Augmentin SR, 1000 mg+62.5 mg, modified-release film-coated tablets, 28 pcs.: instructions for use, reviews and analogues, prices in pharmacies. Buy and deliver to your nearest

Augmentin powder for suspension 200mg+28.5mg/5 ml, 70ml

Registration Certificate Holder

GlaxoSmithKline Trading (Russia)

Dosage form

Medicine - Augmentin® (Augmentin®)

Description

Powder for suspension for oral administration

white or almost white in color, with a characteristic odor; upon dilution, a white or almost white suspension is formed; When standing, a white or almost white precipitate slowly forms.

5 ml of ready-made suspension.

amoxicillin (as amoxicillin trihydrate) 200 mg clavulanic acid (as potassium clavulanate)* 28.5 mg

Excipients

: xanthan gum - 12.5 mg, aspartame - 12.5 mg, succinic acid - 0.84 mg, colloidal silicon dioxide - 25 mg, hypromellose - 79.65 mg, orange flavor 1 - 15 mg, orange flavor 2 - 11.25 mg, raspberry flavor - 22.5 mg, “Light molasses” flavoring – 23.75 mg, silicon dioxide – up to 552 mg.

7.7 g - glass bottles (1) complete with measuring cap - cardboard packs.

* during the production of the drug, potassium clavulanate is added with a 5% excess.

Indications

Bacterial infections caused by microorganisms sensitive to the drug:

infections of the upper respiratory tract and ENT organs (for example, recurrent tonsillitis, sinusitis, otitis media), usually caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis*, Streptococcus pyogenes;
lower respiratory tract infections: exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia, usually caused by Streptococcus pneumoniae, Haemophilus influenzae* and Moraxella catarrhalis*;
genitourinary tract infections: cystitis, urethritis, pyelonephritis, infections of the female genital organs, usually caused by species of the Enterobacteriaceae family (mainly Escherichia coli*), Staphylococcus saprophyticus and species of the genus Enterococcus;
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*;
bone and joint infections (eg, osteomyelitis, usually caused by Staphylococcus aureus*); if long-term therapy is necessary.

* Some representatives of this genus of microorganisms produce β-lactamase, which makes them insensitive to amoxicillin.

Infections caused by microorganisms sensitive to amoxicillin can be treated with Augmentin®, since amoxicillin is one of its active ingredients.

The drug Augmentin® is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as microorganisms producing β-lactamase, sensitive to the combination of amoxicillin with clavulanic acid.

The sensitivity of bacteria to the combination of amoxicillin and clavulanic acid varies regionally and over time. Where possible, local sensitivity data should be taken into account. If necessary, microbiological samples should be collected and bacteriological susceptibility testing should be carried out.

Contraindications for use

history of hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins);
history of previous episodes of jaundice or impaired liver function when using a combination of amoxicillin and clavulanic acid;
children up to 3 months of age (for powder for the preparation of suspension for oral administration 200 mg/28.5 mg in 5 ml and 400 mg/57 mg in 5 ml);
impaired renal function (creatinine clearance less than 30 ml/min) - for powder for the preparation of an oral suspension 200 mg/28.5 mg in 5 ml and 400 mg/57 mg in 5 ml;
phenylketonuria.

Carefully:

liver dysfunction.

pharmachologic effect

Mechanism of action

Amoxicillin

is a semisynthetic broad-spectrum antibiotic with activity against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by β-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce this enzyme.

Clavulanic acid

- a β-lactamase inhibitor, structurally related to penicillins, has the ability to inactivate a wide range of β-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is quite effective against plasmid β-lactamases, which most often determine bacterial resistance, and is less effective against type 1 chromosomal β-lactamases, which are not inhibited by clavulanic acid.

The presence of clavulanic acid in Augmentin® protects amoxicillin from destruction by enzymes - β-lactamases, which allows expanding the antibacterial spectrum of amoxicillin.

Below is the activity of the combination of amoxicillin and clavulanic acid in vitro.

Bacteria usually susceptible to the combination of amoxicillin and clavulanic acid

Gram-positive aerobes:

Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, Streptococcus spp. (other beta-hemolytic streptococci)1,2, Staphylococcus aureus (methicillin sensitive)1, Staphylococcus saprophyticus (methicillin sensitive), Staphylococcus spp. (coagulase-negative, methicillin-sensitive).

