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Details

Stereochemistry ABSOLUTE
Molecular Formula C24H28N2O3.C4H4O4
Molecular Weight 508.5629
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of INDACATEROL FUMARATE

SMILES

OC(=O)\C=C\C(O)=O.CCC1=CC2=C(CC(C2)NC[C@H](O)C3=CC=C(O)C4=C3C=CC(=O)N4)C=C1CC

InChI

InChIKey=IREJFXIHXRZFER-XRQUGHPZSA-N
InChI=1S/C24H28N2O3.C4H4O4/c1-3-14-9-16-11-18(12-17(16)10-15(14)4-2)25-13-22(28)19-5-7-21(27)24-20(19)6-8-23(29)26-24;5-3(6)1-2-4(7)8/h5-10,18,22,25,27-28H,3-4,11-13H2,1-2H3,(H,26,29);1-2H,(H,5,6)(H,7,8)/b;2-1+/t22-;/m0./s1

HIDE SMILES / InChI

Molecular Formula C24H28N2O3
Molecular Weight 392.4907
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Molecular Formula C4H4O4
Molecular Weight 116.0722
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Indacaterol is an ultra-long-acting beta-adrenoceptor agonist developed by Novartis. It was approved by the European Medicines Agency (EMA) under the trade name Onbrez Breezhaler on November 30, 2009, and by the United States Food and Drug Administration (FDA), under the trade name Arcapta Neohaler, on July 1, 2011. It needs to be taken only once a day, unlike the related drugs formoterol and salmeterol. It is licensed only for the treatment of chronic obstructive pulmonary disease (COPD) (long-term data in patients with asthma are thus far lacking). It is delivered as an aerosol formulation through a dry powder inhaler.

Originator

Curator's Comment: # Novartis

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
76.0 nM [Ki]
91.4 nM [Ki]
76.0 nM [Ki]
91.4 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ARCAPTA NEOHALER

Approved Use

UTIBRONTM NEOHALER® is a combination of indacaterol and glycopyrrolate indicated for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Important Limitations of Use: UTIBRON NEOHALER is NOT indicated for the relief of acute bronchospasm or for the treatment of asthma [see Warnings and Precautions (5.1, 5.2)

Launch Date

1.30947835E12
Primary
ARCAPTA

Approved Use

INDICATIONS AND USAGE. ARCAPTA NEOHALER is a long-acting beta2-adrenergic agonist indicated for: The long term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. Important limitations: ARCAPTA NEOHALER is NOT indicated to treat acute deteriorations of chronic obstructive pulmonary disease. ARCAPTA NEOHALER is NOT indicated for asthma.

Launch Date

1.29427204E12
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
528 pg/mL
110 μg 1 times / day steady-state, respiratory
dose: 110 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered: GLYCOPYRROLATE
INDACATEROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
339 pg/mL
110 μg single, respiratory
dose: 110 μg
route of administration: Respiratory
experiment type: SINGLE
co-administered: GLYCOPYRROLATE
INDACATEROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
0.206 ng/mL
150 μg single, respiratory
dose: 150 μg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.518 ng/mL
300 μg single, respiratory
dose: 300 μg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.299 ng/mL
150 μg 1 times / day steady-state, respiratory
dose: 150 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
0.697 ng/mL
300 μg 1 times / day steady-state, respiratory
dose: 300 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2750 pg × h/mL
110 μg 1 times / day steady-state, respiratory
dose: 110 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered: GLYCOPYRROLATE
INDACATEROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
907 pg × h/mL
110 μg single, respiratory
dose: 110 μg
route of administration: Respiratory
experiment type: SINGLE
co-administered: GLYCOPYRROLATE
INDACATEROL plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: UNKNOWN
0.974 ng × h/mL
150 μg single, respiratory
dose: 150 μg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.43 ng × h/mL
300 μg single, respiratory
dose: 300 μg
route of administration: Respiratory
experiment type: SINGLE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
2.51 ng × h/mL
150 μg 1 times / day steady-state, respiratory
dose: 150 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
6.52 ng × h/mL
300 μg 1 times / day steady-state, respiratory
dose: 300 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
116 h
150 μg 1 times / day steady-state, respiratory
dose: 150 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
118 h
300 μg 1 times / day steady-state, respiratory
dose: 300 μg
route of administration: Respiratory
experiment type: STEADY-STATE
co-administered:
INDACATEROL serum
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
800 ug 1 times / day multiple, respiratory
Highest studied dose
Dose: 800 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 800 ug, 1 times / day
Sources:
unhealthy, 43.5 years (range: 12.0–64.0 years)
n = 59
Health Status: unhealthy
Condition: COPD
Age Group: 43.5 years (range: 12.0–64.0 years)
Sex: M+F
Population Size: 59
Sources:
Disc. AE: Dyspnea, Wheezing...
AEs leading to
discontinuation/dose reduction:
Dyspnea (serious, 1 patient)
Wheezing (serious, 1 patient)
Asthma (moderate, 1 patient)
Cough (moderate, 1 patient)
Sources:
75 ug 1 times / day multiple, respiratory
Dose: 75 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 75 ug, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: asthma
Sources:
Other AEs: Adverse event...
AEs

