active substances: 1 tablet contains amoxicillin trihydrate, in terms of amoxicillin – 500 mg and a mixture of potassium clavulanate and microcrystalline cellulose in a ratio (1:1), in terms of clavulanic acid – 125 mg;
excipients: microcrystalline cellulose, sodium starch glycolate (type A), colloidal anhydrous silicon dioxide, magnesium stearate, coating mixture “Opadry II White” 33G28707 (contains: hypromellose (hydroxypropyl methylcellulose); titanium dioxide (E 171); lactose, monohydrate; polyethylene glycol (macrogol) 3000; triacetin).
Main physico-chemical properties: white film-coated tablets, oval in shape with a biconvex surface, with a line on one side of the tablet.
Antibacterial agents for systemic use. Beta-lactam antibiotics, penicillins. Combinations of penicillins with beta-lactamase inhibitors. ATX code J01C R02.
Amoxicillin is a semi-synthetic antibiotic with a broad spectrum of antibacterial activity against many gram-positive and gram-negative microorganisms. Amoxicillin is sensitive to beta-lactamase and breaks down under its influence, so the spectrum of activity of amoxicillin does not include microorganisms that synthesize this enzyme. Clavulanic acid has a beta-lactam structure similar to penicillins and inactivates beta-lactamase enzymes characteristic of microorganisms resistant to penicillins and cephalosporins. In particular, it has a pronounced activity against clinically important plasmid beta-lactamases, which are often responsible for the emergence of cross-resistance to antibiotics. The presence of clavulanic acid in the composition protects amoxicillin from degradation under the action of beta-lactamase enzymes and extends the spectrum of antibacterial action of amoxicillin,
The microorganisms listed below are classified according to susceptibility to amoxicillin/clavulanate in vitro.
Gram-positive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroids, Streptococcus pyogenes, Streptococcus agalactiae, other beta-hemolytic species of Streptococcus, Staphylococcus aureus (methicillin-sensitive strains), Staphylococcus saprophyticus (methicillin-sensitive strains), coagulase-negative staphylococci (methicillin-sensitive strains).
Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae, Haemophilus parainfluenzae, Helicobacter pylori, Moraxella catarrhalis, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholera.
Others: Borrelia burgdorferi, Leptospirosa icterohaemorrhagiae, Treponema pallidum.
Gram-positive anaerobes: Clostridium species, Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus species.
Gram-negative anaerobes: Bacteroides species ( including Bacteroides fragilis ), Capnocytophaga species, Eikenella corrodens, Fusobacterium species, Fusobacterium nucleatum, Porphyromonas species , Prevotella species .
Strains with possible acquired resistance
Gram-negative aerobes : Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Klebsiella species, Proteus mirabilis, Proteus vulgaris, Proteus species, Salmonella species , Shigella species .
Gram-positive aerobes: species of Corynebacterium, Enterococcus faecium, Streptococcus pneumoniae, species of Streptococcus viridans.
Gram-negative aerobes: Acinetobacter species, Citrobacter freundii, Enterobacter species, Hafnia alvei, Legionella pneumophila, Morganella morganii, Providencia species, Pseudomonas species , Serratia species, Stenotrophomas maltophilia, Yersinia enterolitica.
Others: Chlamydia pneumonia, Chlamydia psittaci, Chlamydia species , Coxiella burnetti, Mycoplasma species .
Absorption. Both components of the drug (amoxicillin and clavulanic acid) are completely soluble in aqueous solutions at physiological pH values. Both components are quickly and well absorbed when taken orally. Absorption of the drug Amoxil-K 625 improves when it is used at the beginning of a meal.
The concentration of amoxicillin in the blood serum, which is achieved when taking the combined medicinal product of amoxicillin and clavulanic acid, is similar to that which is achieved when taking equivalent doses of amoxicillin alone.
Concomitant administration of probenecid inhibits the excretion of amoxicillin, but does not affect the renal excretion of clavulanic acid.
Distribution. When administered orally, therapeutic concentrations of amoxicillin and clavulanic acid are observed in tissues and interstitial fluid. Therapeutic concentrations of both substances are found in the gallbladder, abdominal tissues, skin, fat and muscle tissues, as well as in synovial and peritoneal fluids, bile and pus. Amoxicillin and clavulanic acid are weakly bound to proteins; studies have established that protein binding rates are 25% for clavulanic acid and 18% for amoxicillin of their total concentrations in plasma. Animal studies have not shown accumulation of any of these components in any organ.
