Asthma Medications in Clinical Practice - Part 2

5
LABA
DPI Diskus Serevent®
(Salmeterol)
DPI Aerolizer Foradil®
(Formoterol)
DPI Breezhaler Onbrez®
(Indacaterol)
SMI Respimat Striverdi®
(Olodaterol)

fast onset, short duration fast onset, long duration
slow onset, short duration slow onset, long duration
inhaled terbutaline
inhaled salbutamol
inhaled formoterol
oral terbutaline
oral salbutamol inhaled salmeterol
oral bambuterol
M
A
I
N
T
E
N
A
N
C
E
AS NEEDED
Duration
of actionlongShort
Classes of b2-agonists
Speed
of action
Fast
Slow

16
 Long-acting inhaled β2 agonists should only be started
in patients who are already on inhaled corticosteroids,
and the inhaled corticosteroid should be continued.
 The benefits of these medicines used in conjunction with
ICS in the control of asthma symptoms outweigh any
apparent risks.
Safety Of LABA

1. Recent data indicating a possible increased risk of asthma
Related death associated with use of LABA in a
small group of individuals has resulted in increased
emphasis on the message that:
2. LABA should not be used as monotherapy in asthma & must
only be used in combination with an appropriate dose of
ICS.

Children’s Healthcare of AtlantaCutler and Everett. NEJM 2010; 362: 1553-1555
Adherence to treatment
is a weak point
in asthma management

25
 In clinical practice, however, it is generally considered
that combination inhalers (ICS & LABA) aid adherence
and also have the advantage of guaranteeing that the
LABA is not taken without the ICS

Combination Medications
Combination
Medications
ICS LABA
Symbicort®
Budesonide
(Pumicort®)
Formoterol
(Oxeze®)
Seretide®
Fluticasone
(Floxitide®)
Salmeterol
(Severent®)

44
Deposition of particles
> 5 µ Impaction
1-5 µ
Sedimentation
< 1 µ like gas

Poor
asthma
control
Optimal
asthma
control
Time
(months, weeks, days)
Combination Strategy : Traditional
approach
SABA
ICS
+
LABA

54
+or
Traditional approach
Maintenance dose + as needed SABA

Maintenance &reliever therapy (MART) is a form of combined ICS
and LABA treatment in which a single inhaler, containing both ICS
And a fast-acting LABA, is used for both daily maintenance therapy
and the relief of symptoms as required.
MART is only available for ICS and LABA combinations in which
the LABA has a fast-acting component (for example,
within one to three minutes of inhalation .
55
Maintenance and RelieverTherapy (MART)

56
Maintenance and Reliever Therapy (MART)

Symbicort SMART
Symbicort Maintenance And Reliever Therapy
Formoterol
Budesonide
SABA

As needed
β2
As needed
Symbicort
Dailymedicationuse
(maintenanceandrelief)
Traditional Approach
Fixed Symbicort
+ prn SABA
TRADITIONAL APPROACH AND SYMBICORT
MAINTENANCE AND RELIEVER THERAPY
(SMART)
Days with symptoms
Maintenance
Symbicort
SMART
Maintenance
Time
Most days patients
use no reliever
illustrative

Total daily medication use
(maintenance and relief)
Fixed Symbicort
+ prn SABA
Fixed Symbicort
+ prn Symbicort
(Symbicort SMART)
If a combination inhaler containing formoterol and budesonide is
selected, it may be used for both rescue and maintenance. This
approach has been shown to result in reductions in exacerbations and
improvements in asthma control in adults and adolescents at relatively
low doses of treatment (Evidence A) … page60 GINA 2007

Children’s Healthcare of Atlanta
Therapy used over time
MedicationUse
Maintenance
+ prn SABA
Maintenance
+ prn Symbicort
One inhaler:
Maintenance & relief
Rapid adjustments in
controller replacing
SABA
No adjustment in
controller
SMART =
Single inhaler Maintenance
And Reliever Therapy
GOAL
Evolution in Asthma Management

