SabaComb^® (Aerosol) Instructions for Use

Marketing Authorization Holder

Chiesi Pharmaceuticals, LLC (Russia)

Manufactured By

CHIESI FARMACEUTICA, Ltda (Brazil)

Packaging and Quality Control Release

CHIESI FARMACEUTICI, S.p.A. (Italy)

ATC Code

R03AK13 (Salbutamol and Beclomethasone)

Active Substances

Beclometasone (Rec.INN registered by WHO)

Salbutamol (Rec.INN registered by WHO)

Dosage Form

SabaComb®

Metered dose inhalation aerosol 250 mcg+100 mcg/1 dose: canister 200 doses with a spray nozzle

Dosage Form, Packaging, and Composition

Metered dose inhalation aerosol in the form of an almost white suspension.

Excipients : ethanol – 8.25 mg, oleic acid – 0.008 mg, norflurane – 46.372 mg.

200 doses – aluminum canisters (1) with a metering spray nozzle – cardboard packs.

Clinical-Pharmacological Group

Combined bronchodilator drug – selective beta₂-adrenomimetic + topical glucocorticosteroid

Pharmacotherapeutic Group

Bronchodilator agent (selective beta2-adrenomimetic + topical glucocorticosteroid)

Pharmacological Action

A combined bronchodilator containing Salbutamol and beclometasone dipropionate (a glucocorticosteroid active when administered by inhalation).

Salbutamol is characterized by a rapid and safe bronchodilatory effect, leading to rapid improvement in respiratory function. Salbutamol acts selectively on bronchial muscles without causing any cardiovascular effects. In turn, beclometasone dipropionate reduces bronchial hyperreactivity by reducing edema and hypersecretion in the bronchi, thereby gradually suppressing the development of bronchospasm. Beclometasone dipropionate acts at the level of the bronchial tree without causing systemic effects or suppression of adrenal function.

The action of the two active substances in this combination is complementary and mutually reinforcing. This combination is intended for the relief of symptoms and continuous treatment of bronchial asthma and chronic obstructive pulmonary disease with an asthmatic component, aimed at preventing and reducing the frequency of asthma attacks. Since beclometasone dipropionate has an anti-inflammatory effect and reduces bronchial hyperreactivity, its use allows for a reduction in the doses of beta₂-adrenergic receptor agonists taken.

Thus, this combination has a pronounced anti-inflammatory activity, comparable to that of beclometasone dipropionate, and a more pronounced ability to prevent bronchospasm compared to each of the active substances of the drug separately.

Pharmacokinetics

After inhalation of salbutamol (100 mcg), C_max in plasma is reached in 3-5 hours. Approximately 83% of the inhaled dose of salbutamol is excreted by the kidneys, both as unchanged substance (approximately 70%) and as one of its metabolites – salbutamol-o-phenylglucuronide (30%).

Beclometasone dipropionate is a prodrug with weak binding affinity for glucocorticoid receptors, which, under the influence of esterase enzymes present in most tissues, undergoes hydrolysis to form its active metabolite – beclometasone-17-monopropionate (B-17-MP). After inhalation, beclometasone dipropionate and its active metabolite B-17-MP are absorbed from the lungs and from the gastrointestinal tract (absorption of the swallowed portion of the dose). The absolute bioavailability of unchanged beclometasone dipropionate and B-17-MP after inhalation of beclometasone dipropionate from a metered-dose aerosol inhaler is 2% and 62% of the nominal dose, respectively. With an increase in the inhalation dose, an approximately linear increase in systemic exposure is observed. C_max in plasma for beclometasone dipropionate and B-17-MP is reached in 0.3 hours and 1 hour, respectively. The absorbed beclometasone dipropionate and B-17-MP are excreted in the bile as inactive metabolites and eliminated through the intestines. Renal excretion of beclometasone dipropionate and its metabolites is negligible. T_1/2 of beclometasone dipropionate and B-17-MP are 0.5 hours and 2.7 hours, respectively.

Indications

Bronchial asthma; COPD (with an asthmatic component).

ICD codes

Dosage Regimen

Administer by inhalation only.

Each actuation delivers a fixed dose of 250 mcg beclometasone dipropionate and 100 mcg salbutamol.

Determine the dosage individually based on disease severity and response.

For adults and adolescents (18 years and older), the typical dose is one inhalation twice daily.

In severe cases or for inadequate symptom control, increase the frequency to one inhalation three to four times daily.

The maximum daily dose should not exceed four inhalations (1000 mcg beclometasone / 400 mcg salbutamol).

Use the lowest effective dose to maintain symptom control.

Rinse your mouth with water after each inhalation to reduce the risk of oropharyngeal candidiasis.

If a previously effective dosage regimen fails to provide relief, immediately seek medical advice.

Do not alter the prescribed dosage or frequency without consulting a physician.

Adverse Reactions

Respiratory system disorders: hoarseness and dysphonia, paradoxical bronchospasm, the development of which is possible with any type of inhalation therapy.

Infectious and parasitic diseases: localized fungal infections of the oral cavity or pharynx, which resolve quickly without discontinuing SabaComb^® treatment after appropriate local therapy with alkaline solutions and antifungal drugs.

Nervous system disorders: tremor (disappearing after a few days of reducing the drug dose), headache, muscle cramps.

Psychiatric disorders: psychomotor hyperactivity, sleep disorders, anxiety, depression, aggressiveness, behavioral disorders.

Cardiovascular system disorders: tachycardia (increased heart rate), palpitations, disappearing after a few days of reducing the drug dose. Myocardial ischemia and cardiac arrhythmias, including atrial fibrillation, supraventricular tachycardia, and extrasystole, have been reported.

