Augmentin ES

General characteristics. Structure:

Active ingredient: amoxicillin trihydrate * 697.65 mg,
     what corresponds to the content of amoxicillin of 600 mg
potassium clavulanate ** 52.31 mg,
     what corresponds to the content of clavulanic acid of 42.9 mg

Excipients: gum xanthane - 3.26 mg, aspartame - 13.6 mg, silicon dioxide - 153.29 mg, silicon dioxide colloid - 38.08 mg, a karmelloza of sodium - 32.64 mg, fragrance strawberry - 28.29 mg.

12.85 (50 ml of ready suspension) - bottles glass (1) complete with a measured spoon - packs cardboard.
23:13 g (100 ml of ready suspension) - bottles glass (1) complete with a measured spoon - packs cardboard.

* by production of drug of amoxicillin trihydrate is put from 8.8% by surplus.
** by production of drug of potassium clavulanate is put from 8.0% by surplus at an initial stage of mixing of active components and from 8.8% at a stage of mixing of all components of suspension.

Pharmacological properties:

Amoxicillin — the semi-synthetic antibiotic of a broad spectrum of activity having activity against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is subject to destruction by β-lactamelements and therefore the range of activity of amoxicillin does not extend to microorganisms which produce this enzyme.

Clavulanic acid — inhibitor β-лактамаз, structurally related to penicillin, has ability to inactivate a wide range β-лактамаз, found in the microorganisms steady against penicillin and cephalosporins.

Clavulanic acid has sufficient efficiency concerning plasmid β laktamaz-most of which often cause resistance of bacteria, and is less effective concerning chromosomal β laktamaz-of 1 type which are not inhibited by clavulanic acid.

Presence of clavulanic acid at the drug Augmentin® of the EU protects amoxicillin from destruction by enzymes — β-lactamelements that allows to expand an antibacterial range of amoxicillin.

Activity of a combination of amoxicillin with in vitro clavulanic acid is included below.

The bacteria usually sensitive to an amoxicillin combination with clavulanic acid

Gram-positive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pneumoniae1,2, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, Streptococcus of the group Viridans2, Streptococcus spp. (other beta and hemolitic streptococci) 1,2, Staphylococcus aureus (sensitive to Methicillinum) 1, Staphylococcus saprophyticus (sensitive to Methicillinum), Staphylococcus spp. (koagulazonegativny, sensitive to Methicillinum).

Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Others: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Gram-positive anaerobe bacterias: Clostridium spp., Peptococcus niger, Peplostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus spp.

Gram-negative anaerobe bacterias: Bacteroides fragilis, Bacteroides spp., Capnocytophaga spp., Eikenella corrodens, Fusobacterium nucleatum, Fusobacterium spp., Porphyromonas spp., Prevotella spp.

Bacteria for which the acquired resistance to an amoxicillin combination with clavulanic acid is probable

Gram-negative aerobes: Escherichia coli1, Klebsiella oxytoca, Klebsiella pneumoniae1, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Proteus spp., Salmonella spp., Shigella spp.

Gram-positive aerobes: Corynebacterium spp., Enterococcus faecium.

The bacteria having natural resistance to an amoxicillin combination with clavulanic acid

Gram-negative aerobes: Acinetobacter spp., Citrobacter freundii, Enterobacter spp., Hafnia alvei, Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas spp., Serratia spp., Stenotrophomonas maltophilia, Yersinia enterocolitica.

Others: Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia spp., Coxiella burnetti, Mycoplasma spp.

1 — for these species of microorganisms clinical performance of a combination of amoxicillin with clavulanic acid was shown in clinical trials.

2 — strains of these species of bacteria do not produce β-lactamelements. Sensitivity at monotherapy by amoxicillin allows to assume similar sensitivity to an amoxicillin combination with clavulanic acid.

 

Pharmacokinetics. Absorption

Active ingredients of the drug Augmentin® of the EU, amoxicillin and clavulanic acid, are quickly and completely absorbed from a GIT after oral administration. Absorption of active ingredients is optimum in case of administration of drug of Augmentin® of the EU together with meal.

Pharmacokinetic parameters of amoxicillin and clavulanic acid after reception in a dose of 45 mg/kg each 12 h by patients aged up to 12 years are included below.