Asthma
Evolving approaches to
treatment decisions

Step 1 Step 2 Step 3 Step 4 Step 5
As needed rapid-acting b2-agonist
Select one Select one
Add one or
more
Add one or
more
Low-dose
ICS
Low-dose
ICS/LABA
Med-high
ICS/LABA
Oral steroids
Leukotriene
modifier
Med-high
dose ICS
Leukotriene
modifier
Anti-IgE
Low
ICS+LTM
Theophylline
Low
ICS+Theo
GINA 2013
ControllerOptions

76

78

Dosing
 The maximum daily dose of formoterol is 72μg, which
limits the number of inhalations that can be used in a
single day.
 Symbicort SMART regimens use the 6μg formulations
(200/6 or 100/6).
 Symbicort inhalers containing 12μg are not licensed for
use as SMART (Symbicort 400/12 is not suitable for
the SMART regimen).
79

 Combination inhalers of salmeterol with an ICS, such as
Seretide, are not suitable for single inhaler maintenance
and reliever therapy.
 Salmeterol should not be used for the relief of acute asthma
symptoms because it has a significantly slower onset of
action than either formoterol, salbutamol or terbutaline.
80

 As with any symptom-directed therapy, there will be patients
for whom SMART therapy is not suitable, such as habitual
users of reliever medication (patients who tend to overuse
reliever inhalers) and under perceivers of asthma
symptoms.
 It is important that all patients being considered for SMART
therapy have an understanding of the maximum daily
allowance of additional reliever use .
81

 Not all combination products are licenced for maintenance
and reliever therapy.
 At present maintenance and reliever therapy (MART) is only
licenced for use with budesonide/ formoterol (Symbicort) or
beclomethasone/formoterol (Fostair).
 Patients taking rescue doses of their combination inhaler
a day or more on a regular basis should have their treatment
reviewed , as this would suggest that their asthma
control is sub-optimal.
83

85
 Long-acting beta2 agonists are currently overprescribed in
children. They are also often used inappropriately as first-
line therapy and are not recommended for children aged
five years or less.
Due to the paucity of paediatric clinical trials, the evidence
for the efficacy and safety of long-acting beta2agonists in
children is limited.

© Global Initiative for Asthma
Step 3 (children ≤5 years) – medium dose ICS
+ as-needed inhaled SABA
GINA 2017, Box 6-5 (7/8)
Infrequent
viral wheezing
and no or
few interval
symptoms
Symptom pattern consistent with asthma
and asthma symptoms not well-controlled, or
≥3 exacerbations per year
Symptom pattern not consistent with asthma but
wheezing episodes occur frequently, e.g. every
6–8 weeks.
Give diagnostic trial for 3 months.
Asthma diagnosis, and
not well-controlled on
low dose ICS
Not well-
controlled
on double
ICS
First check diagnosis, inhaler skills,
adherence, exposures
CONSIDER
THIS STEP FOR
CHILDREN WITH:
RELIEVER
Other
controller
options
PREFERRED
CONTROLLER
CHOICE
As-needed short-acting beta2-agonist (all children)
Leukotriene receptor antagonist (LTRA)
Intermittent ICS
Low dose ICS + LTRA Add LTRA
Inc. ICS
frequency
Add intermitt ICS
Daily low dose ICS
Double
‘low dose’
ICS
Continue
controller
& refer for
specialist
assessment
STEP 1 STEP 2
STEP 3
STEP 4

88
Asthma management
in children

93
Asthma and Respiratory Foundation NZ child &
adolescent asthma guidelines -1st December 2017
LABAs should not be used in children ≤4 years
of age.

