Indacaterol + Glycopyrronium

Inhalation/Respiratory
Maintenance therapy in chronic obstructive pulmonary disease

Monotherapy for the treatment of asthma, acute bronchospasm, acute episodes of COPD.

Patient with arrhythmia, coronary insufficiency, hypertension, CHF, diabetes mellitus, hyperthyroidism, thyrotoxicosis, hypokalaemia, narrow angle glaucoma, prostatic hyperplasia/bladder neck obstruction, urinary retention, seizure disorder. Severe hepatic or renal impairment, ESRD. Pregnancy and lactation.

Significant: CNS depression, hypersensitivity reactions (e.g. angioedema, urticaria), hypertension, increased heart rate, ECG changes, hyperglycaemia, diabetes mellitus and ketoacidosis exacerbation, thyroid stimulation, hypokalaemia, narrow-angle glaucoma, urinary retention.
Cardiac disorders: Ischaemic heart disease, atrial fibrillation, tachycardia, palpitations.
Gastrointestinal disorders: Dyspepsia, dental carries, gastroenteritis, dry mouth.
General disorders and administration site conditions: Pyrexia, chest pain, fatigue, peripheral oedema.
Musculoskeletal and connective tissue disorders: Musculoskeletal pain, muscle spasm, myalgia, back pain.
Nervous system disorders: Headache, dizziness, paraesthesia.
Psychiatric disorders: Insomnia.
Respiratory, thoracic and mediastinal disorders: Cough, nasopharyngitis, upper respiratory infection, sinusitis, rhinitis.
Skin and subcutaneous tissue disorders: Pruritus, rash.
Potentially Fatal: Asthma-related deaths, rarely, paradoxical bronchospasm.

This drug may cause drowsiness, dizziness, and/or blurred vision, if affected, do not drive or operate machinery.

Obtain FEV₁, FVC, and/or other pulmonary function tests, serum K, blood glucose. Monitor heart rate, blood pressure and signs of CNS stimulation.

Indacaterol: May potentiate hypokalaemic effect with xanthine derivatives, steroids, diuretics. May potentiate CV effects with MAOIs, TCA, QTc-prolonging agents. May cause sever bronchospasm with β-blockers.
Glycopyrronium: Increased adverse effects with other anticholinergic drugs.

Description:
Mechanism of Action: Indacaterol is a long acting beta₂- agonist that acts locally in the lungs and relaxes bronchial smooth muscle.
Glycopyrronium is a long acting muscarinic receptor antagonist. It causes bronchodilatation by inhibiting the acetylcholine at muscarinic receptor subtypes 1-3 in bronchial smooth muscles.
Onset: Within 5 minutes.
Pharmacokinetics:
Absorption: Indacaterol: Absolute bioavailability: 43-45%. Time to peak plasma concentration: Approx 15 minutes.
Glycopyrronium: Poorly absorbed from the gastrointestinal tract. Bioavailability: Approx 10-25%. Time to peak plasma concentration: Approx 5 minutes.
Distribution: Indacaterol: Plasma protein binding: Approx 95%.
Glycopyrronium: Crosses blood-brain barrier (poorly). Volume of distribution: 83 L. Plasma protein binding: 38-41%.
Metabolism: Indacaterol: Metabolised by CYP3A4 isoenzyme and via glucuronidation by uridine diphosphate-glucuronosyltransferase (UGT) 1A1.
Excretion: Indacaterol: Via faeces (54% as unchanged drug, 23% as metabolites); urine. Elimination half-life: 40-56 hours.
Glycopyrronium: Via faeces; urine (23% as parent drug). Terminal elimination half-life: 33-57 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)

Source: National Center for Biotechnology Information. PubChem Database. Glycopyrronium, CID=3494, https://pubchem.ncbi.nlm.nih.gov/compound/Glycopyrronium (accessed on Jan. 21, 2020)

Store between 15-25°C. Protect from light and moisture.

Thuốc trị hen & bệnh phổi tắc nghẽn mạn tính

R03AL04 - indacaterol and glycopyrronium bromide ; Belongs to the class of combination of adrenergics with anticholinergics, that may also include a corticosteroid. Used in the treatment of obstructive airway diseases.

Anon. Indacaterol and Glycopyrrolate. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 06/03/2018.

Buckingham R (ed). Glycopyrronium Bromide. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2018.

Buckingham R (ed). Indacaterol. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2018.

Joint Formulary Committee. Glycopyrronium with Indacaterol. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 06/03/2018.

Utibron Neohaler Capsule (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 06/03/2018.