Clavulanic acid instructions for use. Amoxicillin Clavulanic acid - a combined antibacterial agent

It is a combination drug of clavulanic acid (a beta-lactamase inhibitor) and amoxicillin. The drug inhibits the formation of the wall of microorganisms, acts bactericidal. This drug is active against aerobic gram-negative microorganisms: Moraxella catarrhalis, Escherichia coli, Enterobacter spp., Haemophilus influenzae, Klebsiella spp., aerobic gram-positive microorganisms (including strains that produce beta-lactamase): Staphylococcus aureus. The following microorganisms are sensitive to the drug only in vitro: Listeria monocytogenes, Streptococcus anthracis, Enterococcus faecalis, Streptococcus viridans, Corynebacterium spp., Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus epidermidis; anaerobic gram-positive bacteria: Clostridium spp., Peptostreptococcus spp., Peptococcus spp.; gram-negative anaerobic bacteria (including strains that produce beta-lactamase): Bacteroides spp. (including Bacteroides fragilis); gram-negative aerobic bacteria (including strains that produce beta-lactamases): Salmonella spp., Proteus mirabilis, Shigella spp., Proteus vulgaris, Bordetella pertussis, Gardnerella vaginalis, Yersinia enterocolitica, Neisseria meningitidis, Haemophilus ducreyi, Neisseria gonorrhoeae, Campylobacter jejuni, Yersinia multocida. Clavulanic acid inhibits beta-lactamases (types 3, 2, 5, 4) and is inactive against type 1 beta-lactamase, which form Serratia spp., Pseudomonas aeroginosa, Acinetobacter spp. Clavulanic acid has a high affinity for penicillinases, therefore it forms a stable complex with the enzyme, which prevents the enzymatic degradation of amoxicillin under the action of beta-lactamases.

When taken orally, both active ingredients of the drug are rapidly absorbed in the gastrointestinal tract. The drug binds to plasma proteins as follows: clavulanic acid binds 22-30%, amoxicillin binds 17-20%. Co-administration of the drug with food does not affect absorption. The maximum concentration is reached after 45 minutes. When taken orally every 8 hours at doses of 250/125 mg, the maximum plasma level of amoxicillin is 2.18 - 4.5 μg / ml, the maximum plasma content of clavulanic acid is 0.8 - 2.2 μg / ml, when taken every 12 hours at doses of 500/125 mg, the maximum plasma level of amoxicillin is 5.09 - 7.91 μg / ml, the maximum plasma content of clavulanic acid is 1.19 - 2.41 μg / ml, when taking the drug every 8 hours in doses of 500/125 mg, the maximum plasma content of amoxicillin is 4.94 - 9.46 mcg / ml, the maximum plasma concentration of clavulanic acid is 1.57 - 3.23 mcg / ml, when taking the drug at a dose of 875/125 mg, the maximum the plasma content of amoxicillin is 8.82 - 14.38 μg / ml, the maximum plasma content of clavulanic acid is 1.21 - 3.19 μg / ml. When administered intravenously in doses of 500/100 mg and 1000/200, the maximum concentration of amoxicillin is 32.2 and 105.4 μg / ml, and the maximum concentration of clavulanic acid is 10.5 and 28.5 μg / ml, respectively. The time to reach a maximum inhibitory concentration of 1 µg/mL is similar for amoxicillin when used at 8 and 12 hours in both children and adults. Both active ingredients are metabolized in the liver: clavulanic acid by 50% of the administered dose, amoxicillin by 10%. When taken at doses of 375 and 625 mg, the half-life is 1.2 and 0.8 hours for clavulanic acid, 1 and 1.3 hours for amoxicillin, respectively.

With the introduction of intravenous 1200 and 600 mg of the drug, the half-life is 0.9 and 1.12 hours for clavulanic acid, 0.9 and 1.07 hours for amoxicillin, respectively. The drug is excreted from the body mainly by the kidneys (with tubular secretion, as well as filtration in the glomeruli of the kidneys) as follows: 25 - 40% and 50 - 78% of the administered dose of clavulanic acid and amoxicillin, respectively, is excreted within the first 6 hours after administration in unchanged form .

Indications

Bacterial infections caused by susceptible microorganisms: ENT organs (otitis media, tonsillitis, sinusitis), soft tissues and skin (abscess, erysipelas, secondarily infected dermatoses, impetigo, wound infection, cellulitis), pelvic organs and genitourinary system (pyelitis, pyelonephritis, prostatitis, cystitis, cervicitis, salpingitis, urethritis, tubo-ovarian abscess, salpingoophoritis, septic abortion, endometritis, bacterial vaginitis, chancre, pelvioperitonitis, postpartum sepsis, gonorrhea), lower respiratory tract (lung abscess, pneumonia, pleural empyema, bronchitis) , postoperative infections, osteomyelitis, in surgery for the prevention of infections.

Method of application of amoxicillin + clavulanic acid and doses

The drug is taken orally, administered intravenously. Doses and regimen of the drug are set on an individual basis and depend on the infectious disease and its severity. In terms of amoxicillin, the doses are given below.
Patients under 12 years old - in the form of drops, syrup, suspension for oral use.
Patients over 12 years of age or weighing more than 40 kg: 250 mg 3 times a day or 500 mg 2 times a day. For infections of the respiratory system, as well as for severe infections - 3 times a day 500 mg or 2 times a day 875 mg.
Depending on age, a single dose is established: up to 3 months - in 2 doses of 30 mg / kg per day; 3 months or more - severe infections - in 3 doses of 40 mg / kg per day or in 2 doses of 45 mg / kg per day; infections of mild severity - in 3 doses of 20 mg / kg per day or in 2 doses of 25 mg / kg per day.
The maximum daily dose of clavulanic acid for patients over 12 years old is 600 mg, up to 12 years old - 10 mg / kg of body weight. The maximum daily dose of amoxicillin for patients over 12 years old is 6 g, up to 12 years old - 45 mg / kg of body weight.
The use of the suspension in adults with difficulty in swallowing is recommended.
When preparing syrup, suspension and drops, water must be used as a solvent.
When administered intravenously, patients over 12 years of age are administered 3 times a day 1 g (according to amoxicillin), it is possible, if necessary, to administer 4 times a day. The maximum daily dose is 6 grams. Children 3 months - 12 years - 3 times a day 25 mg / kg; in severe cases - 4 times a day; children under 3 months: in the perinatal period and premature - 2 times a day 25 mg / kg, in the postperinatal period - 3 times a day 25 mg / kg.
The duration of therapy is up to 2 weeks, for acute otitis media - up to 10 days.
Prevention during operations of postoperative infections, the duration of the operation is less than 1 hour, administered intravenously at a dose of 1 g during induction anesthesia. For longer operations, 1 g is administered every 6 hours for 24 hours; the introduction can be continued for several days at a high risk of infection.
In chronic renal failure, depending on creatinine clearance, the frequency of administration and dose are adjusted: with creatinine clearance greater than 30 ml / min, dose adjustment is not necessary; with a creatinine clearance of 10-30 ml / min: inside - 250-500 mg per day every 12 hours; intravenously - 1 g, then 500 mg intravenously; with creatinine clearance less than 10 ml / min - 1 g, 250 - 500 mg per day orally in one dose or then 500 mg per day intravenously. For children, doses should also be reduced. Patients who are on hemodialysis - 500 mg or 250 mg orally in a single dose or 500 mg intravenously, an additional one dose during dialysis and one dose at the end of dialysis.

With course therapy, it is necessary to monitor the state of the liver, hematopoietic organs and kidneys. To reduce the risk of developing adverse reactions from the digestive system, the drug must be taken with meals. The growth of resistant microflora to the drug is possible, which can lead to the development of superinfection, and this will require a change in antibacterial treatment. Taking the drug when determining glucose in the urine can give a false positive result. Therefore, it is recommended to use a glucose oxidant method for determining the content of glucose in the urine. After diluting the suspension, it must be stored in the refrigerator for no more than 1 week, but do not freeze. In patients who have hypersensitivity to penicillins, with cephalosporin antibiotics, cross-allergic reactions may develop. There are cases of development in newborns of necrotizing colitis, whose mothers had a premature rupture of the membranes of the fetus. Since the tablets have an equal amount of clavulanic acid (125 mg), it is necessary to know that two 250 mg tablets (for amoxicillin) to one 500 mg tablet (for amoxicillin) are not equivalent.

Contraindications for use

Hypersensitivity (including to other beta-lactam antibiotics, cephalosporins), phenylketonuria, infectious mononucleosis (including with the development of a measles rash), a history of impaired liver function or episodes of jaundice when using amoxicillin with clavulanic acid; creatinine clearance less than 30 ml / min (for tablets 875 mg / 125 mg).

