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

• 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.

• 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.

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

Release form

Storage conditions

Best before date

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

Terms of dispensing from pharmacies

Manufacturer

Formula: C8H9NO5, chemical name: (2R,5R,Z)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-aza-bicycloheptane-2-carboxylic acid.
Pharmacological group: metabolites/enzymes and antienzymes.
Pharmachologic effect: inhibitory beta-lactamase, antimicrobial.

Pharmacological properties

Clavulanic acid inhibits beta-lactamases, which form gram-negative microorganisms, which include Haemophilus influenzae, Haemophilus ducreyi, Neisseria gonorrhoeae, Bacteroides fragilis and some other Enterobacter spp., Moraxella (Branhamella) catarrhalis; clavulanic acid also acts on beta-lactamases, which form Staphylococcus aureus. Clavulanic acid is produced by Streptomyces clavuligerus. The structure of clavulanic acid is similar to the structure of the core of the penicillin molecule, but differs from it in that instead of the thiazolidine ring it has an oxazolidine ring in its composition. Clavulanic acid has weak antimicrobial activity. Clavulanic acid penetrates the bacterial cell membrane and inactivates the enzymes that are in the cell and at its border. Clavulanic acid competitively and often irreversibly inhibits beta-lactamase.

Indications

Together with ticarcillin or amoxicillin for the treatment of infectious and inflammatory pathology, which is caused by microorganisms sensitive to the combination used.

Method of application of clavulanic acid and doses

The dosing regimen of clavulanic acid is individual and is set, depending on the age of the patient, the indications, and the dosage form used.
Intravenous clavulanic acid should be used with caution in patients with severe hepatic impairment. With the development of an erythematous rash or urticaria, clavulanic acid therapy should be discontinued.

Contraindications for use

Hypersensitivity.

Application restrictions

No data.

Use during pregnancy and lactation

Together with ticarcillin or amoxicillin, the use of clavulanic acid during pregnancy is possible only for health reasons, in other cases its use is not recommended.

Side effects of clavulanic acid

Circulatory system: symptoms of dyspepsia, violations of the functional state of the liver, cholestatic jaundice, hepatitis, pseudomembranous colitis (in some cases); allergic reactions: in some cases - Stevens-Johnson syndrome, erythema multiforme, exfoliative dermatitis, angioedema, urticaria, anaphylactic shock; others: candidiasis (in some cases).

Interaction of clavulanic acid with other substances

No data.

Overdose

No data.

Trade names of drugs with the active substance clavulanic acid

Combined drugs:
Amoxicillin + Clavulanic Acid: Amoxicillin®, Amoxiclav®, Amoxiclav® Quiktab, Amoxicillin + Clavulanic Acid Pfizer, Amoxicillin Sodium and Potassium Clavulanate (5:1), Amoxicillin + Clavulanic Acid, Amoxicillin + Clavulanic Acid-Vial, Amoxicillin Trihydrate + Potassium Clavulanate ( 4:1), (7:1); Amoxicillin trihydrate and potassium clavulanate (2:1), Amoxicillin trihydrate and potassium clavulanate (4:1), Amoxicillin trihydrate + Potassium clavulanate (2:1), (4:1), (7:1); Arlet®, Augmentin®, Augmentin® EC, Augmentin® SR, Baktoclave, Verklav, Klamosar®, Liklav, Medoklav, Panklav, Panklav 2X, Ranklav®, Rapiclav, Taromentin, Fibell, Flemoclav Solutab®, Ecoclave®;
Ticarcillin + Clavulanic acid: Timentin.

Broad-spectrum antibiotics are designed to suppress pathogenic microflora that has entered the patient's body. Commonly prescribed drugs include amoxicillin-clavulanic acid. Experts believe that the drug is quite safe and has a gentle effect on the patient. The drug is a semi-synthetic, penicillin-containing substance.

General information

The main composition of the drug is represented by two active ingredients:

• Amoxicillin;
• clavulanic acid.

Manufacturers produce medicines in various forms:

1. syrupy;
2. Suspension;
3. drip;
4. powdered;
5. Tableted.

The active ingredients included in the main structure are contained in various volumes:

• 250 and 125 mg each;
• 500 and 125 mg each;
• 875 and 125 mg each.

Associated with the severity of the development of the disease, the drug is prescribed with different dosage levels.

