Asthma & COPD with LABA/ICS
Dr. Syed Munis Ul Hasan (Medical Advisor)
Learning objectives
q Basic anatomy & physiology of Respiratory system
q Disease overview of Asthma & COPD
1. Epidemiology
2. Etiology & Risk factors
3. Pathophysiology
4. Signs & Symptoms
5. Diagnosis
q Treatment Guidelines of Asthma (GINA) and COPD (GOLD)
q Product overview of Formoterol/Budesonide, Salmeterol/Fluticasone and Tiotropium
1. Pharmacokinetics and pharmacodynamics
2. Clinical indications
3. Product positioning
ICS- LABA Treatment Options Available in
Pakistan
Budesonide +
Formoterol
Baclomethasone
+Formoterol
Salmeterol
+Fluticasone
• Fortide (MDI)
• Formiget (DPI)
• Venticort (DPI)
• Combivir (DPI)
• Foster (MDI,DPI)
• Xaltide (MDI)
• Saltra (MDI)
• Salmicort (MDI)
• Seretide (MDI, DPI)
Long-acting beta agonists (LABAs)
q These bronchodilator (brong-koh-DIE-lay-tur) medications open airways and reduce
swelling for at least 12 hours. They're used on a regular schedule to control moderate to
severe asthma and to prevent nighttime symptoms. Although they're effective, they've
been linked to severe asthma attacks. For this reason, LABAs are taken only in
combination with an inhaled corticosteroid.
q Examples of LABAs include:
q
Salmeterol
q
Formoterol
Salmeterol/Fluticasone Mode of Action
q Salmeterol provides symptomatic relief while fluticasone propionate improves lung
function and prevents exacerbations of the condition
Salmeterol
q Salmeterol is a selective
long-acting (12 hour)
beta-2-adrenoceptor
agonist.
q It inhibits the early and
late phase response to
inhaled allergen.
Fluticasone propionate
• Fluticasone propionate
given by inhalation at
recommended doses has a
potent glucocorticoid antiinflammatory action within
the lungs, resulting in
reduced symptoms and
exacerbations of asthma
Structure & Function Relationship
Salbutamol
Formoterol
Salmeterol
Hydrophilic
Moderate lipophilic
Highly lipophilic
Onset of Action
Fast
Fast
Delayed
Duration of Action
Short
Long
Long
Receptor Affinity
Partial Agonist
Full agonist
Partial Agonist
Lipophilicity
Pharmacokinetics
B2 Agonists
Onset of Action
Duration of Action
Salbutamol
2 mins
4 – 6 hours
Salmeterol
30 mins
Formoterol
1-3 mins
More than 12 hrs
More than 12 hrs
Salmeterol/Fluticasone Dosage
Asthma:
Adults and adolescents 12 years and older:
q Two inhalations of 25mcg salmeterol and 125mcgFluticasone propionate twice daily.
OR
q Two inhalations of 25mcg salmeterol and 250mcgFluticasone propionate twice daily.
Chronic Obstructive Pulmonary Disease (COPD):
For adult patients the recommended dose is:
q Two inhalation 25mcg + 125mcg to 25mcg + 250mcg (Salmeterol + Fluticasone)
Salmeterol/Fluticasone Clinical evidence
Asthma:
q Clinical studies in patients 12 years of age and older showed that the combination
product (Salmeterol/Fluticasone) was significantly more effective than placebo or
salmeterol alone in all primary efficacy comparisons. It was significantly more effective
than fluticasone propionate alone in almost all the primary efficacy comparisons (p <
0.001)
q In randomized, double-blind, placebo-controlled trials involving 700 patients aged 12
years and over, treatment with 100/50 mcg or 250/50 mcg fluticasone
propionate/salmeterol produced clinically significant improvements in quality of life as
assessed by the Asthma Quality of Life Questionnaire (AQLQ)
Salmeterol/Fluticasone Clinical evidence
COPD:
q A long term (52 week) clinical study in 1465 COPD patients evaluated the safety and
efficacy of Salmeterol/Fluticasone 500/50 (fluticasone propionate/salmeterol xinafoate)
vs placebo and the individual components fluticasone propionate 500 mcg and
salmeterol 50 mcg), all taken twice daily via the DISKUS inhalation device
q The primary measure of efficacy was pre-bronchodilator FEV1. Pre-bronchodilator FEV1
in the Salmeterol/Fluticasone combination 500/50 group was 133mL higher than the
placebo group (p < 0.001), 73mL higher than the salmeterol 50 mcg group (p < 0.001)
and 95 mL higher than the fluticasone 500 mcg group (p < 0.001) throughout the
treatment period
What is the difference between DPI
& MDI?
MDI Vs DPI
Metered dose inhaler
Small and convenient to carry.
Doesn't require a deep, fast
inhaled breath.
Accidently breathing out a little
isn't a problem.
Humidity doesn't affect
medication.
High inspiratory flow rate is not
needed
Easy to use
Suitable for Elderly and children
Does not result in high
pharyngeal deposition
Not susceptible to
contamination
Device is more long lasting
Comparative studies on Metered dose inhalers and Dry powder inhalers | Use Inhalers (use-inhalers.com)
Dry powder inhaler
Multiple devices to be carried
Requires a deep, fast inhaled breath.
Accidently breathing out a little can
blow away the medication.
High humidity can cause medication
to clump.
Higher inspiratory flow rate needed
Complex device for using
Not suitable for children
May result in high pharyngeal
deposition
More susceptible to contamination
due to design and drug delivery
Device might not be long lasting
Mechanism Of Action
Mechanism Of Action
•
Tiotropium competitively & reversibly binds to M3
receptors, antagonizing the cholinergic
(Bronchoconstrictive) effects of acetylcholine,
resulting in bronchial relaxation.
•
In the airways, it exhibits pharmacological effects
through inhibition of M3-receptors at the smooth
muscle leading to bronchodilation. The effect was
dose dependent and lasted longer than 24h. The long
duration is probably due to the very slow
dissociation from the M3 receptor. The
bronchodilation following inhalation of tiotropium is
predominantly a site-specific effect.
Pharmacokinetics
q Maximum tiotropium plasma concentrations were observed 5-7 minutes
after inhalation.
q Tiotropium has a plasma protein binding of 72%
q The effective half-life of tiotropium ranges between 27-45 h in COPD
patients
q After dry powder inhalation by COPD patients to steady-state,
urinary excretion is 7% (1.3μg) of the unchanged drug over 24 hours,
the remainder being mainly non-absorbed drug in gut that is
eliminated via the feces
Indications
q Tioget (Tiotropium) is indicated for the
long-term, once-daily, maintenance
treatment of bronchospasm associated
with chronic obstructive pulmonary
disease (COPD), including chronic
bronchitis and emphysema. Tioget
(Tiotropium) is indicated to reduce
exacerbations in COPD patients
q Not recommended for acute relief of
COPD symptoms
Dosage
q The recommended dose is inhalation of the powder contents of one Tioget (Tiotropium) Dry
Powder Inhaler Capsule (18mcg), once-daily, with the Respomatic (DPI device) at the same time of
the day. Do not take more than one dose in 24 hours.
q Special Population: No dosage adjustment is required for geriatric, hepatically-impaired, or
renally-impaired patients. However, patients with moderate to severe renal impairment given
Tioget (Tiotropium) Dry Powder Inhaler Capsules should be monitored closely for anticholinergic
effects
Why use Tioget
Why use Tioget
Why use Tioget
Why use Tioget
Improvement in Asthma
Exacerbation Risk Reduction
Thank You
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