Aerus^® (Aerosol) Instructions for Use

Marketing Authorization Holder

Binnopharm JSC (Russia)

ATC Code

B02AB01 (Aprotinin)

Active Substance

Aprotinin (Rec.INN registered by WHO)

Dosage Form

Aerus®

Metered inhalation aerosol 85 KIU/dose: 250 dose canister with applicators

Dosage Form, Packaging, and Composition

Metered inhalation aerosol in the form of a transparent colorless or pale-yellow solution.

Excipients: propellant HFC-134A, peppermint leaf oil, ethanol 96%, glycerol 96%.

* (Kallikrein Inactivating Units).

250 doses – metal aerosol cans with a metering valve (1) in a set with a mouthpiece, nasal applicator, and protective caps – cardboard packs.

Clinical-Pharmacological Group

Proteolysis inhibitor with antiviral action

Pharmacotherapeutic Group

Proteolysis inhibitor

Pharmacological Action

The main active substance of the Aerus^® drug – Aprotinin – is a low-molecular-weight natural polypeptide (58 amino acids) isolated from bovine lungs and possessing an inhibitory effect on proteolytic enzymes. Aprotinin inhibits trypsin, chymotrypsin, plasmin, plasma and tissue kallikrein, mast cell tryptase, cathepsin, leukocyte elastase (proteinase 3), prostasin, and other proteases by forming stable complexes with them.

Aprotinin has a dual action. Firstly, it exerts an antiviral effect by inhibiting the proteolysis of a specific viral protein, leading to direct inhibition of virus replication. Secondly, Aprotinin reduces the level of virus-induced and bacteria-induced proteolysis in tissues, preventing the development of pathological inflammatory processes formed as a result of an excess of proteases and a deficiency of their inhibitors.

Aprotinin reduces the concentration of active oxygen species in the focus of viral inflammation by inhibiting the proteolytic formation of xanthine oxidase (XO). Inhibition of the XO-dependent pathway of lipid peroxidation leads to a reduction in pathological inflammatory processes formed in the respiratory organs during viral infections.

Aprotinin suppresses the activation of a number of cytokines and chemokines, inhibits tissue migration of leukocytes, which exerts a pronounced anti-inflammatory effect at the site of infection.

Inhalations of the aprotinin aerosol do not cause local toxicity in the respiratory organs. The drug does not cause allergic reactions or signs of local irritant action upon contact with the mucous membranes of the respiratory tract.

Inhalations of the aprotinin aerosol do not suppress the development of antiviral immunity in infected patients.

Pharmacokinetics

Aprotinin enters the kidneys via the bloodstream. In the lysosomes of the kidneys, aprotinin molecules are completely broken down into shorter peptides and amino acids, after which the products are excreted in the urine.

The T_1/2 of aprotinin from the bloodstream is about 2 hours. There is no excretion of unchanged aprotinin by the kidneys even with large administered doses – about 1 million KIU.

Indications

• Treatment of infectious and inflammatory diseases of viral etiology (influenza and other acute respiratory viral infections).

ICD codes

Dosage Regimen

1 inhalation dose (1 dose 85 KIU) into each nasal passage every 2-4 hours (800-2000 KIU/day).

The maximum daily dose is 50-65 KIU/day per 1 kg of body weight.

The basic recommended course of inhalations: inhalation through the nose, exhalation through the mouth, for viral inflammation in the nasal cavity; inhalation through the mouth and exhalation through the nose – in the presence of symptoms of viral inflammation in the oropharynx, trachea, and bronchi. Combined inhalation of one dose into the nasal passages and through the mouth is possible.

The duration of the course is from 3 to 8 days depending on the severity of the disease with a frequency of every 2-4 hours.

Instructions for correct use

Before first use, press the metering valve twice.

Before each use, follow the following procedure

1. Remove the protective cap and shake the canister.
2. Exhale deeply.
3. Hold the inhaler in the position shown in the figure, when inhaling through the mouth, clasp the mouthpiece with your lips or when inhaling through the nose, insert the nasal applicator into the nostril.
4. Simultaneously with a deep inhalation, vigorously press the metering valve, which will release one aerosol dose. Hold your breath for 1-2 seconds, then remove the mouthpiece from your mouth, the nasal applicator from your nose, and exhale.
5. After use, put the protective cap back on the mouthpiece, which is installed on the metering head to protect it from damage.
6. If the drug has not been used for 3 days, it is necessary to press the metering valve once before a new use.

Adverse Reactions

Compared with parenteral administration, the risk of developing side effects with inhalation administration of aprotinin is unlikely.

From the cardiovascular system: decreased blood pressure, tachycardia, pallor of the skin.

From the central nervous system: psychotic reaction, hallucination, confusion.

Allergic reactions: rash, rhinitis, conjunctivitis, anaphylactic reactions (up to anaphylactic shock).

From the digestive system: nausea, vomiting.

Local reactions: dryness, bleeding of the mucous membranes of the respiratory tract.

Contraindications

• Disseminated intravascular coagulation syndrome;
• Allergic reactions (including to bovine protein);
• Pregnancy;
• Lactation period;
• Children under 18 years of age (due to lack of clinical experience in children);
• Hypersensitivity to aprotinin.

Use in Pregnancy and Lactation

The drug is contraindicated for use during pregnancy and lactation.

Pediatric Use

The drug is contraindicated for use in children under 18 years of age (due to lack of clinical experience in children).

Special Precautions

The mouthpiece and nasal applicator must be kept clean; they can be washed with warm water or a 40% aqueous solution of ethanol. If soap or other cleaning agents are used to wash the applicator, then it is necessary to rinse the applicator thoroughly with a stream of water.

The mouthpiece and nasal applicator from the Aerus^® set must not be used with other inhalation solutions, and the Aerus^® drug should not be used with other applicators.

If an anaphylactic reaction to Aprotinin occurs, generally accepted measures are taken (administration of epinephrine, prednisolone, plasma substitutes). Special attention is required for patients prone to allergies; preliminary administration of antihistamines is possible.

Overdose

Data on overdose of the Aerus^® drug are not provided.

Drug Interactions

Aprotinin inhibits the action of streptokinase and urokinase, therefore Aerus^® should not be used with these drugs.

Aprotinin should be mixed with caution with other medicinal products, especially with beta-lactam antibiotics, heparin, due to the possibility of their direct chemical interaction.

Storage Conditions

The drug should be stored in a dry place, protected from light and out of the reach of children, at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 3 years.

Do not allow damage to the hermetic seal of the canister body and its incineration after using the drug. The canister is under constant pressure, do not open it by force and do not expose it to temperatures above 50°C (122°F). Protect from direct sunlight, heat, and frost.

Dispensing Status

The drug is dispensed by prescription.

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.