AEs

AESignificanceDosePopulation
Asthma moderate, 1 patient
Disc. AE
800 ug 1 times / day multiple, respiratory
Highest studied dose
Dose: 800 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 800 ug, 1 times / day
Sources:
unhealthy, 43.5 years (range: 12.0–64.0 years)
n = 59
Health Status: unhealthy
Condition: COPD
Age Group: 43.5 years (range: 12.0–64.0 years)
Sex: M+F
Population Size: 59
Sources:
Cough moderate, 1 patient
Disc. AE
800 ug 1 times / day multiple, respiratory
Highest studied dose
Dose: 800 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 800 ug, 1 times / day
Sources:
unhealthy, 43.5 years (range: 12.0–64.0 years)
n = 59
Health Status: unhealthy
Condition: COPD
Age Group: 43.5 years (range: 12.0–64.0 years)
Sex: M+F
Population Size: 59
Sources:
Dyspnea serious, 1 patient
Disc. AE
800 ug 1 times / day multiple, respiratory
Highest studied dose
Dose: 800 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 800 ug, 1 times / day
Sources:
unhealthy, 43.5 years (range: 12.0–64.0 years)
n = 59
Health Status: unhealthy
Condition: COPD
Age Group: 43.5 years (range: 12.0–64.0 years)
Sex: M+F
Population Size: 59
Sources:
Wheezing serious, 1 patient
Disc. AE
800 ug 1 times / day multiple, respiratory
Highest studied dose
Dose: 800 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 800 ug, 1 times / day
Sources:
unhealthy, 43.5 years (range: 12.0–64.0 years)
n = 59
Health Status: unhealthy
Condition: COPD
Age Group: 43.5 years (range: 12.0–64.0 years)
Sex: M+F
Population Size: 59
Sources:
Adverse event grade 5
75 ug 1 times / day multiple, respiratory
Dose: 75 ug, 1 times / day
Route: respiratory
Route: multiple
Dose: 75 ug, 1 times / day
Sources:
unhealthy
Health Status: unhealthy
Condition: asthma
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
negligible
negligible
no
no
no
unlikely
unlikely
unlikely
unlikely
weak [IC50 10 uM]
weak [IC50 25 uM]
weak [IC50 25 uM]
weak [IC50 5 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
likely
low
low
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
weak
yes (co-administration study)
Comment: Co-administration of indacaterol with verapamil (P-gp inhibitor) showed 2­ fold increase in indacaterol AUC0-24, and 1.5-fold increase in indacaterol Cmax;
Page: 96.0
yes
weak (pharmacogenomic study)
Comment: Nonsignificant trends toward higher Cmax and AUC0-24 (19% and 20%, respectively) were noted in patients with the (TA)7 genotype
Page: 91.0
yes
yes (co-administration study)
Comment: Co-administration of indacaterol with erythromycin (CYP3A4 inhibitor) showed a 1.4-fold increase in indacaterol AUC0-24, and 1.2-fold increase in indacaterol Cmax; Co-administration of indacaterol with ketoconazole caused a 1.9-fold increase in indacaterol AUC0-24, and 1.3-fold increase in indacaterol Cmax; Co-administration of indacaterol with ritonavir resulted in a 1.7-fold increase in indacaterol AUC0-24 whereas indacaterol Cmax was unaffected.
Page: 91.0
Tox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Ultra long-acting beta 2-agonists in development for asthma and chronic obstructive pulmonary disease.
2005 Jul
In vitro and in vivo pharmacological characterization of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one (indacaterol), a novel inhaled beta(2) adrenoceptor agonist with a 24-h duration of action.
2006 May
Tolerability of indacaterol, a novel once-daily beta2-agonist, in patients with asthma: a randomized, placebo-controlled, 28-day safety study.
2007 Dec
Gateways to clinical trials.
2007 Dec
Efficacy and safety of single therapeutic and supratherapeutic doses of indacaterol versus salmeterol and salbutamol in patients with asthma.
2007 Dec
New approaches to managing asthma: a US perspective.
2008 Apr
Indacaterol provides sustained 24 h bronchodilation on once-daily dosing in asthma: a 7-day dose-ranging study.
2008 Jan
Pharmacological characterization of indacaterol, a novel once daily inhaled 2 adrenoceptor agonist, on small airways in human and rat precision-cut lung slices.
2008 Jan
Gateways to clinical trials.
2008 May
Gateways to clinical trials.
2009 Apr
Bronchodilator effects of indacaterol and formoterol in patients with COPD.
2009 Dec
Indacaterol, a novel inhaled, once-daily, long-acting beta2-agonist for the treatment of obstructive airways diseases.
2009 Jul
24-hour bronchodilator efficacy of single doses of indacaterol in patients with persistent asthma: comparison with placebo and formoterol.
2009 Oct
Gateways to clinical trials.
2009 Sep
[Efficacy and safety of indacaterol - new long-acting beta(2) agonist].
2010
Impact of bronchodilator therapy on exercise tolerance in COPD.
2010 Apr 7
Cardiovascular safety of QVA149, a combination of Indacaterol and NVA237, in COPD patients.
2010 Dec
Indacaterol for chronic obstructive pulmonary disease (COPD).
2010 Mar
The short, the long and the "ultra-long": why duration of bronchodilator action matters in chronic obstructive pulmonary disease.
2010 Mar
Indacaterol provides 24-hour bronchodilation in COPD: a placebo-controlled blinded comparison with tiotropium.
2010 Oct 5
Onset of action of indacaterol in patients with COPD: comparison with salbutamol and salmeterol-fluticasone.
2010 Sep 7
An investigation into the structure-activity relationships associated with the systematic modification of the β(2)-adrenoceptor agonist indacaterol.
2012 Oct 1
Patents

