Drug/Small Molecule:
indacaterol

PharmGKB contains no dosing guidelines for this drug/small molecule. To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.

PharmGKB gathers information regarding PGx on FDA drug labels from the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels", and from FDA-approved FDA and EMA-approved (European Medicines Agency) EMA labels brought to our attention. Excerpts from the label and downloadable highlighted label PDFs are manually curated by PharmGKB.

Please note that some drugs may have been removed from or added to the FDA's "Table of Pharmacogenomic Biomarkers in Drug Labels" without our knowledge. We periodically check the table for additions to this table and update PharmGKB accordingly.

There is currently no such list for European drug labels - we are working with the EMA to establish a list of European Public Assessment Reports (EPAR)s that contain PGx information. We are constructing this list by initially searching for drugs for which we have PGx-containing FDA drug labels - of these 44 EMA EPARs were identified and are being curated for pgx information.

We welcome any information regarding drug labels containing PGx information approved by the FDA, EMA or other Medicine Agencies around the world - please contact feedback.



last updated 10/25/2013

FDA Label for indacaterol and UGT1A1

This label is on the FDA Biomarker List
Informative PGx

Summary

Steady-state AUC and Cmax of indacaterol were 1.2-fold higher in patients with the (TA)7, (TA)7 (*28) genotype than in patients with the (TA)6, (TA)6 genotype, suggesting no relevant effect of UGT1A1 genotype of indacaterol exposure

There's more of this label. Read more.


last updated 10/27/2013

European Medicines Agency (EMA) Label for indacaterol and ADRB2

Informative PGx

Summary

The EMA European Public Assessment Report (EPAR) for indacaterol (Hirobriz Breezhaler) does not contain pharmacogenetic information, but does contain information regarding the pharmacodynamics of the drug as a beta2-adrenoceptor (ADRB2) agonist and also contains information regarding the pharmackinetics of indacaterol involving UGT1A1, CYP3A4 and ABCB1.

There's more of this label. Read more.



PharmGKB contains no Clinical Variants that meet the highest level of criteria.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Gene?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

Gene ? Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs1042713 148206440G>A, 148206440G>G, 46A>A, 46A>G, 46G>A, 5285A>A, 5285A>G, 9369367G>A, 9369367G>G, ADRB2:16Arg>Gly, ADRB2:Arg16Gly, ADRB2:Gly16Arg, Arg16, Arg16=
G > A
Missense
Arg16Gly
No VIP available No Clinical Annotations available VA
rs1042714 148206473G>C, 148206473G>G, 318C>G, 5318C>G, 79C>G, 9369400G>C, 9369400G>G, ADRB2:27Glu>Gln, ADRB2:79C>G, ADRB2:Gln27Glu, Gln27
G > C
Missense
Gln27Glu
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • 5-(2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl)-8-hydroxy-1h-quinolin-2-one
Trade Names
  • Arcapta
  • Onbrez
Brand Mixture Names

PharmGKB Accession Id:
PA165958348

Description

Indacaterol is a novel, ultra-long-acting, beta(2)-adrenoceptor agonist developed for Novartis for the once-daily treatment of asthma and chronic obstructive pulmonary disease. It was approved by the European Medicines Agency (EMA) under the trade name Onbrez on November 30, 2009, and by the United States Food and Drug Administration (FDA), under the trade name Arcapta Neohaler, on July 1, 2011. Indacaterol is provided as a pure R-enantiomer, typically as the salt indacaterol maleate.

Source: Drug Bank

Indication

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.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Indacaterol works by stimulating beta-2 receptors in the smooth muscle of the airways. This causes relaxation of the muscle, thereby increasing the diameter of the airways, which become constricted in asthma and COPD.

The pharmacological effects of beta2-adrenoceptor agonist drugs, including indacaterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic monophosphate). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle. In vitro studies have shown that indacaterol has more than 24-fold greater agonist activity at beta2-receptors compared to beta1-receptors and 20-fold greater agonist activity compared to beta3-receptors. This selectivity profile is similar to formoterol. The clinical significance of these findings is unknown.