Permissions and prohibitions on use

The drug is often prescribed for certain types of lesions:

• lung abscesses;
• bronchitis;
• As preventive measures in surgical practice;
• Vaginitis of a bacterial nature;
• inflammation of the middle ear;
• Inflammation of the cervical canal;
• gonorrheal infection;
• Dermatoses with secondary infection;
• Impetigo;
• Infections on wound surfaces;
• Soft chancres;
• osteomyelitis;
• Pelvioperitonitis;
• Pyelitis;
• Pyelonephritis;
• Pneumonia;
• Postpartum variants of septic lesions;
• Joined infections in the postoperative period;
• prostatitis;
• Erysipelas;
• Salpingitis;
• Salpingoophoritis;
• Spontaneous febrile abortion;
• sinusitis;
• tonsillitis;
• tubo-ovarian abscesses;
• Urethritis of various etiologies;
• Phlegmon;
• cystitis;
• Empyema of pleural tissues;
• Endometritis.

Taking the drug is prohibited under certain conditions:

1. High sensitivity in relation to the active ingredients that make up the drug;
2. Mononucleosis of infectious etiology;
3. Phenylketonuria;
4. jaundice;
5. Disorders of the functionality of the liver caused by the introduction of similar pharmacological preparations.

Increased caution in prescribing is required in the treatment of diseases during periods of gestation, feeding the baby, with the existing insufficient functionality of the liver in severe forms, with certain diseases of the digestive department.

Negative reactions

When prescribing amoxicillin-clavulanic acid, various side effects on the patient's body are possible.

Digestive department:

• Gastroduodenitis;
• Hepatitis;
• Glossitis;
• Diarrhea;
• Jaundice of the cholestatic type;
• Changing the shade of tooth enamel to dark colors;
• Colitis of hemorrhagic and pseudomembranous variants - their appearance may be caused by therapy with the desired drug;
• Insufficiency of liver functionality, especially in the elderly age period in males, with prolonged therapy;
• Increased activity of liver enzymes;
• Stomatitis;
• Nausea with the transition to vomiting;
• Blackish tinge of the tongue;
• Enterocolitis.

1. Reversible increase in the prothrombotic period;
2. Prolongation of the bleeding period;
3. thrombocytopenia;
4. thrombocytosis;
5. eosinophilia;
6. Decrease in the number of leukocytes;
7. Agranulocytosis;
8. Hemolytic type of anemic disorder.

• Headache;
• Increased activity;
• dizziness;
• Unreasonable anxiety;
• Changing the standard behavior;
• Convulsive syndrome.

Allergic manifestations:

• Allergic type of vasculitis;
• Anaphylactic shock;
• Angioedema;
• Eruptions of an erythematous appearance;
• Reddish papules on the skin;
• Multiform exudative erythema;
• Acute phase of generalized exanthematous papulosis;
• Symptomatic manifestations similar to serum sickness;
• Exudative erythema of a malignant nature is a symptom of Stevens-Johnson;
• Exfoliative subtype of dermatitis.

Other manifestations:

1. The development of secondary infection with pathogenic microflora;
2. Interstitial nephritis;
3. The appearance of salt crystals in the urine;;
4. Presence of blood particles in urine;
5. Candidiasis.

Local microreactions of the body can manifest at the points of intravenous injection in the form of phlebitis.

Amoxicillin Clavulanic acid instructions for use

A pharmacological agent is introduced into the patient's body in two ways - intravenously or orally. The required volumes of the drug are set taking into account the general condition of the body, laboratory data and the degree of damage. All dosages are calculated in relation to amoxicillin.

Oral administration

For babies under 12 years of age, the medication is prescribed in the form of drops, suspension or syrup for oral use. One-time amount corresponds to the age period:

• Until the first quarter of life - 30 mg per kg of body weight per day;
• After 3 months - 25 mg per kg of body weight, twice in 24 hours or 20 mg per kg, three times a day (calculation for a mild degree of damage);
• After the first quarter with a severe variant of the disease - 45 mg per kg twice a day or 40 mg per kg three times a day.

The maximum amount of the permitted volume of "Amoxicillin" is 45 mg per kg of the child's weight, "Clavulanic acid" - 10 mg per kg of body weight.

After 12 years and the adult population (total body weight exceeds 40 kilograms), the drug is prescribed in proportions:

1. For mild lesions - 500 mg twice a day or 250 mg three times a day;
2. With complex courses of the disease - 875 mg twice a day or 500 mg three times a day.

The highest one-time measure for the adult population and babies after 12 years of "Amoxicillin" includes 6 g, "Clavulanic acid" - 600 mg.

In cases of problems with swallowing liquids and solids in older people, they are advised to use suspensions.

In the manufacture of syrups, suspensions and drops, drinking pure water is the main solvent.

