Symbicort Flashcards
What is symbicort?
Symbicort Turbohaler 100 micrograms/6 micrograms/inhalation, inhalation powder.
Each delivered dose (the dose that leaves the mouthpiece) contains: budesonide 80 micrograms/inhalation and formoterol fumarate dihydrate 4.5 micrograms/inhalation.
Each metered dose contains: budesonide 100 micrograms/inhalation and formoterol fumarate dihydrate 6 micrograms/inhalation.
Inhalation powder.
White powder.
What is the therapeutic indication of Symbicort?
Symbicort Turbohaler is indicated in adults, adolescents, and children aged 6 years and older.
Symbicort Turbohaler is indicated in the regular treatment of asthma where use of a combination (inhaled corticosteroid and long-acting β2 adrenoceptor agonist) is appropriate:
- patients not adequately controlled with inhaled corticosteroids and “as needed” inhaled short-acting β2 adrenoceptor agonists.
or
- patients already adequately controlled on both inhaled corticosteroids and long-acting β2 adrenoceptor agonists.
Note: Symbicort Turbohaler (100 micrograms/6 micrograms/inhalation) is not appropriate in patients with severe asthma.
Posology and method of administration
Route of administration: For inhalation use
What is the posology of Symbicort?
Symbicort Turbohaler is not intended for the initial management of asthma. The dosage of the components of Symbicort is individual and should be adjusted to the severity of the disease. This should be considered not only when treatment with combination products is initiated but also when the maintenance dose is adjusted. If an individual patient should require a combination of doses other than those available in the combination inhaler, appropriate doses of β2 adrenoceptor agonists and/or corticosteroids by individual inhalers should be prescribed.
The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. Patients should be regularly reassessed by their prescriber/health care provider so that the dosage of Symbicort remains optimal. When long-term control of symptoms is maintained with the lowest recommended dosage, then the next step could include a test of inhaled corticosteroid alone.
For Symbicort there are two treatment approaches:
A. Symbicort maintenance therapy: Symbicort is taken as regular maintenance treatment with a separate rapid-acting bronchodilator as rescue.
B. Symbicort maintenance and reliever therapy: Symbicort is taken as regular maintenance treatment and as needed in response to symptoms.
What are the contraindications of Symbicort?
Hypersensitivity to the active substances or to the excipient (lactose, which contains small amounts of milk protein).
What are the systemic effects of Symbicort?
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur with inhalation treatment than with oral corticosteroids. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma, and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).
What are the pharmacodynamic properties of Symbicort?
Pharmacotherapeutic group: Drugs for obstructive airway diseases: Adrenergics, Inhalants.
What are the Mechanisms of action and Pharmacodynamic effects of Symbicort?
Symbicort contains formoterol and budesonide, which have different modes of action and show additive effects in terms of reduction of asthma exacerbations. The specific properties of budesonide and formoterol allow the combination to be used either as maintenance and reliever therapy, or as maintenance treatment of asthma.
Budesonide
Budesonide is a glucocorticosteroid which when inhaled has a dose-dependent anti-inflammatory action in the airways, resulting in reduced symptoms and fewer asthma exacerbations. Inhaled budesonide has less severe adverse effects than systemic corticosteroids. The exact mechanism responsible for the anti-inflammatory effect of glucocorticosteroids is unknown.
Formoterol
Formoterol is a selective β2adrenoceptor agonist that when inhaled results in rapid and long-acting relaxation of bronchial smooth muscle in patients with reversible airways obstruction. The bronchodilating effect is dose-dependent, with an onset of effect within 1-3 minutes. The duration of effect is at least 12 hours after a single dose.
How is Symbicort absorbed in the body?
The fixed-dose combination of budesonide and formoterol, and the corresponding monoproducts have been shown to be bioequivalent with regard to systemic exposure of budesonide and formoterol, respectively. In spite of this, a small increase in cortisol suppression was seen after administration of the fixed-dose combination compared to the monoproducts. The difference is considered not to have an impact on clinical safety.
There was no evidence of pharmacokinetic interactions between budesonide and formoterol.
Pharmacokinetic parameters for the respective substances were comparable after the administration of budesonide and formoterol as monoproducts or as the fixed-dose combination. For budesonide, AUC was slightly higher, rate of absorption more rapid and maximal plasma concentration higher after administration of the fixed combination. For formoterol, maximal plasma concentration was similar after administration of the fixed combination. Inhaled budesonide is rapidly absorbed and the maximum plasma concentration is reached within 30 minutes after inhalation. In studies, mean lung deposition of budesonide after inhalation via the powder inhaler ranged from 32% to 44% of the delivered dose. The systemic bioavailability is approximately 49% of the delivered dose. In children 6-16 years of age the lung deposition falls in the same range as in adults for the same given dose. The resulting plasma concentrations were not determined.
Inhaled formoterol is rapidly absorbed and the maximum plasma concentration is reached within 10 minutes after inhalation. In studies the mean lung deposition of formoterol after inhalation via the powder inhaler ranged from 28% to 49% of the delivered dose. The systemic bioavailability is about 61% of the delivered dose.
How is Symbicort distributed in the body and how is it metabolised?
Plasma protein binding is approximately 50% for formoterol and 90% for budesonide. Volume of distribution is about 4 l/kg for formoterol and 3 l/kg for budesonide. Formoterol is inactivated via conjugation reactions (active O-demethylated and deformylated metabolites are formed, but they are seen mainly as inactivated conjugates). Budesonide undergoes an extensive degree (approximately 90%) of biotransformation on first passage through the liver to metabolites of low glucocorticosteroid activity. The glucocorticosteroid activity of the major metabolites, 6-beta-hydroxy-budesonide and 16-alfa-hydroxy-prednisolone, is less than 1% of that of budesonide. There are no indications of any metabolic interactions or any displacement reactions between formoterol and budesonide.
How is Symbicort eliminated from the body?
The major part of a dose of formoterol is transformed by liver metabolism followed by renal elimination. After inhalation, 8% to 13% of the delivered dose of formoterol is excreted unmetabolised in the urine. Formoterol has a high systemic clearance (approximately 1.4 l/min) and the terminal elimination half-life averages 17 hours.
Budesonide is eliminated via metabolism mainly catalysed by the enzyme CYP3A4. The metabolites of budesonide are eliminated in urine as such or in conjugated form. Only negligible amounts of unchanged budesonide have been detected in the urine. Budesonide has a high systemic clearance (approximately 1.2 l/min) and the plasma elimination half-life after i.v. dosing averages 4 hours.
The pharmacokinetics of formoterol in children have not been studied. The pharmacokinetics of budesonide and formoterol in patients with renal failure are unknown. The exposure of budesonide and formoterol may be increased in patients with liver disease.
