Bromhexine

I N S T R U C T I O N for medical use of the medicinal product BROMHEXINE (BROMHEXINUM)

Composition:

Active substance: bromhexine;

1 tablet contains bromhexine hydrochloride 8 mg;

Excipients: lactose monohydrate, sucrose, ruberose, potato starch, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: pink-colored tablets, with flat surface and beveled edges.

Pharmacotherapeutic group. Medicinal products used in cough and colds. Mucolytic agents. ATC code R05C B02.

Pharmacological properties.

Pharmacodynamics.

Bromhexine is a synthetic derivative of the active substance vasicine of plant origin. It exerts a secretolytic and secretomotor effect in the bronchial tract, resulting in increased bronchial secretion, reduced viscosity of mucus (sputum), and stimulation of ciliated epithelium activity, which promotes the movement of mucus (sputum) through the airways.

Pharmacokinetics.

After oral administration, bromhexine is almost completely absorbed, with a half-life of approximately 0.4 hours. The first-pass effect is about 80 %, during which biologically active metabolites are formed. Plasma protein binding is 99 %. The decline in plasma concentration is multiphasic. The terminal half-life, which determines the duration of action, is about 1 hour. The final elimination half-life is approximately 16 hours, due to redistribution of small amounts of bromhexine from tissues. The volume of distribution is about 7 L per 1 kg of body weight. Bromhexine does not accumulate. Bromhexine crosses the placenta, enters cerebrospinal fluid and breast milk. It is primarily excreted by the kidneys as metabolites. In acute liver disease, a decrease in the clearance of the active substance is possible. In acute renal failure, an increase in the elimination half-life of bromhexine metabolites cannot be excluded. Nitrosation of bromhexine may occur under physiological conditions in the stomach.

Clinical characteristics.

Indications.

For mucolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired formation and movement of sputum.

Contraindications.

Hypersensitivity to the active substance or to any of the excipients.

The medicinal product must not be used in patients with gastric or duodenal ulcers or with a history of peptic ulcer disease, since bromhexine may affect the mucous membrane of the gastrointestinal tract.

Respiratory diseases characterized by production of large amounts of liquid sputum.

The medicinal product is contraindicated in children under 6 years of age due to the high content of active substance. For this age group, medicinal products with reduced dosage should be prescribed.

The medicinal product contains sugar, which should be taken into account in patients with diabetes mellitus.

Contains lactose; therefore, patients with such rare hereditary conditions as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product. If a patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Interaction with other medicinal products and other forms of interactions.

Bromhexine can be administered in combination with bronchodilators, antibacterial agents, and drugs used in cardiology.

Medicinal products that irritate the gastrointestinal tract (e.g., nonsteroidal anti-inflammatory drugs) – when used concomitantly with bromhexine, mutual enhancement of mucosal irritation effects is possible.

Antibiotics (amoxicillin, cefuroxime, erythromycin, doxycycline) and sulfonamide medicinal products – when used concomitantly with bromhexine, concentrations of antibiotics and sulfonamides in bronchopulmonary secretions and sputum are increased.

Antitussive agents – concomitant use with bromhexine leads to mucus accumulation in the airways and impaired sputum clearance from the bronchi due to reduced coughing. This combination is not recommended.

Special precautions for use.

Lungs and respiratory tract

Bromhexine should be used with particular caution in patients with impaired bronchial motility accompanied by excessive production of bronchial secretions (e.g., in rare conditions such as primary ciliary dyskinesia) due to the possible accumulation of secretions.

Use with caution in patients suffering from bronchial asthma. During treatment, patients should drink sufficient fluids to enhance the expectorant effect of bromhexine.

Liver and kidney disorders

Bromhexine should be used with particular caution (i.e., with longer intervals or in lower doses) in patients with impaired renal function or severe liver disease.

In severe renal insufficiency, accumulation of metabolites of bromhexine formed in the liver may occur.

Periodic monitoring of liver function is recommended, especially during prolonged treatment.

Skin reactions

Severe skin reactions associated with the use of bromhexine have been reported, including erythema multiforme, Stevens-Johnson syndrome / toxic epidermal necrolysis, and acute generalized exanthematous pustulosis. If symptoms or signs of progressive skin rash (sometimes with blisters or mucosal lesions) occur, medical advice must be sought immediately and treatment with bromhexine should be discontinued.