Amoxicillin, like other penicillins, can be detected in breast milk. Trace amounts of clavulanic acid can also be detected in breast milk. Animal reproductive studies have shown that both amoxicillin and clavulanic acid can cross the placental barrier. However, no evidence of impaired fertility or harmful effects on the fetus was found.
Breeding. The main route of elimination of amoxicillin, like other penicillins, is renal excretion, while the elimination of clavulanate is carried out both by the kidneys and by extrarenal mechanisms. Approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted unchanged in the urine during the first 6 hours.
Treatment of bacterial infections caused by microorganisms sensitive to the drug, such as: acute bacterial sinusitis; acute otitis media; confirmed exacerbation of chronic bronchitis; nosocomial pneumonia; cystitis; pyelonephritis; skin and soft tissue infections, including cellulitis, animal bites, severe dentoalveolar abscesses with widespread cellulitis; infections of bones and joints, including osteomyelitis
Hypersensitivity to any components of the drug, to any antibacterial agents of the penicillin group.
History of severe hypersensitivity reactions (including anaphylaxis) associated with the use of other beta-lactam agents (including cephalosporins, carbapenems or monobactams).
A history of jaundice or liver dysfunction associated with the use of amoxicillin/clavulanate.
Dosage and Administration
Amoxil-K 625 (amoxicillin) should be used in accordance with the official recommendations on antibiotic therapy and data on local sensitivity to the antibiotic. Susceptibility to amoxicillin/clavulanate varies between regions and may change over time. If necessary, local susceptibility data should be consulted and, if necessary, microbiological determination and susceptibility testing should be performed.
The dose depends on the expected pathogens and their sensitivity to antibacterial drugs, the severity of the disease and the localization of the infection, the patient’s age, body weight and kidney function.
The daily dose for adults and children with body weight ≥ 40 kg is 1500 mg amoxicillin/ 375 mg clavulanic acid.
The maximum daily dose for children over 6 years of age with a body weight of 25 to 40 kg can reach, if necessary, 2400 mg of amoxicillin/600 mg of clavulanic acid.
If higher doses of amoxicillin are required for treatment, other forms of the drug should be used to avoid excessively high doses of clavulanic acid.
The duration of treatment is determined by the patient’s clinical response to treatment. Some infections (for example, osteomyelitis) require longer treatment.
Adults and children with body weight ≥ 40 kg:
1 tablet of Amoxil-K 625 (amoxicillin) 3 times a day.
Children aged 6 years and over with a body weight of 25 to 40 kg:
The dose is from 20 mg/5 mg/kg of body weight/day to 60 mg/15 mg/kg of body weight/day, divided into 3 doses.
Since Amoxil-K 625 (amoxicillin) tablet cannot be divided, children whose body weight is less than 25 kg, the drug is used in a different dosage form.
Dose adjustment is not required for elderly patients. If necessary, the dose should be adjusted depending on kidney function.
Dosage in case of impaired kidney function
The dosage is based on the calculation of the maximum level of amoxicillin. There is no need to change the patient’s dose if the creatinine clearance is > 30 ml/min.
Adults and children with body weight ≥ 40 kg
|Creatinine clearance 10-30 ml/min||500 mg/125 mg 2 times a day|
|Creatinine clearance < 10 ml/min||500 mg/125 mg once a day|
|Hemodialysis||500 mg/125 mg every 24 hours plus 500 mg/125 mg during dialysis and again at the end of dialysis (as plasma concentrations of amoxicillin and clavulanic acid decrease)|
Children aged 6 years and over with a body weight of 25 to 40 kg
Since the tablet cannot be split, Amoxil-K 625 (amoxicillin) should not be prescribed to children over 6 years of age with a body weight of 25 to 40 kg, a creatinine clearance of less than 30 ml/min or to children on hemodialysis.
Dosage in case of impaired liver function
Apply carefully; liver function should be monitored regularly.
The tablet should be swallowed whole, without chewing. If necessary, the tablet can be broken in half and swallowed without chewing.
For optimal absorption and reduction of possible side effects from the digestive tract, the drug should be taken at the beginning of a meal.
The duration of treatment is determined individually. Treatment should not be continued for more than 14 days without assessment of the patient’s condition.
Treatment can be started parenterally and then continued orally.