Introduction to the veins

Produced according to age:

• For the adult and adolescent period (over 12 years), 1 g is prescribed three times a day, four times a day is allowed in some cases;
• Babies after the first three months - 25 mg per kg of body weight, three times (lightened variants of ailments) or four times a day for severe forms of illness;
• Until the first quarter of life - with prematurity or in the perinatal period - 25 mg per kg, twice, or in the postperinatal period - 25 mg per kg three times a day.

The average duration of the therapeutic effect is up to two calendar weeks, with inflammation in the middle ear area - up to 10 days.

Preventive actions

The appointment of an agent to prevent the occurrence of postoperative processes (with manipulations that take at least an hour) is carried out at the time of induction anesthesia at a dosage of 1 g (intravenously). With a high risk of possible infection, it is allowed to carry out manipulation for several days.

Patients undergoing hemodialysis have their own volumes of prescribed medications:

1. Orally - 250 or 500 mg at a time;
2. In the veins - 500 mg of the substance.

At the time of manipulation and after its completion, an additional one dose of the medicinal substance is administered.

Overdose

• Nausea with transition to vomiting;
• Diarrhea;
• Violations in the water and electrolyte balance - as a result of dehydration of the body due to vomiting, diarrhea;
• neurotoxic reactions;
• thrombocytopenia.

The latter disappear after the withdrawal of the pharmacological agent and are reversible.

If signs of poisoning are detected, patients are applied

1. Gastric lavage;
2. The introduction of activated carbon;
3. Salt laxatives;
4. Correction of water and electrolyte balance;
5. Hemodialysis.

Immediately after the occurrence of an overdose, the patient must be taken to a medical facility for professional assistance.

Possible interaction

When carrying out the treatment of "amoxicillin with clavulanic acid", the drug may react with other drugs:

1. Antacids, laxatives, aminoglycosides and Glucosamine, when combined with the parent substance, cause a slowdown and decrease in the absorption of active ingredients;
2. Ascorbic acid, taken at the same time, increases absorption;
3. Macrolides, chloramphenicols, lincosamides, sulfonamides, tetracycline drugs with simultaneous administration exhibit an antagonistic effect;
4. Anticoagulants of the indirect type increase their effectiveness, while there is a suppression of beneficial microflora in the intestine, a decrease in the synthesis of vitamin K and the prothrombin index;
5. The beneficial effects of oral contraceptives, ethinyl estradiol, are significantly reduced;
6. Pharmacological agents, during the processing of which PABA is produced, reduce their spectrum of action, which can cause the formation of spontaneous bleeding;
7. Diuretic drugs and drugs that block calcium secretion increase the total concentration of the original substance.

Before using the medicine, it is necessary to inform the attending doctor about all previously prescribed drugs - in order to avoid the occurrence of unforeseen reactions and the development of complications.

Features of use

The therapeutic course is carried out under constant monitoring of the functionality of the hematopoietic systems, liver and kidneys. To reduce the risk of developing pathologies in the gastrointestinal tract, the drug is taken exclusively at the time of eating.

With the gradual development of resistance of pathogenic microflora to active ingredients, the development of secondary sub-infection with pathogenic microorganisms may begin. It requires specialized antibacterial therapy. In some cases, false analyzes may be recorded when determining the amount of glucose in urine.

The suspension prepared at home must be stored in a refrigerator for up to one week, avoiding freezing.

At the time of the use of the medicinal substance "amoxicillin clavulanic acid", the use of any alcoholic and low-alcohol drinks is strictly prohibited.

Ethyl alcohol has a diuretic effect and will weaken the therapeutic effects of the treatment. Alcohol can cause various complications during therapy with the desired medication.

Similar drugs

With existing contraindications or side effects that have arisen, the remedy is replaced with similar drugs, with the same therapeutic effect. Common types include:

• "Amocomb";
• "Amoxivan";
• "Amoxicillin trihydrate + potassium clavulanate";
• "Ranclave";
• "Rapiclav";
• "Arlet";
• "Bactoclav";
• "Verklav";
• "Liklav";
• "Fibell";
• "Flemoklav Solutab";

The cost of the drug "Amoxicillin Clavulanic acid" depends on the number of capsules and ampoules in the package, the manufacturer and ranges from 60 to 800 rubles. Typical remedies can either exceed the price of the desired remedy, or be much cheaper. The option required by the pricing policy can be purchased at the pharmacy network, if you have a prescription for the main antibiotic.

Registration number:

Validity period of the registration certificate:

12/29/2014 to 12/29/2019

Compound

active ingredients: 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)).

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, which form stable inactive complex compounds with them and protect 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, resulting in a false positive Coombs test result.

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 fetal membranes, 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. Where 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

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.

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

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

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

Manufacturer

ASTRAPHARM LLC.

