Instructions for Lasolvan Max extended-release capsules 75 mg blister No. 10
Composition
active ingredient: ambroxol hydrochloride;
1 capsule contains ambroxol hydrochloride 75 mg;
excipients: crospovidone, carnauba wax, stearyl alcohol, magnesium stearate;
capsule shell: gelatin, purified water, titanium dioxide (E 171), red iron oxide (E 172), yellow iron oxide (E 172); capsule marking ink: shellac, n-butyl alcohol, propylene glycol (E 1520), titanium dioxide (E 171).
Dosage form
Extended-release capsules.
Main physicochemical properties: oblong hard gelatin capsules consisting of an orange opaque body and a red opaque cap with the inscription "MUC01" in white. Capsule contents: round yellowish-white pellets with a smooth shiny surface, mixed with a small amount of powder.
Pharmacotherapeutic group
Preparations for the treatment of respiratory diseases. Cough preparations and remedies for the treatment of colds. Expectorants, except combinations with antitussives. Mucolytics. Ambroxol.
ATX code R05C B06.
Pharmacological properties
Pharmacodynamics. It has been preclinically proven that the active ingredient of Lasolvan® Max capsules - ambroxol hydrochloride - increases the proportion of serous bronchial secretion. Ambroxol enhances the secretion of pulmonary surfactant by directly affecting type II pneumocytes in the alveoli and Clara cells in the bronchioles, and also stimulates ciliary activity, as a result of which the viscosity of sputum decreases and its excretion improves (mucociliary clearance). Improvement of mucociliary clearance has been proven during clinical and pharmacological studies.
Activation of secretion, reduction of secretion viscosity, and improvement of mucociliary clearance promote mucus excretion and facilitate expectoration of sputum.
COPD patients treated with ambroxol hydrochloride prolonged-release capsules, 75 mg for 6 months had a significant reduction in the number of exacerbations compared to placebo at the end of 2 months of treatment. Patients treated with ambroxol hydrochloride had significantly fewer days of illness and required fewer days of antibiotic therapy. Compared to placebo, treatment with ambroxol hydrochloride prolonged-release capsules showed statistically significant improvements in sputum production, cough, dyspnea and auscultation findings.
In a rabbit eye model, a local anesthetic effect of ambroxol hydrochloride was observed, which may be explained by its sodium channel blocking properties. In vitro studies have shown that ambroxol hydrochloride blocks voltage-gated neuronal sodium channels; binding was reversible and concentration-dependent.
Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. Thus, ambroxol hydrochloride significantly reduces the release of cytokines from mononuclear and polymorphonuclear blood cells and tissues.
Clinical trials involving patients with pharyngitis have shown a significant reduction in pain and redness in the throat when using ambroxol hydrochloride.
Due to the pharmacological properties of ambroxol, pain was quickly relieved during the treatment of upper respiratory tract diseases, which was observed during studies of the clinical efficacy of inhaled forms of ambroxol.
The use of ambroxol hydrochloride increases the concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin and doxycycline) in bronchopulmonary secretions and sputum. The clinical significance of this has not yet been established.
Antiviral properties in vitro and in experimental animal models
In vitro studies on human tracheal epithelial cells showed a reduction in rhinovirus (RV 14) replication. In a mouse respiratory model, a reduction in influenza A virus replication was observed after pretreatment with ambroxol.
To date, the clinical significance of this effect has not been confirmed.
Pharmacokinetics. Absorption. Absorption of ambroxol hydrochloride from oral immediate-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 immediate-release formulations and on average after 6.5 hours with slow-release formulations.
Distribution. 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. The volume of distribution when administered orally is 552 l. In the blood plasma in the therapeutic range, approximately 90% of the drug is bound to proteins.
Metabolism and elimination. Approximately 30% of the dose after oral administration is eliminated by first pass metabolism. Ambroxol hydrochloride is metabolized mainly in the liver by glucuronidation and cleavage to dibromanthranilic acid (approximately 10% of the dose). Studies in human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromanthranilic acid.
The plasma half-life is about 10 hours. Total clearance is about 660 ml/min. Renal clearance is about 8% of the total. After 5 days, about 83% of the total dose is excreted in the urine.
Pharmacokinetics in special patient groups. In patients with impaired liver function, the excretion of ambroxol hydrochloride is reduced, which results in a 1.3-2 times higher level in the blood plasma. Since the therapeutic range of ambroxol hydrochloride is quite wide, it is not necessary to change the dosage.
Age and gender have no clinically significant effect on the pharmacokinetics of ambroxol hydrochloride, therefore no dose adjustment is required.
Indication
Secretolytic therapy for acute and chronic bronchopulmonary diseases associated with disorders of bronchial secretion and impaired mucus movement.