 Oral preparations of beta2 agonists have been
used extensively in the past with children but are
less effective than inhaled preparations and have
more side-effects
94

Leukotriene Modifiers
1. 5 lipoxygenase inhibtor (Leukotriene Synthesis Inhibitor):
 Zileuton
2. Leukotriene Receptors Antagonists:
 Montelukast
 Zafirlukast

Central Role of CysLTs in Asthma
Adapted from Hay DWP et al Trends Pharmacol Sci 1995;16:304-309.
Inflammatory Cells
(mast cells,
eosinophils)
Sensory
Nerves
(C fibers)
CysLTsEdema
Blood
Vessel
Decreased Mucus Transport
Eosinophil
Influx
Cationic Protein Release,
Epithelial-Cell Damage
Contraction and
Proliferation
Airway Smooth Muscle
Increased
Mucus
Secretion
Airway
Epithelium

 Montelukast sodium is a hygroscopic, optically active,
white to off-white powder.
 Protect from moisture and light. Store in original
package.

Dosage Forms And Strengths
 SINGULAIR 4-mg Oral Granules are white granules with 500 mg net
weight, packed in a childresistant foil packet.
 SINGULAIR 4-mg Chewable Tablets are pink, oval, bi-convex-shaped
tablets, with code MSD 711 on one side and SINGULAIR on the other.

Dosage Forms And Strengths
 SINGULAIR 5-mg Chewable Tablets are pink, round, bi-convex-shaped
 SINGULAIR 10-mg Film-Coated Tablets are beige, rounded square-shaped

Montleukast 5 mg Chew-TOR, pink, round
Montleukast 4 mg Chew-TOR, pink, oval
Singulair 10 mg, beige, square

Instructions for Administration of Oral Granules
 Montelukast sodium oral granules can be administered
either directly in the mouth, dissolved in 1 teaspoonful
mL) of cold or room temperature baby formula or breast
milk,or mixed with a spoonful of cold or room
temperature soft foods.
 Based on stability studies, only applesauce, carrots,
or ice cream should be used.

 The packet should not be opened until ready to use. After
opening the packet, the full dose (with or without mixing
baby formula, breast milk, or food) must be administered
within 15 minutes.
 If mixed with baby formula, breast milk, or food, Montelukast
sodium oral granules must not be stored for future use.
Discard any unused portion.

 Montelukast sodium oral granules are not intended to
dissolved in any liquid other than baby formula or
breast milk for administration. However, liquids may be
taken subsequent to administration.
 Montelukast sodium oral granules can be administered
without regard to the time of meals.

 Sprinkle or stir the granules into a small amount of cold
soft food (e.g. yogurt). Your child should then swallow the
food straight away, without. Make sure that they take it
 Do not mix the granules with warm food or liquid.
 Your child must take the granules within 15 minutes of
opening the sachet. If the sachet has been open for more
than 15 minutes, throw the contents away and use a new
sachet.
 Do not keep granules or a granule/food mixture to give
later.

Montelukast - Dosage and How to Use

 Q: Why should Singulair be taken at bedtime? Will it
make me sleepy, or is it for some other reason? Can I
take it earlier in the day instead of at bedtime?
 A: According to the prescribing information for the medication,
Singulair should be dosed once daily in the evening with or
without food, when it is used for asthma.
 There have been no clinical trials in patients with asthma to
evaluate the relative efficacy of morning versus evening

 The pharmacokinetics of montelukast are similar whether
dosed in the morning or evening.
 Efficacy data has been demonstrated for asthma when
montelukast was administered in the evening without regard
to time of food ingestion.

Q: My 13-year-old son takes 5 mg Singulair which is not working. Is it safe
for him to take the 10-mg Singulair I currently take?
 A: According to the package insert, Singulair should be taken once daily in
evening.
 The following doses are recommended: 1- For adults
adolescents 15 years of age and older: one 10-mg tablet
2- For pediatric patients 6 to 14 years of age: one 5-mg chewable tablet.

What if my child is sick (vomits)?
 If your child is sick less than 30 minutes after having a dose of
give them the same dose again.
 If your child is sick more than 30 minutes after having a dose of
montelukast, you do not need to give them another dose. Wait until the
next normal dose.

What if I forget to give it?
 If you remember before your child has gone to sleep, give them the
missed dose. If you remember after your child has gone to sleep, you do
not need to wake them up to give the missed dose.
 You can give the missed dose in the morning, as long as this is at least 6
hours before the next evening dose will be given.

