Augmentin EU - instructions for use, dose, side effects, contraindications

Name of components	amount¹ (mg / 5 mL)
Active substances:
Amoxicillin trihydrate²	697,65
(in terms of amoxicillin)	(600,0)
Potassium clavulanate³	52,32
(in terms of clavulanic acid)	(42,90)
Excipients:
Xanthan gum	3,00
Aspartame	12,50
Silica colloidal dioxide	35,00
Aromatic Strawberry	26,00
Silicon dioxide⁴	28,29

¹ - the amount of all substances is indicated without excess. In the manufacture of the drug, the amount of excipients is laid with 8.8% excess, which is: xanthan gum 3.26 mg, aspartame 13.60 mg, silicon dioxide colloid 38.08 mg, carmellose sodium 32.64 mg, strawberry flavor 28.29 mg, silicon dioxide - up to 1098.84 mg. The total weight of the dry powder, taking into account the excess of 1098.84 mg.

² - In the production of amoxicillin trihydrate is laid with 8.8% excess, which is 759.04 mg (in terms of amoxicillin 652,80 mg). The amount of amoxicillin grihydrate varies depending on the purity of the substance.

³ - in the manufacture of potassium, clavulanate is incorporated with an 8.0% excess in the initial mixing stage of the active components and from 8.8% in the mixing step of all components, which is 61.48 mg (calculated as clavulanic acid 50.41 mg).The amount of potassium clavulanate varies depending on the purity of the substance.

⁴- the amount of silicon dioxide is adjusted taking into account changes in the amounts of amoxicillin trndrat and potassium mixture of clavulanate and silicon dioxide.

Description:

The powder is almost white with a characteristic smell of strawberry. When diluted with water, a suspension of almost white color is formed.

Pharmacotherapeutic group:Antibiotic - penicillin semisynthetic + beta-lactamase inhibitor

ATX: & nbsp

J.01.C.R.02 Amoxicillin in combination with enzyme inhibitors

Pharmacodynamics:Mechanism of action

Amoxicillin is a semisynthetic broad-spectrum antibiotic with activity against many Gram-positive and Gram-negative microorganisms. In the same time amoxicillin is subject to destruction by beta-lactamases, and therefore the spectrum of amoxicillin activity does not extend to microorganisms that produce this enzyme.

Clavulanic acid, a beta-lactamase inhibitor structurally related to penicillins, has the ability to inactivate a wide spectrum of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins.Clavulanic acid has sufficient efficacy against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against type 1 chromosomal beta lactamases that are not inhibited by clavulanic acid.

The presence of clavulanic acid in the preparation of Augmentin ® protects amoxicillin from destruction by enzymes - beta-lactamases, which allows to expand the antibacterial spectrum of amoxicillin.

The activity of a combination of amoxicillin with clavulanic acid in vitro is given below.

Bacteria, usually sensitive to a combination of amoxicillin and clavulanic acid

Gram-positive aerobes

Bacillus anthracis

Enterococcus faecalis

Listeria monocytogenes

Nocardia asteroides

Streptococcus pyogenes^1,2

Streptococcus agalactiae^1,2

Streptococcus spp. (other beta-hemolytic streptococci)^1,2

Staphylococcus aureus (sensitive to methicillin)¹

Staphylococcus saprophyticus (sensitive to methicillin)

Coagulase-negative staphylococci (sensitive to methicillin)

Gram-positive anaerobes

Clostridium spp.

Peptococcus niger

Peptostreptococcus magnus

Peptostreptococcus micros

Peptostreptococcus spp.

Gram-negative aerobes

Bordetella pertussis

Haemophilus influenzae¹

Helicobacter pylori

Moraxella catarrhalis¹

Neisseria gonorrhoeae

Pasteurella multocida

Vibrio cholerae

Gram-negative anaerobes

Bacteroides fragilis

Bacteroides spp.

Capnocytophaga spp.

Eikenella corrodens

Fusobacterium nucleatum

Fusobacterium spp.

Porphyromonas spp.

Prevotella spp.

Other

Borrelia burgdorferi

Leptospira icterohaemorrhagiae

Treponema pallidum

Bacteria for which the acquired resistance to a combination of amoxicillin and 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

Coiynebacterium spp.

