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

Xanthan gum, aspartame, succinic acid, silicon colloidal dioxide, gi-promellose, orange flavor 1, orange flavor 2, raspberry aroma, "Bright molasses" flavor, silicon dioxide.

Ratio of active components in suspension

Dosage form	Ratio of active components	Amoxicilli, mg (in the form of amoxicillin trihydrate)	Clavulanic acid, mg (in the form of potassium clavulanate)
Powder for the preparation of a suspension of 125 mg / 31.25 mg in 5 ml	4: 1	125	31,25
Powder for the preparation of a suspension of 200 mg / 28.5 mg in 5 ml	7 : 1	200	28,5
Powder for the preparation of a suspension of 400 mg / 57 mg in 5 ml	7:1	400	57

Description:

For a dosage of 125 mg / 31.25 mg in 5 ml: powder white or almost white, with a characteristic odor. Dilution produces a white or almost white suspension. When standing, a white or almost white precipitate is slowly formed.

For dosage of 200 mg / 28.5 mg in 5 ml or 400 mg / 57 mg in 5 ml: powder white or almost white, with a characteristic odor.Dilution produces a white or almost white suspension. When standing, a white or almost white precipitate is slowly 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

Streptococci groups 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

Both active substances of the drug Augmentin®, amoxicillin and clavulanic acid, are quickly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of active substances of the drug Augmentin® is optimal in case of taking the drug at the beginning of food intake.

The pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in different studies are shown below when healthy volunteers aged 2-12 years were taken on an empty stomach in three doses of 40 mg / 10 mg / kg per day of the Augmentin preparation, powder for oral suspension, 125 mg / 31.25 mg in 5 ml.

Basic pharmacokinetic parameters

A drug	Dose (mg / kg)	C_max(mg / ml)	T_max (clock)	AUC (mghch) / l)	T_1/2 (hours)
Amoxicillin
Augmentin®, 125 mg / 31.25 mg in 5 ml	40	7,3 ± 1,7	2,1 (1,2- 3,0)	18,6 ± 2,6	1,0 ± 0,33
Clavulanic acid
Augmentin®, 125 mg / 31.25 mg in 5 ml	10	2,7 ± 1,6	1,6 (1,0- 2.0)	5,5 ± 3,1	0,94 + 0,05

C_max - the maximum concentration in blood plasma.

T_max - time to reach the maximum concentration in the blood plasma.

AUC - the area under the concentration-time curve.

T_1/2 - 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® in any organ.

Amoxicillin, like most penicillins, penetrates into breast milk. In breast milk, trace amounts of clavulanic acid.Except for the possibility of sensitization, the development of diarrhea and candidiasis of the oral mucosa, no other adverse effects of amoxicillin and clavulanic acid on the health of infants fed by breast milk 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-hydroxy-butan-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 is mediated by both renal and extrarenal mechanisms. Approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted by the kidneys unchanged in the first 6 hours after the administration of 1 tablet of 250 mg / 125 mg or 1 tablet of 500 mg / 125 mg. Simultaneous administration of probenecid slows the excretion of amoxicillin, but not clavulanic acid (cf.section "Interaction with other medicinal products").

Indications:

Bacterial infections caused by microorganisms sensitive to amoxicillin / clavulanic acid:

- ENT organs infections, for example, relapsing tonsillitis, sinusitis, otitis media, usually caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhal is and Streptococcus pyogenes.

- Lower respiratory tract infections, such as exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia, commonly caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

- Urinary tract infections, such as cystitis, urethritis, pyelonephritis, infections of the female genitalia, usually caused by species of the Enterobacteriaceae family (mainly Escherichia coli), Staphylococcus saprophyticus and species of the genus Enterococcus, and gonorrhea caused by Neisseria gonorrhoeae.

- Infections of the skin and soft tissues, usually caused by Staphylococcus aureus, Streptococcus pyogenes and species of the genus Bacteroides.

- Infections of bones and joints, for example osteomyelitis, usually caused by Staphylococcus aureus, if long-term therapy is necessary.

Infections caused by microorganisms sensitive to amoxicillin can be treated with the drug "Augmentin®" because amoxicillin is one of its active ingredients.

Contraindications:

- Hypersensitivity to beta-lactams, for example to penicillins, cephalosporins and other components of the drug;

- previous episodes of jaundice or impaired liver function as a result of amoxicillin / clavulanic acid in history;

- phenylketonuria.

Carefully:

Patients with violations of liver function treatment with the drug "Augmentin ®" are conducted with caution, regularly monitor 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® is not recommended for use during pregnancy, unless the expected benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding period

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

Dosing and Administration:

For oral administration.

The dosage regimen is set individually depending on the age, body weight, function of the patient's kidneys, and also on the severity of the infection.