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

Ukraine, 08132, Kyiv 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.

Composition and form of release of the drug

Powder for suspension for oral administration (strawberry) granular, white or almost white; prepared suspension of white or almost white color, with a strawberry smell.

* in the form of a mixture of potassium clavulanate + siloid (1: 1) - 152.78 mg.

Excipients: colloidal silicon dioxide - 25 mg, succinic acid - 0.84 mg, hypromellose - 79.65 mg, xanthan gum - 12.5 mg, strawberry flavor - 11.25 mg, aspartame - 10 mg, silicon dioxide - 121.28 mg.

14.7 g - high-density polyethylene bottles with a capacity of 150 ml (1) complete with a measuring cap - packs of cardboard.

pharmachologic effect

Combined preparation of amoxicillin and clavulanic acid, a beta-lactamase inhibitor. It acts bactericidal, inhibits the synthesis of the bacterial wall.

Active against aerobic Gram-positive bacteria(including beta-lactamase producing strains): Staphylococcus aureus; aerobic Gram-negative bacteria: Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis. The following pathogens are sensitive only in vitro: Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp., Listeria monocytogenes; anaerobic Clostridium spp., Peptococcus spp., Peptostreptococcus spp.; as well as aerobic Gram-negative bacteria(including beta-lactamase producing strains): Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus ducreyi, Yersinia multocida (formerly Pasteurella), Campylobacter jejuni; anaerobic gram-negative bacteria (including beta-lactamase producing strains): Bacteroides spp., including Bacteroides fragilis.

Clavulanic acid inhibits II, III, IV and V types of beta-lactamases, is not active against type I beta-lactamases produced by Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high affinity for penicillinases, due to which it forms a stable complex with the enzyme, which prevents the enzymatic degradation of amoxicillin under the influence of beta-lactamases.

Pharmacokinetics

After oral administration, both components are rapidly absorbed in the gastrointestinal tract. Simultaneous food intake does not affect absorption. T Cmax - 45 min. After oral administration at a dose of 250/125 mg every 8 hours C max amoxicillin - 2.18-4.5 mcg / ml, clavulanic acid - 0.8-2.2 mcg / ml, at a dose of 500/125 mg every 12 hours C max amoxicillin - 5.09-7.91 mcg / ml, clavulanic acid - 1.19-2.41 mcg / ml, at a dose of 500/125 mg every 8 hours max amoxicillin - 8.82-14.38 mcg / ml, clavulanic acid - 1.21-3.19 mcg / ml.

After intravenous administration at doses of 1000/200 mg and 500/100 mg C max amoxicillin - 105.4 and 32.2 mcg / ml, respectively, and clavulanic acid - 28.5 and 10.5 mcg / ml.

The time to reach the maximum inhibitory concentration of 1 μg / ml for amoxicillin is similar when applied after 12 hours and 8 hours in both adults and children.

Protein binding: amoxicillin - 17-20%, clavulanic acid - 22-30%.

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

T 1/2 after taking a dose of 375 and 625 mg - 1 and 1.3 hours for amoxicillin, 1.2 and 0.8 hours for clavulanic acid, respectively. T 1/2 after intravenous administration at a dose of 1200 and 600 mg - 0.9 and 1.07 h for amoxicillin, 0.9 and 1.12 h for clavulanic acid, respectively. It is excreted mainly by the kidneys (glomerular filtration and tubular secretion): 50-78 and 25-40% of the administered dose of amoxicillin and clavulanic acid are excreted, respectively, unchanged during the first 6 hours after administration.

Indications

Treatment of infectious and inflammatory diseases caused by susceptible pathogens: infections of the lower respiratory tract (bronchitis, pneumonia, pleural empyema, lung abscess); infections of ENT organs (sinusitis, tonsillitis, otitis media); infections of the genitourinary system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, cervicitis, salpingitis, salpingo-oophoritis, tubo-ovarian abscess, endometritis, bacterial vaginitis, septic abortion, postpartum sepsis, pelvic peritonitis, soft chancre, gonorrhea); infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection); osteomyelitis; postoperative infections.

Prevention of infections in surgery.

Contraindications

Hypersensitivity to the components of the drug (including cephalosporins and other beta-lactam antibiotics); (including with the appearance of a measles-like rash); phenylketonuria; episodes of jaundice or impaired liver function as a result of the use of amoxicillin / clavulanic acid in history; CC less than 30 ml / min (for tablets 875 mg / 125 mg).

Carefully

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

Dosage

Inside, in / in.

Doses are given in terms of amoxicillin. The dosage regimen is set individually depending on the severity of the course and localization of the infection, the sensitivity of the pathogen.

