Asmalib^® Air (Aerosol) Instructions for Use

Marketing Authorization Holder

PSK Pharma, LLC (Russia)

ATC Code

R03BA08 (Ciclesonide)

Active Substance

Ciclesonide (Rec.INN registered by WHO)

Dosage Forms

	Asmalib® Air	Metered-dose inhalation aerosol 40 mcg/dose: 120 doses 1 canister
		Metered-dose inhalation aerosol 80 mcg/dose: 120 doses 1 canister
		Metered-dose inhalation aerosol 160 mcg/dose: 120 doses 1 canister

Dosage Form, Packaging, and Composition

Metered-dose inhalation aerosol

Excipients : lecithin, tetrafluoroethane (HFA-134a), ethanol 3625 mcg.

120 doses – aluminum aerosol canisters with a metering valve (1) – cardboard packs.

Metered-dose inhalation aerosol

Excipients : lecithin, tetrafluoroethane (HFA-134a), ethanol 3625 mcg.

120 doses – aluminum aerosol canisters with a metering valve (1) – cardboard packs.

Metered-dose inhalation aerosol

Excipients : lecithin, tetrafluoroethane (HFA-134a), ethanol 3600 mcg.

120 doses – aluminum aerosol canisters with a metering valve (1) – cardboard packs.

Clinical-Pharmacological Group

Inhaled corticosteroids

Pharmacotherapeutic Group

Drugs for the treatment of obstructive airway diseases; other agents for inhalation administration used for the treatment of obstructive airway diseases; glucocorticosteroids

Pharmacological Action

Glucocorticosteroid for topical use by inhalation. Ciclesonide exhibits low affinity for glucocorticoid receptors.

After inhalation, it is converted in the lungs by enzymes into the main metabolite (des-ciclesonide, C21-desmethylpropionylciclesonide), which has pronounced anti-inflammatory activity and is therefore considered the active metabolite.

Ciclesonide suppresses inflammatory reactions in the airways and thus alleviates the symptoms of bronchial asthma and improves lung function.

Pharmacokinetics

Oral or intravenous administration of radiolabeled ciclesonide showed that the extent of absorption is 24.5%.

When the drug is taken orally, the bioavailability of both ciclesonide and the active metabolite is negligible (<0.5% for ciclesonide, and <1% for the metabolite) due to the significant influence of presystemic metabolism.

The accumulation of ciclesonide in the lungs of healthy patients is over 50%.

According to this figure, the systemic bioavailability for the active metabolite after an inhalation dose is over 50%.

Since the bioavailability of the active metabolite when ciclesonide is taken orally is less than 1%, the drug taken by inhalation does not have a systemic effect.

After intravenous administration to healthy volunteers, ciclesonide is rapidly distributed due to its high lipophilicity.

The V_d averages 2.9 L/kg for ciclesonide and 12.1 L/kg for des-ciclesonide.

The binding of ciclesonide to plasma proteins is about 99%, and that of the active metabolite is 98-99%.

Ciclesonide is hydrolyzed to a biologically active metabolite by the enzyme esterase in the lungs.

The active metabolite of ciclesonide is mainly metabolized to hydroxylated inactive metabolites via catalysis involving the CYP3A4 isoenzyme.

The clearance of ciclesonide is about 152 L/h and that of des-ciclesonide is about 228 L/h, which indicates a high degree of hepatic extraction of the substance.

Ciclesonide is excreted mainly in the feces, both after oral administration and after intravenous administration, indicating its predominant excretion in the bile.

In patients with hepatic insufficiency, a prolonged T_1/2 and a slight increase in the retention time of des-ciclesonide (active metabolite) in the blood were noted.

Because of this, accumulation of this substance when taking the drug in high doses cannot be ruled out.

Indications

Bronchial asthma.

ICD codes

Dosage Regimen

It is used only for oral inhalation.

It is intended for daily use over a long period of time.

The initial dose should be selected depending on the severity of the condition.

When the desired clinical effect is achieved, the dose should be reduced to the minimum necessary to control the manifestations of the disease.

For adults and adolescents over 12 years of age, elderly patients, the recommended daily dose is from 160 mcg to 640 mcg; a dose of 640 mcg should be divided into 2 doses per day.

Maximum dose: 640 mcg 2 times/day.

Children over 6 years: the recommended daily dose is 80-160 mcg once a day or 80 mcg 2 times/day.

Adverse Reactions

From the cardiovascular system: rarely – tachycardia, increased blood pressure.