Application restrictions

Diseases of the gastrointestinal tract (including a history of colitis, which is associated with the use of penicillins), lactation, chronic renal failure, pregnancy, severe liver failure.

Use during pregnancy and lactation

During pregnancy and lactation, the drug is used only when the expected benefit to the mother is higher than the possible risk to the child and fetus.

Side effects of amoxicillin + clavulanic acid

Digestive system: nausea, vomiting, gastritis, glossitis, stomatitis, increased activity of liver transaminases, diarrhea, in rare cases - the development of hepatitis and liver failure (usually in elderly men with prolonged treatment), cholestatic jaundice, hemorrhagic and pseudomembranous colitis (may also develop after treatment), "hairy" black tongue, enterocolitis, darkening of tooth enamel;
hematopoietic organs: reversible increase in bleeding time, as well as prothrombin time, thrombocytopenia, eosinophilia, thrombocytosis, agranulocytosis, leukopenia, hemolytic anemia;
nervous system: dizziness, hyperactivity, headache, anxiety, seizures, behavior change;
local reactions: in some cases, the development of phlebitis at the site of intravenous injection;
allergic reactions: erythematous rashes, urticaria, rarely - the development of angioedema, erythema multiforme exudative, anaphylactic shock, very rarely - malignant exudative erythema, exfoliative dermatitis, allergic vasculitis, acute generalized exanthematous pustulosis syndrome, which is similar to serum sickness;
others: the appearance of superinfection, candidiasis, interstitial nephritis, hematuria, crystalluria.

Interaction of amoxicillin + clavulanic acid with other substances

Glucosamine, antacids, aminoglycosides, laxatives reduce and slow absorption; ascorbic acid increases absorption. Bacteriostatic drugs (chloramphenicol, macrolides, tetracyclines, lincosamides, sulfonamides) act antagonistically. Increases the effectiveness of indirect anticoagulants (by suppressing the intestinal microflora, reducing the prothrombin index and the synthesis of vitamin K). When used together with anticoagulants, it is necessary to control blood clotting parameters. Reduces the effectiveness of oral contraceptives, drugs, during the metabolism of which PABA is formed. When combined with ethinyl estradiol, the risk of breakthrough bleeding increases. Allopurinol increases the chance of developing a skin rash. Diuretics, phenylbutazone, allopurinol, non-steroidal anti-inflammatory drugs and other drugs that block tubular secretion increase the content of amoxicillin.

Overdose

In case of an overdose of the drug, the water-electrolyte balance and the functional state of the gastrointestinal tract are disturbed. Symptomatic treatment is necessary; hemodialysis is effective.

Description of the active ingredient

pharmachologic effect

Beta-lactamase inhibitor. Produced by cultures of Streptomyces clavuligerus. It has a beta-lactam structure similar to the structure of the core of the penicillin molecule, in contrast to which it contains an oxazolidine ring instead of a closed thiazolidine ring. It has weak antimicrobial activity. It is an inhibitor of beta-lactamase produced by gram-negative bacteria, including Haemophilus ducreyi, Haemophilus influenzae, Neisseria gonorrhoeae, Moraxella (Branhamella) catarrhalis, Bacteroides fragilis and some Enterobacter spp. In addition, it inhibits Staphylococcus aureus beta-lactamase. It has the ability to penetrate the wall of a bacterial cell and cause inactivation of enzymes located both inside the cell and at its border. Acts as a competitive and often irreversible inhibitor.

Indications

In combination with amoxicillin or ticarcillin for the treatment of infectious and inflammatory diseases caused by microorganisms sensitive to the combination used.

Dosing regimen

Individual, depending on the indications, the age of the patient, the dosage form used.

Side effect

From the side of the cardiovascular system: rarely when taken orally - dyspepsia, liver dysfunction, hepatitis, cholestatic jaundice; in some cases - pseudomembranous colitis.

Allergic reactions: in some cases - erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, as well as urticaria, Quincke's edema, anaphylactic shock.

Others: in some cases - candidiasis.

Contraindications

Hypersensitivity to clavulanic acid.

Pregnancy and lactation

In combination with amoxicillin or ticarcillin, use during pregnancy is possible only if there are vital indications, in other cases, the use is not recommended.

Application for violations of liver function

special instructions

IV should be used with caution in patients with severe hepatic impairment.

Treatment should be discontinued if urticaria or an erythematous rash occurs.

Catad_pgroup Antibiotics penicillins

Amoxiclav intravenously - instructions for use

INSTRUCTIONS
on the medical use of the drug

Registration number:

P N012124/02

Trade name of the drug:

Amoxiclav ®

International non-proprietary name:

amoxicillin + clavulanic acid.

Dosage form:

powder for solution for intravenous administration.

Compound:

1 vial contains:
Amoxiclav ® 500 mg + 100 mg: 500 mg of amoxicillin (in the form of sodium salt) and 100 mg of clavulanic acid (in the form of potassium salt).
Amoxiclav ® 1000 mg + 200 mg: 1000 mg of amoxicillin (in the form of sodium salt) and 200 mg of clavulanic acid (in the form of potassium salt).

Description:
white to yellowish white powder.

Pharmacotherapeutic group:

antibiotic - semi-synthetic penicillin + beta-lactamase inhibitor.

CodeATX: J01CR02

Pharmacological properties:

Pharmacodynamics
Mechanism of action
Amoxicillin is a semi-synthetic broad-spectrum antibiotic with activity against many gram-positive and gram-negative microorganisms. Amoxicillin inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan metabolism, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death. At the same time, amoxicillin is susceptible to destruction by beta-lactamases, and therefore the spectrum of activity of amoxicillin does not apply 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 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 I chromosomal beta-lactamases, which are not inhibited by clavulanic acid.
The presence of clavulanic acid in the preparation protects amoxicillin from destruction by enzymes - beta-lactamases, which allows expanding the antibacterial spectrum of amoxicillin.
The following is the activity of the combination of amoxicillin with clavulanic acid in vitro.
Bacteria normally sensitive to the combination of amoxicillin with clavulanic acid
Gram-positive aerobes: Bacillus anthracis Enterococcus faecalis Listeria monocytogenes Nocardia asteroiaes Streptococcus pyogenes methicillin), coagulase-negative staphylococci (sensitive to methicillin).
Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae 1 Helicobacter pylori, . Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.
Others : Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.
Gram-positive anaerobes: species of the genus Clostridium, Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, species of the genus Peptostreptococcus.
Gram-negative anaerobes: Bacteroiaes fragilis, species of the genus Bacteroides, species of the genus Capnocytophaga, tikenella corrodens, Fusobacterium nucleatum, species of the genus Fusobacterium, species of the genus Porphyromonas, species of the genus Prevotella.

Bacteria likely to become resistant to the combination of amoxicillin with clavulanic acid
Gram-negative aerobes: Escherichia coH1, Klebsiella oxytoca, Klebsiella pneumoniae, species of the genus Klebsiella, Proteus mirabilis, Proteus vulgaris, species of the genus Proteus, species of the genus Salmonella, species of the genus Shigella.
Gram-positive aerobes: species of the genus Corynebacterium, tnterococcus faecium, Streptococcus pneumoniae 1,2, Streptococcus group Viridans.

Bacteria that are naturally resistant to the combination of amoxicillin with clavulanic acid
Gram-negative aerobes: species of the genus Acinetobacter, Citrobacter freundii, species of the genus tnterobacter, Hafnia alvei, Legionella pneumophila, Morganella morganii, species of the genus Providencia, species of the genus Pseudomonas, species of the genus Serratia Stenotrophomonas maltophilia, Yersinia enterocolitica.
Others : Chlamydia pneumoniae, Chlamydia psittaci, species of the genus Chlamydia, Coxiella burnetii, species of the genus Mycoplasma.
1 for these bacteria, the clinical efficacy of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.
2 strains of these bacterial species do not produce beta-lactamase. Sensitivity with amoxicillin monotherapy suggests a similar sensitivity to the combination of amoxicillin with clavulanic acid.

Pharmacokinetics
Suction
Below are the results of a pharmacokinetic study with intravenous bolus administration of amoxicillin and clavulanic acid at a dosage of 500 mg + 100 mg (0.6 g) or 1000 mg + 200 mg (1.2 g) to healthy volunteers for 30 minutes.

