Active substanceAmoxicillin + Clavulanic acidAmoxicillin + Clavulanic acid
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  • Dosage form: & nbsppowder for solution for intravenous administration
    Composition:

    1 vial contains active substances: amoxicillin, in the form of amoxicillin sodium 500/1000 mg, clavulanic acid, in the form of potassium clavulanate 100/200 mg.

    Description:White or almost white crystalline powder.
    Pharmacotherapeutic group:Antibiotic, semi-synthetic penicillin + beta-lactamase inhibitor
    ATX: & nbsp

    J.01.C.R.02   Amoxicillin in combination with enzyme inhibitors

    Pharmacodynamics:

    Amoxicillin is a semisynthetic aminopenicillin, belonging to the group of beta-lactam antibiotics, which has a broad spectrum of antibacterial activity against many Gram-positive and Gram-negative microorganisms. Amoxicillin is destroyed by the action of microbial enzymes (beta-lactamases) and does not affect the microorganisms that produce these enzymes.

    Clavulanic acid is a beta-lactam, structurally related to penicillins, which has the ability to inactivate beta-lactamases. The presence of clavulanic acid protects amoxicillin from the damaging effect of beta-lactamases and effectively expands the spectrum of amoxicillin activity, which includes many bacteria, usually resistant to amoxicillin, as well as to other penicillins and cephalosporins.

    Amoxicillin + clavulanic acid has a bactericidal effect in vivo on the following microorganisms:

    Gram-positive aerobes: Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes.

    Gram-negative aerobes: species of genus Enterobacter, Escherichia coli, Haemophilus influenzae, species of genus Klebsiella, Moraxella catarrhalis.

    Amoxicillin + clavulanic acid has a bactericidal effect in vitro on the following microorganisms:

    Gram-positive aerobes: Bacillis anthracis, species of genus Corynebacterium, Enterococcus faecalis, Enterococcus faecium, Listeria monocytogenes, Nocardia asteroids, Coagulase-negative staphylococci, incl. Staphylococcus epidermidis, Streptococcus agalactiae, Streptococcus spp. groups viridans.

    Gram-positive anaerobes: Clostridium spp., Peptococcus spp., Peptostreptococcus spp..

    Gram-negative aerobes: Bordetella pertussis, Brucella spp., Gardnerella vaginalis, Helicobacter pylori, Legionella spp., Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Vibrio cholerae, Yersinia enterocolitica

    Gram-negative anaerobes: Bacteroides spp. (incl. Bacteroides fragilis).BHabi kind Fusobacterium spp.

    Other: Borrelia burgdorferi, Chlamydiae spp., Leptospira icterohaemorrhagiae, Treponema pallidum.

    Pharmacokinetics:

    Amoxicillin and clavulanic acid in combination do not affect the pharmacokinetics of each other. The maximum plasma concentration after bolus injection of amoxicillin + clavulanic acid (1000 mg + 200 mg) is 105 mg / l for amoxicillin and 28 mg / l for clavulanic acid,when 500 mg of amoxicillin and 100 mg of clavulanic acid were administered, 32 mg / L and 10 mg / L, respectively. The half-life of amoxicillin 1000 mg is 0.9 hours, clavulanic acid 200 mg - 0.9 hours, when administered. 500 mg of amoxicillin and 100 mg of clavulanic acid - 1 hour and 1 hour, respectively.

    After intravenous administration, therapeutic concentrations of amoxicillin and clavulanic acid are created in the abdominal cavity, fat and muscle tissues and interstitial fluid, in the skin, lungs and pleural fluid, in the gallbladder, as well as in synovial and peritoneal fluids, bile and pus.

    Amoxicillin and clavulanic acid penetrate the placental barrier and in low concentrations are excreted into breast milk. Amoxicillin and clavulanic acid bind to plasma proteins by 13% -20%.

    Amoxicillin is excreted mainly by the kidneys, whereas clavulanic acid is through both renal and extrarenal mechanisms. Approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted by the kidneys unchanged in the first 6 hours after one bolus injection of 1000 mg / 200 mg. Amoxicillin in an amount equivalent to 10-25% of the initial dose of amoxicillin. is excreted by the kidneys in the form of inactive penicillic acid.Clavulanic acid in the human body undergoes intensive metabolism and is excreted by the kidneys and intestines.

    Indications:

    Bacterial infections caused by microorganisms that are sensitive to the drug:

    - Infections of the lower parts of the respiratory bullet (exacerbation of chronic bronchitis, lobar pneumonia and bronchopneumonia);

    - Infections of the ENT organs (otitis media, sinusitis, relapsing tonsillitis)

    - Urinary tract infections (including cystitis, urethritis, pyelonephritis);

    - Infections of the pelvic organs (including salpingitis, salpingoophoritis, endometritis, septic abortion, pelvic peritonitis, postpartum sepsis);

    - Infections of the skin and soft tissues (phlegmon, wound infection, erysipelas, impetigo, abscesses);

    - Infections of bones and joints (including chronic osteomyelitis);

    - Sexually transmitted infections (gonorrhea, soft chancre);

    - Other infectious diseases: septicemia, peritonitis, intra-abdominal sepsis, postoperative infections.

