Amoxicillin+Clavulanic acid EXPRESS, 875 mg+125 mg 14 pcs

The antibiotic is a semisynthetic penicillin + beta-lactamase inhibitor.

The ATC code: J01CR02

Pharmacological properties

Pharmacodynamics

The mechanism of action

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

Clavulanic acid, a beta-lactamase inhibitor structurally related to penicillins, has the ability to inactivate a wide range of beta-lactamases found in microorganisms that are resistant to penicillins and cephalosporins.

Clavulanic acid is sufficiently effective against plasmid beta-lactamases that most often cause bacterial resistance and is not effective against type 1 chromosomal beta-lactamases that are not inhibited by clavulanic acid. The presence of clavulanic acid in the drug Amoxicillin + Clavulanic acid EXPRESS protects amoxicillin from degradation by enzymes – beta-lactamases, which allows to expand the antibacterial spectrum of amoxicillin.

The in vitro activity of the combination of amoxicillin with clavulanic acid is shown below.

Bacteria generally 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 beta-haemolytic streptococci)1,2

Staphylococcus aureus (methicillin-sensitive)1

Staphylococcus saprophyticus (sensitive to methicillin)

Coagulazonegative staphylococci (sensitive to methicillin).

Gram-positive anaerobes:

Clostridium spp.

Peptococcus niger

Peptostreptococcus magnus

Peptostreptococcus micros

Peptostreptococcus spp.

Gram-negative aerobes:

Bordetella pertussis

Haemophilus influenzae1

Helicobacter pylori

Moraxella catarrhalis1

Neisseria gonorrhoeae

Pasteurella multocida

Vibrio cholerae.

Gram-negative anaerobes:

Bacteroides fragilis

Basteroides 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 group Viridans2.

Bacteria with natural resistance 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 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 trials.

2 – strains of these bacterial species do not produce β-lactamases. The sensitivity with amoxicillin monotherapy suggests similar sensitivity to a combination of amoxicillin and clavulanic acid.

Pharmacokinetics

Amoxicillin and clavulanic acid dissociate completely in aqueous solution at physiological pH values. Both active ingredients of the drug, amoxicillin and clavulanic acid, are rapidly and well absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of active ingredients is optimal at the beginning of meals. Bioavailability of amoxicillin and clavulanic acid when taken orally is high. After a single dose of fixed combination of amoxicillin and clavulanic acid (500 mg + 125 mg) maximum concentration of amoxicillin in blood plasma is in 1.5 hours (1.0-2.5 hours), and it is 7.19±2.26 µg/ml (Cmax), clavulanic acid – in 1.5 hours (1.0-2.0 hours), it is 2.4±0.83 µg/ml. The PFC (area under the pharmacokinetic curve) of amoxicillin and clavulanic acid was 53.5±8.87 µg*h/L and 15.72±3.86 µg*h/L, respectively. Plasma concentrations of amoxicillin and clavulanic acid achieved with amoxicillin/clavulanate are similar to those achieved with oral administration of equivalent doses of amoxicillin and clavulanic acid alone.

Distribution

Approximately about 18% of amoxicillin and 25% of clavulanic acid binds to plasma proteins. Apparent volume of distribution is 0.3-0.4 l/kg for amoxicillin and about 0.2 l/kg for clavulanic acid. Amoxicillin is poorly distributed in the cerebrospinal fluid.

In animal studies no cumulation of the drug components in the body tissues was found.

Like most penicillins, amoxicillin penetrates into breast milk. Clavulanic acid is also found in breast milk in trace concentrations. Amoxicillin and clavulanic acid penetrate the placental barrier.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys as an inactive metabolite (penicillic acid). Clavulanic acid is extensively metabolized and excreted by the kidneys, intestines and exhaled air as carbon dioxide.

After a single administration of fixed combination of amoxicillin and clavulanic acid (500 mg + 125 mg) the half-life of amoxicillin is 1.15±0.20 h, clavulanic acid – 0.98±0.12 h, total clearance – about 25 l/h. Approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid is excreted unchanged by the kidneys during the first 6 hours after taking 1 tablet of the drug 500/125 mg. The greatest amount of clavulanic acid is excreted within the first 2 hours after intake. In various studies it has been shown that within 24 hours up to 50-85% of amoxicillin and up to 27-60% of clavulanic acid are excreted through the kidneys.

Concomitant administration of probenecid delays excretion of amoxicillin, but does not affect renal excretion of clavulanic acid (see section “Interaction with other medicinal products”).