Comparing Aminophylline vs Theophylline
 Aminophylline is a compound of the bronchodilator
theophylline with ethylenediamine in 2:1 ratio. ...
 Aminophylline is less potent and shorter-acting than
theophylline.

Individualizing Therapy is Important for Drugs with
a Narrow Therapeutic Range
e.g. penicillin
Safe to prescribe dose effective for
>90% of population
e.g. anticancer drug
Difficult to prescribe effective
non-toxic dose
narrow
therapeutic range
Dose
100
efficacy
toxicity
100
efficacy
toxicity
wide therapeutic
range
Dose
Some drugs have such a wide therapeutic range and
others may have a narrow therapeutic index

Theophylline plasma
concentration mcg/ml
Clinical Consequence
≤ 5 Absence of therapeutic effect
6-10 Sub-optimal therapeutic effect
10-20 Traditionally accepted therapeutic Window
>15 Anxiety, insomnia (possible)
>15 Gastro-intestinal disturbances(possible)
>20 “Toxic effect” (CVS,GI &CNS)
>30* Severe cardiac arrhythmias, *Fatal
>40* Seizures,coma. *Fatal
*Sessier CN, Am j med.1988 Allegra L,Giom It Mal Tor 2006

Theophylline is a xanthine derivative used in the treatment
of asthma and stable COPD to relax the bronchial smooth
muscle.
It has a narrow therapeutic index; a serum theophylline
concentration of 10–20mg/L is required in the majority
of patients, although some may find lower theophylline
levels to be sufficient to control their symptoms.

Small increases in serum concentrations of theophylline
can result in toxicity, particularly in patients with a level
of more than 20mg/L.
Patients may experience serious symptoms of toxicity,such
as convulsions and arrhythmias, before symptoms like
nausea and vomiting appear.

Theophylline metabolism
The drug is metabolised in the liver by cytochrome P450
isoenzymes, principally CYP1A2, to demethylated and
hydroxylated products.
Many drugs interact with theophylline by inhibiting or
potentiating its metabolism by CYP1A2.
Induction of CYP1A2 results in a more rapid clearance of
theophylline, which leads to reduced, and most likely sub-
therapeutic, serum theophylline concentrations.

Factors effecting theophylline elimination
Decreased elimination
(theophylline level increased)
Increased elimination
(theophylline level decreased)
Erythromycin
Cimetidine
Allopurinol
Oral contraceptive
Ciprofloxacine
Propranolol
Old age
Cardiac failure
Liver disease
Viral infection
Fever
Tobacco or marijuana smoking
Rifampicin
Phenobarbitone
Carbamazepine
Phenytoin
Youth

183
Common Drug-Drug Interactions with Theophylline

Smokers taking theophylline generally tend to require
higher doses than non-smokers as tobacco smoke contains
polycyclic hydrocarbons, which induce CYP1A2.
Smoking cessation will therefore result in an increase in
serum theophylline concentrations, and possibly toxicity,
if the dose is not reduced.

Can someone start nicotine replacement therapy
while taking theophylline to manage COPD?
Because it is the polycyclic hydrocarbons in tobacco
smoke — not the nicotine — that increase theophylline
clearance, NRT will not affect theophylline concentrations
and it can be prescribed .

Bupropion or varenicline can also be prescribed to help
stop smoking. However, bupropion has a small dose-
related risk of seizures.
The manufacturers of bupropion state that the
concurrent use of theophylline might lower the
convulsive threshold, further increasing patients’ risk of
seizures, recommend a maximum bupropion dose of
150mg daily

Treatment Options for adult Patients
Not Controlled on low dose Inhaled Steroids
Patients not controlled on Low dose ICS
Increase the
dose of inhaled
steroid
Add leukotriene
receptor
antagonists
Add long-acting
beta2-agonists
Add
theophylline

