Lazolvan solution for inhalation 7.5 mg/ml in a bottle of 100 ml No. 1

Name:
Lazolvan. Release form Solution. MNNAMbroxol. FTGMucolytic agent. Composition 1 ml of solution contains: Active substance: ambroxol hydrochloride 7.5 mg. Excipients: citric acid monohydrate (E330), disodium hydrogen phosphate dihydrate (E339), sodium chloride, benzalkonium chloride, purified water.
Description:
Transparent, colorless or slightly brownish solution. Pharmacotherapeutic group Expectorants, excluding combinations with antitussives. mucolytic agents. ATX code: R05CB06. Pharmacological action Pharmacodynamics Preclinical studies have shown that ambroxol hydrochloride, the active ingredient in Lazolvan, stimulates the secretion of the serous component of bronchial secretions. It also increases the secretion of pulmonary sufractant and stimulates ciliary activity, which results in a decrease in sputum viscosity and an improvement in its excretion (mucociliary clearance). Conducted clinical and pharmacological studies confirm the improvement in mucociliary clearance. Increased sputum fluidity and mucociliary clearance improve sputum discharge and relieve coughing. In patients with COPD who took LAZOLVAN 75 mg extended-release capsules for 6 months, a significant reduction in exacerbations was registered by the end of the 2nd month of treatment compared with placebo. In patients in the LAZOLVANA group, a significant decrease in the number of days of illness and a decrease in the number of days of taking antibacterial drugs were observed. Also, in the LAZOLVANA group, compared with placebo, there was a statistically significant improvement in symptoms, such as difficulty in expectorating sputum, cough, dyspnea, and auscultatory symptoms. The local anesthetic effect of ambroxol hydrochloride has been observed in studies conducted on a rabbit eye model and is likely due to blocking of sodium channels by the drug. Ambroxol hydrochloride in vitro reversibly and dose-dependently blocks cloned neuronal sodium channels. Ambroxol hydrochloride has been found in vitro to have an anti-inflammatory effect. In in vitro tests, it significantly reduced the release of cytokines from circulating and tissue mononuclear and polymorphonuclear cells. Antiviral Properties in In Vitro Studies and Animal Models: Reduced replication of rhinovirus (RV14) has been noted in in vitro studies on human tracheal epithelial cells. After pre-treatment with ambroxol, a decrease in influenza A virus replication in the respiratory tract was observed in studies in experimental mouse models. Pharmacokinetics Absorption Absorption of all oral forms of ambroxol hydrochloride with immediate release is fast and fairly complete with a linear relationship in the therapeutic range. The maximum concentration in blood plasma is reached 1-2.5 hours after oral administration of the immediate release dosage form and, on average, 6.5 hours after taking the prolonged-release dosage form. Absolute bioavailability after taking 30 mg tablets was 79%. The relative bioavailability of the extended release capsules was 95% (normalized dose) compared to a daily dose of 60 mg (30 mg twice daily) immediate release tablets. Distribution The distribution of ambroxol hydrochloride from the blood to the tissues is fast and efficient, with the highest concentration of the active substance found in the lungs. The volume of distribution after oral administration is 552 liters. In the therapeutic range, plasma protein binding is about 90%. Metabolism and excretion Approximately 30% of the oral dose is excreted as a result of first pass metabolism. Metabolism of ambroxol hydrochloride occurs predominantly in the liver by glucuronidation and partial cleavage to dibromanthranilic acid (approximately 10% of the dose). Studies of human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromanthranilic acid. Within 3 days of oral administration, approximately 6% of the dose is found in the free form, and about 26% of the dose appears in the urine in the form of conjugates. The half-life of ambroxol hydrochloride from the body is 10 hours. The total clearance is in the range of 660 ml / min., The renal clearance provides approximately 83% of the total clearance. Pharmacokinetics in special groups of patients In patients with impaired liver function, the excretion of ambroxol hydrochloride is reduced, which leads to an increase in its plasma level by 1.3-2 times. The pharmacokinetics of ambroxol