Average value of pharmacokinetic parameters

Mean (± SD) pharmacokinetic parameters
Operating substances	single dose (mg)	Сmax (µg/ml)	Т½ (h)	AUC (h*mg/l)	excretion with urine, % 0-6 h
Amoxicillin	500	32,2	1,07	25,5	66,5
Amoxicillin	1000	105,4	0,9	76,3	77,4
Clavulanic acid	100	10,5	1,12	9,2	46,0
Clavulanic acid	200	28,5	0,9	27,9	63,8

Cmax - maximum concentration in blood plasma;
AUC - area under the concentration-time curve;
T½ - half-life.
Distribution
With intravenous administration of a combination of amoxicillin with clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are found in various tissues and interstitial fluid (in the gallbladder, abdominal tissues, skin, adipose and muscle tissues, synovial and peritoneal fluids, bile, purulent discharge).
Amoxicillin and clavulanic acid have a weak degree of binding to plasma proteins. Studies have shown that about 13-20% of each of the components of the drug Amoxiclav ® binds to blood plasma proteins.
In animal studies, no accumulation of the components of the drug Amoxiclav ® in any organ was found.
Amoxicillin, like most penicillins, passes into breast milk. Trace amounts of clavulanic acid can also be found in breast milk. With the exception of the possibility of developing diarrhea or candidiasis of the mucous membranes of the oral cavity, no other negative effects of amoxicillin and clavulanic acid on the health of breastfed infants are known. Reproductive studies in animals have shown that amoxicillin and clavulanic acid cross the placental barrier. However, there was no negative effect on the fetus.
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 to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and excreted by the kidneys, through the gastrointestinal tract (GIT), as well as with exhaled air in the form of carbon dioxide.
breeding
Like other penicillins, amoxicillin is excreted mainly by the kidneys, while clavulanic acid is excreted through both renal and extrarenal mechanisms. Approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted unchanged by the kidneys in the first 6 hours after a single bolus injection of Amoxiclav ® at a dosage of 500 mg + 100 mg or 1000 mg + 200 mg.
The simultaneous administration of probenecid slows down the excretion of amoxicillin, but does not slow down the renal excretion of clavulanic acid.
The pharmacokinetics of amoxicillin / clavulanic acid does not depend on the patient's gender.
Patients with impaired renal function
The total clearance of amoxicillin / clavulanic acid decreases in proportion to the decrease in renal function. The decrease in clearance is more pronounced for amoxicillin than for clavulanic acid, tk. Most amoxicillin is excreted by the kidneys. Doses of the drug in renal failure should be selected taking into account the undesirability of cumulation of amoxicillin while maintaining a normal level of clavulanic acid.
Patients with impaired liver function
In patients with impaired liver function, the drug is used with caution, it is necessary to constantly monitor liver function.
Both components are removed by hemodialysis and minor amounts by peritoneal dialysis.

Indications for use

Infections caused by strains of microorganisms sensitive to the combination of amoxicillin with clavulanic acid (including mixed infections caused by gram-negative and gram-positive aerobic and anaerobic bacteria):

infections of the upper respiratory tract and ENT organs (acute and chronic sinusitis, acute and chronic otitis media, tonsillitis);
infections of the lower respiratory tract (exacerbation of chronic bronchitis, lobar pneumonia and bronchopneumonia);
urinary tract infections (cystitis, urethritis, pyelonephritis);
infections in gynecology;
skin and soft tissue infections, including human and animal bites;
bone and joint infections (eg, osteomyelitis);
abdominal infections, incl. biliary tract (cholecystitis, cholangitis);
sexually transmitted infections (gonorrhea, chancre);
prevention of infections after surgical interventions.

Contraindications

hypersensitivity to amoxicillin and other penicillins, clavulanic acid, other components of the drug;
history of severe hypersensitivity reactions (eg, anaphylactic reactions) to other beta-lactam antibiotics (cephalosporin, carbapenem, or monobactam);
cholestatic jaundice and / or other abnormal liver function caused by the use of amoxicillin / clavulanic acid in history.

Carefully
With a history of pseudomembranous colitis, diseases of the gastrointestinal tract, liver failure, severe renal impairment (creatinine clearance

Use during pregnancy and during breastfeeding
Pregnancy
In studies of reproductive function in preclinical studies, parenteral administration of the drug amoxicillin + clavulanic acid 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 neonatal necrotizing enterocolitis. Amoxiclav is not recommended for use during pregnancy unless the expected benefit to the mother outweighs the potential risk to the fetus.
Breast-feeding
With the exception of the possibility of developing sensitization, diarrhea or candidiasis of the mucous membranes of the oral cavity associated with the penetration of trace amounts of the active ingredients of this drug into breast milk, no other adverse reactions were observed in breast-fed infants. However, during breastfeeding, Amoxiclav® is used only if the intended benefit to the mother outweighs the potential risk to the fetus and child. If adverse reactions occur, breastfeeding should be discontinued.

Interaction with other drugs
Co-administration with probenecid is not recommended. Probenecid reduces tubular secretion of amoxicillin. The simultaneous use of probenecid can lead to an increase and prolongation of the concentration of amoxicillin in the blood, but not clavulanic acid.
Diuretics, allopurinol, phenylbutazone, non-steroidal anti-inflammatory drugs (NSAIDs) and other drugs that block tubular secretion increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).
The simultaneous use of the drug Amoxiclav ® and methotrexate increases the toxicity of methotrexate.
Bacteriological drugs ( macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) have an antagonistic effect. Reduces the effectiveness of drugs, in the process of metabolism of which para-aminobenzoic acid is formed, ethinylestradiol - the risk of bleeding "breakthrough". Increases the effectiveness of indirect anticoagulants (suppressing the intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). In some cases, taking the drug may lengthen the prothrombin time, in this regard, care should be taken when using anticoagulants and Amoxiclav ® at the same time.
Indirect anticoagulants and penicillin antibiotics are widely used in practice; interactions were not noted. However, the literature describes cases of an increase in the international normalized ratio (INR) in patients with the simultaneous use of acenocoumarin or warfarin with amoxicillin. If necessary, simultaneous use with anticoagulants, prothrombin time or INR should be carefully monitored when prescribing or discontinuing the drug, dose adjustment of anticoagulants may be required.
In patients receiving mycophenolate mofetil, after the start of the 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 overall changes in mycophenolic acid exposure.
The simultaneous 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. When combined with rifampicin, a mutual weakening of the antibacterial effect is observed.
Avoid concomitant use with disulfiram.
The drug Amoxiclav ® and aminoglycoside antibiotics are physically and chemically incompatible. The simultaneous use of amoxicillin and digoxin can lead to an increase in the concentration of digoxin in the blood plasma.
The drug Amoxiclav ® reduces the effectiveness of oral contraceptives.
Pharmaceutical incompatibility
Amoxiclav should not be mixed with blood products, other protein-containing fluids such as protein hydrolases, or with intravenous lipid emulsions. When used simultaneously with aminoglycosides, antibiotics should not be mixed in the same syringe or in the same vial for intravenous fluids, since under such conditions aminoglycosides lose their activity.
Avoid mixing with solutions of dextrose, dextran, sodium bicarbonate.

special instructions

Before starting treatment, it is necessary to interview the patient to identify a history of hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics.
Serious and sometimes fatal hypersensitivity 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 stop treatment with Amoxiclav ® and prescribe an appropriate alternative therapy. Serious anaphylactic reactions should promptly administer epinephrine to the patient. Oxygen therapy, intravenous glucocorticosteroids, and airway management, including intubation, may also be required. If infectious mononucleosis is suspected, Amoxiclav ® should not be used, since in patients with this disease, amoxicillin can cause a measles-like rash, which makes it difficult to diagnose the disease.
Amoxiclav should be used with caution in patients with signs of hepatic impairment.
Liver complications have been reported predominantly in men and elderly patients and may also be associated with long-term treatment. Such cases have been very rarely reported in children. In all patient groups, signs and symptoms usually appear during or shortly after treatment, but in some cases may not appear until several weeks after treatment is stopped. They are usually reversible. Liver complications can be severe, and deaths have been reported in extremely rare cases. They almost always occurred in patients with severe comorbidities or in the case of the concomitant use of drugs that potentially affect the liver.
Cases of pseudomembranous colitis have been described with antibiotics, the severity of which can vary from mild to life-threatening. Thus, it is important to diagnose it in patients who develop diarrhea during or after antibiotic use. If diarrhea is prolonged 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, the drug Amoxiclav ® is well tolerated and has a low toxicity characteristic of all penicillins. During the course of treatment, it is necessary to monitor the state of the function of the hematopoietic organs, liver, kidneys.
In patients receiving a combination of amoxicillin with clavulanic acid together with indirect (oral) anticoagulants, an increase in prothrombin time (INR) has been reported in rare cases. With the joint appointment of indirect (oral) anticoagulants with a combination of amoxicillin with clavulanic acid, it is necessary to control the relevant indicators. To maintain the desired effect of oral anticoagulants, dose adjustment may be required.
In patients with severely impaired renal function, an adequate dose adjustment or an increase in the intervals between dosing is required, depending on the indicators of creatinine clearance. Perhaps the development of superinfection due to the growth of microflora insensitive to it, which requires a corresponding change in antibiotic therapy.
In patients with hypersensitivity to penicillins, cross-allergic reactions with cephalosporin antibiotics are possible.
In women with premature rupture of membranes, it has been found that prophylactic therapy with the combination of amoxicillin + clavulanic acid may be associated with an increased risk of neonatal necrotizing colitis. Amoxicillin and clavulanic acid can provoke non-specific binding of immunoglobulins and albumins to the erythrocyte membrane, which may be the cause of a false positive Coombs test.
In patients with reduced diuresis, crystalluria very rarely occurs. During the administration of large doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.
The drug contains potassium.
Information for Patients on a Low Sodium Diet: Each 600 mg vial (500 mg + 100 mg) contains 29.7 mg sodium. Each 1.2 g vial (1000 mg + 200 mg) contains 59.3 mg sodium. The amount of sodium in the maximum daily dose exceeds 200 mg.
Lab tests: high concentrations of amoxicillin give a false positive reaction to urine glucose when using Benedict's reagent or Felling's solution.
It is recommended to use enzymatic reactions with glucose oxidase. Cases of positive test results using the Bio-Rad Laboratories Platelia Aspergillus Enzyme Immunoassay have been reported in patients receiving amoxicillin/clavulanic acid who subsequently did not develop infection. Aspergillus. Cross-reactions with polysaccharides of non- Aspergillus and polyfurans with Bio-Rad Laboratories Platelia Aspergillus Enzymatic Immunoassay. Therefore, care should be taken when interpreting positive test results in patients receiving amoxicillin/clavulanic acid, and it is also necessary to confirm them using other diagnostic methods.
Special precautions for the disposal of unused medicinal product.
There is no need for special precautions when destroying the unused drug Amoxiclav ® .

Influence on the ability to drive vehicles, mechanisms
Due to the possibility of developing side effects from the central nervous system, such as: dizziness, headache, convulsions, during treatment, care should be taken when driving and engaging in other activities that require concentration and psychomotor speed.

Release form

Powder for solution for intravenous administration 500 mg + 100 mg, 1000 mg + 200 mg.
500 mg of amoxicillin and 100 mg of clavulanic acid or 1000 mg of amoxicillin and 200 mg of clavulanic acid in a colorless glass bottle, closed with a rubber stopper and crimped with an aluminum cap with a plastic cap. 5 bottles in a carton box along with instructions for use.

Storage conditions

Store in a place protected from light at a temperature not exceeding 25°C.
Keep out of the reach of children!

Best before date

2 years.
Do not use the drug after the expiration date indicated on the package!

Terms of dispensing from pharmacies

On prescription.

Manufacturer

RU holder:
Lek d.d., Verovshkova 57, 1526, Ljubljana, Slovenia.
Produced:
1. Lek d.d. Verovshkova 57, Ljubljana, Slovenia;
2. Sandoz GmbH, Biochemistrasse 10 A-6250, Kundl Austria;
Send consumer claims to ZAO Sandoz:
125315, Moscow, Leningradsky prospect, 72, bldg. 3;

Registration number:

Validity period of the registration certificate:

12/29/2014 to 12/29/2019

Compound

active substances: amoxicillin and clavulanic acid;

1 tablet contains amoxicillin 500 mg and clavulanic acid 125 mg;

Excipients: magnesium stearate, sodium starch glycolate (type A), anhydrous colloidal silicon dioxide, microcrystalline cellulose;

shell: SeleCoat TM coating (hypromelose, polyethylene glycol, titanium dioxide (E 171)).

Dosage form
Coated tablets.

Basic physical and chemical properties: oblong tablets with a biconvex surface, with a line on one side, coated white or almost white.

Pharmacotherapeutic group

Antibacterial agents for systemic use.

ATX code J01C R02.

pharmacological properties.

Pharmacodynamics.

Amoxicillin-Clavulanate is a combination of amoxicillin, an antibiotic with a wide spectrum of antibacterial action, and clavulanic acid, an OI-lactamase inhibitor, forming stable inactive complex compounds with them and protecting amoxicillin from decay. It acts bactericidal, inhibits the synthesis of the bacterial wall.

The drug has a wide spectrum of antimicrobial activity.

The organisms below are categorized according to susceptibility to amoxicillin/clavulanate in vitro.

Sensitive microorganisms:

Gram-positive aerobes: Bacillus anthracis,Entererococcus faecalis,Listeria monocytogenes,Nocardia asteroids,Streptococcus pneumoniae,Streptococcus pyogenes,Streptococcus agalacticae,Streptococcus viridans, other OI-hemolytic species Streptococcus,Staphylococcus aureus(methicillin-sensitive strains), Staphylococcus saprophyticus(methicillin-sensitive strains), coagulase-negative staphylococci (methicillin-sensitive strains);

Gram-negative aerobes: Bordatella pertussis,Heamophilus influenza,haemophilus parainfluenzae,Helicobacter pylori,Moraxella catarrhalis,Neisseria gonorrhoeae,Pasteurella multocida,Vibrio cholera.

Other: Borrelia burgdorferi,Leptospirosa ictterohaemorrhagiae,Treponema pallidum.

Gram positive anaerobes: kinds Clostridium,Peptococcus niger,Peptostreptococcus magnus,Peptostreptococcus micros, kinds Peptostreptococcus.

Gram negative anaerobes: kinds Bacteroides(including Bacteroides fragilis),kinds Capnotophaga,Eikenella corrodens,kinds Fusobacterium,kinds Porphyromonas,kinds Prevotella.

Strains with possible acquired resistance:

Gram-negative aerobes: Escherichia coli,Klebsiella oxytoca,Klebsiella pneumonia, kinds Klebsiella,Proteus mirabilis,Proteus vulgaris, kinds Proteus, kinds Salmonella, kinds Shigella;

Gram-positive aerobes: kinds Corynebacterium,Enterococcus faecium.

Insensitive microorganisms:

Gram-negative aerobes: kinds Acinetobacter,Citrobacter freundii, kinds Enterobacter,Hafnia alvei, Legionella pneumophila,Morganella morganii, kinds Providencia,kinds Pseudomonas,kinds Serratia,Stenotrophomas maltophilia,Yersinia enterolitica.

Other: Chlamydia pneumonia,Chlamydia psittaci,kinds Chlamydia,Coxiella burnetti,kinds Mycoplasma.

Pharmacokinetics.

The pharmacokinetic parameters of the two components of the drug are closely connected. The peak serum concentration of the two components is reached approximately 1 hour after oral administration of the drug. The optimal level of absorption is achieved if the drug is taken at the beginning of a meal.

A double dose of the drug approximately doubles its serum level.

Both components of the drug, both clavulanate and amoxicillin, have a low level of binding to serum proteins, approximately 70% of them remain in the blood serum in an unbound state.

Clinical Characteristics

Indications

Treatment of bacterial infections caused by susceptible microorganisms, such as:

– acute bacterial sinusitis;

- confirmed exacerbation of chronic bronchitis;

- cystitis;

- pyelonephritis;

- infections of the skin and soft tissues, including cellulitis, animal bites, severe dentoalveolar abscesses with widespread cellulitis;

- infections of bones and joints, including osteomyelitis.

Contraindications

Hypersensitivity to any components of the drug, to any antibacterial agents of the penicillin group.

A history of severe hypersensitivity reactions (including anaphylaxis) associated with the use of other OI-lactam agents (including cephalosporins, carbapenems, or monobactams).

A history of jaundice or liver dysfunction associated with the use of amoxicillin/clavulanate.

Interaction with other drugs and other types of interactions.

Co-administration of probenecid is not recommended. Probenecid reduces the renal tubular secretion of amoxicillin. Its simultaneous use with the drug can lead to an increase in blood levels of amoxicillin for a long time, but does not affect the levels of clavulanic acid.

Penicillins can reduce the excretion of methotrexate, which may cause an increase in the toxicity of the latter.

The simultaneous use of allopurinol during treatment with amoxicillin increases the likelihood of allergic skin reactions. There are no data on the simultaneous use of amoxicillin / clavulanic acid and allopurinol.

Like other antibiotics, Amoxicillin-Clavulanate can affect the intestinal flora, which leads to a decrease in estrogen reabsorption and a decrease in the effectiveness of combined oral contraceptives.