GINA 2015 – changes to Steps 4 and 5

GINA 2015 – changes to Steps 4 and 5
© Global Initiative for AsthmaGINA 2015, Box 3-5, Steps 4 and 5
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of
exacerbations; it is not indicated in children <18 years.
Other
controller
options
RELIEVER
STEP 1 STEP 2
STEP 3
STEP 4
STEP 5
Low dose ICS
Consider low
dose ICS
Leukotriene receptor antagonists (LTRA)
Low dose theophylline*
Med/high dose ICS
Low dose ICS+LTRA
(or + theoph*)
As-needed short-acting beta2-agonist (SABA)
Low dose
ICS/LABA*
Med/high
ICS/LABA
Refer for
add-on
treatment
e.g.
anti-IgE
PREFERRED
CONTROLLER
CHOICE
Add tiotropium#
High dose ICS
+ LTRA
(or + theoph*)
Add
tiotropium#
Add low
dose OCS
As-needed SABA or
low dose ICS/formoterol**

FOR INTERNAL USE ONLY. STRICTLY CONFIDENTIAL.
DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY.
What is the Respimat® Soft Mist™ Inhaler?
 The Respimat® Soft Mist™ Inhaler is a highly
efficient and effective inhaler developed by
Boehringer Ingelheim1,2
 It delivers a metered dosage of medication by
mechanical energy, without the use of propellants2,3
 The Respimat® Soft Mist™ Inhaler delivers
medication in a slow-moving fine mist and is
designed to overcome problems such as2,3
 Limited drug deposition in the lung
 Reliance on adequate patient coordination
for effective inhalation
 Use once daily in two consecutive puffs
(2.5 mcg per puff)1
209

DO NOT COPY, DETAIL OR DISTRIBUTE EXTERNALLY
Respimat® unique mist
• The Respimat® unique mist has all the properties needed for deep lung deposition
Aerosol velocity: the unique mist is slow-moving, allowing it to
follow the natural curve of the throat, resulting in lower deposition
in mouth and throat1
Aerosol duration: the unique mist cloud is long-lasting (1.5 s).
Patients have enough time to breathe in the medication1
Highly respirable, fine droplets: up to 77% of the droplets are in
the fine particle fraction, helping patients get the medication deep
into the lungs2
Respimat® generates a unique mist leading to deep lung deposition
Features and benefits
1. Hochrainer 2005.
2. Ziegler 2005.

The Respimat® Soft Mist™ Inhaler delivers a higher
percentage dose than pMDIs
SLOW INHALATION
FINE
PARTICLES
1–5 µm
Whole lung deposition was higher with Respimat® Soft Mist™ Inhaler than
with pMDI in trained patients (53% of delivered vs. 21% of metered dose)
212
TOTAL LUNG DEPOSITION

Pathogenesis of severe allergic asthma and
the therapeutic use of anti- immunoglobulin E
antibody

FcRI
Allergen
C3
Allergens and mast cells
Binding site
IgE
Mast cell

IgE Binds to Mast Cells at the High Affinity Receptor
(FcRI)
IgE molecule
bound to mast cell
Mast cell
FcRI receptor
IgE molecule
FcRI binding site

Omalizumab
IgE
Omalizumab (Xolair) binds to the region of IgE that
interact with IgE receptors
C3
region

Omalizumab Blocks IgE Binding to Mast Cells
Mast cell
IgE molecule
FcRI receptor
Omalizumab Omalizumab

Mechanism of Action of Omalizumab (XOLAIR)

