Ambroxol-kv
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Ambroxol-KV (AMBROXOL-KV)
Composition:
Active substance: 1 tablet contains ambroxol hydrochloride 30 mg;
Excipients: lactose monohydrate; corn starch; colloidal anhydrous silicon dioxide; magnesium stearate.
Pharmaceutical form. Tablets.
Main physicochemical properties: flat cylindrical tablets with bevelled edges and a score line, white or almost white in colour.
Pharmacotherapeutic group. Medicinal products used in cough and colds. Mucolytic agents. ATC code R05C B06.
Pharmacological properties.
Pharmacodynamics.
It has been preclinically proven that the active substance of the medicinal product, ambroxol hydrochloride, enhances the formation of the serous component of bronchial secretion. Ambroxol strengthens the release of pulmonary surfactant by directly affecting type II pneumocytes in alveoli and Clara cells in bronchioles, and also stimulates ciliary activity, thereby reducing the viscosity of sputum and improving its elimination (mucociliary clearance). Improvement of mucociliary clearance has been demonstrated in clinical pharmacological studies.
Enhanced production of serous secretion and improved mucociliary clearance facilitate expectoration and reduce coughing.
In patients with COPD who received prolonged-release ambroxol hydrochloride capsules 75 mg for 6 months, a significant reduction in the number of exacerbations was observed compared to placebo by the end of 2 months of treatment. In patients treated with ambroxol hydrochloride, the duration of illness was significantly shorter, and fewer days of antibiotic therapy were required. They also showed a statistically significant reduction in symptoms such as difficulty in expectoration, cough, dyspnea, and auscultatory sounds compared to placebo.
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 showed that ambroxol hydrochloride blocks neuronal sodium channels; binding was reversible and concentration-dependent.
Ambroxol hydrochloride demonstrated anti-inflammatory effects in vitro. Thus, ambroxol hydrochloride significantly reduces the release of cytokines from mononuclear and polymorphonuclear blood and tissue cells.
Clinical trials involving patients with pharyngitis have demonstrated a significant reduction in throat pain and redness upon administration of the drug.
Due to the pharmacological properties of ambroxol, pain relief occurred rapidly during treatment of upper respiratory tract disorders, as observed in clinical efficacy studies of inhaled ambroxol formulations.
Administration of ambroxol hydrochloride increases the concentration of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum. To date, no clinical significance of this fact has been identified.
Pharmacokinetics.
Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and complete, with linear dose-dependency within the therapeutic range. Maximum plasma concentration is reached within 1–2.5 hours after oral administration of immediate-release formulations and on average within 6.5 hours after administration of sustained-release formulations.
Absolute bioavailability after administration of a 30 mg tablet is 79%.
Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and extensive, with the highest concentration of the active substance found in the lungs. The expected volume of distribution after oral administration is 552 L. In plasma, within the therapeutic dose range, approximately 90% of the drug is protein-bound.
Metabolism and elimination. Approximately 30% of the dose is eliminated due to presystemic metabolism after oral administration. Ambroxol hydrochloride is metabolized primarily in the liver via glucuronidation and cleavage to dibromanthranilic acid (approximately 10% of the dose). Studies using human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromanthranilic acid.
Within 3 days after oral administration, about 6% of the dose is excreted unchanged in urine, and approximately 26% of the dose – in conjugated form.
The elimination half-life from plasma is approximately 10 hours. Total clearance is approximately 660 mL/min. Renal clearance accounts for approximately 8% of total clearance. Within 5 days, approximately 83% of the total dose is excreted in urine.
Pharmacokinetics in special patient populations. In patients with impaired liver function, elimination of ambroxol hydrochloride is reduced, resulting in plasma levels 1.3–2 times higher. However, since the therapeutic range of ambroxol hydrochloride is sufficiently wide, dosage adjustment is not required.
Age and sex have no clinically significant effect on the pharmacokinetics of ambroxol hydrochloride; therefore, no dose adjustment is necessary.
Food intake does not affect the bioavailability of ambroxol hydrochloride.
Clinical characteristics.
Indications.
Secretolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and weakened mucus clearance.
Contraindications.
Ambroxol-KV must not be used in patients with known hypersensitivity to ambroxol hydrochloride or to any of the excipients.
Ambroxol-KV, 30 mg tablets, is not intended for use in children under 6 years of age due to the dosage. This patient group should be prescribed ambroxol hydrochloride in a pharmaceutical form suitable for pediatric use.
Interaction with other medicinal products and other forms of interaction.
Concomitant use of Ambroxol-KV and cough suppressants may lead to excessive mucus accumulation due to suppression of the cough reflex.