Gram-negative aerobes:

Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Gram-positive anaerobes:

Clostridium spp., Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus spp.

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 acquired resistance to the combination of amoxicillin and clavulanic acid is likely

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, Streptococcus pneumoniae1,2, Viridans group Streptococcus2.

Bacteria that are naturally resistant to the combination of amoxicillin and 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.
Other:
Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia spp., Coxiella burnetti, Mycoplasma spp.

1 For these types of microorganisms, the clinical effectiveness of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.

2 Strains of these bacterial species do not produce β-lactamases. Sensitivity during amoxicillin monotherapy suggests similar sensitivity to the combination of amoxicillin and clavulanic acid.

Drug interactions

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

Concomitant use of allopurinol and amoxicillin may increase the risk of allergic skin 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 down the elimination of methotrexate from the body by inhibiting its tubular secretion, therefore, the simultaneous use of Augmentin® and methotrexate may increase the toxicity of methotrexate.

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

The literature describes rare cases of increased MHO in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe Augmentin® with anticoagulants, prothrombin time or MHO should be carefully monitored when prescribing or discontinuing Augmentin®, and dose adjustment of oral anticoagulants may be required.

In patients receiving mycophenolate mofetil, after starting 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 may not accurately reflect overall changes in mycophenolic acid exposure.

Dosage regimen

The drug is taken orally.

The dosage regimen is set individually depending on the age, body weight, kidney function of the patient, as well as the severity of the infection.

For optimal absorption and reduction of possible side effects from the digestive system, Augmentin® is recommended to be taken at the beginning of a meal.

The minimum course of antibacterial therapy is 5 days.

Treatment should not continue for more than 14 days without reviewing the clinical situation.

If necessary, it is possible to carry out stepwise therapy (at the beginning of therapy, parenteral administration of the drug followed by switching to oral administration).

Adults and children over 12 years of age or weighing 40 kg or more

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

Children aged 3 months to 12 years weighing less than 40 kg

The dose is calculated depending on age and body weight, indicated in mg/kg body weight/day (calculation based on amoxicillin) or in ml of suspension.

The frequency of administration of the suspension is 125 mg/31.25 mg in 5 ml - 3 times a day every 8 hours.

The frequency of administration of the suspension is 200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml - 2 times a day every 12 hours.

The recommended dosage regimen and frequency of administration are presented in the table below.

Augmentin® dosage regimen table (dose calculation based on amoxicillin)

Frequency of administration - 3 times/day Suspension 4:1 (125 mg/31.25 mg in 5 ml) Frequency of administration - 2 times/day Suspension 7:1 (200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml )

Low doses 20 mg/kg/day 25 mg/kg/day High doses 40 mg/kg/day 45 mg/kg/day

Low doses of Augmentin® are used to treat skin and soft tissue infections, as well as recurrent tonsillitis.

High doses of Augmentin® are used to treat diseases such as otitis media, sinusitis, lower respiratory tract and urinary tract infections, bone and joint infections

There is insufficient clinical data to recommend the use of Augmentin® at a dose of more than 40 mg/kg/day in 3 divided doses (4:1 suspension) and 45 mg/kg/day in 2 divided doses (7:1 suspension); insufficient clinical data to recommend use in higher dose in children under 2 years of age

Children from birth to 3 months

Due to the immaturity of the excretory function of the kidneys, the recommended dose of Augmentin® (calculated according to amoxicillin) is 30 mg/kg/day in 2 doses in the form of a 4:1 suspension.

The use of a 7:1 suspension (200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml) is contraindicated in this population.

Children born prematurely

There are no recommendations regarding dosage regimen.

Elderly patients

No dose adjustment is required. In elderly patients with impaired renal function

The dose should be adjusted as follows for adults with impaired renal function.

Patients with impaired renal function

Dose adjustments are based on the maximum recommended dose of amoxicillin and are carried out taking into account QC values.

QC Suspension 4:1 (125 mg/31.25 mg in 5 ml)

>30 ml/min No dosage adjustment required 10-30 ml/min 15 mg/3.75 mg/kg 2 times/day, maximum dose - 500 mg/125 mg 2 times/day <10 ml/min 15 mg/3.75 mg/kg 1 time /day, maximum daily dose - 500 mg/125 mg

Suspension 7:1 (200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml) should only be used in patients with creatinine clearance >30 ml/min.

