Instructions Pulmobriz film-coated tablets blister pack No. 20
Composition
active ingredients: acetylcysteine, ambroxol hydrochloride;
1 film-coated tablet contains acetylcysteine 200 mg, ambroxol hydrochloride 30 mg;
excipients: lactose monohydrate; povidone (K-30); colloidal anhydrous silica; crospovidone; sodium lauryl sulfate; hydrogenated vegetable oil;
shell composition: Opadry 200 Orange (polyvinyl alcohol; talc; sunset 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).
Dosage form
Film-coated tablets.
Main physicochemical properties: round, biconvex, film-coated tablets, orange in color. The tablets have a specific odor (vanilla odor).
Pharmacotherapeutic group
Drugs used for coughs and colds. Mucolytics. Combinations. ATX code R05C B10.
Pharmacological properties
Pharmacodynamics.
Ambroxol hydrochloride has a pronounced expectorant, mucolytic, anti-inflammatory, immunomodulatory, antioxidant and slight antitussive effect. Stimulates serous cells of the glands of the bronchial mucosa, increases the amount of serous secretion and thus changes the disturbed ratio of serous and mucous components. This leads to the normalization of the rheological parameters of sputum, reducing its viscosity and adhesive properties. Directly stimulates the mobile activity of the ciliated epithelium of the bronchi, prevents its clumping and improves mucociliary evacuation of sputum. Ambroxol increases the content of surfactant in the lungs by directly affecting type II pneumocytes in the alveoli and Clara cells in the bronchioles, and also prevents its destruction in pneumocytes. Ambroxol does not cause bronchoobstruction, but on the contrary, improves the function of external respiration. It has been proven that ambroxol reduces the hyperreactivity of the bronchial muscles in patients with asthma.
The local anesthetic effect of ambroxol hydrochloride was 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 an anti-inflammatory effect, which has been established in vitro, antioxidant properties, stimulates local immunity and renewal of the natural surfactant layer. When taking Ambroxol, patients' complaints of cough and sputum are significantly reduced according to the intensity of treatment.
Clinical trials involving patients with pharyngitis have shown a significant reduction in pain and redness in the throat when using ambroxol hydrochloride.
The pharmacological properties of rapidly relieving pain during the treatment of upper respiratory tract diseases have been observed in studies of the clinical efficacy of inhaled forms of ambroxol.
Acetylcysteine is a mucolytic and expectorant active substance. Due to the free sulfhydryl group, it breaks the disulfide bonds of mucopolysaccharides of sputum, which leads to a decrease in the viscosity of bronchial secretions. Increases mucociliary clearance. Has an antioxidant effect due to the property of binding free radicals. Increases the synthesis of glutathione, which is an important factor in detoxification; due to this property, acetylcysteine is used to treat acute poisoning with paracetamol, phenols, aldehydes and other substances.
Pharmacokinetics.
Ambroxol hydrochloride
Absorption of ambroxol hydrochloride from oral non-extended release formulations is rapid and fairly complete, with a linear dose dependence in the therapeutic range. Peak plasma levels are reached after 1-2.5 hours with oral administration of immediate-release formulations.
When administered orally, the distribution of ambroxol hydrochloride from the blood to the tissues is rapid and pronounced, with the highest concentration of the active substance in the lungs.
Approximately 30% of the dose after oral administration is excreted by presystemic metabolism. Ambroxol hydrochloride is metabolized mainly in the liver by 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 the urine in unchanged form, about 26% of the dose in conjugated form.
The half-life from blood plasma is about 10 hours.
In patients with impaired liver function, the excretion of ambroxol hydrochloride is reduced, resulting in a 1.3-2-fold higher plasma level.
Age and gender 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.
After oral administration, acetylcysteine is rapidly and completely absorbed and metabolized in the liver to form cysteine, a pharmacologically active metabolite, as well as diacetylcysteine, cystine, and further mixed disulfides. Bioavailability is very low - about 10%. Maximum plasma concentration is reached 1-3 hours after administration. Plasma protein binding is approximately 50%. Acetylcysteine is excreted by the kidneys in the form of inactive metabolites (inorganic sulfates, diacetylcysteine).
The elimination half-life is determined mainly by rapid biotransformation in the liver and is approximately 1 hour. In case of reduced liver function, the half-life is prolonged to 8 hours.
Indication
Treatment of acute and chronic respiratory diseases accompanied by impaired bronchial secretion and secretion evacuation: including acute and chronic bronchitis, chronic obstructive pulmonary diseases, pneumonia, bronchiectasis, bronchial asthma, cystic fibrosis, laryngitis, tracheitis.
Contraindication
Hypersensitivity to ambroxol, acetylcysteine or other components of the drug. Gastric and duodenal ulcer in the acute stage. Hemoptysis, pulmonary hemorrhage, severe exacerbation of bronchial asthma.
Interaction with other medicinal products and other types of interactions
The simultaneous use of Pulmobriz and cough suppressants may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such a combination is possible only after a careful assessment by the doctor of the ratio of the expected benefit and the possible risk of use.
Acetylcysteine reduces the hepatotoxic effect of paracetamol; can be a cysteine donor and increase glutathione levels, which helps detoxify free oxygen radicals and certain toxic substances in the body.
Activated charcoal reduces the effectiveness of acetylcysteine.
Synergism of acetylcysteine with bronchodilators is noted.
When used simultaneously with antibiotics such as tetracycline (except doxycycline), ampicillin, amphotericin B, cephalosporins, aminoglycosides, their interaction with the thiol group of acetylcysteine is possible, which leads to a decrease in the activity of both drugs. Therefore, the interval between the use of these drugs should be at least 2 hours. This does not apply to cefixime and loracarbef.