Therefore, such combination is possible only after careful assessment by a physician of the benefit-risk ratio.
Special precautions for use
Severe skin reactions have been reported: erythema multiforme, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP), associated with the use of ambroxol hydrochloride. If signs of skin rash progression are present (sometimes associated with blistering or mucosal involvement), treatment with ambroxol hydrochloride should be immediately discontinued and medical advice sought.
Ambroxol-KV tablets contain 684 mg of lactose in the maximum recommended daily dose (120 mg).
This medicinal product should not be taken by patients with rare hereditary disorders of galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
Ambroxol-KV should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g., in rare conditions such as primary ciliary dyskinesia) due to the risk of promoting secretion accumulation.
Patients with impaired renal function or severe hepatic insufficiency should take Ambroxol-KV only after consultation with a physician. When ambroxol is administered, as with any active substance metabolized in the liver and subsequently excreted by the kidneys, metabolites formed in the liver may accumulate in patients with severe renal impairment.
Use during pregnancy or breastfeeding
Pregnancy. Ambroxol hydrochloride crosses the placental barrier. Animal studies have not revealed any direct or indirect harmful effects on pregnancy, embryonic/fetal development, labor, or postnatal development. Clinical studies of the drug's use after the 28th week of pregnancy have shown no adverse effects on the fetus.
However, usual precautionary measures regarding the use of medicinal products during pregnancy should be observed. In particular, Ambroxol-KV is not recommended during the first trimester of pregnancy.
Breastfeeding. Ambroxol hydrochloride is excreted into breast milk. Ambroxol-KV is not recommended during breastfeeding.
Fertility. Preclinical studies do not indicate a direct or indirect harmful effect on fertility.
Ability to influence reaction speed when driving or operating machinery
There are no data on the effect on reaction speed when driving or operating machinery. Appropriate studies have not been conducted.
Dosage and Administration.
If not otherwise prescribed, the recommended dose of Ambroxol-KV is as follows:
Children aged 6 to 12 years: The usual dose is 1/2 tablet 2–3 times daily (equivalent to 30–45 mg ambroxol hydrochloride per day).
Adults and children aged 12 years and older: The usual dose is 1 tablet 3 times daily for the first 2–3 days (equivalent to 90 mg ambroxol hydrochloride per day).
Treatment should continue with 1 tablet administered 2 times daily (equivalent to 60 mg ambroxol hydrochloride per day).
If necessary, the therapeutic effect in adults and children aged 12 years and older may be enhanced by administering 2 tablets 2 times daily (equivalent to 120 mg ambroxol hydrochloride per day).
Tablets should be swallowed whole with sufficient liquid (e.g., water, tea, or fruit juice), during or independently of meals.
Ambroxol-KV should not be used for longer than 4–5 days without consulting a physician.
In general, there are no restrictions on duration of use; however, prolonged therapy should be conducted under medical supervision.
Children.
Ambroxol-KV is indicated for children aged 6 years and older who cannot tolerate syrup or oral solution, or inhalation therapy.
Overdose.
There are currently no reports of overdose cases in humans. Symptoms described in isolated reports of overdose and/or medication misuse correspond to the known adverse reactions associated with Ambroxol-KV when used at recommended doses and require symptomatic treatment.
Side effects.
The following classification was used to assess the frequency of adverse events:
| very common |
>10 %; |
| common |
>1 % and <10 %; |
| uncommon |
>0.1 % and <1 %; |
| rare |
>0.01 % and <0.1 %; |
| very rare |
<0.01 %; |
| frequency not known |
cannot be estimated from the available data. |
Immune system side effects:
Rare – hypersensitivity reactions;
Frequency unknown – anaphylactic reactions, including anaphylactic shock, angioedema, and pruritus.
Skin and subcutaneous tissue side effects:
Rare – rash, urticaria;
Frequency unknown – serious skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).
Gastrointestinal side effects:
Common – nausea;
Uncommon – vomiting, diarrhea, dyspepsia, abdominal pain;
Very rare – hypersalivation.
Respiratory, thoracic and mediastinal side effects:
Frequency unknown – dyspnea (as a hypersensitivity reaction).
General disorders:
Uncommon – fever, mucosal reactions.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions to the State Expert Center of the Ministry of Health of Ukraine.
Shelf life. 4 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25°C.
Keep out of reach of children.
Packaging. 10 tablets in a blister; 2 blisters per carton.
Availability category. Over-the-counter.
Manufacturer. JSC "KYIV VITAMIN PLANT".
Manufacturer's address and place of business.
38 Kopilivska Street, Kyiv, 04073, Ukraine.
Web-site: www.vitamin.com.ua.