Lazolvan® max
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Lazolvan® MAX (Lasolvan® MAX)
Composition:
Active substance: 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), iron oxide red (E 172), iron oxide yellow (E 172); printing ink for capsule marking: shellac, n-butyl alcohol, propylene glycol (E 1520), titanium dioxide (E 171).
Pharmaceutical form. Prolonged-release capsules.
Main physicochemical properties: elongated hard gelatin capsules consisting of an opaque orange body and an opaque red cap with the inscription “MUC01” in white. The capsule contents: round whitish-yellow pellets with a smooth shiny surface, mixed with a small amount of powder.
Pharmacotherapeutic group.
Preparations for the treatment of respiratory disorders. Cough preparations and remedies for colds. Expectorants, excluding combinations with antitussives. Mucolytics. Ambroxol.
ATC Code: R05C B06.
Pharmacological Properties.
Pharmacodynamics.
Preclinical studies have demonstrated that the active ingredient of Lasolvan® Max capsules, ambroxol hydrochloride, increases the serous fraction of bronchial secretion. Ambroxol enhances pulmonary surfactant secretion by directly affecting type II pneumocytes in the alveoli and Clara cells in the bronchioles, and also stimulates ciliary activity, thereby reducing sputum viscosity and improving its elimination (mucociliary clearance). Improvement in mucociliary clearance has been confirmed in clinical and pharmacological studies.
Activation of secretion, reduction in secretory viscosity, and improvement of mucociliary clearance promote mucus expulsion and facilitate expectoration.
In patients with COPD who received prolonged-release capsules of ambroxol hydrochloride 75 mg for 6 months, a significant reduction in the number of exacerbations was observed compared to placebo, evident by the end of the second month of treatment. Patients treated with ambroxol hydrochloride experienced significantly fewer days of illness and required fewer days of antibiotic therapy. Compared to placebo, treatment with prolonged-release ambroxol hydrochloride capsules demonstrated a statistically significant improvement in patient outcomes regarding sputum expectoration, cough, dyspnea, and auscultatory findings.
In a rabbit eye model, ambroxol hydrochloride exhibited a local anesthetic effect, which may be explained by its sodium channel-blocking properties. In vitro studies showed that ambroxol hydrochloride reversibly and concentration-dependently blocks potential-dependent neuronal sodium channels.
Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. Specifically, 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 with ambroxol hydrochloride.
Due to its pharmacological properties, ambroxol rapidly alleviates pain during treatment of upper respiratory tract diseases, as observed in clinical efficacy studies of inhaled ambroxol formulations.
Ambroxol hydrochloride increases the concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum. The clinical significance of this effect has not yet been established.
Antiviral properties in vitro and in experimental animal models
In vitro studies using human tracheal epithelial cells showed reduced rhinovirus (RV 14) replication. In a murine respiratory model, pretreatment with ambroxol resulted in reduced replication of influenza A virus.
To date, the clinical relevance of this effect has not been confirmed.
Pharmacokinetics.
Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and nearly complete, with dose-proportional pharmacokinetics within the therapeutic range. Maximum plasma concentrations are reached within 1–2.5 hours after oral administration of immediate-release formulations and on average after 6.5 hours with slow-release formulations.
Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and extensive, with the highest concentrations of the active substance found in the lungs. The volume of distribution after oral administration is 552 L. In plasma within the therapeutic range, approximately 90% of the drug is protein-bound.
Metabolism and elimination. Approximately 30% of the dose is eliminated via presystemic metabolism after oral administration. Ambroxol hydrochloride is primarily metabolized in the liver via glucuronidation and cleavage into dibromoaniline acid (approximately 10% of the dose). Studies using human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromoaniline acid.
After 3 days of oral administration, about 6% of the dose is excreted unchanged in urine, while approximately 26% is excreted in conjugated form.
The elimination half-life from plasma is approximately 10 hours. Total clearance is about 660 mL/min. Renal clearance accounts for approximately 8% of total clearance. After 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.
Clinical characteristics.
Indications.
Mucolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and reduced mucus clearance.
Contraindications.
Lazolvan**®** Max must not be used in patients with known hypersensitivity to ambroxol hydrochloride or to any of the other components of the medicinal product.
Lazolvan**®** Max is not intended for use in children under 12 years of age due to the amount of active substance contained in the capsule.
