Bromhexine 8 berlin-chemi

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT BROMHEXIN 8 BERLIN-CHEMIE (BROMHEXIN 8 BERLIN-CHEMIE)

Composition:

Active substance: bromhexine hydrochloride;

One coated tablet contains 8 mg of bromhexine hydrochloride;

Excipients: lactose monohydrate, maize starch, gelatin, colloidal anhydrous silicon dioxide, magnesium stearate, sucrose, calcium carbonate, light magnesium carbonate, talc, polyethylene glycol 6000, povidone K 25, glucose solution, carnauba wax, titanium dioxide (E 171), quinoline yellow dye (E 104).

Pharmaceutical form. Coated tablets.

Main physico-chemical properties: slightly convex on both sides coated tablets, yellow to greenish-yellow in color, with an almost white core.

Pharmacotherapeutic group. Agents used for cough and common cold. Mucolytic agents. ATC code R05C B02.

Pharmacological Properties.

Pharmacodynamics.

Bromhexine is a synthetic derivative of the active substance of plant origin, vasicine. It exerts a secretolytic and secretomotor effect in the bronchial tract. In animal studies, it increases the proportion of serous bronchial secretion. It is believed that mucus transport is facilitated by reduction of viscosity and activation of ciliated epithelium.

After administration of bromhexine, concentrations of the antibiotics amoxicillin, erythromycin, and oxytetracycline increase in sputum and bronchial secretions. The clinical significance of this effect is unknown.

Pharmacokinetics.

After oral administration, bromhexine is almost completely absorbed, with an elimination half-life of approximately 0.4 hours. Tmax after oral administration is 1 hour. The first-pass effect is approximately 80%. Biologically active metabolites are formed during this process. Plasma protein binding is 99%.

The decline in plasma concentration is multiphasic. The half-life determining the duration of action is about 1 hour. The terminal elimination half-life is about 16 hours. This is due to redistribution of small amounts of bromhexine from tissues. The volume of distribution is approximately 7 L per kg of body weight. Bromhexine does not accumulate. Bromhexine crosses the placenta, enters cerebrospinal fluid, and is excreted into breast milk. It is primarily excreted by the kidneys as metabolites formed in the liver. Due to high plasma protein binding, large volume of distribution, and slow redistribution from tissues into blood, significant elimination of bromhexine via dialysis or forced diuresis is not expected.

In severe liver disease, a reduction in the clearance of the active substance is possible. In severe renal insufficiency, an increase in the elimination half-life of bromhexine metabolites cannot be excluded. Nitrosation of bromhexine may occur under physiological conditions in the stomach.

Safety Pharmacology Data

Preclinical data obtained from traditional safety pharmacology studies show no evidence of specific hazard to humans, and no evidence of chronic toxicity, genotoxicity, carcinogenicity, or toxicity to reproductive organs and development.

Chronic toxicity

Studies in various animal species (rats, mice, dogs) using very high doses and long-term treatment revealed no significant toxic potential for humans under normal therapeutic use.

Mutagenic and carcinogenic potential

In vitro (Ames test) and in vivo/in vitro (mammalian-mediated mutagenicity test) studies showed no mutagenic effect of bromhexine. Carcinogenicity studies conducted in rats showed no carcinogenic potential of bromhexine.

Toxicity to reproductive organs

Bromhexine crosses the placenta. Animal studies showed no evidence of teratogenic effects of bromhexine in rats, mice, or rabbits. Bromhexine at therapeutic doses had no effect on offspring development or behavior. No effect of bromhexine on fertility was observed.

Clinical characteristics.

Indications.

Mucolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired formation and clearance of mucus.

Contraindications.

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

Bromhexine 8 Berlin-Chemi is contraindicated in patients with hereditary galactose intolerance, fructose intolerance, severe lactase deficiency, glucose-galactose malabsorption syndrome, or hereditary sucrase-isomaltase deficiency.

Bromhexine 8 Berlin-Chemi must not be used in patients with gastric or duodenal ulcers or with a history of peptic ulcer disease, as bromhexine may affect the gastrointestinal mucosa.

Bromhexine 8 Berlin-Chemi must not be used during breastfeeding.

Bromhexine 8 Berlin-Chemi is contraindicated in children under 6 years of age due to the high content of the active substance. Medicinal products with reduced dosage should be prescribed for this age group.

Interaction with other medicinal products and other forms of interaction.

When Bromhexine 8 Berlin-Chemi is used concomitantly with antitussive agents (cough suppressants), there may be a dangerous accumulation of secretions due to suppression of the cough reflex. Therefore, the appropriateness of prescribing such a combination should be carefully considered, and particular caution should be exercised during therapy.

Concomitant administration of bromhexine with antibiotics (amoxicillin, erythromycin, cefuroxime, doxycycline) and sulfonamides promotes increased concentrations of these drugs in sputum and bronchial secretions. When used simultaneously with substances that irritate the gastrointestinal tract, mutual enhancement of the irritating effect on the gastric mucosa may occur.

Special precautions for use.

Skin reactions

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

Gastric or duodenal ulcer

Bromhexine 8 Berlin-Chemie must not be administered to patients with gastric or duodenal ulcer or a history of peptic ulcer disease, since bromhexine may affect the gastrointestinal mucosa.