, no dose adjustment is required.

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

Patients on hemodialysis

The recommended dosage regimen is 15 mg/3.75 mg/kg 1 time/day.

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

Patients with liver dysfunction

Treatment is carried out with caution; regularly monitor liver function. There is insufficient data to adjust the dosage regimen in this category of patients.

Rules for preparing the suspension

The suspension is prepared immediately before the first use.

Suspension (125 mg/31.25 mg in 5 ml):

Add approximately 60 ml of boiled water, cooled to room temperature, to the bottle with the powder, then close the bottle with a lid and shake until the powder is completely diluted, let the bottle stand for 5 minutes to ensure complete dilution. Then add water up to the mark on the bottle and shake the bottle again. In total, about 92 ml of water is required to prepare the suspension.

Suspension (200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml):

Add approximately 40 ml of boiled water, cooled to room temperature, to the bottle with the powder, then close the bottle with a lid and shake until the powder is completely diluted, let the bottle stand for 5 minutes to ensure complete dilution.
Then add water up to the mark on the bottle and shake the bottle again. In total, about 64 ml of water is required to prepare the suspension. For children under 2 years of age, a measured single dose of Augmentin® suspension can be diluted with water in a 1:1 ratio.
The bottle should be shaken well before each use. For accurate dosing of the drug, you should use a measuring cap, which must be rinsed well with water after each use. After dilution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.

Overdose

Symptoms:

Gastrointestinal symptoms and water-electrolyte imbalance may occur.
Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure. Convulsions may occur in patients with impaired renal function, as well as in those receiving high doses of the drug. Treatment:
symptoms from the gastrointestinal tract - symptomatic therapy, paying special attention to the normalization of water and electrolyte balance. In case of overdose, amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

The results of a prospective study that was conducted in 51 children at a poison control center showed that amoxicillin administered at a dose of less than 250 mg/kg did not lead to significant clinical symptoms and did not require gastric lavage.

Side effect

The adverse events presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is determined as follows: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10,000, < 1/1000), very rare (<1/10,000, including isolated cases).

Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.

Infectious and parasitic diseases:

often - candidiasis of the skin and mucous membranes.

From the hematopoietic 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.

From the immune system:

very rarely - angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.

From the nervous system:

infrequently - dizziness, headache; very rarely - reversible hyperactivity, convulsions (convulsions can be observed in patients with impaired renal function, as well as in those receiving high doses of the drug), insomnia, agitation, anxiety, behavior changes.

From the digestive system:
adults:
very often - diarrhea, often - nausea, vomiting;
children
- often - diarrhea, nausea, vomiting;
entire population:
nausea is most often observed when taking high doses of the drug. If, after starting to take the drug, adverse reactions from the gastrointestinal tract are observed, they can be eliminated if the drug is taken at the beginning of the meal. Uncommon: digestive disorders; very rarely - antibiotic-associated colitis induced by antibiotics (including pseudomembranous colitis and hemorrhagic colitis), black “hairy” tongue, gastritis, stomatitis. In children, when using the suspension, a change in the color of the surface layer of tooth enamel was very rarely observed.

From the liver and biliary tract:

uncommon - moderate increase in AST and/or ALT activity (observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown); very rarely - hepatitis and cholestatic jaundice (these phenomena were noted during therapy with other penicillins and cephalosporins), increased concentrations of bilirubin and alkaline phosphatase. Adverse liver events have been observed primarily in men and elderly patients and may be associated with long-term therapy. These adverse events are very rarely observed in children.

The listed signs and symptoms usually occur during or immediately after completion of therapy, but in some cases they may not appear for several weeks after completion of therapy.
Adverse effects are usually reversible. Adverse liver events can be severe, and deaths have been reported in extremely rare cases. In almost all cases, these were persons with serious comorbidities or persons receiving concomitantly potentially hepatotoxic drugs. From the skin and subcutaneous tissues:
infrequently - rash, itching, urticaria; rarely - erythema multiforme; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

From the urinary system:

very rarely - interstitial nephritis, crystalluria, hematuria.

special instructions

Before starting treatment with Augmentin®, it is necessary to collect a detailed history regarding previous hypersensitivity reactions to penicillins, cephalosporins or other substances that cause an allergic reaction in the patient.