Source: Drug Bank

Pharmacology

Bronchodilator drugs are the foundation for the treatment of chronic obstructive pulmonary disease. The principal inhaled bronchodilator treatments used are beta(2) -agonists and anticholinergics, either alone or in combination. Currently available beta(2) -agonists are of either short duration and used multiple times/day, or of long duration, which requires twice-daily administration. Indacaterol is considered an ultra-long-acting beta(2) -agonist and was recently approved for use in the United States. Its duration of action is approximately 24 hours, allowing for once-daily administration. Cough was the most commonly reported adverse effect with use of indacaterol. Cough usually occurred within 15 seconds of inhalation of the drug, lasted around 6 seconds, was not associated with bronchospasm, and did not cause discontinuation of the drug. Otherwise, the drug's safety profile was similar to that of other bronchodilators. [Article:22499359]

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

After oral administration of radiolabeled indacaterol, unchanged indacaterol was the main component in serum, accounting for about one third of total drug-related AUC over 24 hours. A hydroxylated derivative was the most prominent metabolite in serum. Phenolic O-glucuronides of indacaterol and hydroxylated indacaterol were further prominent metabolites. A diastereomer of the hydroxylated derivative, a N-glucuronide of indacaterol, and C- and N-dealkylated products were further metabolites identified.

In vitro investigations indicated that UGT1A1 was the only UGT isoform that metabolized indacaterol to the phenolic O-glucuronide. CYP3A4 is the predominant isoenzyme responsible for hydroxylation of indacaterol.

Source: Drug Bank

Protein Binding

The in vitro human serum and plasma protein binding was 94.1-95.3% and 95.1-96.2%, respectively.

Source: Drug Bank

Absorption

The median time to reach peak serum concentrations of indacaterol was approximately 15 minutes after single or repeated inhaled doses. Absolute bioavailability of indacaterol after an inhaled dose was on average 43-45%.

Source: Drug Bank

Half-Life

Indacaterol serum concentrations declined in a multi-phasic manner with an average terminal half-life ranging from 45.5 to 126 hours. The effective half-life, calculated from the accumulation of indacaterol after repeated dosing with once daily doses between 75 mcg and 600 mcg ranged from 40 to 56 hours which is consistent with the observed time-to-steady state of approximately 12-15 days.

Source: Drug Bank

Toxicity

The expected signs and symptoms associated with overdosage of indacaterol are those of excessive beta-adrenergic stimulation and occurrence or exaggeration of any of the signs and symptoms, e.g., angina, hypertension or hypotension, tachycardia, with rates up to 200 bpm, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, metabolic acidosis and insomnia. As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of indacaterol.

Source: Drug Bank

Clearance

Renal clearance of indacaterol is, on average, between 0.46 and 1.2 L/h. Serum clearance of indacaterol is 18.8 L/h to 23.3 L/h.

Source: Drug Bank

Route of Elimination

Renal clearance plays a minor role (about 2 to 6% of systemic clearance) in the elimination of systemically available indacaterol. In a human ADME study where indacaterol was given orally, the fecal route of excretion was dominant over the urinary route. Indacaterol was excreted into human feces primarily as unchanged parent drug (54% of the dose) and, to a lesser extent, hydroxylated indacaterol metabolites (23% of the dose).

Source: Drug Bank

Volume of Distribution

After intravenous infusion the volume of distribution (Vz) of indacaterol was 2,361 L to 2,557 L indicating an extensive distribution.

Source: Drug Bank

Chemical Properties

Chemical Formula

C24H28N2O3

Source: Drug Bank

C24H28N2O3

Source: PubChem Compound

Canonical SMILES

CCC1=C(CC)C=C2CC(CC2=C1)NC[C@H](O)C1=C2C=CC(=O)NC2=C(O)C=C1

Source: Drug Bank

CCC1=C(C=C2CC(CC2=C1)NC[C@@H](C3=C4C=CC(=O)NC4=C(C=C3)O)O)CC

Source: PubChem Compound

Average Molecular Weight

392.4907

Source: Drug Bank

392.49072

Source: PubChem Compound

Monoisotopic Molecular Weight

392.209992772

Source: Drug Bank

392.209993

Source: PubChem Compound

IUPAC Names

  • 5-[(1R)-2-[(5,6-diethyl-2,3-dihydro-1H-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-1H-quinolin-2-one

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available DL No Clinical Annotation available VA No VIP available No VIP available
ADRB2
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
CYP3A4
No Dosing Guideline available DL No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
UGT1A1
No related drugs are available.

Curated Information ?

Publications related to indacaterol: 3

No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of chronic obstructive pulmonary disease. Pharmacogenomics. 2013. Hizawa Nobuyuki. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Challenges in pharmacogenetics. European journal of clinical pharmacology. 2013. Cascorbi Ingolf, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
A pharmacogenetic study of ADRB2 polymorphisms and indacaterol response in COPD patients. The pharmacogenomics journal. 2011. Yelensky R, et al. PubMed

LinkOuts

DrugBank:
DB05039
KEGG Drug:
D09318
PubChem Compound:
6918554

Clinical Trials

These are trials that mention indacaterol and are related to either pharmacogenetics or pharmacogenomics.

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.