Enterococcus faecium

Streptococcus pneumoniae^1,2

Streptococcus group Viridans

Bacteria that have natural resistance to a combination of amoxicillin and clavulanic acid

Gram-negative aerobes

Acinetobacter spp.

Citrobacterfreundii

Enterobacter spp.

Hafnia alvei

Legionella pneumophila

Morganella morganii

Providencia spp.

Pseudomonas spp.

Serratia spp.

Stenotrophomonas maltophilia

Yersinia enterocolitica

Other

Chlamydia pneumoniae

Chlamydia psittaci Chlamydia spp. Coxiella burnetii

Mycoplasma spp.

¹ - for these bacteria, the clinical efficacy of a combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.

² - strains of these bacteria do not produce beta-lactamases.

Sensitivity to monotherapy with amoxicillin suggests a similar sensitivity to the combination of amoxicillin and clavulanic acid.

Pharmacokinetics:

Suction

Active substances of the drug Augmentin® EU, amoxicillin and clavulanic acid, quickly and completely absorbed from the digestive tract (gastrointestinal tract) after oral administration. Absorption of active substances is optimal in case of taking the drug Augmentin® EU together with a meal.

Below are the pharmacokinetic parameters of amoxicillin and clavulanic acid after taking in a dose of 45 mg / kg every 12 hours by patients under the age of 12 years.

Mean value of pharmacokinetic parameters
A drug	FROMmax (mg / L)	Tmah (h)	AUC (mg in h / l)	T1/2 (H)
Amoxicillin
Augmentin® EC	15,7	2,0	59,8	1,4
Clavulanic acid
Augmentin® EC	1,7	1,1	4,0	1,1

FROMmax is the maximum concentration in plasma;

Tmah - the time to reach the maximum concentration in the plasma;

AUC is the area under the concentration-time curve;

T1 / 2 - half-life.

Distribution

As with intravenous combination of amoxicillin with clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are found in various tissues and interstitial fluid (in the gall bladder, abdominal tissues, skin, fat and muscle tissues, synovial and peritoneal fluids, bile secretion) .

Amoxicillin and clavulanic acid have a weak degree of binding to plasma proteins. Studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin in the blood plasma bind to plasma proteins. In animal studies, no cumulation of components of the Augmentin drug® EU in any body.

Amoxicillin, like most penicillins, penetrates into breast milk. Traces of clavulanic acid can also be detected in breast milk. Except for the possibility of developing sensitization. diarrhea and candidiasis of the oral mucosa, no other adverse effects of amoxicillin and clavulanic acid on the health of infants breast-fed are known.

Studies of reproductive function in animals have shown that amoxicillin and clavulanic acid penetrate the placental barrier. However, there was no adverse effect on the fetus.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic acid). Clavulanic acid undergoes intensive metabolism to 2,5-dihydro-4- (2-hydroxyethyl) -5-oxo-1 H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxybutan-2-one and is excreted by the kidneys , through the gastrointestinal tract, and also with exhaled air in the form of carbon dioxide.

Excretion

Like other penicillins, amoxicillin is excreted mainly by the kidneys, whereas clavulanic acid - through both renal and extrarenal mechanisms.Approximately 60-70% amoxicillin and about 40-65% clavulanic acid is excreted by the kidneys unchanged in the first 6 hours after the appointment of 1 tablet of the drug Augmentin®, film-coated tablets, 250 mg / 125 mg or 500 mg / 125 mg.

Simultaneous administration of probenecid slows the excretion of amoxicillin, but not clavulanic acid (see section "Interaction with other drugs").

Indications:

The drug Augmentin® EC is used to treat infections caused by sensitive microorganisms in children.

Upper respiratory tract infections:

Recurrent or persistent acute otitis media caused by Streptococcus pneumoniae (minimum inhibitory concentration <4 μg / ml), Haemophilus influenzae^* and Moraxella catarrhalis^*.

Tonsillo-pharyngitis and sinusitis, usually caused by Streptococcus pneumoniae, Haemophilus influenzae*. Moraxella catarrhalis^* and Streptococcus pyogenes.

Lower respiratory tract infections: lobar pneumonia and bronchopneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis*.