To reduce potential abnormalities from the gastrointestinal tract and to optimize absorption, the drug should be taken at the beginning of the meal. Treatment should not last more than 14 days without reviewing the clinical situation.

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

Adults and children 12 years and older or with a body weight of 40 kg or more

It is recommended to use other medicinal forms of the drug Augmentin or suspension with the ratio of amoxicillin to clavulanic acid 7: 1 (400 mg / 57 mg in 5 ml).

Children aged 3 months to 12 years with a body weight of less than 40 kg

Calculation of the dose is made depending on the age and body weight, indicate in mg / kg of body weight per day or in milliliters of suspension. The daily dose is divided into 3 doses every 8 hours. The recommended dosing regimen and the frequency of reception are shown in the table below.

Table of dosage regimen of the drug Augmentin® (calculation of the dose is made for amoxicillin)

	Suspension 4: 1 (125 mg / 31.25 mg in 5 ml) in 3 divided doses every 8 hours
Low doses	20 mg / kg / day
High doses	40 mg / kg / day

Low doses of the drug Augmentin® are recommended for the treatment of infections of the skin and soft tissues, as well as recurrent tonsillitis.

High doses of Augmentin® are recommended for the treatment of diseases such as otitis media, sinusitis, lower respiratory tract and urinary tract infections, infections of bones and joints.

There is insufficient clinical data to recommend the use of Augmentin® in a dose of more than 40 mg / 10 mg / kg / day in 3 divided doses (4: 1 suspension) in children younger than 2 years.

Children from birth to 3 months

Due to the immaturity of the excretory function of the kidneys, the recommended dose of the drug Augmentin® (calculation for amoxicillin) is 30 mg / kg / day in 2 divided doses as a 4: 1 suspension.

Children born prematurely

There are no recommendations regarding the dosage regimen.

Special patient groups

Patients with impaired renal function

Correction of the dosing regimen is based on the maximum recommended dose amoxicillin and value of ground clearance creatinine.

Creatinine clearance	Dosing regimen of the drug Augmentin® suspension 4: 1 (125 mg / 31.25 mg in 5 ml)
> 30 ml / min	Correction of the dosing regimen is not required.
10-30 ml / min	15 mg / 3.75 mg / kg 2 times a day, the maximum daily a dose of 500 mg / 125 mg twice a day.
<10 ml / min	15 mg / 3.75 mg / kg once a day, the maximum daily dose of 500 mg / 125 mg.

In most cases, parenteral therapy should be preferred where possible.

Patients on hemodialysis

Recommended dosing regimen:

15 mg / 3.75 mg / kg once a day.

Before the hemodialysis session, one additional dose of 15 mg / 3.75 mg / kg should be given. To restore the concentrations of active components of the Augmentin drug in the blood, a second additional dose of 15 mg / 3.75 mg / kg should be administered after a hemodialysis session.

Patients with impaired hepatic function

Treat with caution; regularly monitor liver function. There is insufficient data to change the recommendation for doses in such patients.

Method of preparing the suspension

The suspension is prepared immediately before the first use.

In the vial of powder, add about 60 ml of boiled water cooled to room temperature, then cover 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. In general, about 92 ml of water is required to prepare the slurry.

The vial should be shaken well before each use. To accurately dispense the drug should use a measuring cap, which must be thoroughly rinsed with water after each use. After reconstitution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.

For children under 2 years, a measured single dose of a suspension of the drug Augmentin® can be diluted with water in half.

Side effects:

The undesirable reactions 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 <1/1 000), 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 reactions

Infectious and parasitic diseases

Often: candidiasis of skin and mucous membranes.

Violations of the blood and lymphatic system

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

Disorders from the gastrointestinal tract

Adults Very often: diarrhea. Often: nausea, vomiting.

Children Often: diarrhea, nausea, vomiting.

The entire population

Nausea was most often associated with the use of high doses of the drug. If after the beginning of taking the drug there are undesirable reactions from the digestive tract, they can be eliminated if you take Augmentin at the beginning of the meal.

Infrequent digestion. Very rarely: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis) (see section "Special instructions"), black "hairy" tongue, gastritis, stomatitis. Change in the color of the surface layer of tooth enamel in children.

Disturbances from the liver and bile ducts

Infrequent: moderate increase in activity of aspartate aminotransferase and / or alanine aminotransferase (ACT and / or ALT). This reaction is observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown. Highly rarely: hepatitis and cholestatic jaundice.These reactions are observed in patients receiving penicillin antibiotics and cephalosporins. Increased concentrations of bilirubin and alkaline phosphatase.

Undesirable reactions from the liver have been observed mainly in men and elderly patients and can be associated with long-term therapy. These undesirable reactions 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 reactions are usually reversible.

