Ambrohexal solution for oral administration and inhalation 7.5 mg/ml 50 ml №1

Name:
Ambrohexal solution for injection 50 ml Main active ingredient Ambroxol Release form Solution Composition 1 ml of solution (about 20 drops) contains: active substance – ambroxol hydrochloride 7.5 mg; excipients: methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), sodium metabisulfite (E223), citric acid anhydride, sodium hydroxide, purified water.
Description:
Clear, colorless solution, free from undissolved foreign particles upon visual inspection. Dosage: 50 ml stimulates the serous cells of the glands of the bronchial mucosa, increases the content of the mucous secretion and the release of a surfactant (surfactant) in the alveoli and bronchi; normalizes the disturbed ratio of serous and mucous components of sputum. By activating hydrolyzing enzymes and increasing the release of lysosomes from Clark cells, it reduces the viscosity of sputum. Increases the motor activity of the cilia of the ciliated epithelium, increases the mucociliary transport of sputum. After oral administration, the effect occurs after 30 minutes and lasts for 6-12 hours. PharmacokineticsAbsorption In the therapeutic dose range, absorption of ambroxol hydrochloride from oral dosage forms of immediate release occurs quickly and completely, and is linear. The time to reach maximum concentration is 1-2.5 hours after ingestion. Distribution Distribution of ambroxol hydrochloride from blood to tissue is rapid, with the maximum concentration of the active substance found in the lungs. The apparent volume of distribution after oral administration is 552 liters. Plasma protein binding is about 90%. Metabolism About 30% of the administered dose is excreted during the first pass as a result of first pass metabolism. Ambroxol hydrochloride is metabolized in the liver by glucuronidation and cleavage to dibromanthranilic acid (approximately 10% of the dose). Human liver microsome studies have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromanthranilic acid. Withdrawal After 3 days after administration, approximately 6% of ambroxol hydrochloride is excreted unchanged and approximately 26% is excreted by the kidneys in the form of its conjugates. The terminal half-life of ambroxol hydrochloride is approximately 10 hours. The total clearance is 660 ml / min, while the renal clearance is approximately 8% of the total clearance. It was estimated that after 5 days 83% of the total dose (radiolabeled) was excreted in the urine. Special groups of patients In patients with hepatic insufficiency, the excretion of ambroxol hydrochloride is reduced. As a result, the plasma level increases by 1.3-2 times. Due to the high therapeutic index of the drug, dose adjustment is not required. The age and sex of patients do not have a clinically significant effect on the pharmacokinetics of ambroxol hydrochloride. As such, no separate dosing recommendations are required. Food does not affect the bioavailability of ambroxol hydrochloride. Preclinical safety data Ambroxol has a low level of acute toxicity. Specific oral administration: Repeat doses in rats (52 and 78 weeks), rabbits (26 weeks), mice (4 weeks) and dogs (52 weeks) showed no toxic effects. No observed adverse effects level (NOAEL) in was 50 mg/kg/day in rats, 40 mg/kg/day in rabbits, 150 mg/kg/day in mice, and 10 mg/kg/day in dogs. Intravenous use: Toxicity studies of ambroxol hydrochloride over 4 weeks in rats (4, 16 and 64 mg/kg infusion 3 hours/day) and dogs (45, 90 and 120 mg/kg/day infusion 3 hours/day) did not reveal severe local and systemic toxicity, including histopathology. All adverse events were reversible. Ambroxol hydrochloride did not show embryotoxicity or teratogenicity at oral doses up to 3000 mg/kg/day in rats and up to 200 mg/kg/day in rabbits. Fertility in male and female rats was not altered at doses up to 1500 mg/kg/day. The NOAEL level in the study of peri- and postnatal development was 50 mg/kg/day. Ambroxol hydrochloride had low toxicity to mothers and kittens at a dose of 500 mg/kg/day (delayed development of body weight and reduced offspring size). In vitro (chromosomal aberration test) and in vivo (micronucleus test in mice) genotoxicity studies did not reveal any mutagenic potential of ambroxol hydrochloride. Ambroxol hydrochloride did not show tumorigenicity in carcinogenicity studies in mice (50, 200 and 800 mg/kg/day) and rats (65, 250 and 1000 mg/kg/day) as a dietary supplement for 105 and 116 weeks, respectively. Indications for use Acute and chronic diseases of the respiratory tract with the release of viscous sputum: acute and chronic bronchitis, pneumonia, chronic obstructive pulmonary disease, bronchial asthma with difficulty in sputum discharge, bronchiectasis. Contraindications – hypersensitivity to ambroxol hydrochloride or excipients of the drug; – children’s age up to 6 years (allowed only by prescription of the attending physician); – pregnancy (I trimester). Application during pregnancy and lactation Pregnancy Ambroxol hydrochloride passes through the placental barrier. Preclinical studies have not revealed direct or indirect adverse effects on pregnancy, embryo/fetal development, childbirth or postnatal development. Extensive clinical experience with the use of the drug after the 28th week of pregnancy does not indicate any harmful effects on the fetus. However, the usual precautions regarding the use of medications during pregnancy should be followed. In the first trimester of pregnancy, the use of the drug is contraindicated. In the II-III trimesters of pregnancy, it is permissible to use the drug with caution, while the potential benefit to the mother and the possible risk to the fetus should be assessed. Breastfeeding Animal studies have shown that ambroxol hydrochloride passes into breast milk and is therefore not recommended during breastfeeding. Fertility Preclinical studies do not indicate any direct or indirect harmful effects on fertility. Method of application and dosesIngestion (1 ml = 20 drops). Children over the age of 12 and adults: the first 2-3 days – 3 times 4 ml (30 mg of ambroxol hydrochloride) per day, then – 2 times 4 ml. If necessary, to increase efficiency, the dose for adults and adolescents over 12 years of age can be increased by applying 8 ml of solution 2 times a day (corresponding to 120 mg of ambroxol hydrochloride / day). Children aged 6-12 years: 2-3 times a day, 2 ml (15 mg of ambroxol hydrochloride). Children aged 2-5 years: 3 times a day, 1 ml (7.5 mg of ambroxol hydrochloride) AmbroGEXAL® should be taken after meals in a diluted form with tea, fruit juices, milk or water. During treatment, it is necessary to drink plenty of fluids (juices, tea, water) to enhance the mucolytic effect of the drug. Application for inhalation: Adults and children over the age of 6 are recommended to inhale 1-2 times a day, 2-3 ml (40-60 drops, which corresponds to 15-22.5 mg of ambroxol hydrochloride); For inhalation, you must use a suitable device (for example, a compression or ultrasonic nebulizer). The steam inhaler is not suitable for the use of AmbroGEXAL®. The manufacturer’s instructions for use must be followed. Heating the solution to 80 °C for 10 minutes does not affect the stability. AmbroGEXAL® is mixed with saline and beta-sympathomimetics. AmbroGEXAL® should not be mixed with cromoglycic acid. In addition, mixing should not be carried out with other solutions if the result is a mixture with a pH higher than 6.3, for example, with an alkaline saline solution for inhalation. Increasing the pH may result in precipitation of ambroxol free base or cloudiness of the solution. To achieve optimal humidification of the inhaled air, especially when using a respirator, AmbroGEXAL® 7.5 mg/ml oral and inhalation solution should be mixed with saline in a ratio of 1:1. Ambroxol solution is isotonic and therefore well compatible with mucous membranes. However, coughing may occur when aerosols are inhaled too deeply. Therefore, when inhaling, you should inhale and exhale normally. Before use, the inhalation solution should be warmed to body temperature. The duration of therapy depends on the severity of the disease and is determined by the attending physician. The course of treatment without consulting a doctor is 4-5 days. If the patient has forgotten to take the prescribed dose of the drug, he should postpone taking the drug until the next time, in accordance with the dosing regimen. Do not double your dose to make up for a missed dose. Side effects Like all medicines, AmbroGEXAL® can cause side effects, although not everyone gets them. The evaluation of side effects is based on the frequency of their occurrence: very common: more than 1 in 10 patients common: 1-10 patients in 100 uncommon: 1-10 patients in 1,000 rare: 1-10 patients in 10,000 very rare : less than 1 in 10,000 patients frequency unknown: cannot be determined from the available data Immune system disorders Rare: hypersensitivity reactions. Frequency unknown: anaphylactic reactions, including anaphylactic shock, angioedema and pruritus. Gastrointestinal disorders Common: Nausea, oral hypoesthesia. Uncommon: Vomiting, diarrhea, dyspepsia and abdominal pain, dry mouth. Very rare: constipation, salivation. Frequency unknown: dry throat. Skin and subcutaneous tissue disorders Rare: rash, urticaria. Frequency unknown: severe skin reactions (including erythema multiforme, Stevens-Johnson syndrome / toxic epidermal necrolysis and acute generalized exanthematous pustulosis). Nervous system disorders Common: dysgeusia (change in taste). Respiratory, thoracic and mediastinal disorders Common: pharyngeal hypoesthesia. Very rare: rhinorrhea, dry airways, dyspnea and bronchospasm (usually in patients with known airway hypersensitivity). Frequency unknown: shortness of breath (as a symptom of a hypersensitivity reaction). Renal and urinary disorders Very rare: dysuria. General disorders and reactions at the injection site Rare: drug fever. 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. If the patient experiences any adverse reactions, he should consult a doctor. This recommendation applies to any possible adverse reactions, including those not listed in the package insert. By reporting adverse reactions, you help to get more information about the safety of the drug. Overdose Symptoms of overdose in humans are not described. Specific symptoms in case of accidental overdose and/or medical errors included symptoms similar to adverse reactions and required symptomatic therapy. Interaction with other drugs The use of ambroxol hydrochloride with antitussive drugs leads to a violation of sputum discharge against the background of a decrease in cough, so this combination should not be used. The use of ambroxol hydrochloride with antibiotics (amoxicillin, cefuroxime, erythromycin and doxycycline) increases the concentration of antibiotics in sputum and bronchial secretions. The clinical significance of this has not been established. Precautions Severe skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis and acute generalized exanthematous pustulosis have been reported in association with ambroxol hydrochloride. If symptoms or signs of a progressive skin rash appear (sometimes accompanied by the formation of blisters or changes in the mucous membranes), AmbroGEXAL® should be stopped immediately and a doctor should be consulted. In most cases, such reactions were associated with the severity of the underlying disease of the patient and (or) the use of concomitant drugs. In addition, in the early stages of Stevens-Johnson syndrome or toxic epidermal necrolysis, patients may initially present with flu-like symptoms such as fever, body aches, runny nose, cough, and sore throat. It is possible that because of the confusion about these non-specific flu-like symptoms, symptomatic treatment was started with cold and cough medicines. In case of impaired renal function or severe liver disease, AmbroGEXAL® should be taken only after consulting a doctor. As with any drug with hepatic metabolism followed by excretion via the kidneys, accumulation of ambroxol metabolites should be expected in severe renal insufficiency. Patients with impaired bronchial motility and abundant bronchial secretions (as, for example, with a rare syndrome of primary ciliary dyskinesia), AmbroGEKSAL® should be used with caution due to the risk of difficult discharge of large amounts of sputum and blockage of the bronchi. Since the risk of bronchospastic reactions is present mainly with inhalation, AmbroGEXAL® 7.5 mg / ml, oral and inhalation solution should not be used in patients with known bronchial hyperactivity and / or a history of atopy. The drug contains methyl parahydroxybenzoate, propyl parahydroxybenzoate, which can cause allergic reactions (including delayed), in exceptional cases, bronchospasm. Sodium metabisulphite, which is part of the drug, in rare cases can cause serious hypersensitivity reactions and bronchospasm. Storage conditions Keep out of the reach of children! Store in a place protected from light at a temperature not exceeding 25 ° C. Buy Ambrohexal oral and inhalation solution 7.5mg/ml 50ml №1 Price for Ambrohexal oral and inhalation solution 7.5mg/ml 50ml №1 one