Infections of the skin and soft tissues, usually caused by Staphylococcus aureus^* and

Streptococcus pyogenes.

** - some strains of these bacterial species produce beta-lactamases, which makes them insensitive to amoxicillin monotherapy (see also the section "Pharmacological properties").

Infections caused by microorganisms sensitive to amoxicillin can be treated with the Augmentin® EU drug because amoxicillin is one of its active substances. The Augmentin® EU drug is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as by microorganisms producing beta-lactamase that are sensitive to a combination of amoxicillin and clavulanic acid.

The sensitivity of bacteria to the combination of amoxicillin and clavulanic acid varies depending on the region and over time. Wherever possible, local sensitivity data should be taken into account. If necessary, the collection of microbiological samples and analysis for bacteriological sensitivity should be carried out.

Contraindications:

- Hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (eg, penicillins, cephalosporins) in history;

- previous episodes of jaundice or impaired liver function with a combination of amoxicillin and clavulanic acid in history;

- children up to 3 months;

- impaired renal function (creatinine clearance less than 30 ml / min);

- phenylketonuria.

Carefully:

The drug Augmentin® The EU should be used with caution in patients with impaired liver function.

Pregnancy and lactation:

Pregnancy

In studies of reproductive function in animals, oral and parenteral administration of the Augmentin® drug did not produce teratogenic effects. In a single study in women with premature rupture of membranes, it was found that preventive therapy with the drug may be associated with an increased risk of developing necrotizing enterocolitis in newborns. Like all medicines, Augmentin ® EC is not recommended for use during pregnancy, except when the expected benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding period

The drug Augmentin® EC can be used during breastfeeding. With the exception of the possibility of developing sensitization, diarrhea, or candidiasis of the oral mucosa, associated with the penetration into the breast milk of trace amounts of the active ingredients of this drug.No other adverse effects were observed in infants fed breastfeeding. In the case of adverse effects in infants who are breastfeeding, it is necessary to stop it.

Dosing and Administration:

Dosing of the Augmentin® EC drug is carried out in accordance with the age of the child, the dose is calculated in mg per kg per day or in ml of the finished suspension. Calculation of the dose is carried out for amoxicillin and clavulanic acid, except for cases when dosing is carried out for each component separately. To minimize potential adverse events from the gastrointestinal tract and optimize absorption, the drug should be taken orally at the beginning of the meal. Treatment should not be continued for more than 14 days without reviewing the clinical situation.

If necessary, it is possible to perform stepwise therapy (initially intravenous administration of the drug Augmentin in the form of a powder for the preparation of a solution for intravenous administration, with the subsequent transition to the drug Augmentin in oral dosage forms).

Children

The drug Augmentin® EC is recommended for children aged 3 months and older. There is no experience of the use of the drug Augmentin® EC in children under 3 months. The recommended daily dose is 90 mg of amoxicillin and 6.4 mg of clavulanic acid per 1 kg of body weight divided into two doses every 12 hours for 10 days.

For patients with a body weight above 40 kg, other dosage forms of the Augmentin® preparation are recommended.

According to the content of clavulanic acid, the drug Augmentin® EC differs from other suspensions containing amoxicillin and clavulanic acid. The Augmentin® EC preparation contains 600 mg of amoxicillin and 42.9 mg of clavulanic acid in 5 ml of reconstituted suspension, while preparations 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 the suspension. Drugs in the form of suspensions with a dosage of 200 mg amoxicillin in 5 ml, 400 mg amoxicillin in 5 ml and the drug Augmentin ® EC are not interchangeable.

Special patient groups

Patients with impaired renal function

No dosage adjustment is necessary for creatinine clearance> 30 ml / min.

The drug is contraindicated for use in the clearance of creatinine <30 ml / min.

Patients with impaired hepatic function

Treat with caution; regularly monitor liver function.

There is insufficient data to change the recommendation of the dosing regimen in such patients.

Method of preparing the suspension

The suspension is prepared immediately before the first use.

Add about 2/3 of the volume of boiled water cooled to room temperature in the vial with powder, then close the vial with a lid and shake until the powder is completely diluted, allow the vial to stand for 5 minutes to ensure complete dilution. Then add water to the label on the vial and shake the bottle again. The vial should be shaken well before each use. To accurately dispense the drug should use a measuring spoon, which must be thoroughly washed with water after each use. After reconstitution, the suspension should be stored for no more than 10 days in the refrigerator, but not frozen.