Interaction with other medicinal products and other forms of interaction.
When Lazolvan**®** Max is used concomitantly with cough-suppressant agents, significant accumulation of secretions may occur in patients with pre-existing respiratory diseases associated with mucus hypersecretion, such as cystic fibrosis (mucoviscidosis) or bronchiectasis, due to suppression of the cough reflex.
Special precautions for use
There have been reports of severe skin reactions associated with the use of ambroxol hydrochloride, such as erythema multiforme, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). If symptoms or signs of progressive skin rash (sometimes associated with blistering or mucosal lesions) occur, ambroxol hydrochloride treatment must be discontinued immediately and medical advice should be sought.
Lazolvan**®** Max 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 renal impairment or severe hepatic insufficiency should take Lazolvan**®** Max only after consultation with a physician. In patients with severe renal insufficiency, administration of ambroxol, like any active substance metabolized in the liver and subsequently excreted by the kidneys, may lead to accumulation of metabolites formed in the liver.
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 pregnancy, embryonic/fetal development, parturition, or postnatal development. Based on extensive clinical experience, no harmful effects on the fetus have been observed when the drug is used after the 28th week of pregnancy. However, usual precautionary measures regarding medication use during pregnancy should be followed. Particularly during the first trimester of pregnancy, Lazolvan**®** Max is not recommended.
Breastfeeding. Preclinical studies have shown that ambroxol hydrochloride is excreted into breast milk. Lazolvan**®** Max is not recommended during breastfeeding.
Fertility. Preclinical studies do not indicate any direct or indirect harmful effect on fertility.
Ability to influence the reaction rate while driving or operating machinery. There are no data regarding the effect on reaction speed while driving or operating machinery. Studies on the influence of ambroxol on reaction speed during driving or operating machinery have not been conducted.
Method of Administration and Dosage
Unless otherwise indicated, the recommended dosage regimen for Lazolvan**®** Max is as follows:
Adults and children aged 12 years and older: 1 capsule once daily (equivalent to 75 mg/day of ambroxol hydrochloride).
Lazolvan**®** Max can be taken regardless of food intake. The capsules should be swallowed whole with an adequate amount of liquid (water, tea, fruit juice).
In general, there are no restrictions regarding duration of use; however, long-term therapy should be conducted under medical supervision.
Lazolvan**®** Max should not be used for longer than 4–5 days without consulting a physician.
Children. The medication is not intended for children under 12 years of age due to the amount of active ingredient contained in the capsule.
Overdose.
To date, there have been no reports of specific overdose symptoms in humans.
Symptoms reported in isolated cases of overdose and/or accidental ingestion correspond to the known adverse effects of Lazolvan**®** Max observed at recommended doses and require symptomatic treatment.
Side effects.
The following classification was used to assess the frequency of adverse reactions:
| very common |
≥ 1/10; |
| common |
≥ 1/100 – < 1/10; |
| uncommon |
≥ 1/1000 – < 1/100; |
| rare |
≥ 1/10000 – < 1/1000; |
| very rare |
< 1/10000; |
| not known |
cannot be estimated based on available data. |
Immune system side effects:
Rare: hypersensitivity reactions;
Not known: anaphylactic reactions, including anaphylactic shock, angioneurotic edema, and pruritus.
Skin and subcutaneous tissue side effects:
Rare: rash, urticaria;
Not known: 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:
Not known: dyspnea (as a symptom of hypersensitivity reaction).
General disorders:
Uncommon: fever, mucosal reactions.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after drug registration is an important procedure. It enables continuous monitoring of the benefit-risk balance of this medicinal product. Healthcare professionals are requested to report any adverse reactions via the national reporting system.
Shelf life. 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 pack, 1 blister pack in a cardboard box.
Availability category.
Over-the-counter (without prescription).
Manufacturer.
Delpharm Reims, France / Delpharm Reims, France.
Manufacturer's address and place of business.
10 rue Colonel Charbonneaux, 51100 Reims, France /
10 rue Colonel Charbonneaux, 51100 Reims, France.
Marketing Authorization Holder.
LLC "Opella Health Ukraine".
Address of the Marketing Authorization Holder.
48-50A Zhylyanska St., Kyiv, 01033, Ukraine.
Date of last review.