Pulmobriz®

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PULMOBRISE® (PULMOBREATHE®)

Composition:

Active substances: acetylcysteine, ambroxol hydrochloride;

One coated tablet contains acetylcysteine 200 mg, ambroxol hydrochloride 30 mg;

Excipients: lactose monohydrate; povidone (K-30); colloidal anhydrous silicon dioxide; crospovidone; sodium lauryl sulfate; hydrogenated vegetable oil;

Coating composition: Opadry® 200 Orange (polyvinyl alcohol; talc; yellow FCF dye (E 110); titanium dioxide (E 171); glycerol monostearate; polyvinyl acetate phthalate; sodium lauryl sulfate; sodium bicarbonate); Opaglos® 2 (sodium carboxymethylcellulose; maltodextrin; glucose monohydrate; lecithin; vanillin).

Pharmaceutical form. Coated tablets.

Main physicochemical properties: round, biconvex coated tablets, orange in color. Tablets have a characteristic odor (vanilla scent).

Pharmacotherapeutic group. Medicinal products used in cough and colds. Mucolytic agents. Combinations. ATC code R05C B10.

Pharmacological Properties

Pharmacodynamics

Ambroxol hydrochloride exerts a pronounced expectorant, mucolytic, anti-inflammatory, immunomodulatory, antioxidant, and mild antitussive effect. It stimulates serous cells of bronchial mucosal glands, increases the amount of serous secretion, and thereby corrects the disturbed ratio between serous and mucous components. This leads to normalization of the rheological properties of sputum, reducing its viscosity and adhesive properties. Ambroxol directly enhances the motility of ciliated bronchial epithelium, prevents ciliary clumping, and improves mucociliary clearance of sputum. Ambroxol increases pulmonary surfactant levels by directly acting on type II pneumocytes in alveoli and Clara cells in bronchioles, and also prevents its degradation in pneumocytes. Ambroxol does not cause bronchoconstriction; on the contrary, it improves respiratory function. It has been demonstrated that ambroxol reduces bronchial muscle hyperreactivity in patients with asthma.

The local anesthetic effect of ambroxol hydrochloride has been observed in a rabbit eye model, which may be explained by its sodium channel-blocking properties. In vitro studies have shown that ambroxol hydrochloride blocks neuronal sodium channels; this binding was reversible and concentration-dependent.

Ambroxol has anti-inflammatory effects, as demonstrated in vitro, possesses antioxidant properties, stimulates local immunity, and promotes regeneration of the natural surfactant layer. With ambroxol administration, patient complaints of cough and sputum production are significantly reduced, proportional to the intensity of treatment.

Clinical trials involving patients with pharyngitis have demonstrated a significant reduction in throat pain and redness with the use of ambroxol hydrochloride.

Pharmacological properties contributing to rapid pain relief during treatment of upper respiratory tract disorders have been observed in clinical efficacy studies of ambroxol inhalation formulations.

Acetylcysteine is a mucolytic and expectorant active substance. Due to its free sulfhydryl group, it breaks disulfide bonds in mucopolysaccharides of sputum, thereby reducing the viscosity of bronchial secretions. It enhances mucociliary clearance. It exerts antioxidant effects by scavenging free radicals. It increases glutathione synthesis, an important factor in detoxification; due to this property, acetylcysteine is used in the treatment of acute poisoning with paracetamol, phenols, aldehydes, and other substances.

Pharmacokinetics

Ambroxol hydrochloride

Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and sufficiently complete, with linear dose-dependency within the therapeutic range. Maximum plasma concentrations are reached within 1–2.5 hours after oral administration of immediate-release dosage forms.

Following oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and extensive, with the highest concentration of the active substance found in the lungs.

Approximately 30% of the dose is eliminated via presystemic metabolism after oral administration. Ambroxol hydrochloride is metabolized primarily in the liver through glucuronidation and cleavage to dibromanthranilic acid (approximately 10% of the dose). After 3 days of oral administration, about 6% of the dose is excreted in urine unchanged, and approximately 26% – in conjugated form.

The plasma elimination half-life is approximately 10 hours.

In patients with impaired liver function, elimination of ambroxol hydrochloride is reduced, resulting in plasma levels 1.3–2 times higher.