Approximate volume of water for suspension preparation:

Volume of the bottle

The volume of water for

cooking

suspensions

50 ml

100 ml

90 ml

Side effects:

The adverse events presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: very often (≥1 / 10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1,000 and <1/100), rarely (≥1 / 10,000 and <1/1000), very rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.

Frequency of occurrence of undesirable phenomena

Infectious and parasitic diseases

Often: candidiasis of skin and mucous membranes.

Violations of the blood and lymphatic system

Rarely: reversible leukopenia (including neutropenia) and reversible thrombocytopenia. Very rarely: reversible agranulocytosis and reversible hemolytic anemia, prolongation of prothrombin time and bleeding time, anemia, eosinophilia, thrombocytosis.

Immune system disorders

Very rarely: angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.

Disturbances from the nervous system

Infrequent: dizziness, headache. Very rarely: reversible hyperactivity, convulsions.Seizures can occur in patients with impaired renal function, as well as in those who receive high doses of the drug. Insomnia, agitation, anxiety.

Disorders from the gastrointestinal tract

Often: diarrhea, nausea, vomiting. Nausea is more often observed with oral administration of high doses. If violations from the gastrointestinal tract are confirmed, they can be eliminated if taking the drug at the beginning of the meal. Infrequent: digestive disorders. Very rarely: antibiotic-associated colitis, induced by antibiotics (including pseudomembranous colitis and hemorrhagic colitis - see the "Special instructions" section), a black "hairy" tongue. In children, the discoloration of the surface layer of tooth enamel was very rare. Oral care helps prevent discoloration of tooth enamel, as it is enough to brush your teeth.

Disturbances from the liver and bile ducts

Infrequent: moderate increase in activity of aspartate aminotransferase and / or alanine aminotransferase (ACT and / or ALT). This phenomenon is observed in patients receiving beta-lactam antibiotic therapy, however, clinical its significance is unknown. Very rarely: hepatitis and cholestatic jaundice (noted with concomitant therapy with other penicillins and cephalosporins). Increased concentrations of bilirubin and alkaline phosphatase. Undesirable liver side effects were observed mainly in men and elderly patients and may be associated with long-term therapy.

These undesirable phenomena are very rare in children. These signs and symptoms usually occur in the process or immediately after the end of therapy, but in some cases may not appear for several weeks after the completion of therapy. Undesirable phenomena, as a rule, are reversible. Undesirable phenomena from the liver can be severe, in extremely rare cases there have been reports of lethal outcomes. In almost all cases, these were persons with serious concomitant pathology or persons receiving potentially hepatotoxic drugs at the same time.

Disturbances from the skin and subcutaneous tissues

Infrequent: rash, itching, hives. Rarely: multimorphic erythema. Very rarely: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.In case of skin allergic reactions treatment with the drug Augmentin® EC should be discontinued.

Disorders from the kidneys and urinary tract

Very rarely: interstitial nephritis, crystalluria (see the section "Overdose"), hematuria.

Overdose:

Symptoms

Symptoms on the part of the gastrointestinal tract and violations of the water-electrolyte balance can be observed. Amoxicillin crystalluria is described, in some cases leading to the development of renal failure (see section "Special instructions and precautions"). Cramps can occur in patients with impaired renal function, as well as in those who receive high doses of the drug.

Treatment

Symptoms from the gastrointestinal tract-symptomatic therapy, paying special attention to the normalization of the water-electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

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

Interaction:

Simultaneous use of the drug Augmentin® EC and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore simultaneous use of the drug Augmentin® EC and probenecid can lead to an increase and a persistence in the blood concentration of amoxicillin, but not clavulanic acid.

The simultaneous use of allopurinol and amoxicillin may increase the risk of skin allergic reactions. Currently, there is no data in the literature on the simultaneous use of a combination of amoxicillin with clavulanic acid and allopurinol.

Penicillins can slow the excretion of methotrexate from the body by inhibiting its tubular secretion, so simultaneous use of the drug Augmentin® EC and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, the drug Augmentin® EC can have an effect on the intestinal microflora, leading to a decrease in absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives.

