Augmentin tablets 500 + 125mg, No. 14

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 (eg, 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 family Enterobacteriaceae (mainly Escherichia coli *), Staphylococcus saprophyticus and species of the genus Enterococcus;

• gonorrhea due to Neisseria gonorrhoeae * (except tablets 250 mg / 125 mg);

• 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 necessary, long-term therapy;

• odontogenic infections (eg periodontitis, maxillary sinusitis, severe dental abscesses with spreading cellulitis) - for tablets 500 mg / 125 mg or 875 mg / 125 mg;

• other mixed infections (eg, septic abortion, postpartum sepsis, intra-abdominal sepsis) as part of sequential therapy.

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

Infections caused by microorganisms sensitive to amoxicillin can be treated with AugmentinЃ, as amoxicillin is one of its active ingredients.

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

The sensitivity of bacteria to the combination of amoxicillin with clavulanic acid varies by region and over time. Where possible, local sensitivity data should be taken into account. If necessary, microbiological samples should be collected and analyzed for bacteriological susceptibility.

Inside.

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

Film-coated tablets from white to almost white, oval, with an embossed lettering 'AC' and a line on one side.

1 tab.

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.

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

• previous episodes of jaundice or liver dysfunction when using a combination of amoxicillin with clavulanic acid in history;

• children under 12 years of age and body weight less than 40 kg;

• impaired renal function (CC? 30 ml / min) - (for tablets 875 mg / 125 mg).

• With care: abnormal liver function.

pharmachologic effect

Mechanism of action

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

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

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

1. Inactivation by bacterial ?-lactamases, which themselves are not inhibited by clavulanic acid, including various amino acid sequences belonging to classes B, C, and D according to the Ambler classification.

2. Changes in penicillin-binding proteins that decrease the affinity of the antibacterial agent for the target. Decreased outer membrane permeability and efflux pump mechanisms can induce or contribute to the development of resistance, especially among gram-negative microorganisms.

The presence of clavulanic acid in AugmentinЃ protects amoxicillin from destruction by enzymes - ?-lactamases, which allows you to expand the antibacterial spectrum of amoxicillin.

Pharmacodynamic effects

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

Bacteria commonly susceptible 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? -hemolytic streptococci) 1,2, Staphylococcus aureus (methicillin susceptible) 1, Staphylococcus saprophyticus (methicillin susceptible), 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.

Others: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Bacteria for which acquired resistance is likely to the combination of amoxicillin with clavulanic acid

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 Viridans2 group.

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

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

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

1 For these bacterial species, the clinical efficacy of a combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.

2 Strains of these bacterial species do not produce ?-lactamases. Sensitivity to amoxicillin monotherapy suggests a similar sensitivity to the combination of amoxicillin with clavulanic acid.

Side effect

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, seizures (seizures can occur in patients with impaired renal function, as well as in those receiving high doses of the drug), insomnia, agitation, anxiety, behavior change.

From the digestive system: adults: very often - diarrhea, often - nausea, vomiting; children: often - diarrhea, nausea, vomiting; whole population: nausea is most common with high doses of the drug. If, after the start of taking the drug, there are undesirable reactions from the gastrointestinal tract, they can be eliminated if you take the drug at the beginning of a meal. Uncommon - digestive disorders; very rarely - antibiotic-associated colitis induced by taking antibiotics (including pseudomembranous colitis and hemorrhagic colitis) (see the section 'Special instructions'), black 'hairy' tongue, gastritis, stomatitis.

From the liver and biliary tract: infrequently - a moderate increase in the activity of ACT and / or ALT (observed in patients receiving therapy with beta-lactam antibiotics, but its clinical significance is unknown); very rarely - hepatitis and cholestatic jaundice (these reactions were observed during therapy with other penicillins and cephalosporins), an increase in the concentration 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 rare in children.

The listed signs and symptoms usually occur during or immediately after the end of therapy, but in some cases they may not appear for several weeks after the end of therapy. Adverse reactions are usually reversible. Adverse reactions from the liver can be severe, in extremely rare cases, deaths have been reported. In almost all cases, these were persons with serious comorbidities or persons simultaneously receiving potentially hepatotoxic drugs.

On the part of 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.

In case of allergic skin reactions, treatment with AugmentinЃ should be discontinued.

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

Application during pregnancy and lactation

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

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

AugmentinЃ can be used during breastfeeding. With the exception of the possibility of developing sensitization, diarrhea or candidiasis of the oral mucous membranes 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 babies, breastfeeding should be discontinued.

Application for violations of liver function

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

Contraindicated in previous episodes of jaundice or liver dysfunction when using a combination of amoxicillin with clavulanic acid in history.

Application for impaired renal function

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

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

Application 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.

special instructions

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

Serious, and sometimes 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. In the event of an allergic reaction, it is necessary to discontinue treatment with AugmentinЃ and begin an appropriate alternative therapy. In severe hypersensitivity reactions, epinephrine should be given immediately. Oxygen therapy, intravenous administration of corticosteroids and airway management, including intubation, may also be required.

In case of allergic skin reactions, treatment with AugmentinЃ should be discontinued.

In case of suspicion of infectious mononucleosis, AugmentinЃ should not be used, since in patients with this disease, amoxicillin can cause a measles-like skin rash, which makes it difficult to diagnose the disease.

Long-term treatment with AugmentinЃ sometimes leads to excessive reproduction of insensitive microorganisms.

Cases of pseudomembranous colitis with antibiotics have been described, 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 the diarrhea is prolonged or severe, or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient should be examined. The use of drugs that inhibit intestinal motility is contraindicated.

In general, AugmentinЃ is well tolerated and has low toxicity characteristic of all penicillins.

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

In patients who received a combination of amoxicillin with clavulanic acid in conjunction with indirect (oral) anticoagulants, in rare cases, an increase in prothrombin time (increase in MHO) was reported. With the joint appointment of indirect (oral) anticoagulants with a combination of amoxicillin with clavulanic acid, it is necessary to control the corresponding indicators. Dose adjustments may be required to maintain the desired effect of oral anticoagulants.

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

Taking AugmentinЃ by mouth leads to a high content of amoxicillin in the urine, which can lead to false-positive results in the determination of glucose in the urine (for example, Benedict's test, Fehling's test). In this case, it is recommended to use the glucose-oxidative method for determining the concentration of glucose in the urine.

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

The laminated aluminum foil package contains a desiccant bag that is not intended to be ingested. It is necessary to use the AugmentinЃ preparation within 30 days from the moment of opening the package made of laminated aluminum foil.

Abuse and drug dependence

There were no drug dependence, addiction and euphoric reactions associated with the use of AugmentinЃ.

Influence on the ability to drive vehicles and mechanisms

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

Overdose

Symptoms: Gastrointestinal symptoms and disturbances in water and electrolyte balance may occur. Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure. Seizures 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, with particular 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, which was conducted with the participation of 51 children in a poison control center, showed that the administration of amoxicillin at a dose of less than 250 mg / kg did not lead to significant clinical symptoms and did not require gastric lavage.

Drug interactions

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

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

Penicillins are able to slow down the excretion of methotrexate from the body by inhibiting its tubular secretion, therefore, the simultaneous use of AugmentinЃ and methotrexate can increase the toxicity of methotrexate.

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

The literature describes rare cases of an increase in MHO in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe AugmentinЃ with anticoagulants, prothrombin time or MHO should be carefully monitored when prescribing or discontinuing AugmentinЃ, it may be necessary to adjust the dose of anticoagulants for oral administration.

In patients who received mycophenolate mofetil, after starting the use of a 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 general changes in mycophenolic acid exposure.