Average value of pharmacokinetic parameters

                      Drug Augmentin® EC
                   Amoxicillin          Clavulanic acid
Cmax (mg/l)                                   15.7 1.7
                                         Tmax (ch) 2 1.1
AUC (мкг×ч/мл)                                  59.8 4
                                       T1/2 (ch) 1.4 1.1

Distribution

Therapeutic concentration of amoxicillin and clavulanic acid are created in various fabrics and intersticial liquid (in a gall bladder, tissues of an abdominal cavity, skin, fatty and muscular fabrics, synovial and peritoneal liquids, bile, purulent separated).

Amoxicillin and clavulanic acid possess weak extent of linkng with proteins of a blood plasma. The conducted researches showed that 25% of total quantity of clavulanic acid and 18% of amoxicillin contact proteins of a blood plasma.

In researches on animals cumulation of components of the drug Augmentin® of the EU in any body was not revealed.

Amoxicillin, as well as the majority of penicillin, gets into breast milk. In breast milk also trace amounts of clavulanic acid are found. Except for a possibility of development of diarrhea and candidiasis of mucous membranes of an oral cavity, no other negative impacts of amoxicillin and clavulanic acid on health of the children raised by breast milk are unknown.

Researches of reproductive function on animals at administration of drug of Augmentin® of the EU showed that amoxicillin and clavulanic acid get through a placental barrier. However the negative impact on a fruit was not revealed.

Metabolism

10-25% of an initial dose of amoxicillin are removed by kidneys in the form of an inactive metabolite (penitsilloyevy acid). Clavulanic acid, is exposed to intensive metabolism to 2,5-digidro-4-(2 hydroxyethyl) - 5-oxo-1H-pyrrol-3-carboxylic acid and 1 - amino - 4 - hydroxy - butane - 2 - she also is brought by kidneys, through a GIT, and also with expired air in the form of carbon dioxide.

Removal

As well as other penicillin, amoxicillin is removed generally by kidneys whereas clavulanic acid is removed both renal, and extrarenal mechanisms. Researches showed that, on average, about 60-70% of amoxicillin and about 40-65% of clavulanic acid are removed by kidneys in an invariable look in the first 6 h after reception of 1 tablet of 250 mg / 125 mg or 1 tablets of 500 mg / 125 in mg.

Indications to use:

Treatment of the infections caused by sensitive microorganisms at children:

— infections of ENT organs: the recurrent or persistent acute average otitis caused by Streptococcus pneumoniae (MPK ≤ 4 mkg/ml), Haemophilus influenzae * and Moraxella catarrhalis *;

— tonzillofaringit also sinusitis, usually caused Streptococcus pneumoniae, Haemophilus influenzae *, Moraxella catarrhalis * and Streptococcus pyogenes;

— lower respiratory tract infections: the share pneumonia and bronchial pneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae *, Moraxella catarrhalis *;

— the infections of skin and soft tissues which are usually caused by Staphylococcus aureus * and Streptococcus pyogenes.

* some strains of these species of bacteria produce β-lactamelements that does them insensitive to monotherapy by amoxicillin.

The infections caused by microorganisms, sensitive to amoxicillin, it is possible to treat the drug Augmentin® of the EU as amoxicillin is one of its active ingredients. The drug Augmentin® of the EU is also shown for treatment of the multi-infections caused by the microorganisms sensitive to amoxicillin, and also microorganisms producing the β-lactamazu sensitive to an amoxicillin combination with clavulanic acid.

Sensitivity of bacteria to an amoxicillin combination with clavulanic acid varies depending on the region and eventually. Where it is possible, local data on sensitivity have to be taken into account. In case of need it is necessary to carry out collecting microbiological samples and the analysis on bacteriological sensitivity.

Route of administration and doses:

Dosing mode

The drug dosing of Augmentin® of the EU is carried out according to age of the child, the dose is calculated in mg on kg a day or in ml of ready suspension. Calculation of a dose is conducted on amoxicillin and clavulanic acid, except for cases when dosing is conducted on each component separately.

For minimization of potentially possible undesirable phenomena from a GIT and optimization of absorption drug should be accepted inside at the beginning of meal.

It is longer not necessary to continue treatment 14 days without review of a clinical situation.

If necessary performing step therapy (in the beginning intravenous administration of the drug Augmentin® is possible (powder for preparation of solution for in/in introductions) with the subsequent transition to oral administration).

Children

The drug Augmentin® of the EU is recommended for children aged from 3 months and is more senior. There is no experience of use of the drug Augmentin® of the EU for children up to 3 months.