is not clinically significantly dependent on age and gender, so dosage changes are not required. The bioavailability of ambroxol hydrochloride does not depend on food intake. Preclinical safety data Ambroxol hydrochloride has a low acute toxicity index. In repeated dosing studies, at oral doses of 150 mg/kg/day (greater than 4 weeks in mice), 50 mg/kg/day (greater than 52 and 78 weeks in rats), 40 mg/kg/day (greater than 26 weeks in rabbits) and 10 mg/kg/day (greater than 52 weeks in dogs) showed no notable adverse reactions (NOAELs). Toxicological studies did not reveal damage to target organs. Toxicity studies with intravenous ambroxol hydrochloride at doses of 4, 16, and 64 mg/kg/day in rats and 45, 90, and 120 mg/kg/day in dogs (3 h/day infusion) did not reveal serious systemic and oral toxicity, including histopathology. All adverse reactions were reversible. In studies conducted in rats and rabbits with oral administration of ambroxol hydrochloride at doses up to 3000 mg / kg / day and 200 mg / kg / day, respectively, no embryotoxicity or teratogenicity was detected. Fertility in male and female rats was not impaired at doses up to 500 mg/kg/day. The dose of 50 mg/kg/day was established as the “No observed adverse effects maximum dose” (NOAEL) when administered during peri- and postnatal development, while doses of 500 mg/kg/day were moderately toxic to female rats and offspring. , which manifested itself as a delay in weight gain and a decrease in the number of births. In genotoxicity studies conducted in vitro (Ames test and accounting for chromosomal aberrations) and in vivo (micronuclear test in mice), ambroxol hydrochloride has not been found to have mutagenic potential. Ambroxol hydrochloride showed no oncogenic potential in carcinogenicity studies in mice (50, 200 and 800 mg/kg/day) and rats (65, 250 and 1000 mg/kg/day) when the drug was administered in a mixture with food for 105 and 116 weeks , respectively. Indications for use Mucolytic therapy in the treatment of acute and chronic diseases of the respiratory tract, accompanied by the formation of viscous sputum difficult to separate. Method of application and dosage The following doses are recommended, unless otherwise prescribed by a doctor: Children 5 years and younger: 1-2 ml of solution 1-2 times a day (corresponding to 7.5-15 mg of ambroxol hydrochloride 1-2 times a day). Adults and children from 6 years of age: 2-3 ml of solution 1-2 times a day (corresponding to 15-22.5 mg of ambroxol hydrochloride 1-2 times a day). How to use LASOLVAN solution for inhalation can be used in various modern devices for inhalation. LAZOLVAN solution for inhalation is mixed with physiological saline in a ratio of 1:1 to obtain optimal humidification of the inhaled air. LASOLVAN solution for inhalation must not be mixed with cromoglycic acid; as well as with other solutions, if the result is a mixture with a pH above 6.3, for example, with Emser salt. An elevated pH may cause the free base of ambroxol hydrochloride to precipitate or cloud the solution. During inhalation, it is recommended to breathe normally, as inhalation itself can provoke a cough. Before inhalation, the solution should be warmed to body temperature. Patients with bronchial asthma are advised to use the solution for inhalation after the use of anti-asthma drugs. If there is no improvement in acute respiratory diseases during treatment with LAZOLVAN or worsening of symptoms is observed, it is necessary to consult a doctor. Side effect Criteria for assessing the frequency of adverse drug reactions: very often (≥ 1/10), often (from ≥ 1/100 to < 1/10), infrequently (from ≥ 1/1000 to < 1/100), rarely (from ≥ 1/10000 to < 1/1000), very rare (< 1/10000), frequency unknown (frequency cannot be estimated from the available data). Immune system disorders Rare: hypersensitivity reactions. Frequency unknown: anaphylactic reactions, including anaphylactic shock, angioedema, itching. Skin and subcutaneous tissue disorders Rare: rash, urticaria. Frequency unknown: severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis). Nervous system disorders Common: dysgeusia (change in taste). Gastrointestinal disorders Often: nausea, decreased sensitivity of the oral mucosa. Uncommon: Vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth. Rarely: dryness in the throat. Heartburn has also been reported. Respiratory, thoracic and mediastinal disorders Common: Decreased sensitivity of the pharyngeal