Flavamed® tablets for cough
UkraineTable of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FLAVAMEDâ COUGH TABLETS (FLAVAMEDâ COUGH TABLETS)
Composition:
Active substance: ambroxol hydrochloride;
One tablet contains ambroxol hydrochloride 30 mg;
Excipients: lactose monohydrate, corn starch, povidone K 30, powdered cellulose, sodium croscarmellose, magnesium stearate.
Pharmaceutical form. Tablets.
Main physicochemical properties: white, round, flat-faced tablets with bevelled edges and a score line on one side. The tablet can be divided into two equal doses.
Pharmacotherapeutic group. Medicinal products used for cough and colds. Mucolytic agents. ATC code R05C B06.
Pharmacological properties.
Pharmacodynamics.
Preclinical studies have demonstrated that the active substance of the medicinal product FLAVAMED® COUGH TABLETS – ambroxol hydrochloride – increases secretion of the respiratory tract glands. Ambroxol enhances pulmonary surfactant release by direct action on type II pneumocytes in the alveoli and Clara cells in the bronchioles, and also stimulates ciliary activity, thus facilitating mucus expulsion and clearance (mucociliary clearance). Improvement of mucociliary clearance has been confirmed in clinical pharmacological studies.
Enhanced serous secretion and improved mucociliary clearance facilitate mucus elimination and alleviate cough.
A local anesthetic effect of ambroxol hydrochloride has been observed in a rabbit eye model, which may be explained by its sodium channel blocking properties. In vitro studies showed that ambroxol hydrochloride blocks neuronal sodium channels; binding was reversible and concentration-dependent.
Ambroxol hydrochloride has demonstrated anti-inflammatory effects in vitro. Thus, ambroxol hydrochloride significantly reduces cytokine release from mononuclear and polymorphonuclear cells in blood and tissues.
Following 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 from all immediate-release oral formulations is rapid and complete, with linear dose-dependency within the therapeutic range. Peak plasma concentration is reached within 1–2.5 hours after oral administration of immediate-release formulations, and on average within 6.5 hours after administration of sustained-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 expected volume of distribution after oral administration is 552 L. In plasma, within the therapeutic dose 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 dibromanthranilic acid (approximately 10% of the dose). Studies on 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 in urine in free form, and approximately 26% of the dose – in conjugated form.
The elimination half-life from plasma is approximately 10 hours. Total clearance is about 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 groups. In patients with impaired liver function, elimination of ambroxol hydrochloride is reduced, resulting in 1.3- to 2-fold higher plasma levels. However, since the therapeutic range of ambroxol hydrochloride is sufficiently wide, dosage adjustment is not required.
Age and gender have no 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.
Mucolytic therapy in acute and chronic bronchopulmonary diseases associated with impaired bronchial secretion and impaired mucus clearance.
Contraindications.
Hypersensitivity to ambroxol hydrochloride or to any component of the medicinal product. Due to the high content of active substance, the medicinal product FLAVAMEDâ COUGH TABLETS is contraindicated for use in children under 6 years of age. For children under 6 years of age, Flavamed® oral solution, 15 mg/5 ml or Flavamed® Forte oral solution, 30 mg/5 ml is recommended.
Interaction with other medicinal products and other forms of interaction.
When the medicinal product FLAVAMEDâ COUGH TABLETS is used concomitantly with antitussive medicinal products, (dangerous) secretion retention may occur due to suppression of the cough reflex in patients with existing respiratory diseases associated with mucus hypersecretion, such as cystic fibrosis or bronchiectasis.
Special precautions for use
Severe skin reactions have been reported after administration of ambroxol, 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 should be discontinued immediately and medical advice should be sought urgently.
Due to the potential increase in mucus secretion, FLAVAMED® COUGH TABLETS should be used with caution in patients with impaired bronchial motility and increased mucus secretion (e.g. in the rare immotile cilia syndrome).
FLAVAMED® COUGH TABLETS should be administered to patients with existing renal impairment or severe hepatic dysfunction only after consultation with a physician.
When ambroxol, like any active substance metabolized in the liver and subsequently excreted by the kidneys, is administered, metabolites formed in the liver may accumulate in patients with severe renal insufficiency.
Since mucolytic agents may impair the integrity of the gastric mucosa, ambroxol should be used with caution in patients with a history of gastric ulcer.
This medicinal product contains lactose. Patients with rare hereditary forms of galactose intolerance, severe lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product FLAVAMED® COUGH TABLETS.
