Flavamed^® (Tablets) Instructions for Use

Marketing Authorization Holder

Berlin-Chemie/Menarini Pharma, GmbH (Germany)

Manufactured By

Berlin-Chemie, AG (Germany)

Or

Menarini-Von Heyden, GmbH (Germany)

Contact Information

BERLIN-CHEMIE/MENARINI PHARMA GMBH (Germany)

ATC Code

R05CB06 (Ambroxol)

Active Substance

Ambroxol (Rec.INN registered by WHO)

Dosage Forms

	Flavamed®	Tablets 30 mg: 10, 20 or 50 pcs.
		Oral solution 15 mg/5 ml: 60 ml, 100 ml or 200 ml bottle with a measuring spoon

Dosage Form, Packaging, and Composition

Tablets white or almost white with a yellowish tint, round, flat-parallel, with beveled edges and a score on one side.

Excipients: lactose monohydrate – 40 mg, corn starch – 30 mg, microcrystalline cellulose – 30 mg, croscarmellose sodium – 5.3 mg, povidone (K-30) – 4 mg, magnesium stearate – 0.7 mg.

10 pcs. – blisters (1) – cardboard packs.
10 pcs. – blisters (2) – cardboard packs.
10 pcs. – blisters (5) – cardboard packs.

Oral solution clear, colorless or brownish, with a raspberry smell.

Excipients: benzoic acid – 5.75 mg, glycerol 85% – 500 mg, sorbitol 70% (non-crystallizing) – 2500 mg, hyetellose (hydroxyethylcellulose) (molar substitution degree 2.5; average viscosity 6000 mPa.s) – 5 mg, raspberry flavor No. 516028 – 5 mg, purified water – 2719.25 mg.

60 ml – dark glass bottles (1) with a measuring spoon – cardboard packs.
100 ml – dark glass bottles (1) with a measuring spoon – cardboard packs.
200 ml – dark glass bottles (1) with a measuring spoon – cardboard packs.

Clinical-Pharmacological Group

Mucolytic and expectorant drug

Pharmacotherapeutic Group

Mucolytic agent

Pharmacological Action

Expectorant mucolytic agent. Ambroxol is the active N-desmethylated metabolite of bromhexine. It has secretomotor, secretolytic, and expectorant action. It stimulates the serous cells of the bronchial mucosal glands, increasing the content of mucous secretion and thus changing the disturbed ratio of the serous and mucous components of sputum.

Ambroxol increases the content of mucous secretion and the release of surfactant in the alveoli and bronchi. It increases the motor activity of the ciliated epithelium and enhances mucociliary transport of sputum.

On average, after oral administration, the effect occurs within 30 minutes, and the duration of action is 6-12 hours depending on the size of the single dose.

Pharmacokinetics

Absorption

After oral administration, Ambroxol is rapidly and almost completely absorbed from the gastrointestinal tract. C_max is reached in approximately 1-3 hours. The absolute bioavailability of ambroxol after oral administration decreases by approximately one third due to first-pass metabolism in the liver. The metabolites formed (such as dibromanthranilic acid, glucuronides) are excreted by the kidneys.

Distribution

Plasma protein binding is about 85% (80-90%). Ambroxol crosses the blood-brain barrier and the placental barrier, and is also excreted in breast milk.

Metabolism

Ambroxol is metabolized in the liver by conjugation to form pharmacologically inactive metabolites.

Excretion

T_1/2 is 7-12 hours. The T_1/2 of ambroxol and its metabolites (in total) is about 22 hours. It is excreted mainly by the kidneys – 90% in the form of metabolites formed in the liver. Less than 10% of the amount excreted by the kidneys is unchanged ambroxol.

Pharmacokinetics in special clinical cases

In severe renal impairment, the T_1/2 of ambroxol metabolites increases, but does not change in severe liver disease. Due to the high degree of plasma protein binding and large volume of distribution, as well as slow redistribution from tissues into the blood, significant elimination of ambroxol by dialysis or forced diuresis is not expected.

Indications

Acute and chronic diseases of the respiratory tract accompanied by impaired secretion and transport of sputum

• Acute and chronic bronchitis;
• Pneumonia;
• Chronic obstructive pulmonary disease;
• Bronchial asthma with difficulty in sputum discharge;
• Bronchiectasis.