Age and sex do not have a clinically significant effect on the pharmacokinetics of ambroxol hydrochloride; therefore, no dose adjustment is required.

Food intake does not affect the bioavailability of ambroxol hydrochloride.

Acetylcysteine

After oral administration, acetylcysteine is rapidly and completely absorbed and undergoes hepatic metabolism to form cysteine, a pharmacologically active metabolite, as well as dithioacetylcysteine, cystine, and subsequently mixed disulfides. Bioavailability is very low – approximately 10%. Maximum plasma concentration is reached within 1–3 hours after administration. Plasma protein binding is approximately 50%. Acetylcysteine is excreted by the kidneys as inactive metabolites (inorganic sulfates, dithioacetylcysteine).

The elimination half-life is primarily determined by rapid hepatic biotransformation and is approximately 1 hour. In cases of impaired liver function, the elimination half-life is prolonged to 8 hours.

Clinical characteristics.

Indications.

Treatment of acute and chronic respiratory tract diseases associated with impaired bronchial secretion and mucus clearance, including acute and chronic bronchitis, chronic obstructive pulmonary diseases, pneumonia, bronchiectasis, bronchial asthma, cystic fibrosis, laryngitis, tracheitis.

Contraindications.

Hypersensitivity to ambroxol, acetylcysteine, or any other component of the medicinal product. Acute phase of gastric and duodenal peptic ulcer. Hemoptysis, pulmonary hemorrhage, severe exacerbation of bronchial asthma.

Interaction with other medicinal products and other types of interactions.

Concomitant use of PULMOBRIZ® and cough suppressants may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination is possible only after careful evaluation by a physician of the expected benefit versus potential risk of use.

Acetylcysteine reduces the hepatotoxic effect of paracetamol; it may act as a cysteine donor and increase glutathione levels, promoting detoxification of oxygen free radicals and certain toxic substances in the body.

Activated charcoal reduces the effectiveness of acetylcysteine.

Synergism between acetylcysteine and bronchodilators has been observed.

When used concomitantly with antibiotics such as tetracycline (except doxycycline), ampicillin, amphotericin B, cephalosporins, and aminoglycosides, interaction with the thiol group of acetylcysteine may occur, leading to reduced activity of both agents. Therefore, the interval between administration of these drugs should be at least 2 hours. This does not apply to cefixime and loracarbef.

Ambroxol increases the concentration of amoxicillin, cefuroxime, erythromycin, and doxycycline in sputum and bronchopulmonary secretions.

Concomitant use of nitroglycerin and acetylcysteine has been associated with marked hypotension and significant dilation of temporal arteries. When simultaneous use of nitroglycerin and acetylcysteine is necessary, patients should be monitored for hypotension, which may be severe; patients should also be warned about possible headache.

Effect on laboratory tests. Acetylcysteine may alter results of quantitative colorimetric assays and urine ketone testing.

Special precautions for use.

There have been isolated reports of severe skin reactions (multiform erythema, Stevens-Johnson syndrome, Lyell's syndrome, and acute generalized exanthematous pustulosis) occurring in temporal association with administration of ambroxol hydrochloride or acetylcysteine.

In most cases, these reactions could be explained by the severity of the underlying disease in patients and/or concomitant use of other medications. At the initial stage of Stevens-Johnson syndrome or Lyell's syndrome, patients may present with nonspecific, flu-like symptoms such as fever, malaise, rhinitis, cough, and sore throat. These nonspecific, flu-like symptoms may lead to inappropriate symptomatic treatment with cough and cold remedies. If signs of progressive skin or mucosal rash appear, the drug should be discontinued immediately and medical help should be sought.

Since ambroxol may enhance mucus secretion, the drug should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g., in rare conditions such as primary ciliary dyskinesia) due to the risk of mucus accumulation.

Acetylcysteine may cause liquefaction of bronchial secretions and increase their volume, primarily at the beginning of treatment. If the patient is unable to effectively expectorate sputum, postural drainage and bronchoaspiration may be necessary.

The drug should be used with caution in patients with bronchial asthma due to the risk of bronchospasm. If bronchospasm occurs, treatment with the drug should be discontinued immediately.

