Lasolvan® with strawberry-cream flavor

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT LASOLVAN® WITH STRAWBERRY CREAM FLAVOUR (LASOLVAN® WITH STRAWBERRY CREAM FLAVOUR)

Composition:

Active substance: ambroxol hydrochloride;

5 ml of syrup contain ambroxol hydrochloride 30 mg;

Excipients: benzoic acid (E 210), hydroxyethylcellulose, sucralose, strawberry cream flavour, vanilla flavour, purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: clear or almost clear, colourless or almost colourless, slightly viscous liquid with a strawberry cream fruity odour.

Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytics. ATC code R05C B06.

Pharmacological Properties

Pharmacodynamics

Preclinical studies have demonstrated that the active ingredient of Lazolvan® with strawberry-cream flavor, ambroxol hydrochloride, increases the serous fraction of bronchial secretion. Ambroxol enhances pulmonary surfactant secretion by directly affecting type II pneumocytes in alveoli and Clara cells in bronchioles, and also stimulates ciliary activity, thereby reducing sputum viscosity and improving its clearance (mucociliary clearance). Improvement of mucociliary clearance has been confirmed in clinical pharmacological studies.

Activation of secretion, reduction of secretory viscosity, and improved mucociliary clearance promote mucus elimination 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. In patients treated with ambroxol hydrochloride, the duration of illness was significantly shorter, and fewer days of antibiotic therapy were required. Compared to placebo, treatment with prolonged-release ambroxol hydrochloride capsules showed statistically significant improvement in patient outcomes regarding sputum expectoration, cough, dyspnea, and auscultatory findings.

In a rabbit eye model, ambroxol hydrochloride demonstrated 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 voltage-gated neuronal sodium channels.

Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. Specifically, ambroxol hydrochloride significantly reduces cytokine release from mononuclear and polymorphonuclear blood and tissue cells.

In clinical trials involving patients with pharyngitis, ambroxol hydrochloride significantly reduced throat pain and redness.

Due to the pharmacological properties of ambroxol, rapid relief of pain during treatment of upper respiratory tract disorders was observed in clinical efficacy studies of ambroxol inhalation forms.

Administration of ambroxol hydrochloride increases concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum. The clinical significance of this effect has not yet been established.

Pharmacokinetics

Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and sufficiently complete, with linear dose-dependency within the therapeutic range. Maximum plasma concentrations are reached within 1–2.5 hours after oral administration of immediate-release dosage forms 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 concentration of the active substance found in the lungs. The volume of distribution after oral administration is 552 liters. 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 to 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.

Within 3 days after oral administration, ambroxol hydrochloride is excreted in urine, with approximately 6% of the dose excreted unchanged and about 26% as conjugated metabolites.

The elimination half-life of ambroxol hydrochloride is approximately 10 hours. Total clearance is approximately 660 mL/min, with renal clearance accounting 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 do not have a 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 impaired mucus clearance.

Contraindications.

Lazolvan® with strawberry-cream flavor, syrup, must not be used in patients with hypersensitivity to ambroxol hydrochloride or other components of the medicinal product.

Lazolvan® with strawberry-cream flavor, syrup, must not be used in children under 2 years of age without a physician's prescription.

Interaction with other medicinal products and other forms of interaction.

Concomitant use of Lazolvan® with strawberry-cream flavor, syrup, 30 mg/5 ml, and cough suppressants may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such a combination should only be used after careful evaluation by a physician of the benefit-risk ratio.

Special precautions for use

There have been reports of severe skin reactions associated with the use of ambroxol hydrochloride, including erythema multiforme, Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). If signs of progressive skin rash (sometimes associated with blistering or mucosal involvement) occur, treatment with ambroxol hydrochloride should be discontinued immediately and medical advice should be sought.

Lazolvan® with strawberry-cream flavour, syrup, 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 Lazolvan® with strawberry-cream flavour, syrup, 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.

Lazolvan® with strawberry-cream flavour, syrup 30 mg/5 ml, contains 1.2 g of sorbitol in 5 ml (equivalent to 4.9 g when the maximum recommended daily dose is used). This medicinal product should not be used in patients with rare hereditary fructose intolerance.

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/foetal development, parturition, or postnatal development. Due to extensive clinical experience, no adverse effects on the foetus 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 in the first trimester of pregnancy, Lazolvan® with strawberry-cream flavour, syrup, is not recommended.

Breastfeeding. Ambroxol hydrochloride passes into breast milk. Lazolvan® with strawberry-cream flavour, syrup, is not recommended during breastfeeding.