Pharmacokinetics in special cases

Age specificities

The half-life of amoxicillin in children from 3 months to 2 years does not differ from that of older children and adults. Children of the first week of life (including premature infants) should not prescribe the drug more than 2 times a day because of the immaturity of the renal elimination pathway. Because of the possible decrease of renal function, the drug dose for elderly patients should be selected with caution. Renal function monitoring may be necessary.

Gender specificities

When oral administration of amoxicillin/clavulanic acid in healthy males and females there is no significant effect of patient’s gender on the pharmacokinetics of the active ingredients of the drug.

Renal dysfunction

The total clearance of amoxicillin/clavulanic acid decreases in proportion to decreased renal function. Clearance of amoxicillin is particularly impaired because the kidneys excrete most of it. Thus, in case of impaired renal function the dose of the drug should be adjusted to avoid excessive concentration of amoxicillin and to maintain the necessary level of clavulanic acid.

Hepatic impairment

In patients with hepatic impairment the drug should be prescribed with caution. Liver function should be monitored regularly.

Indications

The combination of amoxicillin with clavulanic acid is indicated for the treatment of bacterial infections of the following localizations caused by microorganisms sensitive to the combination of amoxicillin with clavulanic acid:

– upper respiratory tract infections (including infections of the ENT organs), for example: recurrent tonsillitis, sinusitis, otitis media, usually caused by Streptococcus pneumoniae1,2, Haemophilus influenzae1, Moraxella catarrhalis1 and Streptococcus pyogenes1,2;

– lower respiratory tract infections, for example: exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia, usually caused by Streptococcus pneumoniae1,2, Haemophilus influenzae1 and Moraxella catarrhalis1;

– infections of the genitourinary tract, for example: cystitis, urethritis, pyelonephritis, infections of the female genital organs, usually caused by species of the family Enterobacteriaceae (mainly Escherichia coli1), Staphylococcus saprophyticus and species of the genus Enterococcus, as well as gonorrhea caused by Neisseria gonorrhoeae;

– infections of the skin and soft tissues, usually caused by Staphylococcus aureus1, Streptococcus pyogenes1,2 and species of the genus Bacteroides;

– infections of bones and joints, for example: osteomyelitis, usually caused by Staphylococcus aureus1, if necessary, long-term therapy is possible;

– odontogenic infections, for example: periodontitis, odontogenic maxillary sinusitis, severe dental abscesses with spreading cellulitis;

– 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 beta-lactamase, which makes them insensitive to amoxicillin (see also section “Pharmacological properties”). Infections caused by microorganisms sensitive to amoxicillin can be treated with Amoxicillin + Clavulanic Acid EXPRESS, since amoxicillin is one of its active ingredients. Amoxicillin + Clavulanic acid EXPRESS is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as beta-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.

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.

Pharmacological effect

Antibiotic – semi-synthetic penicillin + beta-lactamase inhibitor.

ATX code: J01CR02

Pharmacological properties

Pharmacodynamics

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 beta-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce this enzyme.

Clavulanic acid is a beta-lactamase inhibitor, structurally related to penicillins, and has the ability to inactivate a wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins.

Clavulanic acid is sufficiently effective against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against type 1 chromosomal beta-lactamases, which are not inhibited by clavulanic acid. The presence of clavulanic acid in the drug Amoxicillin + Clavulanic acid EXPRESS protects amoxicillin from destruction by enzymes – beta-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)

Coagulase-negative staphylococci (sensitive to methicillin).

Gram-positive anaerobes:

Clostridium spp.

Peptococcus niger

Peptostreptococcus magnus

Peptostreptococcus micros

Peptostreptococcus spp.

Gram-negative aerobes:

Bordetella pertussis

Haemophilus influenzae1

Helicobacter pylori

Moraxella catarrhalis1

Neisseria gonorrhoeae

Pasteurella multocida

Vibrio cholerae.

Gram-negative anaerobes:

Bacteroides fragilis

Basteroides 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

streptococci of the Viridans2 group.

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.

Pharmacokinetics

Suction

Amoxicillin and clavulanic acid completely dissociate in aqueous solution at physiological pH values. Both active components of the drug, amoxicillin and clavulanic acid, are quickly and well absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of active ingredients is optimal at the beginning of a meal. The bioavailability of amoxicillin and clavulanic acid when taken orally is high. After a single dose of a fixed combination of amoxicillin and clavulanic acid (500 mg + 125 mg), the maximum concentration of amoxicillin in the blood plasma is created after 1.5 hours (1.0-2.5 hours), and is 7.19 ± 2.26 μg/ml (Cmax), clavulanic acid – after 1.5 hours (1.0-2.0 hours), amounting to 2.4±0.83 µg/ml. The PFC (area under the pharmacokinetic curve) of amoxicillin and clavulanic acid is 53.5±8.87 mcg*h/l and 15.72±3.86 mcg*h/l, respectively. Plasma concentrations of amoxicillin and clavulanic acid achieved with amoxicillin/clavulanate are similar to those achieved with oral administration of equivalent doses of amoxicillin and clavulanic acid alone.