Immune system disorders: hypersensitivity reactions (angioedema, urticaria, decreased blood pressure, collapse).

Results of laboratory and instrumental tests: hypokalemia.

With long-term use of the drug in high doses, the following systemic undesirable effects of glucocorticosteroids may develop: osteoporosis; peptic ulcer of the stomach and duodenum; suppression of adrenal function with signs of secondary adrenal insufficiency; growth retardation in children and adolescents; decreased bone mineral density; cataract and glaucoma (careful monitoring of such patients is required for timely detection of possible systemic effects of glucocorticosteroids).

Contraindications

Viral infections, pulmonary tuberculosis (active and inactive forms) (due to the presence of beclometasone dipropionate in the drug); children and adolescents under 18 years of age; pregnancy; breastfeeding period; hypersensitivity to any component of the combination.

With caution

In patients already taking systemic glucocorticosteroids; in patients with increased sensitivity to the effects of sympathomimetics (with coronary artery disease, ischemic cardiomyopathy, severe heart failure, cardiac arrhythmias, including tachyarrhythmias, with arterial hypertension, glaucoma, hyperthyroidism, pheochromocytoma, diabetes mellitus, and with benign prostatic hyperplasia); in patients taking the drug for a long time, especially in high doses (monitoring of the patient’s condition is required to identify possible systemic effects).

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age.

Special Precautions

To ensure maximum treatment safety, as well as to maintain symptom control and select the minimum effective doses, constant monitoring of the patient’s condition is necessary.

The use, especially long-term, of drugs that have a local effect can cause sensitization and, in exceptional cases, the development of systemic side effects. In any such case, treatment should be discontinued and appropriate therapy initiated.

When using inhaled glucocorticosteroids, the recommended doses should not be exceeded: in case of persistent bronchospasm, additional doses of a beta₂-adrenergic receptor agonist may be required.

Treatment of patients already taking systemic glucocorticosteroids requires special caution and careful medical supervision, because the recovery of adrenal function, suppressed by long-term use of systemic glucocorticosteroids, occurs slowly. Before starting the use of the drug containing this combination, the patient’s condition must be stabilized by prescribing systemic glucocorticosteroids.

Patients who have been switched to inhaled glucocorticosteroids should additionally receive systemic glucocorticosteroids during stress or severe asthma attacks.

In patients with increased sensitivity to the effects of sympathomimetics, the latter should be used with extreme caution. In patients with coronary artery disease, arrhythmias, arterial hypertension, as well as in patients with glaucoma, hyperthyroidism, pheochromocytoma, diabetes mellitus, and benign prostatic hyperplasia, the drug should be used only in case of absolute necessity.

Patients with severe heart disease (e.g., ischemic cardiomyopathy, tachyarrhythmia, or severe heart failure) taking Salbutamol for respiratory diseases should be warned to inform their doctor if they experience chest pain or worsening symptoms of heart disease.

With the inhalation use of glucocorticosteroids, especially in high doses and for a long time, some systemic effects of glucocorticosteroids may develop, the occurrence of which with the inhalation route of administration is less likely than with oral administration of glucocorticosteroids. Possible systemic effects of glucocorticosteroids include: exogenous Cushing’s syndrome, suppression of adrenal function, growth retardation in children and adolescents, decreased bone mineral density, cataract, glaucoma and, less commonly, various psychological or behavioral disorders, including psychomotor hyperactivity, sleep disorders, anxiety, depression, or aggressiveness. Thus, it is important to use inhaled glucocorticosteroids in the minimum effective doses necessary to control bronchial asthma.

The initial and non-specific symptoms of adrenal insufficiency are anorexia, abdominal pain, weight loss, feeling of tiredness, headache, nausea, vomiting. Specific symptoms of adrenal insufficiency when using inhaled glucocorticosteroids are hypoglycemia with confusion and/or seizures. The development of adrenal crises can be triggered by trauma, surgery, infections, and rapid dose reduction. Patients taking high doses of the drug containing this combination require careful medical supervision; dose reduction of the drug should be carried out gradually. Assessment of adrenal reserve may also be required.

Effect on ability to drive vehicles and mechanisms

Patients who experience such adverse events as headache, muscle cramps, cardiac arrhythmias, development of angina attacks should refrain from driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Drug Interactions

Beta-blockers. Concurrent use of this combination and beta-blockers (e.g., propranolol) is not recommended, because Salbutamol and beta-blockers mutually suppress each other’s therapeutic effects. Therefore, the use of beta-blockers by patients with broncho-obstructive diseases while being treated with salbutamol can not only weaken its bronchodilatory effect but also cause bronchospasm. If the use of beta-blockers is absolutely necessary in such patients, the use of selective beta₁-blockers is preferable.

MAO inhibitors, tricyclic antidepressants. Due to the possible enhancement of salbutamol’s side effects when used concurrently with MAO inhibitors and tricyclic antidepressants, the likelihood of cardiac arrhythmias increases.

Digoxin. When salbutamol is used concurrently with digoxin, the likelihood of extrasystole increases.

Phenobarbital, phenytoin, rifampicin and other microsomal oxidation inducers. Phenobarbital, phenytoin, rifampicin and other microsomal oxidation inducers reduce the effectiveness of beclometasone.

Methandienone, estrogens. Methandienone, estrogens enhance the effect of beclometasone.

Disulfiram, metronidazole. Disulfiram and, to a lesser extent, metronidazole are drugs that can inhibit acetaldehyde dehydrogenase and delay the enzymatic biotransformation of ethanol at the acetaldehyde stage, which can lead to its accumulation in the body and cause the development of cardiovascular collapse, arrhythmias, respiratory failure, as well as neurological disorders with CNS depression.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.