ICD codes

Dosage Regimen

Adults and children over 12 years old for the first 2-3 days are prescribed 30 mg (1 tablet or 2 measuring spoons (10 ml) of solution) 3 times/day, which corresponds to 90 mg of ambroxol hydrochloride/day, then – 30 mg (1 tablet or 2 measuring spoons) 2 times/day, (which corresponds to 60 mg of ambroxol hydrochloride/day). If necessary, to enhance the therapeutic effect, 60 mg (2 tablets or 4 measuring spoons (20 ml) of solution) 2 times/day can be prescribed (which corresponds to 120 mg of ambroxol hydrochloride/day).

Children aged 6 to 12 years: 15 mg (1/2 tablet or 1 measuring spoon of solution) 2-3 times/day, which corresponds to 30-45 mg of ambroxol hydrochloride/day.

Children aged 2 to 6 years the drug is prescribed only as a solution, 1/2 measuring spoon (2.5 ml) 3 times/day, which corresponds to 22.5 mg of ambroxol hydrochloride/day.

Children under 2 years of age 1/2 measuring spoon (2.5 ml) of solution 2 times/day, which corresponds to 15 mg of ambroxol hydrochloride/day.

In case of renal impairment or severe liver damage, the interval between doses should be increased or the dose should be reduced.

The drug is taken after meals: tablets – without chewing and with a sufficient amount of liquid, solution – using a measuring spoon. The duration of use is determined individually depending on the indications and the course of the disease. Without a doctor’s prescription, Flavamed^® should not be taken for more than 4-5 days.

Adverse Reactions

Possible side effects are listed below in descending order of frequency: sometimes (>0.1%; <1%), very rarely (<0.01%), including isolated reports.

Allergic reactions sometimes – skin rash, urticaria, angioedema (tablets), facial edema (solution), hyperthermia, shortness of breath; very rarely – anaphylactic shock.

From the digestive system sometimes — diarrhea, dry mouth, constipation (tablets); with long-term use – abdominal pain, nausea, vomiting (tablets and solution).

Dermatological reactions very rarely – toxic epidermal necrolysis, Stevens-Johnson syndrome (tablets).

Other very rarely – weakness, headache, dysuria, exanthema (tablets).

Contraindications

• Congenital fructose intolerance (for solution);
• Children under 6 years of age (for tablets);
• Hypersensitivity to ambroxol or other components of the drug.

With caution the drug should be prescribed for impaired bronchial motility and significant secretion production (for example, in the rare syndrome of immotile cilia), in renal or hepatic impairment, in gastric and duodenal ulcers, and also to children under 2 years of age (solution).

Use in Pregnancy and Lactation

The use of the drug in the first trimester of pregnancy is contraindicated. In the second and third trimesters of pregnancy, the drug should be used with caution.

The use of the drug during lactation is possible only if the expected benefit of treatment for the mother outweighs the possible risk for the infant.

Use in Hepatic Impairment

With caution the drug should be prescribed in hepatic impairment.

Use in Renal Impairment

With caution the drug should be prescribed in renal impairment.

Pediatric Use

Contraindicated in children under 6 years of age (for tablets). Use with caution in children under 2 years of age (solution).

Special Precautions

In severe renal impairment, the possibility of accumulation of ambroxol metabolites formed in the liver should be considered.

To maintain the secretolytic action of ambroxol during the period of drug administration, it is necessary to ensure sufficient fluid intake.

When prescribing the drug to patients with diabetes mellitus, it should be taken into account that 5 ml of solution (1 measuring spoon) contains 1.75 g of sorbitol, which corresponds to 0.15 XE (Bread Units).

Effect on ability to drive vehicles and operate machinery

Not established.

Overdose

Symptoms short-term restlessness, diarrhea, nausea, vomiting. With a significant overdose of the drug (more than 25 mg/kg/day), a decrease in blood pressure, salivation are possible.

Treatment: induction of vomiting, gastric lavage within the first 1-2 hours after drug intake, intake of fat-containing foods, symptomatic therapy.

Drug Interactions

With the combined use of ambroxol and antitussive drugs that suppress the cough reflex, there may be a risk of congestion in the bronchi due to the weakening of the cough reflex.

Increases the penetration into the bronchial secretion of amoxicillin, cefuroxime, erythromycin and doxycycline.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

The shelf life of tablets is 2 years, solution – 3 years. After first opening the bottle, the solution is suitable for use for 6 months.

Dispensing Status

The drug is approved for use as an over-the-counter product.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.