From the digestive system infrequently – nausea, vomiting, unpleasant taste: rarely – abdominal pain, dyspepsia.

Local reactions infrequently – sensation of irritation and sore throat, dryness of the oral and pharyngeal mucosa.

Allergic reactions rarely – angioedema, hypersensitivity.

Infectious and parasitic diseases infrequently – fungal infections of the oral cavity.

From the respiratory system infrequently – dysphonia, cough after inhalation, paradoxical bronchospasm.

From the skin infrequently – eczema and skin rash.

Inhaled corticosteroids can cause systemic effects, especially when used in high doses for a long time.

Possible systemic effects include Cushing’s syndrome and Cushing-like symptoms, such as adrenal suppression, growth retardation in children and adolescents, decreased bone density, cataracts and glaucoma.

This is why it is important that the dose of inhaled corticosteroids is reduced to the minimum effective dose that provides satisfactory control of disease symptoms.

Contraindications

Children under 6 years of age; hypersensitivity to ciclesonide.

Use in Pregnancy and Lactation

Controlled studies in pregnant women have not been conducted.

Nevertheless, after inhalation of the drug, the concentration of ciclesonide in the blood serum is very low, therefore, the effect on the embryo and potential reproductive toxicity are insignificant.

The excretion of ciclesonide or its metabolites in breast milk has not been studied.

Like other inhaled corticosteroids, Ciclesonide can be used during pregnancy and lactation as prescribed by a doctor if the expected therapeutic effect outweighs the risk of possible side effects.

Newborns whose mothers received corticosteroids during pregnancy should be under medical supervision to rule out adrenal hypofunction.

Special Precautions

Use with caution in patients with active or chronic pulmonary tuberculosis; in patients with bacterial, viral or fungal infections of the respiratory tract.

Ciclesonide is not indicated for the treatment of status asthmaticus or other acute attacks of bronchial asthma requiring intensive therapeutic measures.

The dose of ciclesonide may be reduced in patients who require the use of oral corticosteroids.

For patients switched from oral corticosteroid therapy to inhalation treatment with ciclesonide, decreased adrenal cortex function may persist for a significant period of time after the switch.

The possibility of developing adverse effects from the use of oral corticosteroids may persist for some time after their discontinuation.

In such cases, it is recommended to monitor the reserve function of the adrenal cortex.

The possibility of residual impairment of adrenal cortex function in a critical situation (therapeutic or surgical) and in other individual cases that may be caused by a stress reaction should always be taken into account, and therefore appropriate corticosteroid treatment should be initiated.

In case of adrenal cortex insufficiency or serious exacerbations, the dose of ciclesonide should be increased; if necessary, oral corticosteroids should be used.

If an infection develops, antibiotics should be used.

Paradoxical bronchospasm with increased wheezing and other symptoms of bronchial narrowing that appear immediately after inhalation should be treated with a fast-acting bronchodilator, which usually leads to rapid relief.

The patient should be examined, and ciclesonide therapy should be continued only if, after careful consideration, the expected benefit outweighs the possible risk.

The relationship between the severity of asthma and the overall predisposition to acute bronchial reactions should be taken into account.

When transferring patients from systemic corticosteroids to inhalation therapy, allergic reactions (for example, allergic rhinitis, eczema) that were previously suppressed by systemic drugs may appear.

In such cases, symptomatic therapy with antihistamines should be carried out, including topical and local preparations containing corticosteroids.

Use in pediatrics

The use of ciclesonide in children under 6 years of age is contraindicated.

The effect of inhaled corticosteroids with long-term use in children has not been fully elucidated.

The doctor should constantly monitor the growth development of children taking corticosteroids for a long period.

If growth slows, therapy should be reconsidered to reduce the dose of inhaled corticosteroids, if possible, to the minimum effective dose that allows control of bronchial asthma symptoms.

Drug Interactions

According to in vitro data, CYP3A4 is the main enzyme involved in the metabolism of the active metabolite of ciclesonide – M1 (des-ciclesonide) in humans.

In drug interaction studies between ciclesonide and ketoconazole, as a strong CYP3A4 inhibitor, the effect on the active metabolite des-ciclesonide increased approximately 3.5 times, while no effect on Ciclesonide was noted.

Based on this, the simultaneous use of potential CYP3A4 inhibitors and ciclesonide should be avoided.

A study of the interaction between ciclesonide and the CYP3A4 substrate erythromycin did not show any interaction between them.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°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.