Serious and sometimes fatal hypersensitivity reactions (anaphylactic reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. If an allergic reaction occurs, treatment with Augmentin® should be discontinued and appropriate alternative therapy should be initiated. For severe hypersensitivity reactions, epinephrine should be administered immediately. Oxygen therapy, intravenous administration of corticosteroids, and airway management, including intubation, may also be required.

If infectious mononucleosis is suspected, Augmentin® should not be used, since amoxicillin can cause a measles-like skin rash in patients with this disease, which makes diagnosing the disease difficult.

Long-term treatment with Augmentin® sometimes leads to excessive proliferation of insensitive microorganisms.

In general, Augmentin® is well tolerated and has the low toxicity characteristic of all penicillins.

During long-term therapy with Augmentin®, it is recommended to periodically evaluate the function of the kidneys, liver and hematopoietic system.

Cases of pseudomembranous colitis have been described when taking antibiotics, the severity of which can vary 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 receiving a combination of amoxicillin and clavulanic acid together with indirect (oral) anticoagulants, an increase in prothrombin time (increase in MHO) has been reported in rare cases. When co-prescribing indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, monitoring of relevant indicators is necessary. Dosage adjustments may be required to maintain the desired effect of oral anticoagulants.

In patients with impaired renal function, the dose of Augmentin® should be reduced according to the degree of impairment.

In patients with reduced diuresis, crystalluria very rarely occurs, mainly during parenteral therapy. When administering amoxicillin in high doses, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.

When taking Augmentin® orally, a high level of amoxicillin in the urine is observed, which can lead to false-positive results when determining glucose in the urine (for example, Benedict's test, Fehling's test). In this case, it is recommended to use the glucose oxidant method for determining the concentration of glucose in the urine.

Clavulanic acid may cause nonspecific binding of immunoglobulin G and albumin to red blood cell membranes, leading to false-positive Coombs test results.

Oral care can help prevent drug-related tooth discoloration by simply brushing your teeth.

Drug abuse and dependence

There was no drug dependence, addiction, or euphoric reactions associated with the use of Augmentin®.
Effect on the ability to drive vehicles and operate machinery
Since the drug can cause dizziness, it is necessary to warn patients about precautions when driving or working with moving mechanisms.

Storage conditions

The drug should be stored in a dry place, out of reach of children, at a temperature not exceeding 25°C.

Best before date

The shelf life of the powder for preparing a suspension in an unopened bottle is 2 years. Do not take the drug after the expiration date indicated on the package.

The prepared suspension should be stored in the refrigerator at a temperature of 2° to 8°C for 7 days.

Use during pregnancy and breastfeeding

Restrictions during pregnancy - With caution. Restrictions when breastfeeding - With caution.

In studies of reproductive function in animals, oral and parenteral administration of Augmentin® did not cause teratogenic effects.

In a single study in women with premature rupture of membranes, it was found that prophylactic therapy with the drug may be associated with an increased risk of developing necrotizing enterocolitis in newborns. Like all medications, Augmentin® is not recommended for use during pregnancy, unless the expected benefit to the mother outweighs the potential risk to the fetus.

Augmentin® can be used during breastfeeding. With the exception of the possibility of diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active ingredients of the drug into breast milk, no other adverse effects were observed in breastfed infants. If adverse effects occur in breastfed infants, breastfeeding should be discontinued.

Use for renal impairment

Restrictions for impaired renal function - With caution.

The use of the drug is contraindicated in case of impaired renal function (creatinine clearance less than 30 ml/min) - for powder for the preparation of an oral suspension 200 mg/28.5 mg in 5 ml and 400 mg/57 mg in 5 ml.

Use for liver dysfunction

Restrictions for liver dysfunction - With caution.

The drug should be prescribed with caution in case of liver dysfunction.

Contraindicated in case of previous episodes of jaundice or impaired liver function when using a combination of amoxicillin with clavulanic acid in the anamnesis.

Use in elderly patients

Restrictions for elderly patients - No restrictions.

Elderly patients do not need to reduce the dose of Augmentin; doses are the same as for adults.

