Augmentin 875mg+125mg 14 pcs. film-coated tablets

Augmentin 875mg+125mg 14 pcs. film-coated tablets

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 is a β-lactamase inhibitor, structurally related to penicillins, and 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, Streptococcus of the Viridans group2.

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.

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

Composition and release form Augmentin 875mg+125mg 14 pcs. film-coated tablets

White to almost white, oval, film-coated tablets with the inscription “AUGMENTIN” imprinted on one side; at the fracture - from yellowish-white to almost white.

1 tab.

• Active ingredients: amoxicillin (in the form of trihydrate) - 250 mg; clavulanic acid (in the form of potassium salt) - 125 mg;
• Excipients: magnesium stearate - 6.5 mg, sodium carboxymethyl starch - 13 mg, colloidal silicon dioxide - 6.5 mg, microcrystalline cellulose - 650 mg.

Film shell composition: titanium dioxide - 9.63 mg, hypromellose (5cP) - 7.39 mg, hypromellose (15cP) - 2.46 mg, macrogol 4000 - 1.46 mg, macrogol 6000 - 1.46 mg, dimethicone - 0.013 mg, purified water (removed during production ).

10 pieces. - blisters (1) with a bag of silica gel - packages of laminated aluminum foil (2) - cardboard packs.

White to almost white, film-coated tablets, oval, with embossed inscription “AC” and a score line on one side.

1 tab.

• Active ingredients: amoxicillin (in the form of amoxicillin trihydrate) - 500 mg; clavulanic acid (in the form of potassium clavulanate) - 125 mg;
• Excipients: magnesium stearate - 7.27 mg, sodium carboxymethyl starch - 21 mg, colloidal silicon dioxide - 10.5 mg, microcrystalline cellulose - up to 1050 mg.

Film shell composition: titanium dioxide - 11.6 mg, hypromellose (5 cps) - 8.91 mg, hypromellose (15 cps) - 2.97 mg, macrogol 4000 - 1.76 mg, macrogol 6000 - 1.76 mg, dimethicone 500 (silicone oil) - 0.013 mg.

7 pcs. - blisters (1) with a bag of silica gel - packages of laminated aluminum foil (2) - cardboard packs. 10 pieces. - blisters (1) with a bag of silica gel - packages of laminated aluminum foil (2) - cardboard packs.

White to almost white, oval, film-coated tablets, debossed with “AC” on both sides and a score line on one side.

1 tab.

• Active ingredients: amoxicillin trihydrate - 1004.43 mg (corresponds to the content of amoxicillin - 875 mg); potassium clavulanate - 148.91 mg (corresponds to the content of clavulanic acid - 125 mg);
• Excipients: magnesium stearate - 14.5 mg, sodium carboxymethyl starch - 29 mg, colloidal silicon dioxide - 10 mg, microcrystalline cellulose - 243.16 mg.

Composition of the film shell Opadry OY-S-7300 white: titanium dioxide - 43%, hypromellose 5 cP - 33%, hypromellose 15 cP - 11%, macrogol 4000 - 6.5%, macrogol 6000 - 6.5%.

7 pcs. - blisters (1) with a desiccant package - packaging made of laminated aluminum foil (2) - cardboard packs.

Directions for use and doses

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/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 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 indicated below 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.

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

Tablets 875 mg + 125 mg should be used only in patients with CC 30 ml/min, and no dosage adjustment 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.

Pharmacokinetics

Suction

Both active ingredients of Augmentin®, amoxicillin and clavulanic acid, are quickly and completely absorbed from the gastrointestinal tract after oral administration. Absorption of active substances is optimal if the drug is taken at the beginning of a meal.

The following are pharmacokinetic data for amoxicillin and clavulanic acid obtained from separate studies when administered to healthy volunteers on an empty stomach:

• 1 tablet of Augmentin® 250 mg/125 mg (375 mg);
• 2 tablets of Augmentin® 250 mg/125 mg (375 mg);
• 1 tablet of Augmentin® 500 mg/125 mg (625 mg);
• 500 mg amoxicillin;
• 125 mg clavulanic acid;
• 2 tablets of Augmentin® 875 mg/125 mg (1000 mg).

Main pharmacokinetic parameters

Distribution

As with the intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are created in various organs and tissues, interstitial fluid (abdominal organs, adipose, bone and muscle tissues, synovial and peritoneal fluids, skin, bile, purulent separable).

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 are bound to plasma proteins.

In animal studies, accumulation of the ingredients of Augmentin® was not detected.

Amoxicillin, like most penicillins, passes into breast milk. Trace amounts of clavulanic acid have also been found in breast milk. With the exception of the possibility of developing sensitization, diarrhea and candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of breastfed children are known.

