Ambrobene

General characteristics. Structure:

Active agent: Ambroxol hydrochloride of 75,0 mg
Excipients:
Cellulose microcrystallic (PH 102), cellulose microcrystallic (PC 581), gipromelloz (Pharmacoat 603), methacrylic acid and ethyl acrylate copolymer (1:1), triethyl citrate, silicon dioxide colloid anhydrous.
Capsule cover: lid: gelatin, dye ferrous oxide yellow E 172, dye ferrous oxide black E 172, dye ferrous oxide red E 172, titanium dioxide; case: gelatin.

Description
Gelatin capsules with the colourless transparent case and an opaque brown lid. Capsule contents - granules from white till light yellow color.

Pharmacological properties:

Pharmacodynamics. Ambroxol represents benzylamine - a Bromhexine metabolite. Differs from Bromhexine in absence of methyl group and existence of hydroxylic group in a para-trance the provision of a tsiklogeksilny ring. Possesses sekretomotorny, sekretolitichesky and expectorant action.

After intake action comes in 30 minutes and continues within 24 hours. Preclinical trials showed that Ambroxol stimulates serous cells of glands of a mucous membrane of bronchial tubes. Activating cells of a ciliate epithelium and reducing viscosity of a phlegm, improves mukotsiliarny transport.

Ambroxol activates formation of surfactant, making direct impact on alveolar pnevmotsita of the 2nd type and cell Klara of small respiratory tracts.

Researches on cellular cultures and the researches in vivo on animals showed that Ambroxol stimulates education and secretion of substance (surfactant), active on a surface of alveoluses and bronchial tubes of an embryo and the adult.

Also at preclinical trials the antioxidant effect of Ambroxol was proved. Ambroxol at combined use with antibiotics (amoxicillin, tsefuroksy, erythromycin and doxycycline) increases their concentration in a phlegm and a bronchial secret.

Pharmacokinetics. At intake Ambroxol is almost completely soaked up from digestive tract. The maximum concentration makes about 140 ± 54 ng/ml and is reached in 4 hours after intake. Because of presistemny metabolism absolute bioavailability of Ambroxol after intake decreases approximately to Ouse. The metabolites which are formed in this regard (such as dibromoantranilovy acid, glucuronides) eliminirutsya in kidneys. Binding by proteins of plasma makes about 85% (80-90%). Plasma elimination half-life makes about 18 hours. It is removed preferential by kidneys in the form of metabolites - 90%, less than 10% are removed in not changed look.

Considering high communication with proteins of plasma, the large volume of distribution and slow redistribution from fabrics in blood, essential removal of Ambroxol at dialysis or an artificial diuresis does not occur.

At patients with a serious illness of a liver the clearance of Ambroxol decreases by 20-40%. At patients with heavy renal failures the elimination half-life of metabolites of Ambroxol increases.

Ambroxol gets into cerebrospinal fluid and through a placental barrier, and also is emitted in breast milk.

Indications to use:

Respiratory diseases with allocation of a viscous phlegm: acute and chronic bronchitis, pneumonia, HOBL (including bronchial asthma with difficulty of an otkhozhdeniye of a phlegm), a bronchoectatic disease. Stimulation of prenatal maturing of lungs, treatment and prevention (at threat of premature births and at the shown artificial premature births during the period between 28 and 34 weeks of pregnancy if the clinical picture allows to assume extension of duration of gestation for 3 days) respiratory a distress syndrome at premature children and newborns.

Route of administration and doses:

Capsules should be accepted after food, to swallow entirely, without chewing, washing down with a large amount of liquid. To adults and children 12 years are more senior it is necessary to accept on 1 capsule a day (75 mg of Ambroxol a day). Duration of treatment is selected individually depending on the course of a disease. It is not recommended to accept Ambrobene without appointment of the doctor more than within 4-5 days. The mucolytic effect of drug is shown at reception of a large amount of liquid. Therefore during treatment plentiful drink is recommended.

Features of use:

It is not necessary to combine with the antibechic medicines complicating removal of a phlegm.

Extremely seldom at Ambrobene's use skin reactions in a severe form, such as Stephens-Johnson's syndrome and Lyell's disease were observed. At change of integuments or mucous membranes, it is necessary to see urgently a doctor and to stop administration of drug. Influence on ability of driving of transport and on control of cars and mechanisms is until now not known.

Side effects:

General disturbances:
Seldom (from> 0,1% to <1%): allergic reactions (urticaria, skin rash, Quincke's disease of the person, short wind, itch), fever, weakness, headache. Very seldom (<0,01%): anaphylactic reactions, including acute anaphylaxis.

From digestive tract:
Seldom (from> 0,1% to <1%): nausea, abdominal pains, vomiting, diarrhea, locks.

Others:
Seldom (from> 0,1% to <1%): dryness of a mucous membrane of an oral cavity and respiratory tracts, dieback, rhinorrhea, dysuria.

Interaction with other medicines:

At simultaneous use of Ambroxol and antibechics because of suppression of a tussive reflex there can be a stagnation of a secret. Therefore similar combinations should be selected with care.

At joint reception of Ambroxol and antibiotics of amoxicillin, a tsefuroksim, erythromycin and doxycycline concentration of the last in a phlegm and a bronchial secret increases.

Contraindications:

• hypersensitivity to Ambroxol or to one of excipients;
• pregnancy (I trimester);
• use for children up to 12 years.

With care:
Disturbance of motor function of bronchial tubes and the increased formation of a phlegm (at a syndrome. motionless cilia), a peptic ulcer of a stomach and a 12-perstny gut in the period of an aggravation, pregnancy (the II-III trimester), the lactation period.

Patients with renal failures or heavy diseases of a liver have to accept Ambrobene with extra care, observing big intervals between receptions or accepting drug in a smaller dose.

Use during pregnancy and during feeding by a breast

Pregnancy:
There are not enough data on use of Ambroxol during pregnancy. In particular, it concerns the first 28 weeks of pregnancy. The researches conducted on animals did not reveal teratogenic effect. Ambrobene's use at pregnancy (the II-III trimester) is possible only on doctor's orders, after careful assessment of a ratio risk/advantage.

Feeding period breast:
The researches conducted on animals showed that Ambroxol gets into breast milk. Due to the insufficient studying of use of drug for women during feeding by a breast Ambrobene's use is possible only on doctor's orders, after careful assessment of a ratio risk/advantage.

Overdose:

Symptoms:
Symptoms of intoxication at overdose of Ambroxol are not revealed. There are data on nervous excitement and diarrhea.
Ambroxol is well transferred at intake in a dose to 25 mg/kg/day. In case of heavy overdose the increased salivation, nausea, vomiting, a lowering of arterial pressure are possible.

Treatment:
Methods of an intensive care, such as calling of vomiting, a gastric lavage, have to be applied only in cases of heavy overdose, in the first 1 - 2 hour after administration of drug. The symptomatic treatment is shown.

Storage conditions:

To store at a temperature not above 25 °C. To store in the place, unavailable to children! Period of validity of 5 years. Not to apply after expiry date!

Issue conditions:

Without recipe

Packaging:

Capsules of the prolonged action of 75 mg.
On 10 capsules in the PVH/A1 foil blister.
On 1 or 2 blisters together with the application instruction in a cardboard pack.