Since mucolytic agents may damage the mucosal barrier, caution is recommended when administering the drug to patients with a history of gastric or duodenal ulcer, especially when used concomitantly with other medications that irritate the gastric mucosa.

Use with caution in patients with renal impairment or severe liver disease (the dosing interval should be prolonged or the dose reduced). In patients with severe renal insufficiency, accumulation of metabolites formed in the liver may occur.

Acetylcysteine affects histamine metabolism; therefore, long-term therapy should not be prescribed to patients with histamine intolerance, as it may lead to symptoms of intolerance (headache, vasomotor rhinitis, pruritus).

Acetylcysteine may have a slight hydrogen sulfide odor due to the presence of a sulfhydryl group in the acetylcysteine molecule. A sulfur-like odor is not an indication of drug deterioration but is characteristic of the active substance.

Excipients.

The medicinal product contains lactose and glucose. If the patient has a known intolerance to certain sugars, consultation with a physician is recommended before taking this medicinal product.

The colorant Yellow West FCF (E 110) may cause allergic reactions.

Use during pregnancy or breastfeeding.

Pregnancy. The drug is not recommended during the first trimester of pregnancy.

There are no adequate data on the teratogenic effects of ambroxol hydrochloride and acetylcysteine on the fetus. Therefore, the drug may be used during the second and third trimesters of pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding. Since ambroxol hydrochloride and acetylcysteine pass into breast milk, it is undesirable to take the drug during breastfeeding. If treatment is necessary, breastfeeding should be discontinued.

Fertility. There are no data on adverse effects on fertility.

Ability to affect reaction rate when driving or operating machinery.

There are no data on the effect on reaction speed when driving or operating machinery.

Method of Administration and Dosage.

Dosage for adults and children aged 12 years and older: 1 tablet 3 times a day.

Do not exceed the recommended dose.

The duration of treatment should not exceed 5–7 days without consulting a physician.

Children.

For use in children aged 12 years and older.

Overdose.

There is no data on cases of overdose with oral formulations of acetylcysteine and ambroxol.

Ambroxol was well tolerated after oral administration of up to 25 mg/kg/day. In cases of ambroxol or acetylcysteine overdose, no severe signs of intoxication have been observed.

Symptoms reported in individual case reports of overdose and accidental ingestion correspond to known adverse reactions.

Symptoms: nausea, vomiting, short-term restlessness, diarrhea, hypersalivation, reduction in arterial blood pressure. In children, there is a risk of hypersecretion.

Treatment: symptomatic treatment is recommended.

Side effects.

Immune system disorders: hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock, and angioedema.

Skin and subcutaneous tissue disorders: pruritus, urticaria, rash, eczema; severe skin reactions (erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), acute generalized exanthematous pustulosis).

Gastrointestinal disorders: nausea, oral numbness, heartburn, vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth, dry throat, stomatitis, bad breath, hypersalivation.

Respiratory system disorders: decreased sensitivity in the pharynx, dyspnea (as a hypersensitivity reaction), bronchospasm (mainly in patients with bronchial hyperreactivity associated with bronchial asthma), rhinorrhea.

Aural and labyrinthine disorders: tinnitus.

Nervous system disorders: headache, dysgeusia (taste disturbance).

Cardiovascular disorders: tachycardia, arterial hypotension.

General disorders: fever, mucosal reactions.

Very rare cases of bleeding have been reported during acetylcysteine use, mostly associated with hypersensitivity reactions; cases of anemia and hemorrhage have also been observed.

Cases of reduced platelet aggregation have been noted, although there is no clinical confirmation of this effect.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug authorization is important. It allows continuous monitoring of the benefit-risk ratio of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging, out of the reach of children, at a temperature not exceeding 25 °C.

Packaging.

9 tablets per blister, 1 blister per cardboard pack; 20 tablets per blister, 1 or 2 blisters per cardboard pack.

Supply classification.

Over-the-counter.

Manufacturer.

MediTop Pharmaceutical Ltd.

Manufacturer's address and location.

Edi Endre u. 1., Pilisborosjenő, 2097, Hungary.

Marketing Authorization Holder.

TOV "Movi Health"

Address of the Marketing Authorization Holder.

162A, Shevchenka St., Shevchenkove, Kyiv-Sviatoshyn District, Kyiv Oblast, 08140, Ukraine.