In elderly patients with impaired renal function, the dose should be adjusted as for adults with impaired renal function.

Use in children

Restrictions for children - With caution. Use of the drug in children under 3 months is contraindicated (for powder for the preparation of an oral suspension 200 mg/28.5 mg in 5 ml and 400 mg/57 mg in 5 ml).

Terms of sale

The drug is available with a prescription.

Contacts for inquiries

GlaxoSmithKline Trading JSC (Russia)

125167 Moscow Leningradsky Prospekt, 37a, bldg. 4 BC "Arcus III" Tel. Fax

Instructions for use AUGMENTIN® tablets

Before starting treatment with amoxicillin/clavulanic acid, it is necessary to obtain a detailed history regarding previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics (see sections “Contraindications” and “Side effects”).

Serious, sometimes fatal, hypersensitivity reactions (anaphylactoid reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins and in individuals with atopy. If an allergic reaction occurs, treatment with amoxicillin/clavulanic acid should be discontinued and alternative therapy should be initiated.

If the infection is confirmed to be due to amoxicillin-susceptible organisms, a switch from amoxicillin/clavulanic acid therapy to amoxicillin therapy should be considered in accordance with official guidelines.

Augmentin® 875 mg/125 mg and 500 mg/125 mg tablets are not suitable for use in cases where there is a high risk that the suspected pathogens have beta-lactam resistance that is not mediated by clavulanic acid-inhibited beta-lactamases. This dosage form should not be used in the treatment of infections caused by penicillin-resistant Streptococcus pneumoniae.

In patients with impaired renal function or when taking the drug in high doses, seizures may occur (see section "Side effects").

The use of amoxicillin/clavulanic acid is not recommended for suspected infectious mononucleosis, since such patients experience a morbilliform rash after taking amoxicillin.

The combined use of allopurinol and amoxicillin increases the risk of allergic skin reactions.

Long-term treatment may lead to excessive proliferation of insensitive microorganisms.

The appearance of pustules on erythematous areas of the skin with fever at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis. The occurrence of this adverse reaction requires discontinuation of the drug and is a contraindication to further use of amoxicillin.

The combination of amoxicillin/clavulanic acid should be used with caution in patients with signs of liver failure (see sections “Dosage regimen”, “Contraindications”, “Special instructions”).

Adverse liver events have been observed primarily in men and elderly patients and may be associated with long-term therapy. These adverse events are very rarely observed in children. Signs and symptoms of liver dysfunction usually occur during or immediately after completion of therapy, but in some cases may not appear until several weeks after completion of therapy. As a rule, they are reversible. Adverse effects from the liver can be severe, and in extremely rare cases there have been reports of death. In almost all cases, these were patients with serious comorbidities or patients receiving concomitantly potentially hepatotoxic drugs.

Antibiotic-associated colitis has been reported with virtually all antibacterial agents. This adverse reaction can vary in severity from mild to life-threatening (see section "Side effects"). Therefore, this diagnosis should be considered in patients who develop diarrhea during treatment or after administration of any antibiotics. If antibiotic-associated colitis occurs, the drug should be discontinued immediately. The patient should consult a doctor who will prescribe appropriate treatment. In such a situation, the use of drugs that inhibit peristalsis is contraindicated.

During long-term therapy with Augmentin®, it is recommended to periodically evaluate renal, liver and hematopoietic function.

In patients receiving a combination of amoxicillin and clavulanic acid, prolongation of prothrombin time has been observed in rare cases. When co-prescribing a combination of amoxicillin and clavulanic acid with anticoagulants, appropriate monitoring should be carried out. To maintain the desired level of anticoagulation, dose adjustment of the anticoagulant may be necessary (see section “Drug Interactions” and “Side Effects”).

In patients with impaired renal function, the dose of Augmentin® should be adjusted according to the degree of impairment (see section "Dosage regimen").

In patients with reduced diuresis, the development of crystalluria has been reported in very rare cases, mainly with parenteral use of the drug. While taking high doses of amoxicillin, it is recommended to drink enough fluids and maintain adequate diuresis to reduce the chance of amoxicillin crystal formation. In patients with urinary catheters, catheter patency should be checked regularly (see section "Overdose").

During treatment with amoxicillin, if tests for the presence of glucose in urine are necessary, enzymatic methods for determining glucose oxidase should be used due to the possibility of obtaining a false positive result when using non-enzymatic methods.

