Main physico-chemical properties: white round tablets with a break line on one side.
Pharmacotherapeutic group. Drugs used in cough and catarrhal diseases. Mucolytics.Code ATC R05C B06.
Ambroxol is a substituted benzylamine and a metabolite of bromhexine. There is information that ambroxol hydrochloride increases glandular secretion in the respiratory tract and increases secretion of lung surfactant through direct effect on type II pneumocytes in the alveoli and Clara cells in bronchioles. Also, ambroxol hydrochloride stimulates ciliary activity, resulting in easier mucus production and clearance (mucociliary clearance). Activation of fluid secretion and increased mucociliary clearance facilitate mucus discharge and ease cough.
There is information about the presence of local anaesthetic effect of ambroxol hydrochloride due to reversible and concentration-dependent neuron sodium channels blocking.
There is also data on the presence of anti-inflammatory effect of ambroxol hydrochloride (due to significant decrease in cytokine release from blood and tissue binding of mononuclear and polymorphonuclear cells).
In patients with pharyngitis application of ambroxol hydrochloride resulted in a significant reduction of pain and redness in the throat.
The use of ambroxol hydrochloride increases concentration of antibiotics (amoxicillin, cefuroxime, erythromycin and doxycycline) in bronchopulmonary secretions and in the sputum.
Absorption. Absorption of ambroxol hydrochloride from oral non sustained release forms is fast and complete with linear dose dependence within therapeutic range. Maximum plasma level is reached after 1-2.5 hours following oral administration of immediate release dosage forms and on average after 6.5 hours following administration of sustained release dosage forms.
Distribution. In oral administration distribution of ambroxol hydrochloride from blood to tissues is fast and pronounced with the highest concentration of active substance in the lungs. The expected volume of distribution after oral administration is 552 l. In blood plasma within therapeutic dose range, about 90% of the drug is bound to proteins.
Metabolism and excretion. About 30% of dose after oral administration is excreted by presystemic metabolism. Ambroxol hydrochloride is mainly metabolised in the liver by glucuronidation and splitting to dibrom anthranyl acid (about 10% of the dose). Metabolism of ambroxol hydrochloride to dibrom anthranyl acid involves CYP3A4. After 3 days of oral administration about 6% of the dose is excreted with the urine in unchanged form, about 26% of the dose – in conjugated form.
Plasma half-life is about 10 hours. Total clearance is within 60 ml/min. renal clearance is about 83% of the total.
Pharmacokinetics in special populations of patients. In patients with impaired liver function, elimination of ambroxol hydrochloride is reduced, which causes 1.3-2 times higher level in blood plasma. Since therapeutic range of ambroxol hydrochloride is quite wide, there is no need to change the dosage.
Age and sex have no clinically significant effect on pharmacokinetics of ambroxol hydrochloride; therefore no dosage adjustment is required.
Secretolytic therapy in acute and chronic bronchopulmonary diseases associated with bronchial secretion disorders and decreased mucus movement.
Abrol® should not be administered to patients with known hypersensitivity to ambroxol hydrochloride or to other components of the drug.
Abrol® tablets 30 mg is not for use in children less than 6 years old due to the strength. For children aged less than 6 years, ambroxol in appropriate dosage is recommended for use.
Interaction with other medicinal products and other forms of interaction.
Simultaneous administration of Abrol® tablets and drugs that suppress the cough may lead to excessive accumulation of mucus due to suppression of the cough reflex. Therefore, this combination is possible only after careful doctor’s evaluation of the expected benefits and possible risks of use ratio.
Only a few reports about the severe skin reactions – Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome), – are associated with the use of expectorants such as ambroxol hydrochloride. Most of them could be explained by the severity of the underlying disease in patients or by the concomitant administration of another drug.
Also, at the initial stage of Stevens-Johnson syndrome or Lyell's syndrome patients may have nonspecific flu-like symptoms, such as fever, aches, rhinitis, cough and sore throat. By mistake symptomatic treatment with drugs for cough and cold may be used in case of such non-specific symptoms similar to early flu symptoms. Therefore, in case of new lesions of skin or mucous membranes, seek medical attention immediately and stop treatment with ambroxol hydrochloride.
Since ambroxol may increase mucus secretion, Abrol® tablets should be used with caution in case of impaired bronchial motility and increased mucus secretion (e.g. in such rare disease as primary ciliary dyskinesia).
Administration during pregnancy and lactation.
Pregnancy. Ambroxol hydrochloride crosses the placental barrier. Animal studies have found no direct or indirect harmful effects on pregnancy, the embryo/foetal development, parturition or postnatal development.
Clinical studies of the drug administration after 28th week of pregnancy showed no adverse effects on the foetus.
However, follow the usual precautions regarding drug administration during pregnancy. Especially in I trimester of pregnancy Abrol®, tablets administration is not recommended.
Lactation. Ambroxol hydrochloride passes into the breast milk. Although no undesirable effect on infants is expected, the administration of Abrol®, tablets during lactation is not recommended.
Effects on ability to drive and use machines.
There is no data about the influence on the velocity rate while driving a car or operating other machines. No appropriate studies were conducted.
Dosage and administration.
Unless otherwise prescribed, the recommended dose of Abrol®, tablets is as follows:
children aged 6-12 years: the dose is 1/2 tablet 2-3 times a day (equivalent to 30-45 mg of ambroxol hydrochloride per day);
adults and children over 12 years: the dose is 1 tablet 3 times a day for the first 2-3 days (equivalent to 90 mg of ambroxol hydrochloride per day). Continue treatment, using 1 tablet 2 times a day (equivalent to 60 mg of ambroxol hydrochloride per day).
If necessary, therapeutic effect for adults and children over 12 years may be enhanced by using 2 tablets 2 times a day (equivalent to 120 mg of ambroxol hydrochloride per day).
Tablets should be swallowed whole with plenty of fluid (e.g. water, tea or fruit juice) after meals.
In general, there are no restrictions on the duration of use, but long-term treatment should be conducted under medical supervision.
Abrol® tablets should not be administered for more than 4-5 days without consulting your doctor.
Administer to children over 6 years who are intolerant to syrup.
At present there are no reports on cases of overdose in humans. Symptoms known from the rare reports about overdose and/or cases of drug administration by mistake correspond to the known adverse effects of ambroxol in recommended doses and require symptomatic treatment.
Immune system adverse reactions: reactions of hypersensitivity (skin rash, reactions of mucous membranes, angioedema, dyspnoea, pruritus and other allergic reactions), anaphylactic reactions, including anaphylactic shock; urticaria.
General adverse reactions: reactions of mucous membranes fever.
Skin and subcutaneous tissue adverse reactions: erythema, severe skin lesions: Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome).