Flavamed® cough solution
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FLAVAMED® COUGH SOLUTION (FLAVAMED® COUGH SOLUTION)
Composition:
Active substance: ambroxol hydrochloride;
1 ml of oral solution contains 3 mg of ambroxol hydrochloride; 1 measuring spoon of 5 ml contains 15 mg of ambroxol hydrochloride;
Excipients: glycerol (85%), benzoic acid (E 210), sorbitol solution, non-crystallizing 70% (E 420), hydroxyethylcellulose, raspberry-flavored aromatic concentrate, purified water.
Pharmaceutical form. Oral solution.
Main physicochemical properties: clear, colorless to slightly brownish liquid with a raspberry odor.
Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytic agents.
ATC code R05C B06.
Pharmacological properties.
Pharmacodynamics.
The active substance of the medicinal product Flavamed® cough syrup – ambroxol hydrochloride – increases the serous component of bronchial secretion. Ambroxol enhances pulmonary surfactant secretion by direct action on type II pneumocytes in alveoli and Clara cells in bronchioles, and also stimulates ciliary activity. This reduces sputum viscosity and improves its expectoration (mucociliary clearance).
Activation of secretion, reduction of sputum viscosity, and improvement of mucociliary clearance promote sputum expectoration and facilitate productive cough.
On average, the effect of the drug appears within 30 minutes after oral administration and lasts for 6–12 hours, depending on the single dose.
Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. Thus, ambroxol hydrochloride significantly reduces cytokine release from mononuclear and polymorphonuclear blood and tissue cells.
After administration of ambroxol hydrochloride, concentrations of antibiotics (amoxicillin, cefuroxime, erythromycin, and doxycycline) increase in bronchopulmonary secretions and sputum. To date, no clinical significance of this effect has been established.
Pharmacokinetics.
Absorption. Absorption of ambroxol hydrochloride is rapid and nearly complete, with linear dependence within the therapeutic range. Peak plasma concentrations are achieved within 1–2.5 hours after intake.
Distribution. After oral administration, distribution of ambroxol hydrochloride from blood to tissues is rapid and highly 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, approximately 90% of the drug is protein-bound within the therapeutic range.
Metabolism and elimination. Approximately 30% of the orally administered dose is eliminated during first-pass metabolism in the liver. Ambroxol hydrochloride is metabolized mainly in the liver via glucuronidation and cleavage to dibromoaniline 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 dibromoaniline acid.
Within 3 days of 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 groups. 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. Secretolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and impaired mucus clearance.
Contraindications. Flavamed® cough syrup must not be administered to patients with known hypersensitivity to ambroxol hydrochloride or to any of the excipients.
Flavamed® cough syrup should be used in children under 2 years of age only under medical supervision.
Interaction with other medicinal products and other forms of interaction.
Concomitant use of Flavamed® cough syrup and antitussive agents may lead to excessive mucus accumulation due to suppression of the cough reflex. Therefore, such combination should be used only after careful assessment by a physician of the benefit-risk ratio.
Special precautions for use
Cases of severe skin reactions associated with ambroxol administration have been reported, including erythema multiforme, Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), and acute generalized exanthematous pustulosis (AGEP). If symptoms or signs of a progressive skin rash (sometimes associated with blisters and mucosal lesions) occur, treatment with ambroxol should be discontinued immediately and medical advice should be sought.
Since ambroxol may enhance mucus secretion, Flavamed® cough syrup should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g., in primary ciliary dyskinesia).
Patients with impaired renal function or severe hepatic impairment should take Flavamed® cough 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.
This medicinal product contains sorbitol. One measuring spoon (5 mL) of oral solution contains 1.75 g of sorbitol. Patients with rare hereditary fructose intolerance should not use Flavamed® cough syrup.
Caution should be exercised when administering the drug to patients with histamine intolerance. Prolonged therapy in such patients should be avoided, as ambroxol affects histamine metabolism and may cause allergic symptoms (such as headache, nasal congestion, itching).
Since mucolytic agents may impair the barrier function of the gastric mucosa, ambroxol should be used with caution in patients with a history of peptic ulcer disease.
In children aged 2 to 4 years with persistent or recurrent cough, medical evaluation is required before initiating treatment.