The recommended daily dose makes 90 mg of amoxicillin and 6.4 mg of clavulanic acid on 1 kg of body weight, divided into 2 receptions in each 12 h, within 10 days.

For patients with body weight more than 40 kg are recommended other dosage forms of the drug Augmentin®.

On the content of clavulanic acid the drug Augmentin® of the EU differs from other suspensions containing amoxicillin and clavulanic acid. The drug Augmentin® of the EU contains 600 mg of amoxicillin and 42.9 mg of clavulanic acid in 5 ml of the recovered suspension while the drugs containing 200 mg and 400 mg of amoxicillin in 5 ml of suspension contain respectively 28.5 mg and 57 mg of clavulanic acid in 5 ml of suspension. Drugs in the form of suspensions a dosage of 200 mg of amoxicillin in 5 ml, 400 mg of amoxicillin in 5 ml and the drug Augmentin® of the EU are not interchangeable.

Special groups of patients

Correction of the mode of dosing at clearance of creatinine of ≥30 ml/min. is not required. Drug is not recommended to be used at clearance of creatinine <30 ml/min.

At patients with an abnormal liver function treatment is carried out with care; regularly carry out monitoring of function of a liver. There are not enough data for change in the recommendation of the mode of dosing at such patients.

Way of preparation of suspension

Suspension prepares just before the first use.

It is necessary to add to powder about 2/3 further to close a bottle from the volume of the boiled water cooled to room temperature provided in the table below a cover and to stir up before full cultivation of powder, to allow a bottle to stand within 5 minutes for ensuring full cultivation. Then to add water to a tag on a bottle and again to stir up a bottle.

The bottle should be stirred up well before each use. For an exact drug dosing it is necessary to use a measured spoon which needs to be washed out well water after each use After cultivation suspension it is necessary to store no more than 10 days in the refrigerator, but not to freeze.

The approximate volume of water for suspension preparation.

Bottle volume           water Volume for suspension preparation
     50                                            ml 50 ml
    100                                           ml 90 ml

Features of use:

Before an initiation of treatment the drug Augmentin® of the EU it is necessary to collect the detailed anamnesis concerning the previous reactions of hypersensitivity to penicillin, cephalosporins or other allergens.

Hypersensitivity reactions (including anaphylactic reactions) on penicillin are described serious, and sometimes and lethal. The risk of emergence of such reactions is highest at the patients having in the anamnesis of reaction of hypersensitivity to penicillin. In case of allergic reaction it is necessary to stop treatment by the drug Augmentin® of the EU. At serious reactions of hypersensitivity it is necessary to enter Epinephrinum immediately. Can be required also an oxygenotherapy, in/in the introduction of GKS and ensuring passability of respiratory tracts including an intubation.

Purpose of the drug Augmentin® of the EU at suspicion on an infectious mononucleosis as with this disease amoxicillin can cause korepodobny rash in patients that complicates diagnosis of a disease is not recommended.

Prolonged treatment by the drug Augmentin® of the EU sometimes leads to excessive reproduction of insensitive microorganisms.

In general, the drug Augmentin® of the EU is transferred well and possesses a hypotoxicity inherent to all penicillin.

During long therapy the drug Augmentin® of the EU recommends to estimate periodically function of kidneys, liver and hemopoiesis.

For the purpose of decrease in risk of development of side effects from a GIT it is necessary to accept drug at the beginning of meal.

At the patients receiving an amoxicillin combination with clavulanic acid together with indirect (peroral) anticoagulants it was in rare instances reported about increase in a prothrombin time (increase in MHO). At joint purpose of indirect (peroral) anticoagulants with an amoxicillin combination with clavulanic acid control of the corresponding indicators is necessary. For maintenance of necessary effect of peroral anticoagulants correction of their dose can be required.

At patients with a reduced diuresis it was seldom or never reported about development of a crystalluria, it is preferential at parenteral use of drug. During introduction of high doses of amoxicillin it is recommended to accept enough liquid and to support an adequate diuresis for reduction of probability of formation of crystals of amoxicillin.

Administration of drug of Augmentin® of the EU inside leads to the high content of amoxicillin in urine that can result in false positive results when determining glucose in urine (for example, Benedict's test, test of Felinga). In this case it is recommended to apply a glyukozoksidantny method of definition of concentration of glucose in urine.

