Pectolvan® a with strawberry flavor
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PECTOLVAN® A WITH STRAWBERRY FLAVOUR
Composition:
Active substance: ambroxol hydrochloride;
1 ml of the preparation contains ambroxol hydrochloride — 6 mg;
Excipients: hydroxyethylcellulose; sorbitol solution, non-crystallizing, calculated with respect to 100% substance (E 420); acesulfame potassium (E 950); glycerol; benzoic acid (E 210); strawberry flavouring; purified water.
Pharmaceutical form. Syrup.
Main physicochemical properties: clear or nearly clear, colourless or nearly colourless, slightly viscous solution with strawberry taste.
Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytics. ATC code R05C B06.
Pharmacological Properties.
Pharmacodynamics.
Clinically proven that the active substance of the medicinal product "Pectolvan® A with strawberry flavor", ambroxol hydrochloride, increases the serous fraction of bronchial secretion. Ambroxol enhances the secretion of pulmonary surfactant by direct action on 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.
Activation of secretion, reduction of secret viscosity, and improvement of mucociliary clearance promote mucus elimination and facilitate expectoration of sputum.
In patients with chronic obstructive pulmonary disease receiving ambroxol hydrochloride, prolonged-release capsules 75 mg, over 6 months, a significant reduction in the number of exacerbations was observed compared to placebo, by the end of the second month of treatment. In patients treated with ambroxol hydrochloride, the illness lasted significantly fewer days, and fewer days of antibiotic therapy were required. Compared to placebo, treatment with ambroxol hydrochloride prolonged-release capsules showed statistically significant improvement in patient status regarding sputum expectoration, cough, dyspnea, and auscultatory findings.
In a rabbit eye model, ambroxol hydrochloride demonstrated local anesthetic effect, which may be explained by its sodium channel-blocking properties. In vitro studies showed that ambroxol hydrochloride blocks voltage-dependent neuronal sodium channels; binding was reversible and concentration-dependent.
Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. Thus, ambroxol hydrochloride significantly reduces the release of cytokines from mononuclear and polymorphonuclear blood and tissue cells.
In clinical trials involving patients with pharyngitis, significant reduction in throat pain and redness was demonstrated 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 ambroxol inhalation forms.
Administration of ambroxol hydrochloride increases the concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) in bronchopulmonary secretions and sputum. The clinical significance of this has not yet been established.
Pharmacokinetics.
Absorption. Absorption of ambroxol hydrochloride from immediate-release oral formulations is rapid and fairly complete, with linear dose dependence 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 within 6.5 hours with sustained-release formulations.
Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and extensive, with the highest concentration of 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 mainly in the liver through glucuronidation and cleavage to dibromoantranilic acid (approximately 10% of the dose). Studies on human liver microsomes have shown that CYP3A4 is responsible for the metabolism of ambroxol hydrochloride to dibromoantranilic acid.
Within 3 days after oral administration, about 6% of the dose is excreted in urine unchanged, while approximately 26% of the dose 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. 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 adjustment 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 impaired mucus clearance.
Contraindications.
"Pectolvan® A with strawberry flavor" must not be used in patients with hypersensitivity to ambroxol hydrochloride or other components of the medicinal product.
"Pectolvan**®** A with strawberry flavor" 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 the medicinal product "Pectolvan® A with strawberry 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
There have been reports of severe skin reactions, including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis associated with the use of ambroxol hydrochloride. If signs of progressive skin rash (sometimes associated with blistering or mucosal involvement) occur, treatment with ambroxol hydrochloride should be discontinued immediately and medical help should be sought.
Pectolvan® A with strawberry flavor 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 mucus accumulation.
Patients with impaired renal function or severe hepatic impairment should take Pectolvan® A with strawberry 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 strawberry flavor contains 1 g of sorbitol in 5 mL (equivalent to 4 g when the maximum recommended daily dose is used). If a 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, embryonal/fetal development, parturition, or postnatal development. Clinical studies have shown no adverse effects on the fetus when the drug was used after the 28th week of pregnancy. However, usual precautions regarding medication use during pregnancy should be observed. In particular, ambroxol hydrochloride is not recommended during the first trimester of pregnancy.
Breastfeeding. Ambroxol hydrochloride passes into breast milk. Pectolvan® A with strawberry flavor 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 of this medicinal product on the ability to drive or operate machinery. Such studies have not been conducted.
Method of Administration and Dosage.
If otherwise not prescribed, the recommended dosage regimen for the medicinal product "Pectolvan® A with strawberry flavor" 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 up to three 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) for 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).
"Pectolvan® A with strawberry flavor" should be taken independently of food intake. The dose can be measured using the dosing spoon provided.
In general, there are no restrictions regarding duration of use; however, prolonged therapy should be conducted under medical supervision.
"Pectolvan® A with strawberry flavor" should not be used for longer than 4–5 days without consulting a physician.
"Pectolvan® A with strawberry flavor" is suitable for use in patients with diabetes mellitus; 5 ml of syrup corresponds to 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.
There are currently no reports of specific symptoms of overdose. Symptoms described in isolated reports of overdose and/or accidental misuse correspond to the known adverse effects of ambroxol hydrochloride at recommended doses and require symptomatic treatment.
Adverse Reactions
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 numbness;
Uncommon — vomiting, diarrhea, dyspepsia, abdominal pain, dry mouth;
Rare — throat dryness;
Very rare — hypersalivation.
Respiratory, thoracic and mediastinal disorders:
Common — pharyngeal numbness;
Frequency not known — dyspnea (as a symptom of hypersensitivity reaction).
General disorders:
Uncommon — fever, mucosal reactions.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at the following link: https://aisf.dec.gov.ua.
Shelf life. 2 years.
The shelf life of the medicinal product after first opening of the primary packaging is 180 days.
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.
Keep out of reach and sight of children.
Packaging.
100 ml in a glass bottle; 1 bottle with a dosing spoon in a carton.
Supply category. Over-the-counter.
Manufacturer. JSC "Farmak".
Manufacturer's address and place of business.
74, Kyrylivska Street, Kyiv, 04080, Ukraine.