Product Information
Registration Status: ActiveONBREZ BREEZHALER POWDER FOR INHALATION HARD CAPSULE 300mcg is approved to be sold in Singapore with effective from 2011-07-18. It is marketed by NOVARTIS (SINGAPORE) PTE LTD, with the registration number of SIN13989P.
This product contains Indacaterol 0.300mg in the form of CAPSULE. It is approved for RESPIRATORY (INHALATION) use.
This product is manufactured by Novartis Pharma Stein AG in SWITZERLAND, andNovartis Farmaceutica SA (Primary and secondary packaging) in SPAIN.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Indacaterol is a novel, ultra-long-acting, rapid onset β(2)-adrenoceptor agonist developed for Novartis for the once-daily management 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 its maleate salt form. Indacaterol is also a chiral molecule but only the pure R-enantiomer is dispensed.
Indication
For the long term, once-daily-dosing maintenance of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
Mechanism of Action
Indacaterol works by stimulating adrenergic 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. It is also long acting due to its high affinity to the lipid raft domains in the airway membrane so it slowly dissociates from the receptors. Indacaterol also has a high intrinsic efficacy so it is also very rapid acting - onset of action occurs within 5 minutes. 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.
Pharmacokinetics
- 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%.
- Distribution
- After intravenous infusion the volume of distribution (Vz) of indacaterol was 2,361 L to 2,557 L indicating an extensive distribution.
- Metabolism
- 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. The monohydroxylated derivative, glucuronide conjugate, and the 8-O-glucuronide were the most prominent metabolites in serum. Other metabolites identified include a diastereomer of the hydroxylated derivative, a N-glucuronide of indacaterol, and C- and N-dealkylated products. 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.
- Elimination
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.
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.
Active Ingredient/Synonyms
Indacaterol | Indacaterol |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.