    Prevention of postoperative infections, with surgical interventions on the gastrointestinal tract, pelvic organs, head and neck, heart, kidneys, bile ducts, as well as implantation of artificial joints.

    Contraindications:

    - Hypersensitivity to amoxicillin and clavulanic acid;

    - hypersensitivity to penicillins, cephalosporins, other beta-lactam antibiotics;

    - Infectious mononucleosis;

    - episodes of jaundice or impaired liver function as a result of amoxicillin / clavulanic acid in history.

    Carefully:

    Severe hepatic insufficiency, diseases of the gastrointestinal tract (including colitis in history, associated with the use of penicillins), chronic renal failure.

    Pregnancy and lactation:

    The use of the drug during pregnancy is possible only in cases where the intended benefit to the mother exceeds the potential risk to the fetus. If you need to use the drug during lactation, you should decide whether to stop breastfeeding.

    Dosing and Administration:

    The drug is administered intravenously (IV).

    The dosage regimen depends on the age, body weight and function of the patient's kidneys, and also on the severity of the infection.

    The minimum course of antibiotic therapy is 5 days. The maximum duration of therapy can be 14 days, after which its effectiveness and tolerability should be assessed.

    Doses are given for the content of amoxicillin / clavulanic acid.

    Adults and children over 12 years of age with a body weight of more than 40 kg

    Standard dose: 1000 mg / 200 mg every 8 hours.

    Severe infections: 1000 mg / 200 mg every 4-6 hours.

    Prophylaxis in surgery

    Interventions lasting less than 1 hour: 1000 mg / 200 mg during the initial anesthesia.

    Interventions lasting more than 1 h: do 4 doses of 1000 mg / 200 mg for 24 hours.

    Patients with impaired renal function

    Dose adjustment is based on the maximum recommended dose of amoxicillin.

    Creatinine clearance> 30 ml / min

    Correction of dose is not required

    Creatinine clearance 10-30 ml / min

    Initially, 1000 mg / 200 mg and further 500 mg / 100 mg twice daily

    Creatinine clearance <10 ml / min

    Initially 1000 mg / 200 mg and further 500 mg / 100 mg every 24 hours

    Patients on hemodialysis

    Dose adjustment is based on the maximum recommended dose of amoxicillin.

    Initially, a dose of 1000 mg / 200 mg, followed by 500 mg / 100 mg every 24 hours and an additional 500 mg / 100 mg at the end of the hemodialysis session (to compensate for the decrease in amoxicillin and clavulanic acid in plasma).

    Patients with impaired hepatic function

    Treat with caution; regularly monitor liver function.

    Children

    For children under 12 years of age with a body weight of less than 40 kg, the dose is calculated depending on the body weight.

    Less than 3 months with a body weight of less than 4 kg 25 mg / 5 mg / kg every 12 hours.

    Less than 3 months with a body weight of more than 4 kg 25 mg / 5 mg / kg every 8 hours.

    In children younger than 3 months, the drug should be injected only slowly infusion for 30-40 minutes.

    From 3 months to 12 years 25 mg / 5 mg / kg every 6-8 hours, depending on the severity of the infection.

    Children with impaired renal function

    Dose adjustment is based on the maximum recommended dose of amoxicillin.

    Creatinine clearance> 30 ml / min

    Correction of dose is not required

    Creatinine clearance 10-30 ml / min

    25 mg / 5 mg / kg 2 times a day.

    Creatinine clearance <10 ml / min

    25 mg / 5 mg / kg every 24 hours.

    Children on hemodialysis

    Correction of the dose is based on the maximum recommended content of amoxicillin. 25 mg / 5 mg / kg every 24 hours and an additional 12.5 mg / 2.5 mg / kg at the end of the hemodialysis session (to compensate for the decrease in amoxicillin and clavulanic acid in the serum) and further 25 mg / 5 mg / kg in day;

    Children with impaired liver function

    Treat with caution; regularly monitor liver function.

    Mode of application

    Bolus injection

    The powder is diluted with water for injection.

    Proportion / solvent ratio

    Bottle

    Solvent (ml)

    1000 mg / 200 mg

    20

    500 mg / 100 mg

    10

    The drug can be administered as a slow intravenous injection with a duration of 3-4 minutes directly into the vein or through a catheter.

    The resulting solution must be introduced within 20 minutes after dilution.

    Infusion introduction:

    The drug is administered intravenously drip for 30-40 minutes, previously dissolving the powder in the volume of water for injection, indicated in the table above, the resulting solution is added to 100 ml of the solvent.

    Solution for intravenous administration

    Stability period with t 25 ° C (hours)

    A solution of sodium chloride (0.9%) isotonic

    4

    Sodium lactate solution for intravenous administration

    4

    Ringer's solution

    3

    Ringer Lactate solution according to Hartman

    3

    Calcium chloride and sodium chloride solution complex for intravenous administration

    3

    Side effects:

    From the digestive system: diarrhea, nausea, vomiting, dyspeptic disorders, colitis (including pseudomembranous and hemorrhagic).