Lungs and respiratory tract

Bromhexine 8 Berlin-Chemie should be used with particular caution in patients with impaired bronchial motility associated with excessive bronchial secretion (e.g. in rare conditions such as primary ciliary dyskinesia), due to the possible accumulation of secretions.

Liver and kidney disorders

Bromhexine 8 Berlin-Chemie should be administered with particular caution (i.e. with longer intervals or at lower doses) in patients with renal impairment or severe hepatic disease.

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

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

Lactose, glucose, sucrose

Lactose, glucose, and sucrose are components of this medicinal product. Therefore, Bromhexine 8 Berlin-Chemie is contraindicated in patients with rare hereditary conditions such as galactose intolerance, fructose intolerance, total lactase deficiency, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.

Use during pregnancy or breastfeeding.

Pregnancy

Data on the use of bromhexine in pregnant women are limited. Therefore, Bromhexine 8 Berlin-Chemie may be prescribed only by a physician after careful assessment of the benefit-risk ratio and is not recommended during the first trimester of pregnancy.

Period of breastfeeding

Since the active substance passes into breast milk, Bromhexine 8 Berlin-Chemie must not be used during breastfeeding.

Ability to influence reaction speed when driving vehicles or operating machinery.

Bromhexine 8 Berlin-Chemie has no effect or has negligible influence on the ability to drive vehicles or operate machinery.

Method of Administration and Dosage

Tablets with coating should be taken after meals and swallowed with plenty of fluid (e.g., a glass of water).

Recommended doses of Bromhexine 8 Berlin-Chemi:

Adults and children aged 14 years and older: 1–2 coated tablets 3 times daily (corresponding to 24–48 mg/day of bromhexine hydrochloride).

Children aged 6 to 14 years, as well as patients with body weight less than 50 kg: 1 coated tablet 3 times daily (corresponding to 24 mg/day of bromhexine hydrochloride).

Other special patient groups: Bromhexine 8 Berlin-Chemi should be used with particular caution (i.e., with longer intervals or lower doses) in patients with impaired renal function or severe hepatic disorders (see section "Special Warnings and Precautions for Use").

Duration of treatment is determined individually, depending on the indication and disease progression. Bromhexine 8 Berlin-Chemi should not be used for longer than 4–5 days without appropriate medical advice.

Children.

Bromhexine 8 Berlin-Chemi is not intended for use in children under 6 years of age due to the high content of active substance.

Overdose.

Symptoms. There have been no reports of life-threatening overdoses so far. Information has been published on cases of bromhexine hydrochloride overdose in infants, in which vomiting occurred in 4 out of 25 children, and impaired consciousness, ataxia, diplopia, mild metabolic acidosis, and tachypnea were observed in 3 children. No symptoms were observed in infants after ingestion of up to 40 mg of bromhexine, even without decontamination procedures.

No evidence of chronic toxic effects in humans has been identified.

Therapeutic measures. In cases of significant overdose, monitoring of cardiovascular function should be performed and symptomatic treatment administered if necessary. Due to the low toxicity of bromhexine, more invasive procedures aimed at reducing drug absorption or accelerating bromhexine elimination are generally not indicated. Furthermore, considering the pharmacokinetic characteristics of bromhexine (high volume of distribution, slow redistribution, and high plasma protein binding), a significant increase in elimination rate is not expected with dialysis or forced diuresis.

In children aged 2 years and older, even in cases of significant overdose, only mild symptoms are expected; therefore, measures to reduce absorption and accelerate elimination of bromhexine after ingestion of doses up to 80 mg of bromhexine hydrochloride (equivalent to 10 tablets of 8 mg) may not be necessary. The corresponding threshold in younger children is 60 mg of bromhexine hydrochloride (6 mg/kg body weight).

Warning. If the amount of ingested bromhexine exceeds the above-mentioned thresholds, potential adverse effects of the excipients in the medicinal product should also be considered (see section "Special Warnings and Precautions for Use").

Side effects

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

Immune system disorders.

Rare: hypersensitivity reactions (e.g. respiratory distress).

Frequency not known: anaphylactic reactions, including anaphylactic shock, angioedema, pruritus.

Gastrointestinal disorders.

Uncommon: nausea, stomach pain, vomiting, diarrhea.

Exacerbation of gastric or duodenal ulcer.

Skin and subcutaneous tissue disorders.

Rare: rash, urticaria.

Frequency not known: severe cutaneous adverse reactions (including erythema multiforme, Stevens-Johnson syndrome / toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).

General disorders.

Uncommon: fever.

Respiratory disorders, dizziness, respiratory distress, headache, increased sweating, transient increase in serum aspartate aminotransferase levels, chills.

In case of hypersensitivity reactions, anaphylactic reactions, or any skin and mucous membrane disorders, bromhexine should be discontinued immediately and medical advice should be sought.

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions after authorization of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions.

Shelf life. 3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of reach and sight of children.

Packaging. 25 film-coated tablets in a blister; 1 blister per cardboard box.

Classification. Over-the-counter (without prescription).

Manufacturer.

BERLIN-CHEMIE AG.

Manufacturer's name and address of the place of business.

Glinker Weg 125, 12489 Berlin, Germany.