INSTRUCTION

for medical use of the medicinal product

PULMOBRIZ®

(PULMOBREATHE®)

Composition:

Active substances: acetylcysteine, ambroxol hydrochloride;

One coated tablet contains acetylcysteine 200 mg, ambroxol hydrochloride 30 mg;

Excipients: lactose monohydrate; povidone (K-30); colloidal anhydrous silicon dioxide; crospovidone; sodium lauryl sulfate; hydrogenated vegetable oil;

Coating composition: Opadry® 200 Orange (polyvinyl alcohol; talc; yellow azo dye FCF (E 110); titanium dioxide (E 171); glycerol monostearate; polyvinyl acetate phthalate; sodium lauryl sulfate; sodium bicarbonate); Opaglos® 2 (sodium carboxymethylcellulose; maltodextrin; glucose monohydrate; lecithin; vanillin).

Pharmaceutical form. Coated tablets.

Main physicochemical properties: round, biconvex, orange-colored coated tablets. Tablets have a specific odor (vanilla scent).

Pharmacotherapeutic group. Medicinal products used in cough and colds. Mucolytics. Combinations. ATC code: R05C B10.

Pharmacological Properties

Pharmacodynamics

Ambroxol hydrochloride exerts a pronounced expectorant, mucolytic, anti-inflammatory, immunomodulatory, antioxidant, and mild antitussive effect. It stimulates serous cells of bronchial mucosal glands, increases the amount of serous secretion, and thereby normalizes the disturbed ratio between serous and mucous components. This leads to normalization of sputum rheological properties, reducing its viscosity and adhesive characteristics. Ambroxol directly stimulates ciliary activity of bronchial ciliated epithelium, prevents ciliary adhesion, and improves mucociliary clearance of sputum. Ambroxol increases pulmonary surfactant levels by directly affecting type II pneumocytes in alveoli and Clara cells in bronchioles, and also prevents its degradation in pneumocytes. Ambroxol does not cause bronchoconstriction; on the contrary, it improves respiratory function. It has been demonstrated that ambroxol reduces bronchial muscle hyperreactivity in asthmatic patients.

The local anesthetic effect of ambroxol hydrochloride has been observed in a rabbit eye model, which may be explained by its sodium channel-blocking properties. In vitro studies have shown that ambroxol hydrochloride blocks neuronal sodium channels; binding was reversible and concentration-dependent.

Ambroxol has anti-inflammatory effects, as demonstrated in vitro, possesses antioxidant properties, stimulates local immunity, and promotes regeneration of the natural surfactant layer. With ambroxol administration, patient complaints of cough and sputum production significantly decrease in accordance with treatment intensity.

Clinical trials involving patients with pharyngitis have demonstrated a significant reduction in throat pain and redness with ambroxol hydrochloride use.

Pharmacological properties contributing to rapid pain relief during treatment of upper respiratory tract disorders have been observed in clinical efficacy studies of ambroxol inhalation forms.

Acetylcysteine is a mucolytic and expectorant active substance. Due to its free sulfhydryl group, it breaks disulfide bonds in mucopolysaccharides of sputum, resulting in reduced viscosity of bronchial secretions. It enhances mucociliary clearance. It exerts antioxidant effects by scavenging free radicals. It increases glutathione synthesis, an important detoxification factor; due to this property, acetylcysteine is used in the treatment of acute poisoning with paracetamol, phenols, aldehydes, and other substances.

Pharmacokinetics

Ambroxol hydrochloride

Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and sufficiently complete, with linear dose dependency within the therapeutic range. Maximum plasma concentrations are reached within 1–2.5 hours after oral administration of immediate-release dosage forms.

After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and extensive, with the highest concentration of the active substance found in the lungs.

Approximately 30% of the dose is eliminated via presystemic metabolism after oral administration. Ambroxol hydrochloride is metabolized primarily in the liver via glucuronidation and degradation to dibromanthranilic acid (approximately 10% of the dose). After 3 days of oral administration, about 6% of the dose is excreted unchanged in urine, and approximately 26% of the dose – as conjugated forms.

The elimination half-life from plasma is approximately 10 hours.

In patients with impaired liver function, elimination of ambroxol hydrochloride is reduced, resulting in plasma levels 1.3–2 times higher.

