Product Information
Registration Status: ActiveSIN14964P
SYMBICORT RAPIHALER SUSPENSION FOR INHALATION 40/2.25mcg/actuation is approved to be sold in Singapore with effective from 2016-02-24. It is marketed by ASTRAZENECA SINGAPORE PTE LTD, with the registration number of SIN14964P.
This product contains Budesonide 40mcg/actuation, and Formoterol 2.25mcg/actuation in the form of AEROSOL, METERED for INHALATION. It is approved for RESPIRATORY (INHALATION) use.
This product is manufactured by AstraZeneca Dunkerque Production (AZDP) in FRANCE.
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.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
Budesonide is a glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. [PubChem] The extended release oral tablet, marketed as Uceris, was FDA approved on January 14, 2013 for the management of ulcerative colitis. Budesonide is provided as a mixture of two epimers (22R and 22S). Interestingly, the 22R form is two times more active than the 22S epimer. The two forms do not interconvert.
Indication
The oral capsule is used for the treatment of mild to moderate active Crohn's disease. The oral tablet is used for induction of remission in patients with active, mild to moderate ulcerative colitis. The oral inhalation formulation is used for the treatment of asthma, non-infectious rhinitis (including hay fever and other allergies), and for treatment and prevention of nasal polyposis.
Mechanism of Action
Budesonide is an anti-inflammatory corticosteroid that exhibits potent glucocorticoid activity and weak mineralocorticoid activity. The precise mechanism of corticosteroid actions on inflammation in asthma, Crohn's disease, or ulcerative colitis is not known. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of inhibitory activities against multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, and lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, and cytokines) involved in allergic and non-allergic-mediated inflammation. These anti-inflammatory actions of corticosteroids may contribute to their efficacy in the aforementioned diseases. Because budesonide undergoes significant first-pass elimination, the both oral preparations are formulated as an extended release tablet. As a result, budesonide release is delyaed until exposure to a pH ≥ 7 in the small intestine.
Pharmacokinetics
- Absorption
- Absorption is complete following oral administration. The pharmacokinetic parameters of the inhaled powder formulation are as follows: Tmax = 30 minutes; Absolute systemic availability = 39%. When a single oral administration of 9 mg of Uceris are given, the pharmacokinetic parameters are as follows: Tmax = 13.3 ± 5.9 hours; Cmax = 1.35 ± 0.96 ng/mL; AUC = 16.43 ± 10.52 ng·hr/mL. It is important to note that the parameters have a high degree of variability. When a single oral administration of Entocort EC are given, the pharmacokinetic parameters are as follows: Tmax = 3- 600 minutes; Cmax = 5 nmol/L; AUC = 30 nmol•hr/L.
- Distribution
- Tablet and capsule, healthy subjects and patients = 2.2 - 3.9 L/kg; Powder, metered = 3 L/kg
- Metabolism
- Following absorption, budesonide is subject to high first pass metabolism (80-90%). Budesonide is rapidly and extensively biotransformed, mainly by CYP3A4, to its 2 major metabolites, 6b-hydroxybudesonide and 16a- hydroxyprednisolone. The glucocorticoid activity of these metabolites is negligible (
- Elimination
Clearance
Plasma clearance, tablet = 0.9 - 1.8 L/min; Systemic clearance, powder, 22R = 1.4 L/min; Systemic clearance, powder, 22S = 1.0 L/min; 0.5 L/min [Athmatic children 4 to 6 years of age]
Toxicity
Single oral doses of 200 and 400 mg/kg were lethal in female and male mice, respectively. The signs of acute toxicity were decreased motor activity, piloerection and generalized edema.
Active Ingredient/Synonyms
(11beta,16alpha)-16,17-(Butylidenebis(oxy))-11,21-dihydroxypregna-1,4-diene-3,20-dione | Budesonide |
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.
Description
Formoterol is a long-acting (12 hours) beta2-agonist used in the management of asthma and/or chronic obstructive pulmonary disease (COPD). Inhaled formoterol works like other beta2-agonists, causing bronchodilatation through relaxation of the smooth muscle in the airway so as to treat the exacerbation of asthma.
Indication
For use as long-term maintenance treatment of asthma in patients 6 years of age and older with reversible obstructive airways disease, including patients with symptoms of nocturnal asthma, who are using optimal corticosteroid treatment and experiencing regular or frequent breakthrough symptoms requiring use of a short-acting bronchodilator. Not indicated for asthma that can be successfully managed with occasional use of an inhaled, short-acting beta2-adrenergic agonist. Also used for the prevention of exercise-induced bronchospasm, as well as long-term treatment of bronchospasm associated with COPD.
Mechanism of Action
The pharmacologic effects of beta2-adrenoceptor agonist drugs, including formoterol, 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 AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibits the release of pro-inflammatory mast-cell mediators such as histamine and leukotrienes. Formoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper-responsiveness. The relevance of these in vitro and animal findings to humans is unknown.
Pharmacokinetics
- Absorption
- Rapidly absorbed into plasma following administration by oral inhalation. It is likely that the majority of the inhaled formoterol delivered is swallowed and then absorbed from the gastrointestinal tract.
- Distribution
- Metabolism
- Metabolized primarily by direct glucuronidation at either the phenolic or aliphatic hydroxyl group and O-demethylation followed by glucuronide conjugation at either phenolic hydroxyl groups. Minor pathways involve sulfate conjugation of formoterol and deformylation followed by sulfate conjugation. The most prominent pathway involves direct conjugation at the phenolic hydroxyl group. The second major pathway involves O-demethylation followed by conjugation at the phenolic 2'-hydroxyl group. Four cytochrome P450 isozymes (CYP2D6, CYP2C19, CYP2C9 and CYP2A6) are involved in the O-demethylation of formoterol.
- Elimination
Clearance
* Renal cl=150 mL/min [Healty subjects receiving oral administration of 80 mcg]
Toxicity
An overdosage is likely to lead to effects that are typical of ß2-adrenergic stimulants: nausea, vomiting, headache, tremor, somnolence, palpitations, tachycardia, ventricular arrhythmias, metabolic acidosis, hypokalemia, hyperglycemia.
Active Ingredient/Synonyms
2'-Hydroxy-5'-(1-hydroxy-2-((P-methoxy-alpha-methylphenethyl)amino)ethyl)formanilide | 2'-Hydroxy-5'-{1-hydroxy-2-[(P-methoxy-alpha-methylphenethyl)amino]ethyl}formanilide | Formoterolum | N-[2-Hydroxy-5-(1-hydroxy-2-{[2-(4-methoxyphenyl)-1-methylethyl]amino}ethyl)phenyl]formamide | Formoterol |
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.