Espa-Nats^® (Powder) Instructions for Use

Marketing Authorization Holder

Aristo Pharma, GmbH (Germany)

Manufactured By

Lindopharm, GmbH (Germany)

ATC Code

R05CB01 (Acetylcysteine)

Active Substance

Acetylcysteine (Rec.INN registered by WHO)

Dosage Forms

	Espa-Nats®	Powder for oral solution 200 mg: sachets 20 pcs.
		Powder for oral solution 600 mg: sachets 20 pcs.

Dosage Form, Packaging, and Composition

Powder for oral solution white or almost white, homogeneous, without agglomerates and foreign particles, with a fruity odor.

Excipients: sucrose – 2744 mg, orange flavor – 50 mg, colloidal silicon dioxide – 3 mg, tartaric acid – 2 mg, sodium chloride – 0.9 mg.

3 g – sachets made of three-layer material (20) – cardboard packs.

Powder for oral solution white or almost white, homogeneous, without agglomerates and foreign particles, with a fruity odor.

Excipients: sucrose – 2344 mg, orange flavor – 50 mg, colloidal silicon dioxide – 3 mg, tartaric acid – 2 mg, sodium chloride – 0.9 mg.

3 g – sachets made of three-layer material (20) – cardboard packs.

Clinical-Pharmacological Group

Mucolytic drug

Pharmacotherapeutic Group

Mucolytic agent

Pharmacological Action

Mucolytic agent, a derivative of the amino acid cysteine. It has a mucolytic effect, increases the volume of sputum, and facilitates its discharge due to a direct effect on the rheological properties of sputum. The action of acetylcysteine is associated with the ability of its sulfhydryl groups to break intra- and intermolecular disulfide bonds of acidic mucopolysaccharides of sputum, which leads to depolarization of mucoproteins and a decrease in sputum viscosity.

It reduces induced hyperplasia of mucoid cells, enhances the production of surfactant compounds by stimulating type II pneumocytes, stimulates mucociliary activity, which leads to an improvement in mucociliary clearance.

It remains active in the presence of purulent, mucopurulent and mucous sputum.

It increases the secretion of less viscous sialomucins by goblet cells, reduces bacterial adhesion to epithelial cells of the bronchial mucosa. It stimulates bronchial mucosal cells, the secretion of which lyses fibrin. It has a similar effect on the secretion formed in inflammatory diseases of the ENT organs.

It has an antioxidant effect due to the ability of its reactive sulfhydryl groups (SH-groups) to bind with oxidative radicals and thus neutralize them.

Acetylcysteine easily penetrates into the cell, is deacetylated to L-cysteine, from which intracellular glutathione is synthesized. Glutathione is a highly reactive tripeptide, a powerful antioxidant and cytoprotector, neutralizing endogenous and exogenous free radicals and toxins. Acetylcysteine prevents depletion and helps increase the synthesis of intracellular glutathione, which is involved in the redox processes of cells, promoting the detoxification of harmful substances. This explains the action of acetylcysteine as an antidote for paracetamol poisoning.

It protects alpha1-antitrypsin (elastase inhibitor) from the inactivating effect of HOCI, an oxidant produced by myeloperoxidase of active phagocytes. It also has an anti-inflammatory effect (due to suppression of the formation of free radicals and reactive oxygen species responsible for the development of inflammation in the lung tissue).

Pharmacokinetics

When taken orally, it is well absorbed from the gastrointestinal tract. It is largely subject to the first-pass effect through the liver, which leads to a decrease in bioavailability. Plasma protein binding is up to 50% (4 hours after oral administration). It is metabolized in the liver and possibly in the intestinal wall. It is detected in plasma unchanged, as well as in the form of metabolites – N-acetylcysteine, N,N-diacetylcysteine and cysteine ester.

Renal clearance is 30% of total clearance.

Indications

As a mucolytic agent for the treatment of acute and chronic respiratory diseases associated with excessive bronchial secretion: bronchitis; tracheitis; bronchiolitis; pneumonia; bronchiectasis; cystic fibrosis; lung abscess; pulmonary emphysema; laryngotracheitis; interstitial lung diseases; lung atelectasis (due to bronchial blockage by a mucous plug); for catarrhal and purulent otitis media, sinusitis, sinusitis (to facilitate secretion discharge); for the removal of viscous secretion from the respiratory tract in post-traumatic and postoperative conditions.