Animal reproductive studies have shown that amoxicillin and clavulanic acid cross the placental barrier, with no evidence of adverse effects 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 is extensively metabolized to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and is excreted by the kidneys , through the gastrointestinal tract, as well as with exhaled air in the form of carbon dioxide.

Removal

Like other penicillins, amoxicillin is eliminated primarily by the kidneys, whereas clavulanic acid is eliminated through both renal and extrarenal mechanisms. Studies have shown that, on average, approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted unchanged by the kidneys in the first 6 hours after administration of the drug.

Indications for use Augmentin 875mg+125mg 14 pcs. film-coated tablets

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.

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

• 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).

With caution: liver dysfunction.

Application of Augmentin 875mg+125mg 14 pcs. film-coated tablets during pregnancy and breastfeeding

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 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.

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

Overdose

Symptoms: Gastrointestinal symptoms and fluid and 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 effects Augmentin 875mg+125mg 14 pcs. film-coated tablets

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: 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) (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.

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 reactions are usually reversible. Adverse reactions from the liver 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.

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

From the urinary system: very rarely - interstitial nephritis, crystalluria, hematuria.

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 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.

Precautionary measures

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

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.

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. The use of drugs that inhibit intestinal motility is contraindicated.

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 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 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 operate machinery

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

Augmentin tablets p/o 875mg/125mg No. 14)

A country

Great Britain, United Kingdom
Country of origin may vary depending on product batch. Please check with the operator for detailed information when confirming your order.

Active substance

Amoxicillin + Clavulanic acid

Compound

1 tablet contains: amoxicillin trihydrate 1004.43 mg, potassium clavulanate 148.91 mg.
Excipients: magnesium stearate - 14.5 mg, sodium carboxymethyl starch - 29 mg, colloidal silicon dioxide - 10 mg, microcrystalline cellulose - 243.16 mg. Composition of the film shell Opadry OY-S-7300 white: titanium dioxide - 43%, hypromellose 5 cP - 33%, hypromellose 15 cP - 11%, macrogol 4000 - 6.5%, macrogol 6000 - 6.5%. 7 pcs. - blisters (1) with a desiccant package - packaging made of laminated aluminum foil (2) - cardboard packs. White to almost white, oval, film-coated tablets, debossed with “AC” on both sides and a score line on one side.

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 is a β-lactamase inhibitor, structurally related to penicillins, and 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: 1. Inactivation by bacterial β-lactamases that are not themselves inhibited by clavulanic acid, including various amino acid sequences belonging to Ambler classes B, C, and D. 2. Changes in penicillin-binding proteins, reducing the degree of affinity of the antibacterial agent to 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 sensitive to the combination of amoxicillin with 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 with 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, Streptococcus of the Viridans group2. 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 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.

Indications for use

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; - infections of the lower respiratory tract (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); - infections of the genitourinary tract: 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 for 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 cellulite) - 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. 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.

Side effects

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 on the basis of clinical studies of the drug and post-registration surveillance. Infectious and parasitic diseases: often - candidiasis of the skin and mucous membranes. From the side hematopoietic systems: - 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 who receive 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; - the 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 taking 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. 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 reactions are usually reversible. Adverse reactions from the liver 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: - 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.

Contraindications

- history of hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins);
- previous episodes of jaundice or impaired liver function when using a combination of amoxicillin with clavulanic acid in the anamnesis; - 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). With caution: liver dysfunction. Use during pregnancy and lactation In studies of reproductive function in animals, oral and parenteral administration of the drug 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 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.

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.

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.

Mode of application

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 tablet. 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 Augmentin® are recommended - 1 tablet. 500 mg/125 mg 3 times a day or 1 tablet. 875 mg/125 mg 2 times/day. Special groups of patients 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 indicated below 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/day | 1 tab. 500 mg + 125 mg (for moderate and severe infection) 2 times a day. In most cases, if possible, preference should be given to parenteral therapy. Tablets 875 mg + 125 mg should be used only in patients with CC >30 ml/min, and no dosage adjustment 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 impaired liver function Treatment is carried out with caution; regularly monitor liver function. There is insufficient data to adjust the dosage regimen in this category of patients.

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 allergic skin reactions occur, treatment with Augmentin® should be discontinued. 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. 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. The use of drugs that inhibit intestinal motility is contraindicated. 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 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 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 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. 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. Abuse and drug dependence No drug dependence, addiction, or euphoria reactions associated with the use of Augmentin® were observed. 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.

Overdose

Symptoms: Gastrointestinal symptoms and fluid and 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.

Interaction with other drugs

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 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.

Dispensing conditions in pharmacies

On prescription