Distribution

Approximately 18% of amoxicillin and 25% of clavulanic acid are bound to plasma proteins. The apparent volume of distribution is 0.3-0.4 l/kg for amoxicillin and about 0.2 l/kg for clavulanic acid. Amoxicillin is poorly distributed into the cerebrospinal fluid.

In animal studies, accumulation of drug components in body tissues was not detected.

Like most penicillins, amoxicillin passes into breast milk. Clavulanic acid is also found in trace concentrations in breast milk. Amoxicillin and clavulanic acid penetrate the placental barrier.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic acid). Clavulanic acid undergoes intensive metabolism and is excreted by the kidneys, intestines, and also with exhaled air in the form of carbon dioxide.

Removal

After a single dose of a fixed combination of amoxicillin and clavulanic acid (500 mg + 125 mg), the half-life of amoxicillin is 1.15 ± 0.20 hours, that of clavulanic acid is 0.98 ± 0.12 hours, and the total clearance is about 25 l/h. Approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted unchanged by the kidneys during the first 6 hours after taking 1 tablet of the drug 500/125 mg. The largest amount of clavulanic acid is excreted during the first 2 hours after administration. Various studies have shown that up to 50-85% of amoxicillin and up to 27-60% of clavulanic acid are excreted through the kidneys within 24 hours.

Concomitant use of probenecid delays the elimination of amoxicillin, but does not affect the renal excretion of clavulanic acid (see section “Interaction with other drugs”).

Pharmacokinetics in special cases

Age characteristics

The half-life of amoxicillin in children from 3 months to 2 years does not differ from that in older children and adults. Children in the first week of life (including premature infants) should not be prescribed the drug more than 2 times a day due to the immaturity of the renal elimination pathway. Due to a possible decrease in renal function, dose selection for elderly patients should be done with caution. Monitoring of renal function may be required.

Sexual characteristics

When amoxicillin/clavulanic acid is taken orally by healthy men and women, no significant effect of the patient’s gender on the pharmacokinetics of the active components of the drug has been established.

Renal dysfunction

The total clearance of amoxicillin/clavulanic acid decreases in proportion to the decrease in renal function. The clearance of amoxicillin is especially noticeably impaired, since most of it is excreted by the kidneys. Thus, if renal function is impaired, the dose of the drug should be adjusted to avoid excessive concentrations of amoxicillin and to maintain the required level of clavulanic acid.

Liver dysfunction

In patients with impaired liver function, the drug should be prescribed with caution. Liver function should be regularly monitored.

Special instructions

Special patient groups

Elderly patients

No dosage regimen 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

In patients with renal failure, the excretion of clavulanic acid and amoxicillin through the kidneys is slow. Depending on the severity of renal failure, the total dose of Amoxicillin + Clavulanic acid EXPRESS (expressed as amoxicillin dose) should not exceed the amount.

Tablets 875 mg/125 mg should be used only in patients with creatinine clearance more than 30 ml/min, and no dosage adjustment is required.

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

Patients on hemodialysis

Correction of the dosage regimen is based on the maximum recommended dose of amoxicillin, presented in the table.

Patients with liver dysfunction

Treatment is carried out with caution, and liver function is regularly monitored.

There is insufficient data to change the recommended dosage regimen in these patients.

Active ingredient

Amoxicillin, Clavulanic acid

Composition

One tablet 875 mg + 125 mg contains:

Active ingredients:

amoxicillin trihydrate in terms of amoxicillin – 1004.43 mg (875.00 mg);

potassium clavulanate + microcrystalline cellulose (1:1) in terms of clavulanic acid – 297.82 mg (125.00 mg).

Excipients:

microcrystalline cellulose 302 – 1.70 mg;

crospovidone – 421.51 mg;

vanillin – 1.00 mg;

saccharin – 16.11 mg;

magnesium stearate – 7.43 mg;

tangerine flavor – 9.00 mg,

lemon flavor – 11.00 mg.

Pregnancy

Pregnancy

In animal reproductive studies, oral and parenteral administration of amoxicillin + clavulanic acid 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.

The drug is not recommended for use during pregnancy, unless the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding period

The drug Amoxicillin + Clavulanic acid EXPRESS 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.