Care of an oral cavity helps to prevent change of coloring of teeth as for this purpose it is enough to brush teeth.

Abuse and medicinal dependence

The medicinal dependence, accustoming and reactions of euphoria connected with the use of the drug Augmentin® of the EU was not observed.

Influence on ability to driving of motor transport and to control of mechanisms

As drug can cause dizziness, it is necessary to warn patients about precautionary measures during the driving or work with moving mechanisms.

Side effects:

The undesirable phenomena given below are listed according to defeat of bodies and systems of bodies and occurrence frequency. Frequency of occurrence is defined as follows: very often (≥1/10), it is frequent (≥1/100, <1/10), infrequently (≥1/1000, <1/100), is rare (≥1/10 000, <1/1000), is very rare (<1/10 000).

Categories of frequency were created on the basis of clinical trials of drug and post-registration observation.

Infectious and parasitic diseases: often - candidiasis of skin and mucous membranes.

From blood and lymphatic system: seldom - a reversible leukopenia (including a neutropenia) and reversible thrombocytopenia; very seldom - a reversible agranulocytosis and reversible hemolitic anemia, lengthening of a prothrombin time and a bleeding time, anemia, an eosinophilia, a thrombocytosis.

From immune system: very seldom - a Quincke's disease, anaphylactic reactions, the syndrome similar to a serum disease, an allergic vasculitis.

From a nervous system: infrequently - dizziness, a headache; very seldom - a reversible hyperactivity, spasms (spasms can be observed at patients with renal failures, and also at those who receive high doses of drug), sleeplessness, excitement, alarm, change of behavior.

From a GIT: often - diarrhea, nausea, vomiting (nausea is more often observed at oral administration of high doses. If disturbances from a GIT are confirmed, they can be eliminated if to accept drug at the beginning of food); infrequently - digestive disturbances; very seldom - the antibiotiko-associated colitis induced by reception of antibiotics (including pseudomembranous colitis and hemorrhagic colitis), black "hairy" language. At children change of coloring of a blanket of an adamantine substance of tooth was very seldom noted. Care of an oral cavity helps to prevent change of coloring of an adamantine substance of tooth as for this purpose it is enough to brush teeth.

From a liver and biliary tract: infrequently - moderate increase in activity of ACT and/or ALT (it is observed at the patients receiving therapy beta лактамными antibiotics, however its clinical importance is unknown); very seldom - hepatitis and cholestatic jaundice (these phenomena were noted at therapy by other penicillin and cephalosporins), increase in concentration of bilirubin and an alkaline phosphatase. The undesirable phenomena from a liver were observed, mainly, at men and patients of advanced age and can be connected with long therapy. These undesirable phenomena are very seldom observed at children.

The listed signs and symptoms usually meet in process or at once upon termination of therapy, however in some cases can not be shown within several weeks after completion of therapy. The undesirable phenomena, as a rule, are reversible. The undesirable phenomena from a liver can be heavy, in exclusively exceptional cases there were messages on lethal outcomes. Almost in all cases it were persons with the serious accompanying pathology or the persons receiving at the same time potentially gepatotoksichny drugs.

From skin and hypodermic fabrics: infrequently - rash, an itch, urticaria; seldom - a mnogomorfny erythema; very seldom - Stephens-Johnson's syndrome, a toxic epidermal necrolysis, violent exfoliative dermatitis, acute generalized exanthematous пустулез.

In case of skin allergic reactions treatment by the drug Augmentin® of the EU needs to be stopped.

From kidneys and urinary tract: very seldom - intersticial nephrite, a crystalluria, a hamaturia.

Interaction with other medicines:

Simultaneous use of the drug Augmentin® of the EU and probenetsid is not recommended. Probenetsid reduces canalicular secretion of amoxicillin and therefore simultaneous use of the drug Augmentin® of the EU and a probenetsid can lead to increase and a persistention in blood of concentration of amoxicillin, but not clavulanic acid.

Simultaneous use of Allopyrinolum and amoxicillin can increase risk of emergence of skin allergic reactions. Now in literature there are no data on simultaneous use of a combination of amoxicillin with clavulanic acid and Allopyrinolum.

Penicillin is capable to slow down removal from a methotrexate organism at the expense of inhibition of its canalicular secretion therefore, simultaneous use of the drug Augmentin® of the EU and a methotrexate can increase toxicity of a methotrexate.

