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Appendix 2. Asthma – Summary of Inhaler Costs

*Refers to reimbursed cost only. Private/DPS patients pay significantly more than the reimbursed cost

*The recommended total daily dose of beclometasone dipropionate extrafine aerosol from Qvar is lower than that for current beclometasone dipropionate CFC product and should be adjusted to the individual patient.

Medicinal product subject to additional monitoring by the European Medicines Agency BA MDI – Breath-actuated metered dose inhaler; pMDI – Pressurised metered dose inhaler; DPI – Dry powder inhaler; SMI – Soft mist inhaler

Costs listed reflect the reimbursed price. Private/DPS patients pay significantly more than the reimbursed price. Cost per day will vary depending on the inhaler, the dose and frequency prescribed (refer to SmPC for licensed doses for each inhaler)

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Appendix 3. New in this update – version 1.3

Bufomix® is now available as 80mcg/4.5mcg strength.

Bufomix® 80 /4.5mcg and 160/4.5 mcg are licensed for maintenance and reliever therapy

for asthma in adults.

Costs have been updated to October 2016 prices.

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