Age and sex have no clinically significant effect on the pharmacokinetics of ambroxol hydrochloride; therefore, no dose adjustment is required.

Food intake does not affect the bioavailability of ambroxol hydrochloride.

Acetylcysteine

After oral administration, acetylcysteine is rapidly and completely absorbed and undergoes hepatic metabolism to form cysteine, a pharmacologically active metabolite, as well as diacetylcysteine, cystine, and subsequently mixed disulfides. Bioavailability is very low – approximately 10%. Maximum plasma concentration is reached within 1–3 hours after administration. Plasma protein binding is approximately 50%. Acetylcysteine is excreted by the kidneys as inactive metabolites (inorganic sulfates, diacetylcysteine).

The elimination half-life is primarily determined by rapid hepatic biotransformation and is approximately 1 hour. In cases of impaired liver function, the elimination half-life is prolonged to 8 hours.

Clinical characteristics.

Indications.

Treatment of acute and chronic respiratory tract diseases associated with impaired bronchial secretion and mucus clearance, including acute and chronic bronchitis, chronic obstructive pulmonary diseases, pneumonia, bronchiectasis, bronchial asthma, cystic fibrosis, laryngitis, tracheitis.

Contraindications.

Hypersensitivity to ambroxol, acetylcysteine, or other components of the medicinal product. Acute peptic ulcer of the stomach or duodenum. Hemoptysis, pulmonary hemorrhage, severe exacerbation of bronchial asthma.

Interaction with other medicinal products and other forms of interactions.

Concomitant use of PULMOBRIZ® and cough suppressants may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination should only be used after careful assessment by a physician of the expected benefit versus possible risk.

Acetylcysteine reduces the hepatotoxic effect of paracetamol; it may act as a cysteine donor and increase glutathione levels, promoting detoxification of oxygen free radicals and certain toxic substances in the body.

Activated charcoal reduces the efficacy of acetylcysteine.

Synergism between acetylcysteine and bronchodilators has been observed.

When used concomitantly with antibiotics such as tetracyclines (except doxycycline), ampicillin, amphotericin B, cephalosporins, and aminoglycosides, interaction with the thiol group of acetylcysteine may occur, leading to reduced activity of both agents. Therefore, the interval between administration of these drugs should be at least 2 hours. This does not apply to cefixime and loracarbef.

Ambroxol increases the concentration of amoxicillin, cefuroxime, erythromycin, and doxycycline in sputum and bronchopulmonary secretions.

Significant hypotension and marked dilation of temporal arteries have been reported when nitroglycerin and acetylcysteine are used concomitantly. If simultaneous use of nitroglycerin and acetylcysteine is necessary, patients should be monitored for potentially severe hypotension; they should also be warned about the possibility of headache.

Effect on laboratory tests. Acetylcysteine may alter results of quantitative colorimetric assays and urine ketone testing.

Special precautions for use.

There have been isolated reports of severe skin reactions (erythema multiforme, Stevens–Johnson syndrome, Lyell’s syndrome, and acute generalized exanthematous pustulosis) occurring in temporal association with the use of ambroxol hydrochloride or acetylcysteine.

In most cases, these reactions could be explained by the severity of the underlying disease in patients and/or concomitant use of other medications. At the initial stage of Stevens–Johnson syndrome or Lyell’s syndrome, patients may experience nonspecific, flu-like symptoms such as fever, malaise, rhinitis, cough, and sore throat. These nonspecific flu-like symptoms may lead to inappropriate symptomatic treatment with cough and cold remedies. If signs of progression of skin or mucosal rash appear, the medication should be discontinued immediately and medical help should be sought.

Since ambroxol may enhance mucus secretion, the drug should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g., in rare conditions such as primary ciliary dyskinesia) due to the risk of mucus accumulation.

Acetylcysteine may cause liquefaction of bronchial secretions and increase their volume, particularly at the beginning of treatment. If the patient is unable to effectively expectorate sputum, postural drainage and bronchoaspiration may be necessary.

The drug should be used with caution in patients with bronchial asthma due to the risk of bronchospasm. If bronchospasm occurs, treatment with the drug should be discontinued immediately.