The use of ambroxol increases the concentration of the antibiotics amoxicillin, cefuroxime, erythromycin, and doxycycline in sputum and bronchopulmonary secretions.
Concomitant administration of nitroglycerin and acetylcysteine has been associated with significant hypotension and significant temporal artery dilation. If concomitant administration of nitroglycerin and acetylcysteine is necessary, patients should be monitored for hypotension, which may be severe, and patients should be warned of the possibility of headache.
Effect on laboratory tests: The use of acetylcysteine may alter the results of colorimetric quantitative determination and the results of urine ketone determination.
Application features
There have been isolated reports of severe skin reactions (erythema multiforme, Stevens-Johnson and Lyell syndromes and acute generalized exanthematous pustulosis) coinciding with the use of ambroxol hydrochloride or acetylcysteine.
Most of them could be explained by the severity of the underlying disease in the patients and/or the concomitant use of another drug. Also, in the initial stage of Stevens-Johnson syndrome or Lyell syndrome, patients may have nonspecific, flu-like symptoms such as fever, aches, rhinitis, cough and sore throat. Symptomatic treatment with cough and cold medications may be mistakenly used for such nonspecific, flu-like symptoms. If signs of progression of the rash on the skin or mucous membranes appear, the drug should be discontinued immediately and medical attention should be sought.
Since ambroxol may increase mucus secretion, the drug should be used with caution in cases of impaired bronchial motility and increased mucus secretion (for example, in a rare disease such as primary ciliary dyskinesia) due to the risk of secretion accumulation.
The use of acetylcysteine may cause liquefaction of bronchial secretions and increase their volume, especially at the beginning of treatment. If the patient is unable to cough up sputum effectively, postural drainage and bronchoaspiration are necessary.
Use the drug with caution in patients with bronchial asthma due to the risk of bronchospasm. If bronchospasm occurs, treatment with the drug should be discontinued immediately.
Use with caution in patients with impaired renal function, severe liver disease (the interval between administrations should be increased or the dose should be reduced); in patients with severe renal failure, accumulation of metabolites formed in the liver is expected.
Acetylcysteine affects histamine metabolism, so long-term therapy should not be prescribed to patients with histamine intolerance, as this may lead to symptoms of intolerance (headache, vasomotor rhinitis, itching).
Acetylcysteine may have a slight odor of hydrogen sulfide due to the presence of a sulfhydryl group in the acetylcysteine molecule - the sulfurous odor is not a sign of a change in the drug, but is specific to the active ingredient.
Excipients.
This medicinal product contains lactose and glucose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.
The dye sunset yellow FCF (E 110) may cause allergic reactions.
Use during pregnancy or breastfeeding
Pregnancy. The drug is not recommended for use in the first trimester of pregnancy.
There is no relevant data on the teratogenic effect of ambroxol hydrochloride and acetylcysteine on the fetus, therefore the drug can be used in the II-III trimesters of pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus.
Breastfeeding. Since ambroxol hydrochloride and acetylcysteine penetrate into breast milk, it is undesirable to take the drug during breastfeeding. If necessary, the drug should be prescribed, breastfeeding should be discontinued.
Fertility: There are no data on harmful effects on fertility.
Ability to influence reaction speed when driving vehicles or other mechanisms
There is no data on the effect on the reaction speed when driving vehicles or other mechanisms.
Method of administration and doses
Dosage for adults and children over 12 years of age: 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 doctor.
Children.
Use for children over 12 years of age.
Overdose
There are no data on cases of overdose of acetylcysteine and ambroxol dosage forms intended for oral administration.
Ambroxol was well tolerated after oral administration of up to 25 mg/kg/day. No severe signs of intoxication were observed in cases of overdose with ambroxol or acetylcysteine.
Symptoms known from isolated reports of overdose and cases of mistaken administration correspond to known adverse reactions.
Symptoms: nausea, vomiting, short-term anxiety, diarrhea, hypersalivation, decreased blood pressure. Children are at risk of hypersecretion.
Treatment: symptomatic treatment is recommended.
Adverse reactions
Immune system disorders: Hypersensitivity reactions, including anaphylactic reactions, anaphylactic shock and angioedema.
Skin and subcutaneous tissue disorders: itching, urticaria, rash, eczema; severe skin lesions (erythema multiforme, Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), acute generalized exanthematous pustulosis).
Gastrointestinal: nausea, decreased sensitivity in the oral cavity, heartburn, vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth, dry throat, stomatitis, bad breath, drooling.
Respiratory system: decreased sensitivity in the pharynx, dyspnea (as a hypersensitivity reaction), bronchospasm (predominantly in patients with bronchial hyperreactivity associated with bronchial asthma), rhinorrhea.
On the part of the organs of hearing: ringing in the ears.
From the nervous system: headache, dysgeusia (taste disorder).
Cardiovascular system: tachycardia, arterial hypotension.
General disorders: fever, mucous membrane reactions.
When using acetylcysteine, bleeding has been reported very rarely, most often associated with the development of hypersensitivity reactions; cases of anemia, hemorrhage.
There have been cases of decreased platelet aggregation, but there is no clinical confirmation of this.
Expiration date
4 years.
Storage conditions
Store out of the reach of children in the original packaging at a temperature not exceeding 25 °C.
Packaging
9 tablets in a blister, 1 blister in a cardboard box; 20 tablets in a blister, 1 or 2 blisters in a cardboard box.
Vacation category
Without a prescription.
Producer
Meditop Pharmaceutical Ltd.
Location of the manufacturer and address of its place of business.
Hungary, Edi Endre y. 1., Pilisboroszeno, 2097.
Applicant.
Movie Health GmbH.
Location of the applicant.
35 Egerischstrasse, Baar, 6340, Switzerland.