As well as other antibacterial drugs, the drug Augmentin® of the EU can exert impact on intestinal microflora, leading to decrease in absorption of estrogen from a GIT and to decrease in efficiency of the combined oral contraceptives.

In literature exceptional cases of increase in the international normalized relation (MHO) at patients at combined use of an atsenokumarol or warfarin and amoxicillin are described. In need of co-administration of the drug Augmentin® of the EU with anticoagulants the prothrombin time or MHO have to be controlled carefully at appointment or drug withdrawal of Augmentin® of the EU, dose adjustment of anticoagulants for intake can be required.

Contraindications:

— hypersensitivity to amoxicillin, clavulanic acid, other components of drug, beta лактамным to antibiotics (for example, penicillin, cephalosporins) in the anamnesis;

— the previous episodes of jaundice or an abnormal liver function at use of a combination of amoxicillin with clavulanic acid in the anamnesis;

— children's age up to 3 months;

— renal failure (KK <30 ml/min.);

— fenilketonuriya.

With care: abnormal liver functions.

 

Use of the drug AUGMENTIN® of the EU at pregnancy and feeding by a breast

In researches of reproductive function peroral and parenteral administration of the drug Augmentin® of the EU did not cause teratogenic effects in animals.

In a single research at women with a premature rupture of fetal membranes it was established that preventive therapy by drug can be connected with increase in risk of development of a necrotizing coloenteritis in newborns. As well as all medicines, Augmentin® of the EU are not recommended to be applied during pregnancy unless the expected advantage of use for mother exceeds potential risk for a fruit.

The drug Augmentin® of the EU can be used during breastfeeding. Except for a possibility of development of diarrhea or candidiasis of the mucous membranes of an oral cavity tied with penetration into breast milk of trace amounts of active ingredients of this drug, any other adverse effects at the babies who are on breastfeeding it was not observed. In case of adverse effects at the babies who are on breastfeeding it is necessary to stop breastfeeding.

 

Use at abnormal liver functions

With care appoint at an abnormal liver function (when monitoring function of a liver).

 

Use at renal failures

Correction of the mode of dosing at KK is not required ≥ 30 ml/min., it is not recommended at KK <30 ml/min.

 

Use for children

The drug Augmentin® of the EU is recommended for children aged from 3 months and is more senior. The recommended daily dose makes 90 mg / 6.4 body weight mg/kg, divided into 2 receptions in each 12 h within 10 days (see tab. 1).

Table 1.

The body weight (kg)                  the Volume of suspension (ml) at the rate of 90 mg/kg /
     8                                                         3 ml 2 
                                                             12 4.5 ml 2
      16                                                        6 ml 2
                                                             20 7.5 ml 2
      24                                                         9 ml 2
      28                                                      10.5 ml 2
      32                                                      12.5 ml 2
      36                                                      13.5 ml 2

For patients with body weight higher than 40 kg are recommended other dosage forms of the drug Augmentin®.

Overdose:

Symptoms: there can be symptoms from a GIT and disturbance of water and electrolytic balance. The amoksitsillinovy crystalluria in certain cases leading to development of a renal failure is described.

Spasms at patients with renal failures, and also at those who receive high doses of drug can be observed.

Treatment: symptoms from a GIT - symptomatic therapy, paying special attention to normalization of water and electrolytic balance. In case of overdose amoxicillin and clavulanic acid can be removed from a blood-groove by a hemodialysis.

Results of a prospective research which was conducted with participation of 51 children in the toxicological center showed that administration of amoxicillin in a dose of less than 250 mg/kg did not lead to significant clinical symptoms and did not demand a gastric lavage.

Storage conditions:

Drug should be stored in the place, unavailable to children, at a temperature not above 25 °C.

The prepared suspension should be stored in the refrigerator at a temperature of 2-8 °C in densely closed bottle.

Period of validity - 2 years, a period of validity of the prepared suspension - 10 days.

Issue conditions:

According to the recipe

Packaging:

• powder for пригот. сусп. for intake of 600 mg +42.9 mg / 5 ml: фл. 1 in set. with мерн. a spoon - LSR-003616/10, 30.04.10. Validity period рег. уд. it is not limited. VED.

• powder for пригот. сусп. for intake of 600 mg +42.9 mg / 5 ml: фл. 1 in set. with мерн. a spoon - LSR-003616/10, 30.04.10. Validity period рег. уд. it is not limited. VED.