An increase in international normalized ratio (INR) has been reported in patients treated with acenocoumarol or warfarin and taking amoxicillin. If such use is necessary, the prothrombin time or MHC level should be carefully monitored, and, if necessary, treatment with this drug.

In patients treated with mycophenolate mofetil, after initiation of oral amoxicillin with clavulanic acid, the predose concentration of the active metabolite of mycophenolic acid may decrease by approximately 50%. This change in pre-dose level may not correspond to a change in total exposure to mycophenolic acid.

Application features

Before starting therapy with the drug, it is necessary to accurately determine whether the patient has a history of hypersensitivity reactions to penicillins, cephalosporins or other allergens.

Serious and sometimes even fatal cases of hypersensitivity (anaphylactic reactions) have been observed during penicillin therapy. These reactions are most likely in patients with similar reactions to penicillin in the past. In the event of allergic reactions, therapy with this drug should be discontinued and alternative therapy initiated. Serious anaphylactic reactions require immediate treatment with epinephrine. Oxygen therapy, intravenous steroids, and respiratory support, including intubation, may also be needed.

If it is proven that the infection is caused by microorganisms sensitive to amoxicillin, it is necessary to evaluate the possibility of switching from the combination of amoxicillin / clavulanic acid to amoxicillin in accordance with official recommendations.

Amoxicillin-clavulanate should not be prescribed if infectious mononucleosis is suspected, since cases of a measles-like rash have been observed during the use of amoxicillin in this pathology.

Prolonged use of the drug can sometimes cause an excessive increase in microflora insensitive to it.

The development of erythema multiforme associated with pustules at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis. In this case, it is necessary to stop treatment, and further use of amoxicillin is contraindicated.

Adverse reactions from the liver occurred mainly in men and elderly patients and were associated with long-term treatment. In children, such phenomena were observed very rarely. In all patient groups, symptoms usually occurred during or immediately after treatment, but in some cases they appeared several months after treatment was stopped. In general, these phenomena were reversible. Adverse reactions from the liver can be severe and very rarely fatal. They have always occurred in patients with severe comorbidities or concomitant use of drugs known to have potential adverse effects on the liver.

Patients with impaired renal function should adjust the dose in accordance with the degree of renal insufficiency (see section "Method of application and dosage").

When treating with amoxicillin, enzymatic reactions with glucose oxidase should be used to determine the level of glucose in the urine, since other methods may give false positive results.

The presence of clavulanic acid in the preparation can cause non-specific binding of IgG and albumin on erythrocyte membranes, as a result of which a false positive Coombs test result is possible.

There are reports of false positive test results for Aspergillus in patients receiving amoxicillin/clavulanic acid (using the Bio-Rad Laboratories Platelis Aspergillus EIA test). Therefore, such positive results in patients treated with amoxicillin/clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.

With the use of almost all antibacterial drugs, antibiotic-associated colitis has been reported, which can range from mild to life-threatening. Therefore, it is important to keep this in mind if patients develop diarrhea during or after antibiotic use. In the event of antibiotic-associated colitis, treatment with the drug should be stopped immediately and appropriate treatment initiated.

Occasionally, patients taking Amoxicillin-Clavulanate and oral anticoagulants may experience an increase in prothrombin time (increased MHC levels) above normal. When taking anticoagulants at the same time, appropriate monitoring is necessary. Dose adjustment of oral anticoagulants may be required to maintain the required level of anticoagulation.

For patients with impaired renal function and creatinine clearance of 30 ml / min or more, it is not necessary to change the dose of the drug. If the level of creatinine clearance is less than 30 ml / min, it is not recommended to use the drug (see section "Method of administration and doses").

In patients with reduced urinary excretion, crystalluria can very rarely be observed, mainly with parenteral administration of the drug. Therefore, to reduce the likelihood of crystalluria, it is recommended to maintain an adequate water balance during treatment with high doses of amoxicillin (see section "Overdose").

Amoxicillin-Clavulanate should be used with caution in patients with signs of hepatic impairment.

Use during pregnancy or lactation.

In one study in women with premature rupture of the membranes of the fetus, prophylactic use of amoxicillin with clavulanic acid was associated with an increased risk of neonatal necrotizing enterocolitis. The use of the drug during pregnancy should be avoided, except when the doctor considers it necessary.

Both active components of the drug are excreted into breast milk (there is no information on the effect of clavulanic acid on children who are breastfed). Breastfeeding babies may develop diarrhea and fungal infections of the mucous membranes, so breastfeeding should be discontinued.

The ability to influence the reaction rate when driving vehicles or operating other mechanisms.

Studies of the effect of the drug on the reaction rate when driving vehicles or operating other mechanisms have not been conducted. However, adverse reactions (such as allergic reactions, dizziness, convulsions) are possible, which may affect the ability to drive vehicles or operate other mechanisms.

Dosage and administration

The drug should be used in accordance with official recommendations for antibiotic therapy and local antibiotic susceptibility data. Sensitivity to amoxicillin/clavulanate varies by region and may change over time. If available, local susceptibility data should be consulted and, if necessary, microbiological determination and susceptibility testing performed.

The range of suggested doses depends on the expected pathogens and their sensitivity to antibacterial drugs, the severity of the disease and the location of the infection, the age, body weight and kidney function of the patient.

For adults and children weighing ≥ 40 kg, the daily dose is 1500 mg amoxicillin / 375 mg clavulanic acid (3 tablets), when prescribed as follows.

For children over 6 years of age with a body weight of 25 to 40 kg, the maximum daily dose is 2400 mg amoxicillin / 600 mg clavulanic acid (4 tablets), when prescribed as follows.

If high doses of amoxicillin are to be prescribed for treatment, other dosage forms of this combination should be used to avoid prescribing unnecessary high doses of clavulanic acid.

The duration of treatment is determined by the patient's clinical response to treatment. Some infections (such as osteomyelitis) require longer treatment.

Adults and children weighing ≥ 40 kg appoint 1 tablet 3 times a day.

Children over 6 years of age with a body weight of 25 to 40 kg- a dose of 20 mg / 5 mg per 1 kg of body weight per day to 60 mg / 15 mg per 1 kg of body weight per day, divided into 3 doses.

Since the tablet cannot be divided, children whose body weight is less than 25 kg are not prescribed this form of the drug.

Elderly patients

Dose adjustment in elderly patients is not needed. If necessary, the dose is adjusted depending on the function of the kidneys.

Dosing for impaired renal function

Dosing is based on the calculation of the maximum level of amoxicillin. There is no need to change the dose to the patient with creatinine clearance> 30 ml / min.

Adults and children weighing ≥ 40 kg

Children over 6 years of age weighing 25 to 40 kg with impaired renal function

Since the tablet cannot be divided, children over 6 years old with a body weight of 25 to 40 kg, a creatinine clearance of less than 30 ml / min, or children on hemodialysis, are not prescribed this form of the drug.

Dosing in Impaired Liver Function Apply with caution; it is necessary to regularly monitor liver function.

The tablet should be swallowed whole, without chewing. If necessary, the tablet can be broken in half and swallowed in half without chewing.

For optimal absorption and to reduce 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 assessing the patient's condition.

Treatment can begin with parenteral administration, and then continue with oral administration.

Children.

The drug in this dosage is used for children over 6 years old with a body weight of at least 25 kg.

Overdose

An overdose may be accompanied by symptoms from the digestive tract (nausea, vomiting, diarrhea) and disorders of the water and electrolyte balance, agitation, insomnia, dizziness, and sometimes convulsions are possible. These symptoms are treated symptomatically, special attention is paid to the correction of water and electrolyte balance.

Crystalluria of amoxicillin may be observed, which in some cases can lead to renal failure. There are reports of precipitation of amoxicillin in the urinary catheter when high doses of intravenous amoxicillin with clavulanic acid are used. The patency of the catheter should be checked regularly.

Treatment: symptomatic therapy. The drug can be removed from the bloodstream by hemodialysis.

Adverse reactions

Infections and infestations: genital candidiasis, candidiasis of the skin and mucous membranes, excessive increase in insensitive microflora.

From the blood system: reversible leukopenia (including neutropenia) and thrombocytopenia, reversible agranulocytosis, hemolytic anemia, increased bleeding time and prothrombin index.

From the immune system: angioedema, anaphylaxis, serum-like syndrome, allergic vasculitis.

From the nervous system: dizziness, headache, reversible hyperactivity, convulsions, aseptic meningitis. Seizures may occur in patients with impaired renal function or in those receiving high doses of the drug.

From the digestive tract: diarrhea, nausea, abdominal pain, vomiting, indigestion, antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis), black "hairy" tongue.