Use during pregnancy or breastfeeding
Pregnancy
Ambroxol hydrochloride crosses the placental barrier. Animal studies have not revealed any direct or indirect adverse effects on pregnancy, embryonal/fetal development, parturition, or postnatal development. Clinical studies have shown no harmful effects on the fetus when the drug is used after the 28th week of pregnancy. However, usual precautions for drug use during pregnancy should be observed. In particular, Flavamed® cough syrup is not recommended during the first trimester of pregnancy.
Breastfeeding
Ambroxol passes into breast milk.
Although no adverse effects on the infant are expected during breastfeeding, Flavamed® cough syrup is not recommended for use in breastfeeding mothers.
Fertility
Preclinical studies have not shown any direct or indirect adverse effects on fertility.
Effect on the ability to drive or operate machinery
There are no data on the effect of ambroxol on the ability to drive or operate machinery. No studies on the effect on reaction speed during driving or operating machinery have been conducted.
Method of Administration and Dosage
Dosage
If otherwise not prescribed, the following doses are recommended for the use of the medicinal product Flavamed® cough solution.
Children under 2 years of age: ½ measuring spoon (2.5 ml) of oral solution twice daily, providing a total daily dose of 15 mg of ambroxol hydrochloride.
Children aged 2 to 5 years: ½ measuring spoon (2.5 ml) of oral solution three times daily, providing a total daily dose of 22.5 mg of ambroxol hydrochloride.
Children aged 6 to 12 years: 1 measuring spoon (5.0 ml) of oral solution 2–3 times daily, providing a total daily dose of 30–45 mg of ambroxol hydrochloride.
Adults and adolescents aged 12 years and older: 2 measuring spoons (10.0 ml) of oral solution three times daily, providing 90 mg of ambroxol hydrochloride daily during the first 2–3 days, followed by 2 measuring spoons (10 ml) of oral solution twice daily, providing 60 mg of ambroxol hydrochloride daily thereafter.
If necessary, the therapeutic effect in adults may be enhanced by increasing the dose to 20 ml twice daily (equivalent to 120 mg of ambroxol hydrochloride daily).
For dosage recommendations in patients with renal or hepatic impairment, see section "Special Warnings and Precautions for Use".
For further information on use in children, see section "Use in Paediatric Population".
Method and Duration of Administration
Flavamed® cough solution is intended for oral administration.
Flavamed® cough solution may be taken independently of meals using the provided measuring spoon. In general, there are no restrictions regarding the duration of treatment; however, prolonged therapy should be conducted under medical supervision.
Flavamed® cough solution should not be used for longer than 4–5 days without consulting a physician.
Flavamed® cough solution is alcohol-free. One measuring spoon (5 ml) of oral solution contains 1.75 g of sorbitol.
Children. Flavamed® cough solution may be used in pediatric practice. It should be administered to children under 2 years of age only under medical supervision. Persistent or recurrent cough in children aged 2 to 4 years requires medical evaluation prior to initiating treatment.
Overdose.
There have been no reports of specific symptoms of overdose in humans. Based on case reports of overdose and/or medication errors, observed symptoms are consistent with the known adverse effects of recommended doses and may require symptomatic treatment.
Adverse reactions.
The following classification was used to assess the frequency of adverse events:
| 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;
Unknown: anaphylactic reactions (including anaphylactic shock, angioedema, pruritus).
Skin and subcutaneous tissue disorders:
Rare: rash, urticaria;
Unknown: severe 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;
Unknown: dyspnea (as a symptom of hypersensitivity reaction).
Renal and urinary disorders:
Very rare: dysuria.
General disorders:
Uncommon: fever, mucosal reactions.
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals are encouraged to report any suspected adverse reactions via the national pharmacovigilance system.
Shelf life. 3 years. After first opening of the bottle – 6 months. Do not use the medicine after the expiry date stated on the packaging.
Storage conditions. No special storage conditions required. Keep out of reach and sight of children.
Packaging. 60 ml or 100 ml of solution in a bottle; 1 bottle with a measuring spoon in a cardboard box.
Supply category. Over-the-counter.
Manufacturer.
BERLIN-CHEMIE AG.
Manufacturer's name and address.
Glienicker Weg 125, 12489 Berlin, Germany.