Contraindication
Lasolvan® Max should not be used in patients with known hypersensitivity to ambroxol hydrochloride or any other components of the drug.
Lasolvan® Max is not intended for use in children under 12 years of age due to the amount of active ingredient contained in the capsule.
Interaction with other medicinal products and other types of interactions
In the case of simultaneous use of Lasolvan® Max and cough suppressants in patients with pre-existing respiratory diseases associated with mucus hypersecretion, such as cystic fibrosis (cystic fibrosis) or bronchiectasis, significant accumulation of secretions is possible due to suppression of the cough reflex.
Application features
Severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) and acute generalised exanthematous pustulosis (AGEP) have been reported in association with the use of ambroxol hydrochloride. If symptoms or signs of progressive skin rash (sometimes associated with blistering or mucosal lesions) occur, ambroxol hydrochloride treatment should be discontinued immediately and medical advice should be sought.
In case of impaired bronchial motility and increased mucus secretion (for example, in a rare disease such as primary ciliary dyskinesia), Lasolvan® Max should be used with caution due to the risk of promoting secretion accumulation.
Patients with impaired renal function or severe hepatic insufficiency should take Lasolvan® Max only after consulting a doctor. In patients with severe renal insufficiency, when using ambroxol, as with any active substance that is metabolized in the liver and then excreted by the kidneys, accumulation of metabolites formed in the liver is possible.
Use during pregnancy or breastfeeding
Pregnancy. Ambroxol hydrochloride crosses the placental barrier. Preclinical studies have not revealed any direct or indirect harmful effects of the drug on the course of pregnancy, embryonal/fetal development, childbirth or postnatal development. Based on extensive clinical experience with the drug after the 28th week of pregnancy, no harmful effects on the fetus have been identified. However, the usual precautions for use during pregnancy should be observed. Lazolvan® Max is not recommended, especially in the first trimester of pregnancy.
Breastfeeding. According to preclinical studies, ambroxol hydrochloride penetrates into breast milk. Lasolvan® Max is not recommended for use during breastfeeding.
Fertility: Preclinical studies do not indicate direct or indirect harmful effects with respect to fertility.
The ability to influence the reaction speed when driving or working with other mechanisms
There are no data on the effect on the reaction rate when driving vehicles or working with other mechanisms. Studies on the effect on the reaction rate when driving vehicles or working with other mechanisms have not been conducted.
Method of administration and doses
Unless otherwise specified, the following regimen for taking Lasolvan® Max is recommended:
Adults and children over 12 years of age: 1 capsule once a day (equivalent to 75 mg/day of ambroxol hydrochloride).
Lasolvan® Max can be taken regardless of meals; the capsules should be swallowed whole with sufficient liquid (water, tea, fruit juice).
In general, there are no restrictions on the duration of use, but long-term therapy should be carried out under medical supervision.
Lasolvan® Max should not be used for longer than 4–5 days without consulting a doctor.
Children
The drug is not used in children under 12 years of age due to the amount of active ingredient contained in the capsule.
Overdose
To date, there are no reports of specific symptoms of overdose in humans.
Symptoms known from isolated reports of overdose and/or cases of mistaken use of the drug correspond to the known side effects of the drug Lasolvan® Max at recommended doses and require symptomatic treatment.
Side effects
The following classification was used to assess the frequency of adverse events:
| very often | ≥ 1/10; | | often | ≥ 1/100 – < 1/10; |
| infrequently | ≥ 1/1000 – < 1/100; |
| rarely | ≥ 1/10000 – < 1/1000; |
| very rarely | < 1/10000; |
| unknown | cannot be estimated based on available data. |
On the part of the immune system:
rarely - hypersensitivity reactions;
not known - anaphylactic reactions, including anaphylactic shock, angioedema and pruritus.
Skin and subcutaneous tissue disorders:
rarely - rash, urticaria;
not known - serious skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis and acute generalized exanthematous pustulosis).
From the gastrointestinal tract:
often - nausea;
infrequently - vomiting, diarrhea, dyspepsia, abdominal pain;
very rarely - drooling.
From the respiratory system, chest organs and mediastinum:
unknown - dyspnea (as a symptom of a hypersensitivity reaction).
General disorders:
uncommon – fever, mucous membrane reactions.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. This allows for continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report all adverse reactions via the national reporting system.
Expiration date
3 years.
Storage conditions
Store at a temperature not exceeding 30 ° C. Keep out of the reach of children.
Packaging
10 capsules in a blister, 1 blister in a cardboard box.
Vacation category
Without a prescription.
Producer
Delpharm Reims, France.
Location of the manufacturer and address of its place of business
10 rue Colonel Charbonneaux, 51100 Reims, France.
Applicant
Opel Healthcare Ukraine LLC.
Location of the applicant.
Ukraine, 01033, Kyiv, Zhylyanska St., 48-50A.