Nausea is often associated with high doses of the drug; gastrointestinal symptoms may be relieved by taking the drug at the beginning of a meal.

From the hepatobiliary system: a moderate increase in the level of aspartate aminotransferase and / or alanine aminotransferase is observed in patients who are treated with antibiotics of the OI-lactam group; hepatitis and cholestatic jaundice. These phenomena occur with the use of other penicillins and cephalosporins.

Hepatitis occurs mainly in men and elderly patients, and their occurrence may be associated with long-term treatment with the drug. Symptoms of the disease occur during or immediately after treatment, but in some cases may occur several weeks after the end of treatment. These effects can be severe, but are usually reversible. Fatal cases are very rarely observed in patients with a severe underlying disease or in patients who are simultaneously treated with drugs that have a negative effect on the liver.

From the side of the skin: skin rash, pruritus, urticaria, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, blistering exfoliative dermatitis, acute generalized exanthematous pustulosis.

From the urinary system: interstitial nephritis, crystalluria.

In the event of any allergic dermatitis, treatment should be discontinued.

Best before date

3 years.

Storage conditions.

Store below 25°C in original packaging.

Keep out of the reach of children.

Package

7 tablets in a blister; 1 or 2 blisters in a box.

Holiday category

On prescription.

Manufacturer

ASTRAPHARM LLC.

The location of the manufacturer and its address of the place of business.

Ukraine, 08132, Kiev region, Kiev-Svyatoshinsky district, Vyshneve, st. Kyiv, 6.

End of the text of the official instructions

Additional Information

Amoxicillin and enzyme inhibitor

Pharmacotherapeutic group:

Antibacterial agents for systemic infection. Amoxicillin and enzyme inhibitor.

Amoxicillin + Clavulanic acid: instructions for use and reviews

Latin name: Amoxicillin + Clavulanic acid

ATX Code: J01CR02

Active substance: amoxicillin + clavulanic acid (amoxicillin + clavulanic acid)

Manufacturer: Kraspharma (Russia), Aurobindo Pharma (India), Lek d.d. (Slovenia), Hemofarm A.D. (Serbia), Sandoz (Switzerland)

Description and photo update: 26.10.2018

Amoxicillin + Clavulanic acid is a broad-spectrum antibiotic.

Release form and composition

Dosage forms Amoxicillin + Clavulanic acid:

film-coated tablets: oval, biconvex, almost white or white, on one side engraved "A", on the other - "63" (tablets 250 mg + 125 mg), or "64" (tablets 500 mg + 125 mg ), or engraving divided by risk - “6 | 5” (tablets 875 mg + 125 mg); on the cross section, a light yellow core is visible, surrounded by a white or almost white shell (7 pieces in blisters, 2 blisters in a cardboard box);
powder for suspension for oral administration (strawberry): granular, almost white or white (at a dosage of 125 mg + 31.25 mg / 5 ml - 7.35 g each in translucent 150 ml vials, at a dosage of 250 mg + 62 .5 mg / 5 ml - 14.7 g in translucent vials of 150 ml; each vial in a cardboard box);
powder for the preparation of a solution for intravenous (in / in) administration: from white to white with a yellowish tint (in 10 ml vials, 1 or 10 vials in a carton box; packaging for hospitals - from 1 to 50 vials in a carton box) .

Composition of 1 tablet:

active ingredients: amoxicillin (in the form of trihydrate) - 250 mg, or 500 mg, or 875 mg, clavulanic acid (in the form of potassium clavulanate) - 125 mg;
auxiliary (inactive) components: sodium carboxymethyl starch, microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, white opadry 06B58855 (titanium dioxide, macrogol, hypromellose-15cP, hypromellose-5cP).

Composition of 5 ml suspension (made from suspension powder):

active ingredients: amoxicillin (in the form of trihydrate) - 125 mg and clavulanic acid (in the form of potassium clavulanate) - 31.25 mg, or amoxicillin - 250 mg and clavulanic acid - 62.5 mg;
auxiliary components: xanthan gum, silicon dioxide, hypromellose, aspartame, succinic acid, colloidal silicon dioxide, strawberry flavor.

Active ingredients in 1 vial of powder for the preparation of a solution for intravenous administration: amoxicillin - 500 mg and clavulanic acid - 100 mg, or amoxicillin - 1000 mg and clavulanic acid - 200 mg.

Pharmacological properties

Pharmacodynamics

The action of the drug Amoxicillin + Clavulanic acid is due to the properties of its active substances.

Amoxicillin is a semi-synthetic antibiotic. It has a wide spectrum of activity, is active against many gram-negative and gram-positive microorganisms. It has no effect on microorganisms producing beta-lactamase enzymes, since it is destroyed by their action.

Clavulanic acid is a beta-lactamase inhibitor structurally related to penicillins. It has the ability to inactivate most of the beta-lactamases found in microorganisms resistant to cephalosporins and penicillins. Clavulanic acid is quite effective against plasmid beta-lactamases, which are most often resistant, but is not active against type 1 chromosomal beta-lactamases.

Clavulanic acid in the composition of the drug protects amoxicillin from the damaging effects of beta-lactamases and expands the spectrum of its activity, including against bacteria that are usually resistant to amoxicillin.

The following microorganisms are sensitive to the combination of amoxicillin + clavulanic acid:

gram-positive aerobes: Streptococcus agalactiae 1, 2 , Listeria monocytogenes, Bacillus anthracis, Nocardia asteroids, Enterococcus faecalis, Streptococcus pyogenes 1, 2 , methicillin-sensitive Staphylococcus aureus, methicillin-sensitive coagulase-negative Staphylococcus spp., Staphylococcus saprophyticus, other beta-hemolytic streptococci Streptococcus spp. 12 ;
gram-positive anaerobes: Clostridium spp., Peptostreptococcus magnus, Peptostreptococcus spp., Peptococcus niger, Peptostreptococcus micros;
gram-negative aerobes: Neisseria gonorrhoeae, Haemophilus influenzael, Vibrio cholerae, Pasteurella multocida, Moraxella catarrhalisl (Branhamella catarrhalis), Helicobacter pylori, Bordetella pertussis;
gram-negative anaerobes: Porphyromonas spp., Capnocytophaga spp., Prevotella spp., Eikenella corrodens, Bacteroides spp. (including Bacteroides fragilis), Fusobacterium spp., Fusobacterium nucleatum;
others: Leptospira icterohaemorrhagiae, Treponema pallidum, Borrelia burgdorferi.

For the following microorganisms, acquired resistance to the drug Amoxicillin + Clavulanic acid is likely:

Gram-negative aerobes: Proteus spp. (including Proteus vulgaris and Proteus mirabilis), Escherichia coli 1 , Salmonella spp., Klebsiella spp. (including Klebsiella pneumoniae 1 and Klebsiella oxytoca), Shigella spp.;
gram-positive aerobes: Enterococcus faecium, Streptococcus pneumonia 1, 2, Corynebacterium spp., Streptococcus spp. groups

The following microorganisms are naturally resistant to the action of amoxicillin in combination with clavulanic acid:

gram-negative aerobes: Stenotrophomonas maltophilia, Pseudomonas spp., Enterobacter spp., Yersinia enterocolitica, Legionella pneumophila, Hafnia alvei, Citrobacter freundii, Serratia spp., Providencia spp., Morganella morganii, Acinetobacter spp.;
others: Mycoplasma spp., Chlamydia psittaci, Chlamydia spp., Coxiella burnetii, Chlamydia pneumoniae.

Notes:

1 For these bacteria, clinical studies have established the efficacy of amoxicillin in combination with clavulanic acid.

2 Strains of these types of microorganisms do not produce beta-lactamase, are sensitive to amoxicillin, and therefore, presumably, to the combination of amoxicillin + clavulanic acid.

Pharmacokinetics

After taking the drug Amoxicillin + Clavulanic acid, the active substances are quickly and completely absorbed from the gastrointestinal tract. The maximum concentration is reached in 1-2 hours. Optimal absorption is noted in the case of taking the drug at the beginning of a meal.

When administered orally and intravenously, the active substances have a moderate degree of binding to plasma proteins: amoxicillin - 17-20%, clavulanic acid - 22-30%.

Both components are characterized by a good volume of distribution in body fluids and tissues. Found in the lungs, middle ear, pleural and peritoneal fluids, uterus, ovaries. Penetrate into the secret of the paranasal sinuses, palatine tonsils, synovial fluid, bronchial secret, muscle tissue, prostate gland, gallbladder and liver. Amoxicillin is able to penetrate into breast milk, as well as most penicillins. Trace amounts of clavulanic acid have also been found in breast milk.

Amoxicillin and clavulanic acid cross the placental barrier. Do not penetrate the blood-brain barrier, provided that the meninges are not inflamed.