Contraindications

– hypersensitivity to amoxicillin, clavulanic acid, other penicillins or any other component of the drug;

– a history of severe immediate hypersensitivity reactions (for example, anaphylaxis) to other beta-lactam antibiotics (for example, cephalosporins, carbapenems or monobactams);

– a history of jaundice or liver failure due to taking amoxicillin/clavulanic acid;

– children under 1 year of age and/or body weight up to 10 kg (due to the impossibility of dosing the dosage form in this category of patients).

The drug is contraindicated at a dose of 875 mg + 125 mg for children under 12 years of age with CC≤30 ml/min.

With caution

Severe liver failure, gastrointestinal diseases (including a history of colitis associated with the use of penicillins), chronic renal failure.

Side Effects

The adverse reactions presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000) unknown (cannot be determined based on available data). Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.Frequency of occurrence of adverse reactionsInfectious and parasitic diseases: often: candidiasis of the skin and mucous membranes; unknown: overgrowth of non-susceptible microorganisms.Disorders of the blood and lymphatic system: rarely: reversible leukopenia (including neutropenia), thrombocytopenia; unknown: reversible agranulocytosis and reversible hemolytic anemia, prolongation of bleeding time and prothrombin time.Immune system disorders: unknown: angioedema, anaphylactic reactions, serum sickness-like syndrome, allergic vasculitis; acute coronary syndrome associated with hypersensitivity (Kounis syndrome).Nervous system disorders: uncommon: dizziness, headache; unknown: reversible hyperactivity, aseptic meningitis, convulsions in cases of renal impairment or drug overdose.Gastrointestinal disorders: adults: very common: diarrhea; often: nausea, vomiting; children: often: diarrhea, nausea, vomiting; entire population: nausea was most often associated with the use of high doses of the drug. If, after starting to take the drug, undesirable reactions from the gastrointestinal tract are observed, they can be eliminated if you take the drug Amoxicillin + Clavulanic acid EXPRESS at the beginning of the meal; uncommon: indigestion; unknown: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis), black “hairy” tongue.Liver and biliary tract disorders: uncommon: moderate increase in aspartate aminotransferase and/or alanine aminotransferase (AST and/or ALT) activity.This reaction has been observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown; unknown: hepatitis and cholestatic jaundice. These reactions are observed in patients receiving therapy with penicillin antibiotics and cephalosporins.
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 individuals with serious comorbidities or patients simultaneously receiving potentially hepatotoxic drugs.

Skin and subcutaneous tissue disorders: uncommon: rash, itching, urticaria; rarely: erythema multiforme; unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP), drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

If allergic skin reactions occur, treatment with Amoxicillin + Clavulanic acid EXPRESS must be discontinued.

Renal and urinary tract disorders: unknown: interstitial nephritis, crystalluria.

Interaction

The simultaneous use of Amoxicillin + Clavulanic acid EXPRESS and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of the drug Amoxicillin + Clavulanic acid EXPRESS and probenecid can 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 Amoxicillin + Clavulanic Acid EXPRESS and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, the drug Amoxicillin + Clavulanic acid EXPRESS 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 an increase in the international normalized ratio (INR) in patients with the combined use of acenocoumarol or warfarin and amoxicillin.

If it is necessary to simultaneously prescribe the drug Amoxicillin + Clavulanic acid EXPRESS with anticoagulants, the prothrombin time or INR should be carefully monitored when prescribing or discontinuing the drug Amoxicillin + Clavulanic acid EXPRESS; dose adjustment of anticoagulants for oral administration 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.

Overdose

Symptoms

Gastrointestinal symptoms and water and electrolyte imbalance may occur. Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure (see section “Special Instructions”).

Convulsions may occur in patients with impaired renal function, as well as in those who receive high doses of the drug (see section “Dosage and Administration”, “Side Effects”, “Special Instructions”).

Treatment

Gastrointestinal symptoms – symptomatic therapy, paying special attention to normalizing water and electrolyte balance. 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.

Short product description

Amoxicillin is a semisynthetic broad-spectrum antibiotic that is active against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by beta-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce these enzymes.

Clavulanic acid is a beta-lactamase inhibitor, structurally related to penicillins, and has the ability to inactivate a wide range of beta-lactamases commonly found in microorganisms resistant to penicillins and cephalosporins.

Clavulanic acid is quite effective against plasmid beta-lactamases, which most often cause bacterial resistance.