Preparation for bronchoscopy, bronchography, aspiration drainage.

For washing abscesses, nasal passages, maxillary sinuses, middle ear, treatment of fistulas, surgical field during operations on the nasal cavity and mastoid process.

As an antidote in adults and children for the treatment of paracetamol overdose.

ICD codes

Dosage Regimen

It is taken orally, in the form of inhalations, intratracheally, and also topically. It is administered intravenously.

The dose depends on the age of the patient. The frequency and duration of the course are set individually.

Topically – instilled into the external auditory canal and nasal passages.

Intravenous therapy is intended for use in ICU patients and only when oral administration of acetylcysteine is not possible.

Adverse Reactions

Blood and lymphatic system disorders very rarely – decreased platelet aggregation.

Immune system disorders uncommon – hypersensitivity reactions, angioedema; very rarely – anaphylactic reactions up to anaphylactic shock, bleeding (single reports due to the presence of a hypersensitivity reaction).

Nervous system disorders rarely – headache.

Ear and labyrinth disorders uncommon – tinnitus.

Cardiovascular system disorders uncommon – tachycardia, decreased blood pressure, cases of collapse have been described with the use of acetylcysteine.

Respiratory system disorders rarely – shortness of breath, bronchospasm (mainly in patients with bronchial hyperreactivity in bronchial asthma).

Gastrointestinal system disorders uncommon – stomatitis, abdominal pain, diarrhea, nausea, vomiting; rarely – heartburn, dyspepsia.

Skin and subcutaneous tissue disorders uncommon – skin itching, skin rash, exanthema, urticaria; very rarely – Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome).

General disorders very rarely – fever; frequency unknown – facial edema.

Contraindications

Hypersensitivity to acetylcysteine; peptic ulcer of the stomach and duodenum in the acute phase, breastfeeding period, children under 2 years of age (except for use as an antidote).

Contraindications for use in children under 18 years of age depend on the dosage form and are indicated in the instructions for use of the drug used.

With caution

Hemoptysis, pulmonary hemorrhage; history of peptic ulcer of the stomach and duodenum; esophageal varices; bronchial asthma; obstructive bronchitis; hepatic and/or renal failure; adrenal diseases; arterial hypertension; histamine intolerance.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and breastfeeding.

Use in Hepatic Impairment

Acetylcysteine should be used with caution in patients with liver diseases.

Use in Renal Impairment

Acetylcysteine should be used with caution in patients with kidney diseases.

Pediatric Use

Contraindicated for use in children under 2 years of age.

Contraindications for use in children under 18 years of age depend on the dosage form and are indicated in the instructions for use of the drug used.

Special Precautions

In patients with bronchial asthma and obstructive bronchitis, Acetylcysteine should be used with caution and under systematic control of bronchial patency.

Acetylcysteine may slightly affect the metabolism of histamine, so caution should be exercised when using this agent for long-term treatment of patients suffering from histamine intolerance, if symptoms of intolerance appear (headache, vasomotor rhinitis, itching).

If changes in the skin and mucous membranes occur, you should immediately consult a doctor, and the use of acetylcysteine should be discontinued.

Use should be avoided in patients with renal and/or hepatic insufficiency to avoid additional formation of nitrogenous compounds.

If the patient is unable to cough effectively, drainage or aspiration of the secretion should be performed.

Acetylcysteine should not be taken immediately before bedtime (it is recommended to take it 4 hours before bedtime).

Strict adherence to the correspondence between the route of administration and the dosage form used must be observed.

Drug Interactions

Simultaneous use of acetylcysteine with antitussives may increase sputum stagnation due to suppression of the cough reflex.

When used simultaneously with antibiotics (including tetracycline, ampicillin, amphotericin B), their interaction with the thiol group of acetylcysteine is possible.

Simultaneous administration of acetylcysteine and nitroglycerin may cause a pronounced decrease in blood pressure and headache.

Simultaneous use of acetylcysteine and carbamazepine may be accompanied by a decrease in the concentration of carbamazepine to a subtherapeutic level.

Acetylcysteine eliminates the toxic effects of paracetamol.

Acetylcysteine may affect the results of the colorimetric determination of salicylates.

Acetylcysteine may affect the results of the analysis of ketones in urine.

When acetylcysteine comes into contact with metals and rubber, sulfides with a characteristic odor are formed.

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

Over-the-Counter

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.