foracort

Esproute | 1st July 2021

Science Behind the mega brand

Science
behind
Mega brand
(Asthma)
Which are the treatment options?

LABA ICS
Salmeterol + Fluticasone Seroflo
Lets understand
Formoterol + Budesonide foracort Why?

Formoterol + Fluticasone Maxiflo

Formoterol + Beclomethasone Fullform
 Changing concepts in OAD management
Evolution of Budesonide-Formoterol
NOVEL
FACET STAY SYGMA 1, 2 GINA PRACTICAL
Foracort Foracort Foracort Foracort
Maintenance SMART One stop solution As reliver medication
Therapy + SOS SABA Therapy for all severities for all
Budesonide+
Combined use of Formoterol anti-
ICS and LABA Budesonide+ inflammatory Reliever
Formoterol in mild asthma
Widespread ICS Budesonide+Formoterol For
use of short-
acting b2-
Maintenance and Relief
agonists
Maintenance
Budesonide + formoterol GOLD
PATHOS recommendation
Inflammation

Bronchospasm Budesonide + Formoterol in COPD

70s 80s 90s

 Foracort the most
preferred ICS LABA
1 2 4
Combination of the
Established Evidence available
most potent LABA
combination since with >12 landmark
and the safest
~20 years trials
steroid

3 5 Preferred 6
SMART (Single
controller + reliver
inhaler for Anti- inflammatory
across all asthma
maintenance & reliver
severities : GINA
relief) concept
2020

7 Safe to be used 8 Recommended in

9 4 SKUS in pMDI,
even in children COPD: DPI and BAI,
over 6 years/ Respules with
pregnancy/comorbi One stop solution for devices – for patient
d contions OAD convenience
How is Formoterol + Budesonide is different ?

foracort

LABA ICS

Formoterol + Budesonide
2

What makes formoterol unique?

Parameter Formoterol Salmeterol
Potency Very potent Potent

Onset of action Rapid (within 3 min) Delayed (~15 min)

Peak bronchodilation 30 min 1-2 hours

Duration of action >15 hrs >12 hrs

Daily dose (mcg) 12-24 50-100

Pulmonary Pharmacology & Therapeutics (2002) 15, 463±466

2

What makes formoterol unique?

Form/Bude Sal/Flu
Peak
Broncho
dilation

Time
30 mins
1-2 Hrs

Pulmonary Pharmacology & Therapeutics (2002) 15, 463±466

2

What makes formoterol unique?

Form/Bude Sal/Flu
Duration of
action

12 hrs
Time
>15 hrs

Pulmonary Pharmacology & Therapeutics (2002) 15, 463±466

2
How is Formoterol + Budesonide is different ?

foracort

LABA ICS

Formoterol + Budesonide
2
What makes budesonide unique?
• Safest ICS :
• Administration up to 13 years shows no significant effect on growth in children
• Pregnancy Category B drug- safe to given in Pregnancy

• Potent steroid

• Unique esterification in the airway provides prolonged action

• Budesonide shows dose response relationship

Maximum Formoterol Budesonide

Allowed dose 72 mcg 1600-2400 mcg
 Combination of the most potent LABA
2 and the safest steroid

foracort

LABA ICS

Formoterol + Budesonide
Most potent LABA with Safest ICS with dose
Rapid action: in 3 min response relation
3
What is asthma treatment plan?

Why !!!

Controller Reliever
(as and when required)
ICS (Inflammation) +
LABA (Bronchodilation)
3 Patients often do not
understand the
differences between their Why
maintenance and
reliever medication and complicate?
the importance of regular
ICS
 SMART

Controller medication Reliever medication

 How do we simplify?

foracort

3 SMART
LABA ICS

SIT: Single Maintenance

Formoterol & Reliever Therapy
+ Budesonide
Most potent LABA with Safest ICS with dose
Rapid action: in 3 min response relation
4 Key
landmark
trials
12
 Budesonide + Formoterol As
FACET STUDY Maintenance Therapy
For the Formoterol and
Corticosteroid Establishing Therapy

Aim: To evaluate the effects of

adding inhaled formoterol to
both lower and higher doses of
the inhaled glucocorticoid -
budesonide

Study Groups
• Budesonide 100 µg b.i.d. + Placebo Significant reduction in severe exacerbations when
• Budesonide 100 µg b.i.d. + the combination of long-acting beta2-agonist and
Formoterol 9 µg b.i.d
• Budesonide 400 µg b.i.d. + Placebo
an inhaled corticosteroid has been used as regular
• Budesonide 400 µg b.i.d. + therapy
Formoterol 9 µg b.i.d.