This medicinal product contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially "sodium-free".
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 precautionary measures regarding medication intake during pregnancy should be observed. Particularly, the use of FLAVAMED® COUGH TABLETS is not recommended during the first trimester of pregnancy.
Breastfeeding. Ambroxol hydrochloride is excreted in breast milk. Although adverse effects on breastfed infants are not expected, FLAVAMED® COUGH TABLETS are not recommended for use in women who are breastfeeding.
Fertility. Animal studies have shown no adverse effect of ambroxol on fertility.
Effect on ability to drive and use machines
There is no evidence of an effect on the ability to drive or operate machinery. Studies on the influence on the ability to drive or operate machinery have not been conducted.
Method of Administration and Dosage
Dosage
Unless otherwise prescribed, the following dosages are recommended for FLAVAMEDâ COUGH TABLETS:
Children under 6 years of age:
FLAVAMEDâ COUGH TABLETS are contraindicated in children under 6 years of age (see section "Contraindications").
Children aged 6 to 12 years:
Usually ½ tablet of FLAVAMEDâ COUGH TABLETS 2–3 times daily (equivalent to 15 mg of ambroxol hydrochloride 2–3 times daily).
Adults and adolescents aged 12 years and older:
Initially, 1 tablet of FLAVAMEDâ COUGH TABLETS 3 times daily for the first 2–3 days (equivalent to 30 mg of ambroxol hydrochloride 3 times daily); thereafter, 1 tablet 2 times daily (equivalent to 30 mg of ambroxol hydrochloride 2 times daily).
Important
If necessary, the adult dose may be increased to 60 mg twice daily (equivalent to 120 mg of ambroxol hydrochloride per day).
Pediatric population
See section "Contraindications" regarding use in children under 6 years of age.
Method of Administration
FLAVAMEDâ COUGH TABLETS are intended for oral administration.
The tablets should preferably be swallowed whole with sufficient fluid, taken during or after meals.
FLAVAMEDâ COUGH TABLETS should not be used for longer than 4–5 days without medical supervision.
See section "Special Warnings and Precautions for Use" for dosage adjustments in patients with renal or hepatic impairment.
Children.
FLAVAMEDâ COUGH TABLETS are contraindicated in children under 6 years of age. For children under 6 years of age, Flavamed® oral solution 15 mg/5 ml or Flavamed® Forte oral solution 30 mg/5 ml is recommended.
Overdose.
There are currently no reports of overdose in humans. Symptoms reported from isolated cases of overdose and/or medication errors correspond to the known adverse effects that may occur with FLAVAMEDâ COUGH TABLETS at recommended doses and require symptomatic treatment.
Adverse reactions.
The following classification was used to assess the frequency of adverse events:
| very common |
≥1/10; |
| common |
≥1/100 to <1/10; |
| uncommon |
≥1/1000 to <100; |
| rare |
≥1/10000 to <1/1000; |
| very rare |
<1/10000; |
| not known |
cannot be estimated from available data. |
Gastrointestinal system:
Common – nausea;
Uncommon – stomach pain, vomiting, diarrhea, abdominal pain, and dyspepsia;
Very rare – hypersalivation.
Immune system:
Rare – hypersensitivity reactions;
Not known – anaphylactic reactions, including anaphylactic shock, angioedema, and pruritus.
Skin and subcutaneous tissue:
Rare – rash, urticaria;
Not known – severe skin adverse reactions (including erythema multiforme, Stevens-Johnson syndrome/toxic epidermal necrolysis, and acute generalized exanthematous pustulosis).
Respiratory system:
Not known – dyspnea (as a symptom of hypersensitivity reaction).
General disorders and administration site conditions:
Uncommon – fever, mucosal reactions.
Reporting of adverse reactions.
Reporting suspected adverse reactions after medicine authorization is important. This allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals are asked to report any suspected adverse reactions to the State Expert Center of the Ministry of Health of Ukraine via the national reporting system.
Shelf life.
2 years. Do not use after the expiry date.
Storage conditions.
Store at a temperature not exceeding 25 °C. Keep out of the reach of children.
Packaging.
Blister packs of 10 tablets; 1, 2, or 5 blisters in a cardboard box.
Release category.
Over-the-counter.
Manufacturer.
Manufacturer responsible for batch release:
BERLIN-CHEMIE AG.
Manufacturer's address and place of business.
Glienicker Weg 125, 12489 Berlin, Germany.