Ascon-F

Uses

Asthma: Beclomethasone dipropionate/Formoterol fumarate dihydrate is used for the regular treatment of asthma where use of a combination product (inhaled corticosteroid and long-acting β2-agonist) is appropriate: patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled rapid-acting β2-agonist or patients already adequately controlled on both inhaled corticosteroids and long-acting β2-agonists.

COPD: Symptomatic treatment of patients with severe COPD (FEV1 <50% predicted normal) and a history of repeated exacerbations, who have significant symptoms despite regular therapy with long-acting bronchodilators.

Ascon-F is also used to associated treatment for these conditions: Asthma, Bronchial Asthma, Bronchoconstriction, Chronic Obstructive Pulmonary Disease (COPD), Exercise-Induced Bronchospasm, Moderate to Severe COPD

How Ascon-F works

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

Ascon-F dosage

Adults 18 years and above: One or two inhalations twice daily. The maximum daily dose is 4 inhalations.

Children and adolescents under 18 years: The safety and efficacy in children and adolescents under 18 years of age have not been established yet. No data are available with the drug in children under 12 years of age. Therefore the drug is not recommended for children and adolescents under 18 years until further data become available.

Using an Inhaler seems simple, but most patients do not know how to use it in the right way. If the Inhaler is used in the wrong way, less medicine can reach the lungs. Correct and regular use of the Inhaler will prevent or lessen the severity of asthma attacks.

Following simple steps can help to use Inhaler effectively (According to "National Asthma Guidelines for Medical Practitioners" published by Asthma Association):

1. Take off the cap.
2. Shake the inhaler (at least six times) vigorously before each use.
3. If the inhaler is new or if it has not been used for a week or more, shake it well and release one puff into the air to make sure that it works.
4. Breathe out as full as comfortably possible & hold the inhaler upright.
5. Place the actuator into mouth between the teeth and close lips around the mouthpiece.
6. While breathing deeply and slowly through the mouth, press down firmly add fully on the canister to release medicine.
7. Remove the inhaler from mouth. Continue holding breath for at least for 10 seconds or as long as it is comfortable.
8. If doctor has prescribed more than one inhalation per treatment, wait 1 minute between puffs (inhalations). Shake the inhaler well and repeat steps 4 to 7.
9. After use, replace the cap on the mouthpiece. After each treatment, rinse mouth with water.
10. Check your technique in front of a mirror from time to time, if you see a white mist during the inhalation, you may not have closed your lips properly around mouthpiece, or you may not be breathing in as you press the can. This indicates failure of technique. If this happens, repeat the procedure from step 4 carefully.

Side Effects

As the drug contains beclometasone dipropionate and formoterol fumarate dihydrate, the type and severity of adverse reactions associated with each of the compounds may be expected. Common side effects are pharyngitis, oral candidiasis, headache, dysphonia.

Toxicity

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

The drug should be used with caution (which may include monitoring) in patients with cardiac arrhythmias, especially third degree atrioventricular block and tachyarrhythmias (accelerated and/or irregular heart beat), idiopathic subvalvular aortic stenosis, hypertrophic obstructive cardiomyopathy, severe heart disease, particularly acute myocardial infarction, ischaemic heart disease, congestive heart failure, occlusive vascular diseases, particularly arteriosclerosis, arterial hypertension and aneurysm. Caution should also be observed when treating patients with known or suspected prolongation of the QTc interval, either congenital or drug induced (QTc >0.44 seconds). Formoterol itself may induce prolongation of the QTc interval.

Interaction

Beta-blockers (including eye drops) should be avoided in asthmatic patients. If beta-blockers are administered for compelling reasons, the effect of formoterol will be reduced or abolished. On the other hand, concomitant use of other beta adrenergic drugs can have potentially additive effects, therefore caution is required when theophylline or other beta adrenergic drugs are prescribed concomitantly with formoterol. Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines, monoamine oxidase inhibitors and tricyclic antidepressants can prolong the QTc-interval and increase the risk of ventricular arrhythmias.

Elimination Route

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 T_max ranged from 0.167 to 0.5 hours. Following a single dose of 10 mcg, C_max and AUC were 22 pmol/L and 81 pmol.h/L, respectively. In asthmatic adult patients, T_max ranged from 0.58 to 1.97 hours. Following single-dose administration of 10mcg, C_max and AUC_0-12h were 22 pmol/L and 125 pmol.h/L, respectively; following multiple-dose administration of 10 mcg, C_max and AUC_0-12h were 41 pmol/L and 226 pmol.h/L, respectively. Absorption appears to be proportional to dose across standard dosing ranges.

Half Life

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

Renal clearance of formoterol following inhalation is approximately 157 mL/min.

Elimination Route

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

There are no relevant clinical data on the use of the drug in pregnant women. Animal studies using beclometasone dipropionate and formoterol combination showed evidence of toxicity to reproduction after high systemic exposure. There are no relevant clinical data on the use of the drug in lactation in humans. Although no data from animal experiments are available, it is reasonable to assume that beclometasone dipropionate is secreted in milk, like other corticosteroids.

Contraindication

Contraindicated in patients with hypersensitivity to any component of this product.

Storage Condition

Prior to dispensing to the patient: Store in a refrigerator (2-8°C) (for a maximum of 15 months). After dispensing: Store at temperatures not exceeding 30°C (for a maximum of 2 months).

Innovators Monograph

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