Baseline IgE
(IU/mL)
Body Weight (Kg)
> 20 - 25> 25 - 30 > 30 - 40 > 40 - 50 > 50 - 60 > 60 - 70 > 70 - 80 > 80 -90 > 90 - 125 > 125 - 150 > 150 - 200
≥30 -100 75 75 75 150 150 150 150 150 300 300 225
> 100 - 200 150 150 150 300 300 300 300 300 225 300 375
> 200 - 300 150 150 225 300 300 225 225 225 300 375 525
> 300 - 400 225 225 300 225 225 225 300 300 450 525
> 400 - 500 225 300 225 225 300 300 375 375 525 600
> 500 - 600 300 300 225 300 300 375 450 450 600
> 600 - 700 300 225 225 300 375 450 450 525
> 700 - 800 225 225 300 375 450 450 525 600
> 800 - 900 225 225 300 375 450 525 600
> 900 - 1000 225 300 375 450 525 600
> 1000 - 1100 225 300 375 450 600
> 1100 - 1200 300 300 450 525 600
> 1200 - 1300 300 375 450 525
> 1300 - 1500 300 375 525 600
Omalizumab Dose is calculated
according to the below Table:
Dose (mg) to be administered every 4 weeks
Dose (mg) to be administered every 2 weeks
Omalizumab core data sheet

24
3

Criteria for Indication
Severe asthma?
Patient > 6 years?
Multiple severe exacerbations?
Frequent daytime and nighttime symptoms?
Weight 20–150 Kg and total IgE 30-1300 IU/ml?
FEV1 % predicted < 80%?
Positive prick test or serum specific IgE?
OMALIZUMAB
NO
NO
NO
NO
NO
NO
NO
NO
NOT INDICATED
Not controlled with ICS + LABA?
YES
YES
YES
YES
YES
YES
YES
YES

248
Stepwise Approach for Managing Asthma
Short-acting Beta2-agonists
Low-dose Inhaled Corticosteroids
(ICS)
Low-dose ICS +
Long-acting Beta2-agonists (LABA)
or Medium-dose ICS
Medium-dose ICS + LABA
High-dose ICS + LABA
and Consider Omalizumab
High-dose ICS + LABA +
Oral Corticosteroids
and Consider Omalizumab
1
2
3
4
5
6
Adapted from National Asthma Education and Prevention Program (NAEPP) Guidelines. Expert Panel Report 3: Guidelines for the Diagnosis and Management of
Asthma. National Heart, Lung, and Blood Institute, NIH Publication No. 07-4051, Revised August 2007.

Children’s Healthcare of Atlanta© Global Initiative for AsthmaGINA 2015, Box 3-5, Steps 4 and 5
*For children 6-11 years, theophylline is not recommended, and preferred Step 3 is medium dose ICS
**For patients prescribed BDP/formoterol or BUD/formoterol maintenance and reliever therapy
# Tiotropium by soft-mist inhaler is indicated as add-on treatment for patients with a history of exacerbations; it is not
indicated in children <18 years.
Other
controller
options
RELIEVER
STEP 1 STEP 2
STEP 3
STEP 4
STEP 5
Low dose ICS
Consider low
dose ICS
Med/high dose ICS
Low dose ICS+LTRA
(or + theoph*)
Low dose
ICS/LABA*
Med/high
ICS/LABA
Refer for
add-on
treatment
e.g.
anti-IgE
PREFERRED
CONTROLLER
CHOICE
Add tiotropium#
High dose ICS
+ LTRA
(or + theoph*)
Add
tiotropium#
Add low
dose OCS
As-needed SABA or
low dose ICS/formoterol**
Step 5 – higher level care and/or add-on treatment

Step 5 – higher level care and/or add-on
treatment
GINA 2016, Box 3-5, Step 5 (8/8)
Other
controller
options
RELIEVER
STEP 1 STEP 2
STEP 3
STEP 4
STEP 5
Low dose ICS
Consider low
dose ICS
Med/high dose ICS
Low dose ICS+LTRA
(or + theoph*)
Low dose
ICS/LABA**
Med/high
ICS/LABA
PREFERRED
CONTROLLER
CHOICE
*Not for children <12 years
**For children 6-11 years, the preferred Step 3 treatment is medium dose ICS
#For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy
 Tiotropium by mist inhaler is an add-on treatment for patients ≥12 years with a history of exacerbations
Refer for
add-on
treatment
e.g.
tiotropium,*
omalizumab,
mepolizumab*
As-needed SABA or
low dose ICS/formoterol#
Add tiotropium*
High dose ICS
+ LTRA
(or + theoph*)
Add low
dose OCS
GINA 2016