The presence of clavulanic acid in the drug may cause nonspecific binding of IgG and albumin to red blood cell membranes, which may lead to a false-positive Coombs test result.

Patients taking the amoxicillin/clavulanic acid combination may have a false-positive test result for Aspergillus infection using the Platelia Aspergillus EIA tests. There have been reports of cross-reactions between the Platelia Aspergillus EIA test and non-Aspergillus polysaccharides and polyfuranoses. Therefore, positive test results in patients taking the combination of amoxicillin/clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.

Impact on the ability to drive vehicles and machinery

No special studies have been conducted. However, adverse reactions may occur (allergic reactions, dizziness, convulsions), which may affect the ability to drive vehicles and other mechanisms.

Augmentin tab.p.p.o.500mg+125mg No. 14

Indications

Bacterial infections caused by microorganisms sensitive to the drug:

infections of the upper respiratory tract and ENT organs (for example, recurrent tonsillitis, sinusitis, otitis media), usually caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis*, Streptococcus pyogenes;
lower respiratory tract infections (for example, exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia), usually caused by Streptococcus pneumoniae, Haemophilus influenzae* and Moraxella catarrhalis* (except 250 mg/125 mg tablets);
genitourinary tract infections: cystitis, urethritis, pyelonephritis, infections of the female genital organs, usually caused by species of the Enterobacteriaceae family (mainly Escherichia coli*), Staphylococcus saprophyticus and species of the genus Enterococcus;
gonorrhea caused by Neisseria gonorrhoeae* (except 250 mg/125 mg tablets);
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;
odontogenic infections (for example, periodontitis, maxillary sinusitis, severe dental abscesses with spreading cellulitis) - for tablets 500 mg/125 mg or 875 mg/125 mg;
other mixed infections (for example, septic abortion, postpartum sepsis, intra-abdominal sepsis) as part of stepwise therapy.

* Some representatives of this genus of microorganisms produce β-lactamase, which makes them insensitive to amoxicillin.

Infections caused by microorganisms sensitive to amoxicillin can be treated with Augmentin®, since amoxicillin is one of its active ingredients.

Augmentin® is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as β-lactamase-producing microorganisms sensitive to the combination of amoxicillin with clavulanic acid.

pharmachologic effect

Mechanism of action

Amoxicillin

Clavulanic acid

is an inhibitor of β-lactamases, structurally related to penicillins, has the ability to inactivate a wide range of β-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is quite effective against plasmid β-lactamases, which most often cause bacterial resistance.

The two main mechanisms of resistance to the combination of amoxicillin and clavulanic acid are:

Inactivation by bacterial β-lactamases that are not themselves inhibited by clavulanic acid, including various amino acid sequences classified as Ambler classes B, C, and D.
Changes in penicillin-binding proteins that reduce the affinity of the antibacterial agent for the target. Reduced outer membrane permeability and efflux pump mechanisms may cause or contribute to resistance, especially among Gram-negative microorganisms.

The presence of clavulanic acid in Augmentin® protects amoxicillin from destruction by enzymes - β-lactamases, which allows expanding the antibacterial spectrum of amoxicillin.

Pharmacodynamic effects

Below is a classification of microorganisms according to their in vitro sensitivity to the combination of amoxicillin and clavulanic acid.

Bacteria usually susceptible to the combination of amoxicillin and clavulanic acid

Gram-positive aerobes:

Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, Streptococcus spp. (other β-hemolytic streptococci)1,2, Staphylococcus aureus (methicillin sensitive)1, Staphylococcus saprophyticus (methicillin sensitive), Staphylococcus spp. (coagulase-negative, methicillin-sensitive).

Gram-negative aerobes:

Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Gram-positive anaerobes:

Clostridium spp., Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus spp.

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 acquired resistance to the combination of amoxicillin and clavulanic acid is likely

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, Streptococcus pneumoniae1,2, Viridans group Streptococcus2.

Bacteria that are naturally resistant to the combination of amoxicillin and clavulanic acid

Gram-negative aerobes:

Other:

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

1 For these bacterial species, the clinical effectiveness of the combination of amoxicillin and clavulanic acid has been demonstrated in clinical studies.