Recommendations for use

Before starting treatment with Amoxicillin + Clavulanic acid EXPRESS, 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 (including anaphylactic and severe skin adverse 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 Amoxicillin + Clavulanic Acid EXPRESS should be discontinued and appropriate alternative therapy should be initiated.

If the infection is proven to be caused by organisms sensitive to amoxicillin, consideration should be given to replacing the amoxicillin/clavulanic acid combination with amoxicillin in accordance with official clinical guidelines.

Amoxicillin/clavulanic acid is not suitable for use in cases where there is a high risk that the suspected pathogen has reduced sensitivity or resistance to beta-lactam drugs that is not due to beta-lactamases susceptible to inhibition by clavulanic acid.

Amoxicillin/clavulanic acid should not be used to treat infections caused by penicillin-resistant strains of S. pneumoniae.

Acute coronary syndrome associated with hypersensitivity (Kounis syndrome)

In rare cases, hypersensitivity reactions have been reported during treatment with amoxicillin (acute coronary syndrome associated with hypersensitivity), in these cases it is necessary to discontinue the drug and institute appropriate treatment.

In patients with impaired renal function, as well as when taking high doses of the drug, convulsions may occur (see section “Side effects”).

If infectious mononucleosis is suspected, Amoxicillin + Clavulanic acid EXPRESS should not be used, since amoxicillin can cause exanthema (measles-like skin rash) in patients with this disease.

Concomitant use of allopurinol during treatment with amoxicillin may increase the likelihood of allergic skin reactions.

Long-term treatment with Amoxicillin + Clavulanic acid EXPRESS may lead to excessive proliferation of insensitive microorganisms.

The occurrence at the beginning of treatment of generalized erythema with fever, accompanied by the formation of pustules, may be a symptom of acute generalized exanthematous pustulosis (AGEP). Such a reaction requires discontinuation of the drug containing amoxicillin/clavulanic acid and is a contraindication to the subsequent use of amoxicillin drugs.

Drugs containing amoxicillin/clavulanic acid should be used with caution in patients with impaired liver function.

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. In all populations, the signs and symptoms listed usually occur during or shortly after completion of therapy, but in some cases may not appear until several weeks after completion of therapy. They are usually reversible. Hepatic adverse events may be severe and death has been reported in extremely rare cases. In almost all cases, these were patients with serious underlying medical conditions or patients concomitantly receiving drugs that potentially affect the liver.

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 antibiotic-associated colitis occurs, you should immediately stop treatment with the amoxicillin/clavulanic acid combination, consult a doctor and begin appropriate treatment. Drugs that inhibit peristalsis are contraindicated in this situation. During long-term therapy with Amoxicillin + Clavulanic acid EXPRESS, it is recommended to periodically evaluate renal, liver and hematopoietic function.

Increased prothrombin time (increased INR) has been reported in rare cases in patients receiving a combination of amoxicillin and clavulanic acid. 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 Amoxicillin + Clavulanic acid EXPRESS should be reduced according to the degree of impairment (see section “Method of administration and dosage” – Patients with impaired renal function).

In patients with reduced diuresis, crystalluria very rarely occurs, mainly during parenteral therapy. 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 (see section “Overdose”). Patients with bladder catheters should have their patency checked regularly. Taking the drug Amoxicillin + Clavulanic acid EXPRESS 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.

Positive results of the Bio-Rad Laboratories Platelia Aspergillus ELISA have been reported in patients receiving the amoxicillin/clavulanic acid combination who were subsequently found not to have Aspergillus infection. Cross-reactions with polysaccharides and polyfurans not characteristic of the Aspergillus genus have been reported in the Aspergillus Platelium ELISA test. Therefore, positive Aspergillus Platelia ELISA results in patients treated with amoxicillin/clavulanic acid should be interpreted with caution and confirmed with other diagnostic methods.

One dispersible tablet Amoxicillin + Clavulanic acid 125 mg/31.25 mg contains 0.16 mmol (6.13 mg) of potassium, 250 mg/62.5 mg – 0.32 mmol (12.3 mg), 500 mg/125 mg – 0.64 mmol (24.53 mg), 875 mg/125 mg – 0.64 mmol (25 mg).

Potassium intake of more than 1 mmol per day requires special attention in patients with reduced renal function and in those on a controlled potassium diet.

Impact on the ability to drive vehicles and machinery

No studies have been conducted to study the effect on the ability to drive vehicles and operate machinery. Since the drug may cause side effects (for example, allergic reactions, dizziness, convulsions) (see section “Side Effects”), patients should be warned about precautions when driving or working with moving machinery.

Storage conditions

In original packaging at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life

2 years.

Manufacturer

Lecco CJSC, Russia