Instructions for use Lasolvan solution for infusions 15 mg/2 ml ampoule 2 ml No. 10
Composition
active ingredient: ambroxol hydrochloride;
1 ampoule contains 15 mg of ambroxol hydrochloride;
Excipients: citric acid, monohydrate (E 330); sodium hydrogen phosphate, dihydrate; sodium chloride; water for injections.
Dosage form
Solution for infusion.
Main physicochemical properties: clear, colorless solution, practically free from particles.
Pharmacotherapeutic group
Medicines used for coughs and colds. Mucolytics. ATX code R05C B06.
Pharmacological properties
Pharmacodynamics
Ambroxol hydrochloride, a substituted benzylamine, is a metabolite of bromhexine. It differs from bromhexine in the absence of a methyl group and the presence of a hydroxyl group in the para-trans position of the cyclohexyl ring.
Ambroxol has a secretolytic and secretomotor effect in the bronchial tract.
In preclinical studies, it increased the proportion of the serous component of bronchial secretions. Ambroxol promotes mucus clearance by reducing viscosity and activating the ciliary epithelium.
Ambroxol activates the surfactant system by directly acting on type II pneumocytes in the alveoli and Clara cells in the small airways. It enhances the production and release of surfactant in the alveoli and bronchial tree of the fetus and adult. These effects have been demonstrated in various species in cell cultures and in vivo.
In addition, the antioxidant effects of ambroxol have been demonstrated in various preclinical studies.
Pharmacokinetics
When administered intravenously, the bioavailability of the drug is determined to be 100%. After intravenous administration, the kinetics of ambroxol in the therapeutic range of use is 15-90 mg with a linear dependence on the dose, and even with intravenous administration of 1.0 g, no significant deviations from dose linearity are observed.
Distribution
Approximately 85% (80-90%) of the drug is bound to plasma proteins. In lung tissue, ambroxol reaches higher concentrations than in plasma after parenteral administration. Ambroxol can penetrate into the cerebrospinal fluid, through the placental barrier and is excreted in breast milk.
Biotransformation
The formation of metabolites capable of penetrating the kidneys (e.g., dibromantranilic acid, glucuronide) occurs in the liver.
Breeding
Almost 90% of the drug is excreted by the kidneys in the form of metabolites formed in the liver. Less than 10% of ambroxol is excreted by the kidneys in unchanged form. Due to the high degree of protein binding, large volume of distribution and slow redistribution of the drug from tissues to the blood during dialysis or forced diuresis, significant excretion of ambroxol is unlikely.
The terminal plasma half-life is 7–12 hours. The plasma half-life of ambroxol and its metabolites is approximately 22 hours.
Patients with impaired liver and kidney function
In patients with severe liver disorders, the clearance of ambroxol is reduced by 20-40%. In patients with severe renal impairment, the accumulation of ambroxol metabolites should be taken into account.
Children
In neonates who received repeated intravenous administration of ambroxol, the half-life approximately doubled, indicating reduced clearance.
Indication
To enhance pulmonary surfactant production in premature infants and newborns with respiratory distress syndrome.
Contraindication
Known hypersensitivity to ambroxol hydrochloride or other components of the drug.
Interaction with other medicinal products and other types of interactions
To date, no clinically significant interactions of the drug with other drugs have been identified.
The simultaneous use of Lasolvan® and cough suppressants may lead to excessive mucus accumulation due to suppression of the cough reflex; 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.
Laboratory tests
Simultaneous use of ambroxol and antibiotics (amoxicillin, cefuroxime, doxycycline and erythromycin) leads to an increase in the concentration of antibiotics in bronchopulmonary secretions and sputum.
Application features
Severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis and acute generalised exanthematous pustulosis have been reported in association with the use of ambroxol hydrochloride. If symptoms 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.
Since ambroxol may increase mucus secretion, Lasolvan®, solution for infusion, should be used with caution in cases of impaired bronchial motility and increased mucus secretion (for example, in rare diseases such as primary ciliary dyskinesia).
Lasolvan®, solution for infusion, contains less than 1 mmol (23 mg) sodium per ampoule, i.e. essentially sodium-free.
Lasolvan®, solution for infusion, should be used with caution in patients with impaired renal function or severe liver disease. 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 can be expected in patients with severe renal insufficiency.
Use during pregnancy or breastfeeding
Data are missing due to lack of indications.
Ability to influence reaction speed when driving vehicles or using mechanisms
Not applicable, as the drug is used in premature infants and newborns.
Method of administration and doses
For intravenous infusion.
Dosage
30 mg per 1 kg of body weight per day, divided into 4 single doses.
Dosage in renal and/or hepatic insufficiency
In severe renal insufficiency or severe hepatic insufficiency, the maintenance dose should be reduced or the interval between doses increased accordingly.
The solution should be administered using an infusion pump device by short infusion over at least 5 minutes.
Duration of treatment is 5 days.
The contents of 1-6 ampoules should be diluted in 250-500 ml of saline or Ringer's solution. The solution diluted with saline or Ringer's solution is stable from a physicochemical point of view for 24 hours at 15-25°C. From a microbiological point of view, if opening the ampoules and dilution involves a risk of microbiological contamination, the solution should be used immediately after preparation. If this is not the case, the user is responsible for the storage conditions and times. If none of these solvents are available, 5% glucose solution can be used as an alternative. When using 5% glucose solution, the contents of the ampoules should be diluted immediately before use. If the solution is not used immediately after preparation, it should be discarded.
Children
Used in premature babies and newborns according to indications.
Overdose
There are currently no reports of specific symptoms of overdose. Symptoms observed in case of accidental overdose or medical error are similar to known adverse reactions when used at recommended doses and may 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 | ≥ 1/10,000 – < 1/1000; |
| very rarely | < 1/10,000; |
| 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
infrequently – erythema;
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:
infrequently - dry mouth, constipation, drooling, dry throat;
unknown - nausea, vomiting, diarrhea, dyspepsia, abdominal pain.
From the respiratory system, chest organs and mediastinum:
infrequently - rhinorrhea, dyspnea (as a symptom of a hypersensitivity reaction).
From the kidneys and urinary system:
uncommon – urination disorders.
General disorders and pathological phenomena at the site of drug administration:
infrequently - increased body temperature and chills, reactions from the mucous membrane.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after registration of a medicinal product is an important procedure. This allows for continued monitoring of the benefit/risk balance of this medicinal product. Healthcare professionals are asked to report all suspected adverse reactions to the State Expert Center of the Ministry of Health of Ukraine.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C in a place inaccessible to children.
Incompatibility
Lasolvan®, solution for infusion, should not be mixed with other solutions, except saline and Ringer's solution.
Packaging
2 ml in glass ampoules; 10 ampoules in a cardboard box.
Vacation category
According to the recipe.
Producer
SANOFI SRL, Italy.
Location of the manufacturer and its business address
Via Valcanello, 4 – 03012 ANAGNI (FR), Italy.
Applicant
Applicant's location
Ukraine, 01033, Kyiv, Zhylyanska St., 48-50A.