2 Strains of these bacterial species do not produce β-lactamases. Sensitivity during amoxicillin monotherapy suggests similar sensitivity to the combination of amoxicillin and clavulanic acid.

Drug interactions

In patients receiving mycophenolate mofetil, after starting the combination of amoxicillin and clavulanic acid, there was a decrease in the concentration of the active metabolite, mycophenolic acid, before taking the next dose of the drug by approximately 50%. Changes in this concentration may not accurately reflect overall changes in mycophenolic acid exposure.

Dosage regimen

The drug is taken orally.

The dosage regimen is set individually depending on the age, body weight, kidney function of the patient, as well as the severity of the infection.

For optimal absorption and reduction of possible side effects from the digestive system, Augmentin® is recommended to be taken at the beginning of a meal.

The minimum course of antibacterial therapy is 5 days.

Treatment should not continue for more than 14 days without reviewing the clinical situation.

If necessary, it is possible to carry out stepwise therapy (initially, intravenous administration of the drug Augmentin® in powder dosage form for the preparation of a solution for intravenous administration, followed by a transition to the drug Augmentin® in dosage forms for oral use).

It must be remembered that 2 tablets of 250 mg/125 mg are not equivalent to 1 tablet of 500 mg/125 mg.

Adults and children over 12 years of age or weighing 40 kg or more

1 tab. 250 mg/125 mg 3 times a day for mild to moderate infections

For severe infections (including chronic and recurrent urinary tract infections, chronic and recurrent lower respiratory tract infections)

other dosages of the drug Augmentin® are recommended - 1 tablet. 500 mg/125 mg 3 times a day or 1 tablet. 875 mg/125 mg 2 times/day.

Special patient groups

Children under 12 years of age weighing less than 40 kg

It is recommended to use other dosage forms of Augmentin®.

Elderly patients

No dose adjustment is required. In elderly patients with impaired renal function

The dose should be adjusted as follows for adults with impaired renal function.

Patients with impaired renal function

Dose adjustments are based on the maximum recommended dose of amoxicillin and are carried out taking into account QC values.

QC	Tablets 250 mg+125 mg	Tablets 500 mg+125 mg
>30 ml/min	No dosage adjustment required	No dosage adjustment required
10-30 ml/min	1 tab. 250 mg+125 mg (for mild to moderate infection) 2 times a day	1 tab. 500 mg+125 mg (for moderate and severe infection) 2 times a day
1 tab. 250 mg+125 mg (for mild to moderate infection) 1 time/day	1 tab. 500 mg+125 mg (for moderate and severe infection) 1 time/day

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

Tablets 875 mg + 125 mg should be used only in patients with creatinine clearance >30 ml/min

, no adjustment of the dosage regimen is required.

Patients on hemodialysis

Dose adjustment is based on the maximum recommended dose of amoxicillin: 2 tablets. 250 mg/125 mg or 1 tablet. 500 mg/125 mg in one dose every 24 hours. During a hemodialysis session, an additional 1 dose (1 tablet) and another 1 dose (1 tablet) at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

Patients with liver dysfunction

Treatment is carried out with caution; regularly monitor liver function. There is insufficient data to adjust the dosage regimen in this category of patients.

Overdose

Symptoms:

Treatment:

symptoms from the gastrointestinal tract - symptomatic therapy, paying special attention to the normalization of water and electrolyte balance. In case of overdose, amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

Contraindications for use

history of hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins);
history of previous episodes of jaundice or impaired liver function when using a combination of amoxicillin and clavulanic acid;
children under 12 years of age and body weight less than 40 kg;
impaired renal function (creatinine clearance ≤30 ml/min) - (for tablets 875 mg/125 mg).

Carefully:

liver dysfunction.

Use in children

The use of the drug is contraindicated in children under 12 years of age and with a body weight of less than 40 kg.

Restrictions for children

Use with caution

Use in elderly patients

Elderly patients do not need to reduce the dose of Augmentin; doses are the same as for adults. In elderly patients with impaired renal function, the dose should be adjusted as for adults with impaired renal function.

Restrictions for elderly patients

Possible use

Use for liver dysfunction

The drug should be used with caution in case of liver dysfunction.

Contraindicated in case of previous episodes of jaundice or impaired liver function when using a combination of amoxicillin with clavulanic acid in the anamnesis.