Both components are metabolized in the liver: amoxicillin - about 10% of the dose, clavulanic acid - about 50% of the dose.

Amoxicillin (50-78% of the dose) is excreted almost unchanged by the kidneys by glomerular filtration and tubular secretion. Clavulanic acid (25-40% of the dose) is excreted by glomerular filtration by the kidneys, partly as metabolites and unchanged. Both components are eliminated within the first 6 hours. Small amounts can be excreted through the lungs and intestines.

In severe renal failure, the half-life increases: for amoxicillin - up to 7.5 hours, for clavulanic acid - up to 4.5 hours.

Both active substances of the antibiotic are removed during hemodialysis, in small amounts by peritoneal dialysis.

Indications for use

According to the instructions, Amoxicillin + Clavulanic acid is used to treat infectious and inflammatory diseases caused by microorganisms that are sensitive to a combination of active ingredients:

infections of the ENT organs and upper respiratory tract: acute and chronic sinusitis, recurrent tonsillitis, acute and chronic otitis media, pharyngitis and pharyngeal abscess, usually caused by Streptococcus pyogenes, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis;
lower respiratory tract infections: exacerbation of chronic bronchitis, acute bronchitis with bacterial superinfection, bronchopneumonia, pneumonia, usually caused by Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis;
infections of the bone and connective tissues and joints, including osteomyelitis, usually caused by Staphylococcus aureus;
biliary tract infections: cholangitis, cholecystitis;
urinary tract infections: pyelitis, pyelonephritis, urethritis, cystitis, chancre, prostatitis, gonorrhea (caused by Neisseria gonorrhoeae), infections of the female genital organs, usually caused by species of the family Enterobacteriaceae (mainly Escherichia coli), species of the genus Enterococcus, Staphylococcus saprophyticus, such as bacterial vaginitis, salpingitis, endometritis, salpingoophoritis, cervicitis, tubo-ovarian abscess, septic abortion;
infections of the skin and soft tissues: secondarily infected dermatoses, phlegmon, erysipelas, abscess, impetigo and wound infections, usually caused by species of the genus Bacteroides, Streptococcus pyogenes, Staphylococcus aureus;
meningitis, peritonitis, endocarditis, sepsis;
odontogenic infections;
other mixed infections, for example, intra-abdominal infections, post-abortion or post-partum sepsis (as part of stepwise therapy).

In surgery, an antibiotic is used to prevent postoperative infections.

Contraindications

infectious mononucleosis (including with the appearance of a measles-like rash);
abnormal liver function and cholestatic jaundice associated with the use of a combination of amoxicillin and clavulanic acid or penicillin in history;
children's age up to 12 years (for tablets);
phenylketonuria (for suspension);
creatinine clearance less than 30 ml / min (for tablets 875 mg + 125 mg);
hypersensitivity to the components of the drug, beta-lactam antibiotics, cephalosporins or penicillins.

Amoxicillin + Clavulanic Acid should be used with caution in the following cases:

severe liver failure;
chronic renal failure;
diseases of the gastrointestinal tract (including a history of colitis due to the use of penicillins);
pregnancy and lactation.

Instructions for use Amoxicillin + Clavulanic acid: method and dosage

Film-coated tablets

In the form of tablets, the drug is indicated for oral administration. For optimal absorption and to reduce the risk of side effects from the digestive system, it is recommended to take the tablets at the beginning of a meal.

If necessary, staged therapy is carried out: first, the drug Amoxicillin + Clavulanic acid is administered intravenously, after which they switch to oral administration.

mild to moderate infections: 250 mg + 125 mg every 8 hours or 500 mg + 125 mg every 12 hours;
severe infections, infections of the respiratory system: 500 mg + 125 mg 3 times a day or 875 mg + 125 mg 2 times a day.

The maximum daily dose of amoxicillin should not exceed 6000 mg, clavulanic acid - 600 mg.

The minimum duration of treatment is 5 days, the maximum is 14 days. 2 weeks after the start of the therapeutic course, the doctor evaluates the clinical situation and, if necessary, decides to continue the treatment. The duration of therapy for uncomplicated acute otitis media is 5-7 days.

It is important to consider that 2 tablets of 250 mg + 125 mg in terms of clavulanic acid content are not equivalent to 1 tablet of 500 mg + 125 mg.

In case of impaired renal function, the dose of amoxicillin is adjusted depending on creatinine clearance (CC):

QC >
CC 10-30 ml / min: 2 times a day, 1 tablet of 250 mg (for mild and moderate infections) or 1 tablet of 500 mg;
QC< 10 мл/мин: 1 раз в сутки по 1 таблетке 250 мг (при легких и среднетяжелых инфекциях) или 1 таблетке 500 мг.

Tablets 875 mg + 125 mg can only be used in patients with CC> 30 ml / min.

Adults on hemodialysis are prescribed 1 tablet 500 mg + 125 mg or 2 tablets 250 mg + 125 mg 1 time per day. Additionally, one dose is prescribed during the dialysis session and another dose at the end of the session.

Powder for suspension for oral administration

Suspension Amoxicillin + Clavulanic acid is usually prescribed for children under the age of 12 years.

In this dosage form, the drug is intended for oral administration. A suspension is prepared from the powder: boiled and cooled to room temperature drinking water is poured into the vial by 2/3, shaken well, then the volume is adjusted to the mark (100 ml) and shaken vigorously again. Shake the bottle before each dose.

For accurate dosing, the kit includes a measuring cap with risks of 2.5 ml, 5 ml and 10 ml. It must be washed with clean water after each use.

The doctor determines the dosage regimen individually, depending on the severity of the infectious process, the age of the patient, his body weight and kidney function.

For optimal absorption of active substances and to reduce the risk of side effects from the digestive system, it is recommended to take Amoxicillin + Clavulanic Acid Suspension at the beginning of a meal.

The duration of treatment is at least 5 days, but not more than 14 days. 2 weeks after the start of the therapeutic course, the doctor evaluates the clinical situation and, if necessary, decides to continue the treatment.

For children from 3 months to 12 years old or weighing up to 40 kg, the suspension is prescribed at a dose of 125 mg + 31.25 mg per 5 ml or 250 mg + 62.5 mg per 5 ml three times a day at intervals of 8 hours.

The minimum daily dose for amoxicillin is 20 mg/kg, the maximum is 40 mg/kg. In low doses, the drug is used for recurrent tonsillitis, infections of the skin and soft tissues. In high doses - with sinusitis, otitis media, infections of the lower respiratory tract, urinary tract, bones and joints.

In case of impaired renal function, the dose of amoxicillin is adjusted depending on the CC:

QC> 30 ml / min: correction is not required;
CC 10-30 ml / min: 15 mg + 3.75 mg per kg of body weight twice a day, but not more than 500 mg + 125 mg twice a day;
QC< 10 мл/мин: по 15 мг + 3,75 мг на кг массы тела один раз в сутки, но не более чем 500 мг + 125 мг.

Children on hemodialysis are prescribed 15 mg + 3.75 mg per kg of body weight once a day. Additionally, one dose is prescribed before a hemodialysis session, the second - after the end of the session.

Powder for solution for intravenous administration

A solution for intravenous injection / infusion is prepared from the powder.

To prepare a solution for intravenous injection, the contents of the vial are dissolved in water for injection: at a dose of 500 mg + 100 mg (600 mg) - in 10 ml, at a dose of 1000 mg + 200 mg (1200 mg) - in 20 ml. Enter slowly (within 3-4 minutes).

For infusion administration, further dilution of the drug is required: the resulting solutions are diluted in 50 ml (500 mg + 100 mg) or 100 ml (1000 mg + 200 mg) of the infusion solution. Ringer's, sodium chloride or potassium chloride solutions can be used as a solvent. The duration of the infusion is 30-40 minutes.

The doctor determines the dosage regimen individually, depending on the sensitivity of the pathogen, the severity and location of the infection, the age of the patient, his body weight and kidney function.

Adults and adolescents from 12 years of age are prescribed 1200 mg 3 times a day (at intervals of 8 hours), for severe infections - 4 times a day (at intervals of 6 hours).

The maximum allowable daily dose is 6000 mg.

Children from 3 months to 12 years of age are prescribed 30 mg / kg (based on the entire drug) 3 times a day, with a severe course of the infectious process - 4 times a day.

Children under the age of 3 months are prescribed 30 mg / kg (based on the entire drug): in the postperinatal period - 3 times a day, premature and in the perinatal period - 2 times a day.

The duration of treatment is 5-14 days.