mucosa. Reporting adverse reactions It is important to report suspected adverse reactions after registration of a medicinal product in order to ensure continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse drug reactions through national adverse drug reaction and drug failure reporting systems. The patient, if he experiences any adverse reactions, is advised to consult a doctor. This recommendation applies to any possible adverse reactions, including those not listed in the instructions for use of the drug. You can also report adverse reactions to the adverse drug reactions (actions) information database, including reports of drug failures. By reporting adverse reactions, you help to get more information about the safety of the drug. Contraindications - Hypersensitivity to the active substance, ambroxol hydrochloride, or other components of the drug. - Serious disorders of the liver and kidneys. - The use of the drug is contraindicated in case of rare hereditary diseases in which any of the excipients can cause the development or exacerbation of the disease (see section "Precautions"). Overdose Symptoms of overdose in humans are not described. In case of accidental overdose or cases of medical errors, it has been reported that the observed symptoms correspond to known adverse reactions when using the drug at recommended doses, and symptomatic therapy may be required to stop them. Precautions Ambroxol hydrochloride should be used with caution in patients with peptic ulcers. There have been reports of the development of severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis in patients taking ambroxol. It is necessary to immediately stop using the drug if symptoms of a progressive skin reaction (sometimes associated with the development of blisters and lesions of the mucous membranes) appear and consult a doctor. Most of these reactions can be explained by the severity of the underlying disease or concomitant therapy. In addition, in the early stages of Stevens-Johnson syndrome or toxic epidermal necrolysis (TEN), the patient may experience non-specific flu-like symptoms such as fever, chills, rhinitis, cough, and sore throat. The presence of these symptoms can lead to inappropriate symptomatic treatment with cough and cold remedies. If the patient has impaired renal function, LAZOLVAN can be used only after consulting a doctor. Important information about the excipients contained in LAZOLVAN solution for inhalation contains the preservative benzalkonium chloride, which, after inhalation, can cause bronchospasm in patients with hypersensitivity and hyperreactivity of the airways. Fertility, pregnancy and lactation Pregnancy Ambroxol hydrochloride crosses the placental barrier. Animal studies have not shown direct or indirect negative effects on pregnancy, embryonic/fetal development, childbirth or postnatal development. Extensive clinical experience with the use of the drug after the 28th week of pregnancy did not reveal any evidence of a negative effect on the fetus. However, the usual precautions regarding the use of any drug during pregnancy are recommended. In particular, the use of LASOLVAN is not recommended during the first trimester of pregnancy. Breastfeeding period Ambroxol is excreted from the body with breast milk. Use during breastfeeding is not recommended. Fertility Animal studies have shown no direct or indirect adverse effects on fertility. Influence on the ability to drive a car and mechanisms There are no known cases of the effect of the drug on the ability to drive a car and mechanisms. Relevant studies have not been conducted. Interaction with other drugs After taking ambroxol, the concentration of antibiotics (amoxicillin, cefuroxime, erythromycin) in bronchopulmonary secretion and in saliva increases. No other interactions with other drugs have been reported. Packaging Solution for inhalation 7.5 mg/ml. 100 ml in a dark glass bottle with a polyethylene dropper and a polypropylene screw cap with first opening control. The bottle is placed in a cardboard box with instructions for use and a measuring cup. Storage conditionsDoes not require special storage conditions. Keep out of the reach of children. Shelf life 3 years. Shelf life after the first opening of the vial is 12 months. Do not use after the expiration date. Terms of dispensing from pharmacies Without a prescription. Buy Lazolvan solution for inhalation 7.5 mg / ml in a bottle of 100 ml No. 1 bottle 100ml №1