Restrictions for liver dysfunction

Use with caution

Use during pregnancy and breastfeeding

In studies of reproductive function in animals, oral and parenteral administration of Augmentin® did not cause teratogenic effects.

Augmentin® can be used during breastfeeding. With the exception of the possibility of sensitization, diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active ingredients of this drug into breast milk, no other adverse effects were observed in breastfed children. If adverse effects occur in breastfed infants, breastfeeding should be discontinued.

Restrictions when breastfeeding

Use with caution

Restrictions during pregnancy

Use with caution

Use for renal impairment

The use of the drug is contraindicated in case of impaired renal function (creatinine clearance ≤30 ml/min) - for tablets 875 mg/125 mg.

Dose adjustment for impaired renal function is based on the maximum recommended dose of amoxicillin and is carried out taking into account CC values.

Restrictions for impaired renal function

Use with caution

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C.

Terms of sale

The drug is available with a prescription.

special instructions

If allergic skin reactions occur, treatment with Augmentin® should be discontinued.

Long-term treatment with Augmentin® sometimes leads to excessive proliferation of insensitive microorganisms.

In general, Augmentin® is well tolerated and has the low toxicity characteristic of all penicillins.

During long-term therapy with Augmentin®, it is recommended to periodically evaluate the function of the kidneys, liver and hematopoietic system.

In patients with reduced diuresis, the development of crystalluria has been reported in very rare cases, mainly with parenteral use of the drug. During administration of high doses of amoxicillin, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.

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

Clavulanic acid may cause nonspecific binding of immunoglobulin G and albumin to red blood cell membranes, leading to false-positive Coombs test results.

The laminated aluminum foil package contains a desiccant pouch that is not intended for ingestion. Augmentin® must be used within 30 days of opening the laminated aluminum foil package.

Drug abuse and dependence

There was no drug dependence, addiction, or euphoric reactions associated with the use of Augmentin®.

Impact on the ability to drive vehicles and machinery

Since the drug may cause dizziness, patients should be warned to take precautions when driving or operating moving machinery.

Side effect

Adverse reactions presented below are listed according to damage to organs and organ systems and frequency of occurrence. The frequency of occurrence is determined as follows: very often (≥1/10), often (≥1/100,

Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.

Infectious and parasitic diseases:

often - candidiasis of the skin and mucous membranes.

From the hematopoietic system:

From the immune system:

very rarely - angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.

From the nervous system:

From the digestive system:
adults:
very often - diarrhea, often - nausea, vomiting;
children:
often - diarrhea, nausea, vomiting;
entire population:
nausea is most often observed when taking high doses of the drug. If, after starting to take the drug, adverse reactions from the gastrointestinal tract are observed, they can be eliminated if the drug is taken at the beginning of the meal. Uncommon: digestive disorders; very rarely - antibiotic-associated colitis induced by antibiotics (including pseudomembranous colitis and hemorrhagic colitis) (see section "Special Instructions"), black "hairy" tongue, gastritis, stomatitis.

From the liver and biliary tract:

uncommon - moderate increase in AST and/or ALT activity (observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown); very rarely - hepatitis and cholestatic jaundice (these reactions were observed during therapy with other penicillins and cephalosporins), increased concentrations of bilirubin and alkaline phosphatase. Adverse reactions from the liver were observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse reactions are very rarely observed in children.

For the skin and subcutaneous tissues:

uncommon - rash, itching, urticaria; rarely - erythema multiforme; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

If allergic skin reactions occur, treatment with Augmentin® should be discontinued.

From the urinary system:

very rarely - interstitial nephritis, crystalluria, hematuria.

Possible product names

Augmentin tablet. By. 500 mg.+125 mg. No. 14
AUGMENTIN 625 MG TAB. P/OB. No. 14
AUGMENTIN 0.625 N14 TABLE P/O
AUGMENTIN TABLE. P/O PLEN 500 MG+125 MG X14
AUGMENTIN TAB. FILM COATED 500MG+125MG (BLISTERS) No. 14
AUGMENTIN 500MG+125MG TAB. P/PL/OB. X14 (R) (THE PACK IS TORN)
(Augmentin) Augmentin tablet. By. 500 mg.+125 mg. No. 14