N Engl J Med 1997; 337: 1405-11

 Budesonide + Formoterol Single Inhaler
STAY STUDY For Both Maintenance And Relief
N=2,760 pats. with asthma aged 12-80 yrs

Aim: Low dose regular ICS +

LABA for maintenance and
relief, thus introducing steroid in
immediate phase of asthma
worsening

Study Groups Bud/Form SMART can be used: to reduce the incidence of

• BUD (400 mcg bid) + SABA (N= 926)
• BUD/FORM (100/6 mcg bid) + SABA (
N = 909)
• BUD/FORM (100/6 mcg bid) SMART
(N=925)
first and repeated severe exacerbations instead of high
maintenance dose of budesonide
Beneficial in patients who do not adhere fully to ICS and
instead over-rely on SABAs as reliever medication
Am J Respir Crit Care Med 2005; 171:129-136
5 GINA 2020
Recommends

Formoterol + Budesonide
in Mild Asthma and As an
Anti-Inflammatory Reliever
 ICS-formoterol is the
preferred reliever for
patients prescribed
maintenance and reliever
therapy. For other
ICS-LABAs, the reliever
is SABA

GINA 2020, Box 3-5A © Global Initiative for Asthma, www.ginasthma.org

 5

FORACORT
400,
FORACORT FORACORT
200, 400, FORTE +
FORACORT add on
FORACORT FORACORT
FORACORT 100, 200* 100, 200
100, 200* FORTE treatment

AEROCORT AEROCORT

FORACORT 200*
LEVOLIN, ASTHALIN

*Formoterol-budesonide 200/6 approved for use as an anti-inflammatory reliever in 27 countries

**SMART Therapy is only indicated for FORACORT 100 & 200 strengths
Disclaimer: The recommendation for the use of formoterol-budesonide differ by region, hence, country specific regulations should be taken into consideration before
prescribing formoterol-budesonide. The data used in this scientific symposium should not be regarded as a direct recommendation for the use of medicine.
 GINA 2020: Quick Summary!
Low dose ICS containing treatment in step 1 and 2

As-needed low dose ICS/Formoterol is the preferred reliever option

if the patient is taking ICS/Formoterol as the controller as well.

Theophylline is no longer recommended for the management of

asthma at any step.

For stepping down the treatment, if asthma is well controlled, the

treatment can be stepped down to low dose ICS/Formoterol.

Under no circumstance must ICS be completely stopped in an

asthmatic patient.
 Budesonide + Formoterol in
SYGMA 1 STUDY Mild Asthma

N=3849 patients.

Aim: to show that budesonide–

formoterol used as needed was
superior to terbutaline used as
needed in terms of asthma
symptom control, measured
according to the weeks with
well controlled asthma

Study Group
• Placebo (bid)+ terbutaline (0.5 mg)
as needed
• Placebo (bid)+(200 μg of
budesonide+ 6 μg of formoterol)l as
needed budesonide–formoterol treatment group resulted in 64%
• 200 μg budesonide (bid)+ reduction in the rate of severe exacerbation
terbutaline used as needed
N Engl J Med 2018;378:1865-1876

The odds of having a well controlled week
were 14% higher in the bud/form group
than the terbutaline group
The budesonide–formoterol treatment
group was as effective as the budesonide
maintenance group in reducing
exacerbation risk with less than 1/5th of the
dose of inhaled glucocorticoid.
N Engl J Med 2018;378:1865-1876
 Budesonide + Formoterol as
PRACTICAL STUDY anti-inflammatory reliever
Real world study

Aim: To compare ICS-

Formoterol reliever therapy with
maintenance ICS + SABA
reliever therapy in adults with
mild to moderate asthma in a
real world setting
In BUD-F group, 31% reduction in severe exacerbation risk was
achieved despite participants using about 60% of the dose of
budesonide and with no difference in symptom control
Study Group
between the groups
• 1. Budesonide+ Formoterol
(200/6mcg), one inhalation SOS
(n=437)
• Budesonide (200mcg) maintenance The rate of severe exacerbation was lower with as
one inhalation BID + terbutaline needed BUD-F than BUD maintenance + SABA
250mcg , 2 inhalations SOS (n-448)

http://dx.doi.org/10.1016/S0140-6736(19)31948-8
 SAFETY OF
FORMOTEROL +BUDESONIDE
 Cardiac Safety: Formoterol

• Although the heart has both β1 and β2 adrenoceptors, the

predominant receptor type in the heart is β1.