Since mucolytic agents may impair the mucosal barrier, caution is recommended when administering the drug to patients with a history of gastric or duodenal ulcer, especially when used concomitantly with other medications that irritate the gastric mucosa.

Use with caution in patients with renal impairment or severe hepatic disorders (the dosing interval should be prolonged or the dose reduced). In patients with severe renal insufficiency, accumulation of metabolites formed in the liver is expected.

Acetylcysteine affects histamine metabolism; therefore, long-term therapy should not be prescribed to patients with histamine intolerance, as it may lead to symptoms of intolerance (headache, vasomotor rhinitis, itching).

Acetylcysteine may have a slight hydrogen sulfide odor due to the presence of a sulfhydryl group in the acetylcysteine molecule. A sulfur-like odor is not an indication of product deterioration but is characteristic of the active substance.

Excipients.

The medicinal product contains lactose and glucose. If the patient has a known intolerance to certain sugars, consultation with a physician is recommended before taking this medicinal product.

The colorant Yellow FCF (E 110) may cause allergic reactions.

Use during pregnancy or breastfeeding.

Pregnancy. The drug is not recommended during the first trimester of pregnancy.

There are no adequate data on the teratogenic effects of ambroxol hydrochloride and acetylcysteine on the fetus. Therefore, the drug may be used during the second and third trimesters of pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding. Since ambroxol hydrochloride and acetylcysteine pass into breast milk, it is not recommended to take the drug during breastfeeding. If treatment is necessary, breastfeeding should be discontinued.

Fertility. There are no data on adverse effects on fertility.

Ability to affect reaction speed when driving or operating machinery.

There are no data on the effect on reaction speed when driving or operating machinery.

Dosage and Administration.

Dosage for adults and children aged 12 years and older: 1 tablet 3 times daily.

Do not exceed the recommended dose.

Duration of treatment should not exceed 5–7 days without consulting a physician.

Children.

For use in children aged 12 years and older.

Overdose.

There are no data on cases of overdose with oral formulations of acetylcysteine and ambroxol.

Ambroxol was well tolerated after oral administration of up to 25 mg/kg/day. In cases of ambroxol or acetylcysteine overdose, no severe signs of intoxication have been observed.

Symptoms reported in isolated overdose cases and accidental misuse correspond to known adverse reactions.

Symptoms: nausea, vomiting, transient restlessness, diarrhea, hypersalivation, decreased arterial blood pressure. In children, there is a risk of hypersecretion.

Treatment: symptomatic treatment is recommended.

Side effects.

Immune system disorders: hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock, and angioedema.

Skin and subcutaneous tissue disorders: pruritus, urticaria, rash, eczema; severe skin reactions (erythema multiforme, Stevens−Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), acute generalized exanthematous pustulosis).

Gastrointestinal disorders: nausea, oral hypoaesthesia, heartburn, vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth, dry throat, stomatitis, bad breath, hypersalivation.

Respiratory system disorders: pharyngeal hypoaesthesia, dyspnea (as a hypersensitivity reaction), bronchospasm (mainly in patients with bronchial hyperreactivity associated with bronchial asthma), rhinorrhea.

Auditory system disorders: tinnitus.

Nervous system disorders: headache, dysgeusia (taste disturbance).

Cardiovascular disorders: tachycardia, hypotension.

General disorders: fever, mucosal reactions.

Very rare cases of bleeding have been reported during acetylcysteine use, mostly associated with hypersensitivity reactions; cases of anemia and hemorrhage have also been reported.

Cases of reduced platelet aggregation have been observed; however, there is no clinical confirmation of this effect.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after drug registration is important. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 4 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

9 tablets in a blister, 1 blister per cardboard pack; 20 tablets in a blister, 1 or 2 blisters per cardboard pack.

Supply classification.

Over-the-counter (without prescription).

Manufacturer.

Sava Helsea Ltd.

Manufacturer's address and location of operations.

India, GIDC Estate, 507-B-512, Vadodwan City - 363 035, Surendranagar.

Marketing Authorization Holder.

TOV "Movi Hels"

Address of the Marketing Authorization Holder.

08140, Ukraine, Kyiv Oblast, Kyiv-Sviatoshyn district, village Shevchenkove, Shevchenka Street, 162 A