    From the liver and bile ducts: moderate increase in activity of aspartate aminotransferase (ACT) and alanine aminotransferase (ALT), hepatitis, cholestatic jaundice (when combined with other penicillins and cephalosporins), increased activity of alkaline phosphatase and / or bilirubin concentrations.

    From the side of the kidneys and urinary tract: interstitial nephritis, crystalluria, hematuria.

    From the nervous system: dizziness, headache, convulsions (can occur in patients with impaired renal function when taking high doses of the drug), insomnia, agitation, anxiety, behavior change, reversible hyperactivity.

    From the hematopoietic and lymphatic system: reversible leukopenia (including neutropenia), thrombocytopenia, reversible agranulocytosis and hemolytic anemia, prolongation of prothrombin time and bleeding time, eosinophilia, thrombocytosis, anemia.

    Superinfection: Candidiasis of the skin and mucous membranes.

    Local reactions: in some cases - phlebitis in the place of intravenous administration.

    Allergic reactions: skin rash, itching, urticaria, multiforme exudative erythema, angioedema, anaphylactic reactions, whey-like syndrome, allergic vasculitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

    Overdose:

    Gastrointestinal disorders and disturbances in the water-electrolyte balance may occur. These overdose symptoms should be treated symptomatically, focusing on the normalization of the water-electrolyte balance.

    Amoxicillin + clavulanic acid is removed by hemodialysis.

    Interaction:

    Bactericidal antibiotics (including aminoglycosides, cephalosporins, vancomycin, rifampicin) have a synergistic effect; bacteriostatic medicinal products (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) - antagonistic.

    Reduces the effectiveness of oral contraceptives, drugs, in the process of metabolism of which parahaminobenzoic acid is formed, ethinyl estradiol - risk of bleeding "breakthrough".

    Diuretics, allopurinol, phenylbutazone, non-steroidal anti-inflammatory drugs and other drugs that block tubular secretion, increase the concentration of amoxicillin. Allopurinol increases the risk of skin rash. When combined with methotrexate, the toxicity of methotrexate is increased. Do not use concomitantly with disulfiram.Probenecid reduces the excretion of amoxicillin, increasing its serum concentration.

    Taking the drug 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, the Benedict test, Feeling's test). In this case, it is recommended to use a glucose oxidative method to determine the concentration of glucose in the urine.

    Pharmaceutical incompatibility

    Pharmaceutically incompatible with solutions containing blood, proteins, lipids. When used simultaneously with aminoglycosides, antibiotics should not be mixed in a single syringe and in a vial for intravenous fluids, because aminoglycosides lose activity in such conditions.

    The drug solution can not be mixed with solutions of glucose, dextran or sodium bicarbonate.

    Do not mix in a syringe or infusion bottle with other medicines.

    In the literature, rare cases of an increase in the international normalized ratio (INR) in patients with joint use of acenocoumarol or warfarin and amoxicillin are described. If it is necessary to simultaneously prescribe the drug with anticoagulants, prothrombin time or MNO shouldcarefully monitored when the drug is prescribed or withdrawn.

    Special instructions:

    In course treatment it is necessary to monitor the status of the functions of the organs of hematopoiesis, liver and kidneys. With the appointment of patients with sepsis, the development of a bacteriolysis reaction (the Yarisch-Gerxheimer reaction) is possible. In patients who are hypersensitive to penicillins, there may be cross-allergic reactions with cephalosporin antibiotics. If parenteral administration of large doses of the drug is necessary for patients on a diet low in salt, the presence of sodium ion in the preparation should be taken into account. Amoxicillin and clavulanic acid may provoke non-specific binding of immunoglobulins and albumins to the erythrocyte membrane, which may be the cause of a false positive reaction in the Coombs sample. In the presence of high concentrations of amoxicillin in urine, it can precipitate in urinary catheters at room temperature. It is necessary to regularly check the patency of such catheters. Crystalluria, due to the use of amoxicillin-containing drugs, in some cases led to kidney failure.

    Effect on the ability to drive transp. cf.and fur:Given the likelihood of side effects from the central nervous system, care should be taken when driving and working with machinery.
    Form release / dosage:

    Powder for the preparation of a solution for intravenous administration of 500 mg + 100 mg, 1000 mg + 200 mg.

    Packaging:

    For 500 mg of amoxicillin and 100 mg of clavulanic acid or 1000 mg of amoxicillin and 200 mg of clavulanic acid in a bottle of colorless transparent glass (hydrolytic class I), sealed with a rubber stopper and an aluminum cap with a protective plastic lid.

    1 bottle is placed in a cardboard box together with instructions for use.
    Storage conditions:

    Store in a dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-006246/10
    Date of registration:01.07.2010
    Expiration Date:Unlimited
    The owner of the registration certificate:VIAL, LLC VIAL, LLC Russia
    Manufacturer: & nbsp
    Representation: & nbspVIAL, LLCVIAL, LLC
    Information update date: & nbsp19.08.2017
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