Aclidinium And Formoterol
Aclidinium And Formoterol Uses, Dosage, Side Effects, Food Interaction and all others data.
Aclidinium is an anticholinergic for the long-term management of chronic obstructive pulmonary disease (COPD). It has a much higher propensity to bind to muscarinic receptors than nicotinic receptors. FDA approved on July 24, 2012.
Aclidinium does not prolong the QTc interval or have significant effects on cardiac rhythm.
Formoterol fumarate is a long-acting β2-adrenergic receptor agonist (β2-agonist). Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In vitro studies have shown that formoterol has more than 200-fold greater agonist activity at β2-receptors than at β1-receptors. Although β2-receptors are the predominant adrenergic receptors in bronchial smooth muscle and β1-receptors are the predominant receptors in the heart, there are also β2-receptors in the human heart comprising 10%-50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective β2-agonists may have cardiac effects.
The pharmacologic effects of β2-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 inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells.
In vitro tests show that formoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. 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.
Formoterol works locally in the lungs as a bronchodilator, relaxing smooth muscle and opening up the airways. It possesses both a rapid onset of action (approximately 2-3 minutes) and a long duration of action (up to 12 hours). The use of long-acting beta-agonists (LABAs), such as formoterol, without concomitant inhaled corticosteroids in asthmatic patients should be avoided, as LABA monotherapy has been associated with an increased risk of asthma-related death.
| Trade Name | Aclidinium And Formoterol |
| Generic | Aclidinium + formoterol |
| Weight | 400mcg + 12mcg/inh, |
| Type | Inhalation Powder, Inhalation |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Aclidinium is an inhaled long-acting anticholinergic used as a maintenance bronchodilator in patients with chronic obstructive pulmonary disease (COPD).
Aclidinium bromide inhalation powder is indicated for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.
Treatment of Asthma: Formoterol Fumarate is used for the treatment of asthma and in the prevention of bronchospasm only as concomitant therapy with a long-term asthma control medication, such as an inhaled corticosteroid, in adults and children 5 years of age and older with reversible obstructive airways disease, including patients with symptoms of nocturnal asthma.
Prevention of Exercise-Induced Bronchospasm: Formoterol Fumarate is also used for the acute prevention of exercise-induced bronchospasm in adults and children 5 years of age and older, when administered on an occasional, as-needed basis. Use of Formoterol Fumarate as a single agent for the prevention of exercise-induced bronchospasm may be clinically used for patients who do not have persistent asthma. In patients with persistent asthma, use of Formoterol Fumarate for the prevention of exercise-induced bronchospasm may be clinically used, but the treatment of asthma should include a long-term asthma control medication, such as an inhaled corticosteroid.
Maintenance Treatment of Chronic Obstructive Pulmonary Disease: Formoterol Fumarate is used for the long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with Chronic Obstructive Pulmonary Disease including chronic bronchitis and emphysema.
Aclidinium And Formoterol is also used to associated treatment for these conditions: Chronic Obstructive Pulmonary Disease (COPD)Asthma, Bronchial Asthma, Bronchoconstriction, Chronic Obstructive Pulmonary Disease (COPD), Exercise-Induced Bronchospasm, Moderate to Severe COPD
How Aclidinium And Formoterol works
Aclidinium is a long-acting, competitive, and reversible anticholinergic drug that is specific for the acetylcholine muscarinic receptors. It binds to all 5 muscarinic receptor subtypes to a similar affinity. Aclidinium's effects on the airways are mediated through the M3 receptor at the smooth muscle to cause bronchodilation. Prevention of acetylcholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours.
Formoterol is a relatively selective long-acting agonist of beta2-adrenergic receptors, although it does carry some degree of activity at beta1 and beta3 receptors. Beta2 receptors are found predominantly in bronchial smooth muscle (with a relatively minor amount found in cardiac tissue) whereas beta1 receptors are the predominant adrenergic receptors found in the heart - for this reason, selectivity for beta2 receptors is desirable in the treatment of pulmonary diseases such as COPD and asthma. Formoterol has demonstrated an approximately 200-fold greater activity at beta2 receptors over beta1 receptors.
On a molecular level, activation of beta receptors by agonists like formoterol stimulates intracellular adenylyl cyclase, an enzyme responsible for the conversion of ATP to cyclic AMP (cAMP). The increased levels of cAMP in bronchial smooth muscle tissue result in relaxation of these muscles and subsequent dilation of the airways, as well as inhibition of the release of hypersensitivity mediators (e.g. histamine, leukotrienes) from culprit cells, especially mast cells.
Dosage
Aclidinium And Formoterol dosage
Inhalation Acute bronchospasm; Reversible airways obstruction:
- As inhalation cap: 12 mcg twice daily, up to 24 meg twice daily in severe cases.
- As dry powder inhaler: 6 or 12 mcg 1 -2 times/day, up to to 24 mcg twice daily in sever cases. As metered doses from aerosol inhaler: 12 or 24 mcg twice daily.
Prevention of exercise-induced bronchospasm: 6 or 12 mcg at least 15 mins before exercise. Additional doses may be given 12 hr later.