Sample Use Guides

The recommended dosage of Indacaterol is the once-daily inhalation of the contents of one 75 mcg Indacaterol capsule using the NEOHALER inhaler.
Route of Administration: Respiratory
In the isolated tracheal strip preparation, indacaterol, demonstrated concentration-dependent inhibition of electrically induced contraction (EC50= 45 ± 13 nM)
Substance Class Chemical
Created
by admin
on Sun Dec 18 15:28:23 UTC 2022
Edited
by admin
on Sun Dec 18 15:28:23 UTC 2022
Record UNII
J3BI9P40XE
Record Status Validated (UNII)
Record Version
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Name Type Language
INDACATEROL FUMARATE
Common Name English
2(1H)-QUINOLINONE, 5-((1R)-2-((5,6-DIETHYL-2,3-DIHYDRO-1H-INDEN-2-YL)AMINO)-1-HYDROXYETHYL)-8-HYDROXY-, (2E)-2-BUTENEDIOATE (1:1)
Common Name English
Code System Code Type Description
PUBCHEM
10255695
Created by admin on Sun Dec 18 15:28:23 UTC 2022 , Edited by admin on Sun Dec 18 15:28:23 UTC 2022
PRIMARY
CAS
1000160-87-1
Created by admin on Sun Dec 18 15:28:23 UTC 2022 , Edited by admin on Sun Dec 18 15:28:23 UTC 2022
PRIMARY
FDA UNII
J3BI9P40XE
Created by admin on Sun Dec 18 15:28:23 UTC 2022 , Edited by admin on Sun Dec 18 15:28:23 UTC 2022
PRIMARY
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