Undesirable reactions from the liver can be severe, in extremely rare cases there have been reports of lethal outcomes. In almost all cases, these were patients with severe concomitant pathologies or patients who received potentially hepatotoxic drugs at the same time.

Disturbances from the skin and subcutaneous tissues

Infrequent: rash, itching, hives. Rarely: erythema multiforme. Very rarely: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

Disorders from the kidneys and urinary tract

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

Overdose:

Gastrointestinal disorders and disturbances in the water-electrolyte balance may occur. These overdose symptoms should be treated symptomatically, focusing on the normalization of the water-electrolyte balance. Amoxicillin crystalluria is described, in some cases leading to the development of renal failure.

Cases of interstitial nephritis, leading to renal insufficiency with oliguria, were rarely observed in patients with an overdose of amoxicillin. The drug "Augmentin ®" is excreted from the blood by hemodialysis.

Interaction:

Simultaneous use of the drug Augmentin® and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore simultaneous use of the drug Augmentin and probenecid can lead to an increase and 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 the simultaneous use of the drug Augmentin and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, the drug Augmentin can affect the intestinal microflora, leading to a decrease in absorption of estrogens from the digestive 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 Augmentin® drug with anticoagulants, prothrombin time or INR should be carefully monitored with the appointment or discontinuation of the Augmentin® drug.) Correction of the dose of anticoagulants for oral administration may be required.

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 Augmentin, you need to collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins, or other substances that cause an allergic reaction in the patient. Serious, and sometimes lethal, hypersensitivity reactions (anaphylactic reactions) to penicillins are described. The risk of occurrence of such reactions is highest in patients who have a history of hypersensitivity reactions to penicillins. In case of an allergic reaction, it is necessary to stop treatment with the drug Augmentin® and begin the appropriate alternative therapy. Serious anaphylactic reactions should be promptly administered to the patient epinephrine. Oxygen therapy, intravenous glucocorticosteroids, and airway patency, including intubation, may also be required.

In case of suspected infectious mononucleosis, the drug Augmentin® should not be used, since in patients with this disease amoxicillin can cause a skinlike skin rash, which makes it difficult to diagnose the disease. Long-term treatment with the drug Augmentin® can lead to excessive reproduction of insensitive microorganisms.

In general, the drug Augmentin® is well tolerated and has a characteristic of all penicillins of low toxicity. During prolonged therapy with the drug Augmentin, it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis.

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 long 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 together with indirect (oral) anticoagulants,In rare cases, increased prothrombin time (increased INR) was reported. With the joint appointment 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, correction of the dose of anticoagulants for oral administration may be required.

In patients with reduced diuresis, crystalluria is very rare, mainly with parenteral therapy. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain an adequate diuresis to reduce the likelihood of amoxicillin crystals (see section "Overdose").

When taking Augmentin®, a high content of amoxicillin in the urine is observed, which can lead to false-positive results in the determination of 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.

Clavulanic acid can cause a non-specific binding of class G and albumin immunoglobulin to erythrocyte membranes,which leads to false positive results of the Coombs test.

Oral care helps prevent tooth discoloration associated with taking the drug, as it is enough 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.

Effect on the ability to drive transp. cf. and fur:The drug Augmentin® does not adversely affect these functions.

Form release / dosage:

Powder for the preparation of a suspension for oral administration.

Packaging:

For a dosage of 125 mg / 31.25 mg in 5 ml: powder for the preparation of a suspension for ingestion of 11.5 g in a bottle of clear glass, closed with a screwed aluminum cover with the control of the first opening. One bottle together with instructions for use and a measuring cup in a cardboard box.

For dosage of 200 mg / 28.5 mg in 5 ml or 400 mg / 57 mg in 5 ml: powder for the preparation of a suspension for ingestion of 7.7 g (for a dosage of 200 / 28.5 mg in 5 ml) or 12.6 g (for a dosage of 400/57 mg in 5 ml) in a vial of clear glass, closed with a screw-on aluminum cover with the control of the first opening.One bottle together with instructions for use and a measuring cup in a cardboard box.

Storage conditions:

Unopened vial should be stored in a dry place at a temperature not exceeding 25 ° C. The prepared suspension is stored in a refrigerator at a temperature of 2-8 ° C.

Keep out of the reach of children.

Shelf life:

Unopened vial - 2 years.

The prepared suspension is 7 days.

Do not take the drug after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N015030 / 01

Date of registration:09.09.2008 / 02.04.2010

Expiration Date:Unlimited

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

Manufacturer: & nbsp

SmithKline Beecham, PLC United Kingdom

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

Information update date: & nbsp04.10.2017

Illustrated instructions

Instructions

Augmentin® (Augmentin®)