Indacaterol

Pharmacogenomics:

Indacaterol is metabolised by uridine diphosphate glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) enzyme via glucuronidation into phenolic O-glucuronide metabolite.

According to FDA-approved drug label, patients with UGT1A1 (TA)₇/(TA)₇ (*28/*28) low expression genotype have 1.2-fold higher steady-state AUC and Cmax than in patients with (TA)₆/(TA)₆ (*1/*1) genotype. This suggests that UGT1A1 genotype has no significant effect in the exposure of indacaterol.

As monotherapy in the treatment of asthma. Concomitant use with other long-acting ß₂-adrenergic agonists.

Patient with CV disorders (e.g. coronary artery disease, acute MI, cardiac arrhythmias, hypertension, known or suspected QT interval prolongation); convulsive disorders, hyperthyroidism, diabetes mellitus, hypokalaemia. Pregnancy and lactation. Not indicated for the relief of acute bronchospasm.

Significant: Hypersensitivity reactions (e.g. swelling of tongue, lips and face, rash, urticaria, difficulty in breathing or swallowing), hypokalaemia, hyperglycaemia, new-onset or exacerbation of diabetes mellitus, increased pulse rate or blood pressure, ECG changes (e.g. flattening of T wave, QT interval prolongation, ST-segment depression).
Cardiac disorders: Chest pain, palpitations, tachycardia.
Metabolism and nutrition disorders: Peripheral oedema.
Musculoskeletal and connective tissue disorders: Muscle spasm, musculoskeletal pain.
Nervous system disorders: Headache, dizziness.
Respiratory, thoracic and mediastinal disorders: Upper respiratory tract infection, nasopharyngitis, sinusitis, cough, oropharyngeal pain, rhinorrhoea.
Potentially Fatal: Paradoxical bronchospasm.

Inhalation/Respiratory: C

Monitor forced expiratory volume in the 1st second (FEV₁), forced vital capacity (FVC), other pulmonary function tests; serum K, blood glucose, blood pressure, heart rate. Monitor deterioration of COPD and re-evaluate therapy as needed.

Symptoms: Increased pulse rate, systolic blood pressure, QTc interval; other exaggerated adverse effects (e.g. tachycardia, palpitations, headache, ventricular arrhythmias, hypokalaemia, hyperglycaemia). Management: Supportive and symptomatic treatment. Administer cardioselective β-blockers under physician supervision. Monitor cardiac function.

Sympathetic effects may be potentiated with sympathomimetic agents. Enhanced hypokalaemic effect of methylxanthine derivatives, steroids or non-potassium-sparing diuretics (loop or thiazide diuretics). Increased risk of prolonged QTc interval with MAOIs, TCAs, or other agents known to prolong QTc interval. Antagonistic effect with ß-adrenergic blockers. Increased serum concentration with inhibitors of CYP3A4 and P-glycoprotein (e.g. ketoconazole, erythromycin, verapamil, ritonavir).

Description:
Mechanism of Action: Indacaterol is a long-acting β₂-adrenergic agonist. It acts by stimulating intracellular adenyl cyclase thus increasing the level of cyclic 5’-adenosine monophosphate (AMP) resulting in the relaxation of bronchial smooth muscle. Indacaterol is a long-acting ß₂-adrenergic agonist. It acts by stimulating intracellular adenyl cyclase thus increasing the level of cyclic 5’-adenosine monophosphate (AMP) resulting in the relaxation of bronchial smooth muscle.
Onset: 5 minutes.
Duration: 24 hours.
Pharmacokinetics:
Absorption: Bioavailability: 43-45%. Time to peak plasma concentration: Approx 15 minutes.
Distribution: Volume of distribution: 2,557 L (IV). Plasma protein binding: Approx 95%.
Metabolism: Metabolised in the liver by CYP3A4, CYP2D6 and CYP1A1 to hydroxylated indacaterol and by UGT1A1 to phenolic O-glucuronides.
Excretion: Via faeces (>90%; 54% as unchanged drug, 23% as hydroxylated metabolites); urine (<2% as unchanged drug). Elimination half-life: 40-56 hours.

Source: National Center for Biotechnology Information. PubChem Database. Indacaterol, CID=6918554, https://pubchem.ncbi.nlm.nih.gov/compound/Indacaterol (accessed on Jan. 21, 2020)

Store below 30°C. Protect from light and moisture.

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R03AC18 - indacaterol ; Belongs to the class of adrenergic inhalants, selective beta-2-adrenoreceptor agonists. Used in the treatment of obstructive airway diseases.

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Arcapta Neohaler Capsule (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 10/09/2014.

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Novartis New Zealand Limited. Onbrez Breezhaler 150 mcg Inhalation Powder Hard Capsules data sheet 15 September 2017. Medsafe. http://www.medsafe.govt.nz/. Accessed 14/11/2019.