The medicinal product contains sugar, which should be taken into account in patients with diabetes mellitus.

The product contains lactose; therefore, patients with rare hereditary disorders such as galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product. If you have been diagnosed with intolerance to certain sugars, consult your doctor before taking this medicinal product.

Gastric or duodenal ulcer

Bromhexine must not be used in patients with gastric or duodenal ulcer or a history of peptic ulcer disease, as bromhexine may affect the mucous membrane of the gastrointestinal tract. In patients with a history of gastrointestinal bleeding, bromhexine should be used under medical supervision.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of bromhexine in pregnant women are limited. Therefore, bromhexine should be prescribed only by a physician after careful assessment of the benefit-risk ratio. The medicinal product is not recommended for use during the first trimester of pregnancy.

Breastfeeding period

Since the active substance passes into breast milk, bromhexine must not be used by women during breastfeeding.

Ability to influence reaction rate when driving or operating machinery.

Bromhexine has no effect or has a negligible effect on the ability to drive or operate machinery.

Method of Administration and Dosage

The medicinal product should be taken orally after meals, with a large amount of liquid (e.g., a glass of water).

Adults and children aged 14 years and older: 8–16 mg (1–2 tablets) three times daily, corresponding to a daily dose of 24–48 mg of bromhexine hydrochloride.

Children aged 6 to 14 years, as well as patients with body weight below 50 kg: 8 mg (1 tablet) three times daily, corresponding to a daily dose of 24 mg of bromhexine hydrochloride.

Other special patient groups: bromhexine hydrochloride should be administered with particular caution (i.e., with longer intervals or in reduced doses) in patients with impaired renal function or severe hepatic disorders (see section "Special Warnings and Precautions for Use").

The duration of treatment should be determined individually, depending on the indication and disease progression, but should not exceed 4–5 days without appropriate medical recommendation.

Children.

The medicinal product in this pharmaceutical form is contraindicated in children under 6 years of age.

Overdose.

Symptoms: dyspeptic disorders, nausea, vomiting, diarrhea. Dizziness, headache, ataxia, diplopia, metabolic acidosis, rapid breathing.

No symptoms were observed in young children after administration of up to 40 mg of bromhexine, even without decontamination procedures. No chronic toxic effects in humans have been identified.

Treatment: induce vomiting and perform gastric lavage (within the first 1–2 hours after ingestion). In cases of significant overdose, cardiovascular monitoring is recommended and symptomatic therapy should be administered if necessary. Due to the high degree of plasma protein binding, large volume of distribution, and slow redistribution of bromhexine from tissues into blood, enhanced elimination of the drug is not expected with hemodialysis or forced diuresis.

Warning: If the amount of ingested bromhexine exceeds the aforementioned limits, possible adverse effects of the excipients in the medicinal product should also be considered (see section "Special Warnings and Precautions for Use").

Adverse Reactions

The frequency of adverse reactions is defined as follows: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), not known (frequency cannot be estimated from the available data).

Gastrointestinal system disorders

Uncommon: nausea, stomach pain, dyspeptic disorders, vomiting, diarrhea.

Exacerbation of gastric or duodenal ulcer.

Central nervous system disorders

Uncommon: headache (migraine-type), dizziness.

Skin and subcutaneous tissue disorders

Uncommon: increased sweating.

Rare: rash, urticaria.

Not known: severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome, Lyell's syndrome, and acute generalized exanthematous pustulosis).

Immune system disorders

Rare: hypersensitivity reactions.

Not known: anaphylactic reactions, including anaphylactic shock, angioedema, pruritus.

Respiratory, thoracic and mediastinal disorders

Uncommon: breathing disorders, increased cough, respiratory distress.

Rare: bronchospasm.

General disorders

Uncommon: fever, transient increase in serum aspartate aminotransferase levels, chills.

If hypersensitivity reactions, anaphylactic reactions, or any disorders affecting the skin or mucous membranes occur, bromhexine should be discontinued immediately and medical advice should be sought.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life

3 years.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 ºC.

Keep out of reach and sight of children.

Packaging

20 tablets in a blister;

20 tablets in a blister; 1, 2, or 3 blisters per carton.

Pharmaceutical category

Over-the-counter (OTC).

Manufacturer

JSC "Monfarm".

Manufacturer's name and address of manufacturing site

8, Zavodska Street, Avramivka village, Uman district, Cherkasy region, 19161, Ukraine.