Fertility. Preclinical studies do not indicate a direct or indirect harmful effect on fertility.

Effect on the ability to drive vehicles or operate machinery

There are no data regarding the effect of ambroxol on the ability to drive vehicles or operate machinery. Studies on the influence of ambroxol on the ability to drive vehicles or operate machinery have not been conducted.

Method of Administration and Dosage

Unless otherwise indicated, the recommended dosage regimen for Lazolvan® with Strawberry-Cream Flavor, Syrup, 30 mg/5 ml, is as follows:

Children under 2 years of age: 1.25 ml twice daily (equivalent to 15 mg of ambroxol hydrochloride per day).

Children aged 2 to 5 years: 1.25 ml three times daily (equivalent to 22.5 mg of ambroxol hydrochloride per day).

Children aged 6 to 12 years: 2.5 ml 2–3 times daily (equivalent to 30–45 mg of ambroxol hydrochloride per day).

Adults and children aged 12 years and older: The usual dose is 5 ml three times daily (equivalent to 90 mg of ambroxol hydrochloride per day) during the first 2–3 days, followed by 5 ml twice daily (equivalent to 60 mg of ambroxol hydrochloride per day).

If necessary, the therapeutic effect in adults and children aged 12 years and older may be enhanced by increasing the dose to 10 ml twice daily (equivalent to 120 mg of ambroxol hydrochloride per day).

Lazolvan® with Strawberry-Cream Flavor, Syrup, 30 mg/5 ml, can be administered regardless of food intake. The dose of Lazolvan® with Strawberry-Cream Flavor, Syrup, can be measured using the dosing cap provided.

In general, there are no restrictions regarding duration of use; however, prolonged therapy should be conducted under medical supervision.

Lazolvan® with Strawberry-Cream Flavor, Syrup, 30 mg/5 ml, should not be used for longer than 4–5 days without consulting a physician.

Lazolvan® with Strawberry-Cream Flavor, Syrup, 30 mg/5 ml, is suitable for use in patients with diabetes mellitus; 5 ml of syrup corresponds to 1.2 g of carbohydrates.

Lazolvan® with Strawberry-Cream Flavor, Syrup, 30 mg/5 ml, does not contain alcohol.

Children

The medication may be used in pediatric practice. For children under 2 years of age, use only as directed by a physician.

Overdose

There are currently no reports of specific symptoms of overdose. Symptoms reported in isolated cases of overdose and/or accidental misuse correspond to the known adverse effects of Lazolvan® at recommended doses and require symptomatic treatment.

Adverse Reactions

To assess the frequency of adverse events, the following classification was used:

very common ≥1/10
common ≥1/100 to <1/10
uncommon ≥1/1000 to <1/100
rare ≥1/10,000 to <1/1000
very rare <1/10,000
not known cannot be estimated based on available data

Immune system and skin and subcutaneous tissue disorders:

rare – hypersensitivity reactions;
not known – anaphylactic reactions, including anaphylactic shock, angioneurotic edema, and pruritus.

Skin and subcutaneous tissue disorders:

rare – rash, urticaria;
not known – serious skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).

Nervous system disorders:

common – dysgeusia (taste disturbance).

Gastrointestinal disorders:

common – nausea, oral hypoaesthesia;
uncommon – vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth;
rare – dry throat;
very rare – hypersalivation.

Respiratory, thoracic and mediastinal disorders:

common – pharyngeal hypoaesthesia;
not known – dyspnea (as a symptom of hypersensitivity reaction).

General disorders:

uncommon – pyrexia, mucosal reactions.

Reporting of 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 Enterprise "State Expert Centre of the Ministry of Health of Ukraine".

Shelf life. 3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Shelf life after first opening of the bottle – 6 months.

Storage conditions.

Store at a temperature not exceeding 25 °C in a place inaccessible to children.

Packaging.

100 ml in a glass bottle; 1 bottle with a plastic measuring cap in a cardboard box.

Supply classification. Over-the-counter.

Manufacturer.

Boehringer Ingelheim Espana, S.A., Spain
or
Delpharm Reims, France

Manufacturer's address and location of its operations.

Prat de la Riba, 50, 08174 Sant Cugat del Valls (Barcelona), Spain
or
10 rue Colonel Charbonneaux, 51100 Reims, France

Marketing Authorisation Holder.

LLC "Opella Healthcare Ukraine", Ukraine.

Address of the Marketing Authorisation Holder and/or its representative.

48-50A Zhylianska St., Kyiv, 01033, Ukraine