• Formoterol is a highly selective β2-agonist combining the clinical

advantage of rapid bronchodilation with a long duration of action.

• Therefore, Formoterol predominantly binds with the beta 2 receptors.

Cardiac safety of formoterol 12 mcg twice daily in patients with chronic obstructive #5
pulmonary disease
Sammy C. Campbella,, Gerard J. Crinerb, Bernard E. Levine
204 patients randomized to receive formoterol 12 mcg dry powder inhalation or matching placebo twice daily for 8 weeks.
24hrs continuous electrocardiography (Holter monitoring) was performed at screening and after 2 and 8 weeks of treatment.

2-h postdose FEV1 least-squares mean measurements over time by treatment group .
Randomized,
Baseline (n = 96) End (n = 92) Baseline (n =107) End (n = 106) multicentre,
Formoterol Formoterol Placebo Placebo double-blind,
placebo-
12mcg bid 12mcg bid controlled,
parallel-group
Maximimum 124±14.7 123+13.6 126+16.4 123+14.8 study.
heart rate (bpm)
Mean±𝑆𝐷
Male/ female,
Mean heart 81+9.0 80+8.6 81+10.3 80+10.6 >40 years of
rate(bpm) age.
History of
Mean±𝑆𝐷 smoking: 4-10
pack-years.
Mean ventricular 0.01±0.048 0.02±0.082 0.05±0.354 0.05±0.479
tachycardia
events/h Pre-bronchodilator
Mean±𝑆𝐷 FEV1<70% of
predicted normal value
FEV1/FVC ratio <70%.

Pulmonary Pharmacology & Therapeutics 20 (2007) 571–579

Result:
▪ The data showed no clinically meaningful increase in cardiac
rhythm events for patients treated with formoterol compared with
matching placebo.
▪ Vital signs and ECG data, including QTc interval, were similar for
active and placebo groups. The pattern of reported adverse events
was consistent with the expected profile for COPD patients.
▪ Treatment group comparisons showed that 2-h postdose FEV1 was
statistically significantly improved in the formoterol group compared
with the placebo group at all visits during the treatment period
 Based on 25 years of experience with different doses and in different populations, inhaled budesonide therapy only
in very rare cases appears to be associated with an increased risk of adrenal crisis, reduction in final height, increases
in the number of fractures or complications during pregnancy

17 epidemiological studies 4 studies showed there was

investigating the risk of
fractures were found. No
risk of increased fractures
has been shown in control
led trials of inhaled
budesonide
no increased risk for
congenital malformations,
cardiovascular defects,
decreased gestational age,
birth weight or birth length
among infants born to
women using inhaled
budesonide during
pregnancy compared with
the general population
4 studies assessed final
height were reported.
None of them showed any
reduced final height in
patients receiving inhaled
budesonide during
childhood or
adolescence.

Drug Safety 2008; 31 (11)

 PRECISE Study: Prescribing Patterns for the Combination of ICS/LABA for
Obstructive Airways Disease in India (responses form 349 doctors from across India)
CS/LABA is the most prescribed regimen for both Asthma Formoterol/Budesonide is the most widely prescribed
& COPD. ICS/LABA, with more doctors preferring it for Asthma.

Improvement in patient symptoms was cited the most important characteristic in determining the choice of
ICS/LABA followed by improvement in lung function, positive feedback from patients and safety &
tolerability of the ICS/LABA.

Presented at NAPCON 2019, Kochi

Summary of key trials
 Foracort the most
preferred ICS LABA
1 2 4
Combination of the
Established Evidence available
most potent LABA
combination since with >12 landmark
and the safest
~19 years trials
steroid

3 5 Preferred 6
SMART (Single
controller + reliver
inhaler for Anti- inflammatory
across all asthma
maintenance & reliver
severities : GINA
relief) concept
2020

7 Safe to be used 8 Recommended in

9 4 SKUS in pMDI,
even in children COPD: DPI and BAI,
over 6 years/ Respules with
pregnancy/comorbi One stop solution for devices – for patient
d contions OAD convenience
 KOL Dr. Sujeet Rajan,
Why Foracort will always be first choice of treatment amongst all
ICS LABA
foracort
hai toh mumkin hai