For the prevention of postoperative infections, the drug Amoxicillin + Clavulanic acid is prescribed at a dose of 1200 mg during induction anesthesia during an operation lasting less than 1 hour, 1200 mg every 6 hours during the day - for longer operations. If there is a high risk of infection, it is possible to use the drug for several days.

For patients with renal insufficiency, the dose and / or interval between injections is adjusted depending on the CC:

CC 10-30 ml / min: initial dose - 1200 mg, then - 600 mg every 12 hours;
QC< 10 мл/мин: начальная доза – 1200 мг, далее – по 600 мг 1 раз в сутки.

For children, doses and frequency of administration are reduced in the same way.

For patients undergoing hemodialysis, an additional dose is indicated at the end of each session.

With peritoneal dialysis, dose adjustment is not required.

Side effects

from the side of the central nervous system: infrequently - headache, dizziness; very rarely - agitation, insomnia, anxiety, confusion, behavioral changes, reversible hyperactivity and convulsions (convulsions are possible in patients receiving the drug in high doses and patients with impaired renal function);
from the gastrointestinal tract: very often - diarrhea; often - nausea and vomiting; infrequently - dyspeptic phenomena; very rarely - glossitis, black "hairy" tongue, stomatitis, enterocolitis, gastritis, antibiotic-associated pseudomembranous or hemorrhagic colitis;
from the hematopoietic system: rarely - reversible thrombocytopenia, reversible leukopenia (including neutropenia); very rarely - eosinophilia, anemia, reversible hemolytic anemia, thrombocytosis, thrombocytopenic purpura, reversible agranulocytosis, increased prothrombin time and bleeding time;
from the skin and subcutaneous tissues: infrequently - urticaria, itching, skin rash; rarely - erythema multiforme; very rarely - erythematous rashes, erythema, allergic vasculitis, a syndrome similar to serum sickness, bullous exfoliative dermatitis, anaphylactic reactions, anaphylactic shock, angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis;
from the kidneys and urinary tract: very rarely - hematuria, crystalluria, interstitial nephritis;
on the part of the liver *: infrequently - a moderate increase in the activity of alanine aminotransferase and / or aspartate aminotransferase; very rarely - an increase in the concentration of bilirubin and alkaline phosphatase, impaired liver function; with the simultaneous use of other penicillins and cephalosporins - cholestatic jaundice, hepatitis;
other: discoloration of teeth (yellow, gray or brown staining); often - candidiasis of the mucous membranes.

* Side effects from the liver are usually reversible, occur during treatment or shortly after treatment. They occur mainly in the elderly and men. May be associated with long-term use of the drug. Impaired liver function can range in severity from mild to life-threatening (predominantly in patients with severe pre-existing conditions and people treated with potentially hepatotoxic drugs).

Overdose

In most cases, overdose occurs gastrointestinal disorders (diarrhea, abdominal pain, vomiting) and disturbances in water and electrolyte balance. Anxiety, dizziness, insomnia are also possible, in isolated cases (in patients receiving the drug in high doses and patients with impaired renal function) - convulsive seizures. The development of amoxicillin crystalluria, in some cases leading to renal failure, has been described.

Treatment of overdose is symptomatic. Particular attention is paid to the normalization of water and electrolyte balance. If necessary, carry out hemodialysis.

special instructions

Prior to initiating antibiotic therapy, the clinician should take a detailed personal history of the patient regarding prior sensitivity reactions to penicillins, cephalosporins, or other allergens.

There are reports of the development of serious hypersensitivity reactions to penicillins, including fatal ones. The risk of such reactions is especially high in patients with a history of hypersensitivity reactions to penicillins. With the development of allergic reactions, the drug Amoxicillin + Clavulanic acid is immediately canceled and alternative therapy is prescribed. In the event of serious anaphylactic reactions, urgent action is required (administration of epinephrine). Intravenous administration of glucocorticosteroids, oxygen therapy and airway patency (if necessary, intubation) may be required.

During therapy, it is necessary to remember the possible development of superinfection (it is usually caused by Candida fungi and Pseudomonas bacteria). In this case, cancel the drug and / or prescribe appropriate therapy.

If infectious mononucleosis is suspected, Amoxicillin + Clavulanic acid is not recommended, since the risk of a measles-like skin rash is high, which makes it difficult to diagnose the disease.

During long-term therapy, the growth of insensitive microorganisms is possible.

Amoxicillin + Clavulanic acid, like other antibacterial drugs, can cause mild to life-threatening pseudomembranous colitis. In this regard, with diarrhea that occurs during treatment or after its completion, it is necessary to assume the presence of pseudomembranous colitis. If diarrhea is severe or observed for a long time, the drug is canceled and the patient is examined. You should not take drugs that inhibit intestinal motility.

In rare cases, patients with reduced diuresis may develop crystalluria, mainly during parenteral therapy. When amoxicillin is administered at high doses, drinking plenty of fluids and maintaining adequate diuresis is recommended to reduce the risk of amoxicillin crystal formation.

Due to the clavulanic acid in the composition of the antibiotic, it can cause a false positive result of the Coombs test.

Amoxicillin + Clavulanic acid in oral dosage forms leads to a high content of amoxicillin in the urine, which distorts the results when determining urine glucose (for example, Fehling's test or Benedict's test). If necessary, this diagnostic test should use the glucose oxidant method.

With the simultaneous appointment of anticoagulants, it is necessary to carefully monitor the prothrombin time or INR (international normalized ratio). If necessary, their dose should be adjusted.

Amoxicillin + Clavulanic acid in oral dosage forms can cause discoloration of the surface layer of tooth enamel. To prevent this, you should ensure sufficient oral care (regularly and thoroughly brush your teeth).

Influence on the ability to drive vehicles and complex mechanisms

Amoxicillin + Clavulanic Acid can cause side effects from the central nervous system, so care should be taken when performing any work that requires speed of reactions and / or attention.

Use during pregnancy and lactation

In reproductive studies in animals with oral and parenteral administration of the combination of amoxicillin + clavulanic acid, no teratogenic effect was detected. In a single study in women with premature rupture of the membranes, it was found that the prophylactic use of amoxicillin in combination with clavulanic acid may increase the risk of developing necrotizing enterocolitis in newborns. During pregnancy, the drug is prescribed only if the expected benefit of therapy for a woman outweighs the potential risks to the fetus.

Amoxicillin + Clavulanic acid can be used during lactation. No adverse effects were observed in children receiving breastfeeding, with the exception of the risk of developing hypersensitivity reactions, candidiasis of the mucous membranes of the oral cavity or diarrhea, which is due to the penetration of trace amounts of the active substances of the drug into breast milk. If these reactions occur in a child, breastfeeding should be discontinued for the duration of treatment.

Application in childhood

Amoxicillin + Clavulanic acid tablets are not suitable for children under 12 years of age.

For impaired renal function

In chronic renal failure, the drug should be used with caution.

For impaired liver function

The drug Amoxicillin + Clavulanic acid is contraindicated in cases of impaired liver function and cholestatic jaundice associated with the use of a combination of amoxicillin and clavulanic acid or penicillin in history.

In severe liver failure, the drug should be used with caution. Treatment should be carried out under regular monitoring of liver function.

drug interaction

Bacteriostatic agents (sulfonamides, macrolides, tetracyclines, lincosamides, chloramphenicol) have an antagonistic effect.

With the simultaneous use of bactericidal antibiotics (including cephalosporins, aminoglycosides, rifampicin, vancomycin, cycloserine), a synergistic effect is noted.

The drug Amoxicillin + Clavulanic acid enhances the effect of indirect anticoagulants (suppresses the intestinal microflora, reduces the prothrombin index and the synthesis of vitamin K). If necessary, the use of such a combination should be monitored for blood clotting.

Diuretics, non-steroidal anti-inflammatory drugs, phenylbutazone, allopurinol and drugs that block tubular secretion, while used, increase the concentration of amoxicillin.

The drug Amoxicillin + Clavulanic acid increases the toxicity of methotrexate, reduces the effect of oral contraceptives. When combined with ethinyl estradiol or with drugs that metabolize para-aminobenzoic acid, there is a risk of breakthrough bleeding.

Allopurinol increases the likelihood of skin allergic reactions.

The drug solution is pharmaceutically incompatible with solutions containing bicarbonate, glucose, dextran, lipids, proteins, blood. Incompatible with aminoglycosides. The solution must not be mixed with any other medicinal products in the same syringe/infusion vial.

The absorption of amoxicillin and clavulanic acid is increased by ascorbic acid, reduced by laxatives, glucosamine, aminoglycosides, antacids.

The suspension prepared from the powder can be stored for no more than 7 days in the refrigerator (at a temperature of + 6 ° C). Do not freeze.