 Preferred option is referral for specialist investigation and consideration
of add-on treatment
 If symptoms uncontrolled or exacerbations persist despite Step 4
treatment, check inhaler technique and adherence before referring
 Add-on tiotropium for patients ≥12 years with history of exacerbations
 Add-on omalizumab (anti-IgE) for patients with severe allergic asthma
 Add-on mepolizumab (anti-IL5) for severe eosinophilic asthma (≥12
yrs)
 Other add-on treatment options at Step 5 include:
 Sputum-guided treatment: this is available in specialized centers;
reduces exacerbations and/or corticosteroid dose
 Add-on low dose oral corticosteroids (≤7.5mg/day prednisone
equivalent): this may benefit some patients, but has significant systemic
side-effects. Assess and monitor for osteoporosis
 See ERS/ATS Severe Asthma Guidelines (Chung et al, ERJ 2014) for
more detail
GINA 2016
treatment

treatment
GINA 2017, Box 3-5, Step 5 (8/8)
Other
controller
options
RELIEVER
STEP 1 STEP 2
STEP 3
STEP 4
STEP 5
Low dose ICS
Consider low
dose ICS
Med/high dose ICS
Low dose ICS+LTRA
(or + theoph*)
Low dose
ICS/LABA**
Med/high
ICS/LABA
PREFERRED
CONTROLLER
CHOICE
UPDATED
2017
*Not for children <12 years
**For children 6-11 years, the preferred Step 3 treatment is medium dose ICS
#For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy
 Tiotropium by mist inhaler is an add-on treatment for patients ≥12 years with a history of exacerbations
Refer for
add-on
treatment
e.g.
tiotropium,*
anti-IgE,
anti-IL5*
As-needed SABA or
low dose ICS/formoterol#
Add tiotropium*
High dose ICS
+ LTRA
(or + theoph*)
Add low
dose OCS
GINA 2017

 Preferred option is referral for specialist investigation and consideration of
add-on treatment
 If symptoms uncontrolled or exacerbations persist despite Step 4 treatment,
check inhaler technique and adherence before referring
 Add-on tiotropium for patients ≥12 years with history of exacerbations
 Add-on omalizumab (anti-IgE) for patients with severe allergic asthma
 Add-on anti-IL5 (mepolizumab (SC) or reslizumab (IV)) for severe
eosinophilic asthma (≥12 yrs)
 Other add-on treatment options at Step 5 include:
 Sputum-guided treatment: this is available in specialized centers; reduces
exacerbations and/or corticosteroid dose
 Add-on low dose oral corticosteroids (≤7.5mg/day prednisone equivalent):
this may benefit some patients, but has significant systemic side-effects.
Assess and monitor for osteoporosis
 See ERS/ATS Severe Asthma Guidelines (Chung et al, ERJ 2014) for more
detail
GINA 2017
treatment

GINA 2018

© Global Initiative for AsthmaGINA 2017
Treatment Steps – changes in 2018
 Step 1
 It is explained that the reason ICS should be considered for patients with mild
asthma (rather than prescribing SABA alone) is to reduce their risk of serious
exacerbations (Pauwels, Lancet 2003; O’Byrne AJRCCM 2001; Reddel Lancet 2017)
 Steps 3-4
 From the large FDA LABA safety studies: adding LABA to ICS in a combination
inhaler reduces risk of exacerbations and improves symptoms and lung
function, compared with the same dose of ICS alone, but with only a small
reduction in reliever use (Stempel NEJM 2016, Peters NEJM 2016)
 Step 5 : management of severe asthma
 Subcutaneous benralizumab (monoclonal anti-IL5 receptor α
antibody) is another add-on treatment for patients aged ≥12 years
with severe eosinophilic asthma

Asthma Medications in Clinical Practice - Part 2

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Asthma Medications in Clinical Practice - Part 2