Pektolvane® a with forest fruit flavor
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PECTOLVAN® A WITH WOODBERRY FLAVOUR
Composition:
Active substance: ambroxol hydrochloride;
1 ml of the preparation contains ambroxol hydrochloride — 3 mg;
Excipients: hydroxyethylcellulose; sorbitol solution, non-crystallizing, calculated with respect to 100% substance (E 420); potassium acesulfame (E 950); glycerin; benzoic acid (E 210); "Woodberry" flavour; purified water.
Pharmaceutical form. Syrup.
Main physicochemical properties: clear or almost clear, colourless or almost colourless, slightly viscous solution with a woodberry taste.
Pharmacotherapeutic group. Preparations used in cough and colds. Mucolytic agents. ATC code R05C B06.
Pharmacological Properties.
Pharmacodynamics.
The active ingredient of "Pectolvan® A with forest berries flavor" syrup, ambroxol hydrochloride, increases the serous component 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 epithelium motility. As a result, sputum viscosity decreases and its expectoration improves (mucociliary clearance). Improvement of mucociliary clearance has been demonstrated in clinical pharmacological studies.
Enhanced secretion production, reduced viscosity, and improved mucociliary clearance promote productive cough and facilitate sputum expulsion.
Long-term use (6 months) of ambroxol hydrochloride (prolonged-release capsules 75 mg) in patients with chronic obstructive pulmonary disease (COPD) led to a significant reduction in exacerbations after a 2-month treatment period. In patients receiving ambroxol hydrochloride, the duration of illness and antibiotic therapy was significantly shorter. Compared to placebo, treatment with ambroxol hydrochloride in prolonged-release capsules showed statistically significant improvement in symptoms related to expectoration difficulties, cough, dyspnea, and auscultatory findings.
The local anesthetic effect of ambroxol hydrochloride, possibly explained by sodium channel blocking properties, was observed in a rabbit eye model. In vitro studies showed that ambroxol hydrochloride reversibly and concentration-dependently blocks neuronal sodium channels.
Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. It significantly reduces cytokine release from mononuclear and polymorphonuclear blood and tissue cells.
Clinical trials involving patients with pharyngitis demonstrated a significant reduction in throat pain and redness with the use of the drug.
Due to the pharmacological properties of ambroxol, pain relief during treatment of upper respiratory tract disorders occurs rapidly, as observed in clinical efficacy studies of ambroxol inhalation forms.
After administration of ambroxol hydrochloride, concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) increase 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 dependence 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 with slow-release formulations.
Absolute bioavailability after a 30 mg tablet dose is 79%.
Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and pronounced, with the highest concentration 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 metabolized primarily in the liver via glucuronidation and cleavage to dibromanthranilic acid (approximately 10% of the dose). Clinical 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, while approximately 26% of the dose — is excreted in conjugated form in urine.
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. 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, dose correction is not necessary.
Food intake does not affect the bioavailability of ambroxol hydrochloride.
Clinical characteristics.
Indications.
For secretolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and weakened mucus clearance.
Contraindications.
**«Pectolvan® A with forest berry flavor» must not be used in patients with hypersensitivity to ambroxol hydrochloride or other components of the medicinal product.
«Pectolvan® A with forest berry flavor» should be used in children under 2 years of age only on medical advice.
Interaction with other medicinal products and other forms of interaction.
Concomitant use of the medicinal product «Pectolvan® A with forest berry flavor» and cough-suppressant agents may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such a combination should be used 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 stopped immediately and medical advice should be sought.
In patients with impaired bronchial motility and increased mucus secretion (e.g., in rare conditions such as primary ciliary dyskinesia), the medicinal product "Pectolvan® A with forest berry flavor" should be used with caution due to the risk of secretion accumulation.
Patients with impaired renal function or severe hepatic insufficiency should take "Pectolvan® A with forest berry flavor" 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.
"Pectolvan® A with forest berry flavor" contains sorbitol. If the patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.
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 have shown no harmful effects on the fetus when the drug was administered after the 28th week of pregnancy. However, usual precautions regarding medication use during pregnancy should be observed. In particular, "Pectolvan® A with forest berry flavor" is not recommended during the first trimester of pregnancy.
Breastfeeding. Ambroxol hydrochloride passes into breast milk. "Pectolvan® A with forest berry flavor" is not recommended during breastfeeding.
Fertility. Preclinical studies do not indicate a direct or indirect harmful effect on fertility.
Ability to influence reaction rate when driving or operating machinery.
There are no data on the effect on reaction speed when driving or operating machinery. No studies have been conducted.
Method of administration and dosage. If otherwise not prescribed, the recommended dosage of the medicinal product "Pectolvan® A with forest berry flavor" is as follows:
Children under 2 years of age: 2.5 mL twice daily (equivalent to 15 mg ambroxol hydrochloride per day);
Children aged 2–5 years: 2.5 mL three times daily (equivalent to 22.5 mg ambroxol hydrochloride per day);
Children aged 6–12 years: 5 mL two to three times daily (equivalent to 30–45 mg ambroxol hydrochloride per day);
Adults and children aged 12 years and older: 10 mL three times daily (equivalent to 90 mg ambroxol hydrochloride per day) for the first 2–3 days, then reduce to 10 mL twice 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 increasing the dose to 20 mL twice daily (equivalent to 120 mg ambroxol hydrochloride per day).
For adults and children aged 12 years and older, syrup with higher concentration is recommended ("Pectolvan**®** A with strawberry flavor", syrup, 30 mg / 5 mL).
"Pectolvan® A with forest berry flavor" can be taken independently of food intake. The dose of "Pectolvan® A with forest berry flavor" can be measured using the provided dosing syringe.
Generally, there are no restrictions on duration of use, but prolonged therapy should be conducted under medical supervision.
"Pectolvan® A with forest berry flavor" should not be used for longer than 4–5 days without consulting a physician.
"Pectolvan® A with forest berry flavor" is suitable for use in patients with diabetes mellitus; 5 mL contain 1 g of carbohydrates.
Children. The medicinal product can be used in pediatric practice. For children under 2 years of age, use only as directed by a physician.
Overdose.
To date, there have been no reports of specific overdose symptoms. Symptoms described in isolated reports of overdose and/or accidental drug administration correspond to known adverse reactions associated with ambroxol hydrochloride 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 to <1/10;
Uncommon: ≥1/1,000 to <1/100;
Rare: ≥1/10,000 to <1/1,000;
Very rare: <1/10,000;
Frequency not known: cannot be estimated based on available data.
Immune system disorders:
Rare: hypersensitivity reactions;
Frequency not known: anaphylactic reactions, including anaphylactic shock, angioedema, and pruritus.
Skin and subcutaneous tissue disorders:
Rare: rash, urticaria;
Frequency 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 hypoesthesia;
Uncommon: vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth;
Rare: throat dryness;
Very rare: hypersalivation.
Respiratory, thoracic and mediastinal disorders:
Common: pharyngeal hypoesthesia;
Frequency not known: dyspnea (as a hypersensitivity reaction).
General disorders:
Uncommon: pyrexia, mucosal reactions.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after medicine authorization is highly important. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.
Shelf life. 2 years.
Do not use the medicinal product after the expiry date stated on the packaging.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C. The shelf life of the medicinal product after first opening of the primary packaging is 180 days.
Keep out of reach and sight of children.
Packaging.
100 ml in a glass bottle; 1 bottle with a dosing syringe in a carton.
Supply category.
Over-the-counter (without prescription).
Manufacturer.
JSC "Farmak".
Manufacturer's name and address of manufacturing site.
74, Kyrylivska Street, Kyiv, 04080, Ukraine.