Side Effects
Common side effects are Viral infection, Bronchitis, Chest infection, Dyspnea , Chest pain, Tremor, Dizziness, Angina, Arrhythmias, Hypo/hypertension, Tachycardia, Hypokalemia, Hyperglycemia, Metabolic acidosis, Headache, Insomnia, Paradoxical bronchospasm, Severe asthma exacerbation
Toxicity
Most common adverse reactions (≥3% incidence and greater than placebo) are headache, nasopharyngitis and cough.
The oral LD50 in rats is 3130 mg/kg.
Symptoms of overdose are likely consistent with formoterol's adverse effect profile (i.e. consistent with excessive beta-adrenergic stimulation) and may include angina, hyper or hypotension, tachycardia, arrhythmia, nervousness, headache, tremor, seizures, dry mouth, etc. Patients may experience laboratory abnormalities including hypokalemia, hyperglycemia, and metabolic acidosis. Treatment of overdosage should consist of symptomatic and supportive therapy, with a particular focus on cardiac monitoring. Consider the use of a cardioselective beta-adrenergic blocker to oppose excessive adrenergic stimulation if clinically appropriate.
Precaution
Thyrotoxicosis; severe CV disorders e.g. ischaemic heart disease, tachyarrhythmias or severe heart burn; prolonged QT-interval. DM; pregnancy; lactation; children, do not initiate or increase the dose during an exacerbation. May produce paradoxical bronchospasm.
Interaction
Concomitant treatment with xanthine derivatives, steroids or diuretics may potentiate a possible hypokalaemic effect of beta-agonists. Increased susceptibility to cardiac arrhythmias in patients treated with digitalis. Concomitant use with quinidine, disopyramide, procainamide, phenothiazines, antihistamines, MAOI or TCAs can prolong the QT-interval and increase the risk of ventricular arrhythmias. L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards beta2-sympathomimetics. beta-adrenergic blockers can inhibit the effect of formoterol. Increased risk of arrhythmias in patients receiving concomitant anaesthesia with halogenated hydrocarbons.
Volume of Distribution
Following IV administration, the volume of distribution is 300 L
Elimination Route
Bioavailability, healthy subjects = 6%; T max, healthy subjects = 10 minutes; Time to steady state, healthy subjects = 2 days;
The pulmonary bioavailability of formoterol has been estimated to be about 43% of the delivered dose, while the total systemic bioavailability is approximately 60% of the delivered dose (as systemic bioavailability accounts for absorption in the gut).
Formoterol is rapidly absorbed into plasma following inhalation. In healthy adults, formoterol Tmax ranged from 0.167 to 0.5 hours. Following a single dose of 10 mcg, Cmax and AUC were 22 pmol/L and 81 pmol.h/L, respectively. In asthmatic adult patients, Tmax ranged from 0.58 to 1.97 hours. Following single-dose administration of 10mcg, Cmax and AUC0-12h were 22 pmol/L and 125 pmol.h/L, respectively; following multiple-dose administration of 10 mcg, Cmax and AUC0-12h were 41 pmol/L and 226 pmol.h/L, respectively. Absorption appears to be proportional to dose across standard dosing ranges.
Half Life
Plasma half-life = 2.4 minutes (indicating that aclidinium is very rapidly hydrolyzed in plasma into its two inactive metabolites and has a low chance of causing systemic side effects). Effective half-life = 5-8 hours.
The average terminal elimination half-life of formoterol following inhalation is 7-10 hours, depending on the formulation given. The plasma half-life of formoterol has been estimated to be 3.4 hours following oral administration and 1.7-2.3 hours following inhalation.
Clearance
Total clearance, IV dose, young healthy subjects = 170 L/h (inter-individual variability of 36%)
Renal clearance of formoterol following inhalation is approximately 157 mL/min.
Elimination Route
Intravenously administered radiolabelled aclidinium bromide was administered to healthy volunteers and was extensively metabolized with 1% excreted as unchanged aclidinium. Approximately 54% to 65% of the radioactivity was excreted in urine and 20% to 33% of the dose was excreted in feces. The combined results indicated that almost the entire aclidinium bromide dose was eliminated by hydrolysis. After dry powder inhalation, urinary excretion of aclidinium is about 0.09% of the dose.
Elimination differs depending on the route and formulation administered. Following oral administration in 2 healthy subjects, approximately 59-62% and 32-34% of an administered dose was eliminated in the urine and feces, respectively. Another study which attempted to mimic inhalation via combined intravenous/oral administration noted approximately 62% of the administered dose in the urine and 24% in the feces. Following inhalation in patients with asthma, approximately 10% and 15-18% of the administered dose was excreted in urine as unchanged parent drug and direct formoterol glucuronides, respectively, and corresponding values in patients with COPD were 7% and 6-9%, respectively.
Pregnancy & Breastfeeding use
Pregnancy Category-C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
Lactation: Not known if it is excreted in breast milk or not.
Contraindication
Hypersensitivity.
Storage Condition
Prior to dispensing: Store in a refrigerator, 2°C to 8°C
After dispensing to patient: Store at 20°C to 25°C
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