In the literature, rare cases of an increase in the international normalized ratio (INR) in patients with joint use of acenocoumarol or warfarin and amoxicillin are described.If it is necessary to simultaneously prescribe the drug Augmentin® EC with anticoagulants prothrombin time or INR should be carefully monitored with the appointment or discontinuation of the drug Augmentin® EC, it may be necessary to adjust the dose of anticoagulants for oral administration.

In patients who received mycophenolate mofetil, after the start of the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite, mycophenolic acid, was observed, before taking the next dose of the drug by approximately 50%. Changes in this concentration can not accurately reflect the overall changes in the exposure of mycophenolic acid.

Special instructions:

Before starting treatment with the Augmentin ® EC, you need to collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Serious, and sometimes lethal, hypersensitivity reactions (including anaphylactic reactions) to penicillins have been described. The risk of occurrence of such reactions is highest in patients who have a history of hypersensitivity reactions to penicillins.In the event of an allergic reaction, it is necessary to stop treatment with the drug Augmentin ® EC and prescribe appropriate therapy. When serious hypersensitivity reactions should be immediately introduced epinephrine. Oxygen therapy, intravenous glucocorticosteroids, and airway patency, including intubation, may also be required.

It is not recommended the appointment of the drug Augmentin ® EC in case of suspected infectious mononucleosis, since in patients with this disease amoxicillin can cause a measles-like rash, which makes it difficult to diagnose the disease.

Long-term treatment with the drug Augmentin ® EC sometimes leads to excessive reproduction of insensitive microorganisms.

In general, the drug Augmentin® EC is well tolerated and has a characteristic of all penicillins of low toxicity. During prolonged therapy with the Augmentin® EC, it is recommended that the kidneys, liver and hematopoiesis should be evaluated periodically. There are cases of pseudomembranous colitis occurring when taking antibiotics, the severity of which can range from mild to life-threatening.Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after antibiotic use. If diarrhea is prolonged or severe, or the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be examined.

In patients who received a combination of amoxicillin with clavulanic acid in conjunction with indirect (oral) anticoagulants, in rare cases, increased prothrombin time (increased INR) was reported. When co-administration of indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, monitoring of the relevant indicators is necessary. To maintain the necessary effect of oral anticoagulants, their dose may need to be adjusted.

In patients with reduced diuresis, in very rare cases, the development of crystalluria was reported. preferably with parenteral administration of the drug. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain adequate diuresis to reduce the likelihood of amoxicillin crystals (see section "Overdose").

Taking the drug Augmentin® EC inside leads to a high content of amoxicillin in the urine, which can lead to false-positive results in determining glucose in the urine (for example, the Benedict test, Feeling's test). In this case, it is recommended to use a glucose oxidant method for determining the concentration of glucose in the urine.

Oral care helps prevent tooth discoloration, as it is sufficient to brush your teeth.

Abuse and drug dependence

There was no drug dependence, addiction and reactions of euphoria associated with the use of the drug Augmentin® EC.

Effect on the ability to drive transp. cf. and fur:

Since the drug may cause dizziness, it is necessary to warn patients about precautions when driving a vehicle or working with moving machinery.

Form release / dosage:Powder for suspension for oral administration, 600 mg + 42.9 mg / 5 ml.

Packaging:12.85 g of powder (for the preparation of 50 ml of the finished suspension) or 23.13 g of powder (for the preparation of 100 ml of the finished suspension) into a vial of clear glass,Closed with a screw-on aluminum cover with a PVC or polyolefin gasket with a first opening control. 1 bottle with instructions for use and a measuring spoon in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

The prepared suspension should be stored in a refrigerator at a temperature of 2-8 ° C in a tightly closed vial.

Keep out of the reach of children.

Shelf life:

2 years.

Shelf life of the prepared suspension: 10 days.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003616/10

Date of registration:30.04.2010 / 13.05.2015

Expiration Date:Unlimited

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GLAXO WELLCOME PRODUCTION France

Representation: & nbspGlaxoSmithKline group of companies GlaxoSmithKline group of companies Unknown

Information update date: & nbsp04.10.2017

Illustrated instructions

Instructions

Augmentin® EC (Augmentin® ES)