Children under 12 children up to 3 months- 30 mg / kg / day in 2 divided doses; 3 months and older- at severe infections

Adults and children over 12 years old or with a body weight of 40 kg or more: 500 mg 2 times / day or 250 mg 3 times / day. For severe infections and respiratory tract infections - 875 mg 2 times / day or 500 mg 3 times / day.

The maximum daily dose of amoxicillin for adults and children over 12 years old is 6 g, for children under 12 years old - 45 mg / kg of body weight.

The maximum daily dose of clavulanic acid for adults and children over 12 years of age is 600 mg, for children under 12 years of age - 10 mg / kg of body weight.

When preparing a suspension, syrup and drops, water should be used as a solvent.

At in / in the introduction adults and adolescents over 12 years of age are administered 1 g (according to amoxicillin) 3 times / day, if necessary - 4 times / day. The maximum daily dose is 6 g. For children 3 months to 12 years old, 25 mg / kg 3 times / day; in severe cases - 4 times / day; for children under 3 months: premature and in the perinatal period - 25 mg / kg 2 times / day, in the postperinatal period - 25 mg / kg 3 times / day.

Duration of treatment - up to 14 days, acute otitis media - up to 10 days.

For prevention of postoperative infections during operations, lasting less than 1 hour during induction anesthesia is administered at a dose of 1 g IV. At longer operations- 1 g every 6 hours during the day. If there is a high risk of infection, administration may be continued for several days.

At CC more than 30 ml / min QC 10-30 ml/min QC less than 10 ml / min- 1 g, then 500 mg/day IV or 250-500 mg/day orally in one dose. For children, doses should be reduced in the same way.

Patients on hemodialysis

Side effects

From the digestive system: nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, increased activity of hepatic transaminases, in rare cases - cholestatic jaundice, hepatitis, liver failure (more often in the elderly, men, with long-term therapy), pseudomembranous and hemorrhagic colitis (may also develop after therapy ), enterocolitis, black "hairy" tongue, darkening of tooth enamel.

From the side of the hematopoietic organs: reversible increase in prothrombin time and bleeding time, thrombocytopenia, thrombocytosis, eosinophilia, leukopenia, agranulocytosis, hemolytic anemia.

From the nervous system: dizziness, headache, hyperactivity, anxiety, behavior change, seizures.

Local reactions: in some cases - phlebitis at the site of the / in the introduction.

Allergic reactions: urticaria, erythematous rashes, rarely - exudative erythema multiforme, anaphylactic shock, angioedema, extremely rarely - exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), allergic vasculitis, a syndrome similar to serum sickness, acute generalized exanthematous pustulosis.

Others: candidiasis, development of superinfection, interstitial nephritis, crystalluria, hematuria.

drug interaction

Antacids, glucosamine, laxative drugs, aminoglycosides slow down and reduce absorption; enhances absorption.

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

Increases efficiency indirect anticoagulants(suppressing the intestinal microflora, reduces the synthesis of K and the prothrombin index). While taking anticoagulants, it is necessary to monitor the indicators of blood clotting.

Reduces efficiency oral contraceptives, drugs, during the metabolism of which PABA is formed, ethinyl estradiol- risk of breakthrough bleeding.

Diuretics, phenylbutazone, NSAIDs and other drugs that block tubular secretion, increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).

Allopurinol increases the risk of developing a skin rash.

special instructions

During the course of treatment, it is necessary to monitor the state of the function of the hematopoietic organs, liver and kidneys.

In order to reduce the risk of side effects from the gastrointestinal tract, the drug should be taken with meals.

Perhaps the development of superinfection due to the growth of microflora insensitive to it, which requires a corresponding change in antibiotic therapy.

May give false positive results when determined in urine. In this case, it is recommended to use a glucose oxidant method for determining the concentration of glucose in the urine.

In patients with hypersensitivity to penicillins, cross-allergic reactions with cephalosporin antibiotics are possible.

Pregnancy and lactation

Caution should be used during pregnancy and lactation (breastfeeding).

Application in childhood

Children under 12- in the form of a suspension, syrup or drops for oral administration. A single dose is set depending on age: children up to 3 months- 30 mg / kg / day in 2 divided doses; 3 months and older - at mild infections- 25 mg / kg / day in 2 doses or 20 mg / kg / day in 3 doses, with severe infections- 45 mg/kg/day in 2 divided doses or 40 mg/kg/day in 3 divided doses.
The maximum daily dose of amoxicillin for children under 12 years old is 45 mg/kg of body weight.

The maximum daily dose of clavulanic acid for children under 12 years old is 10 mg/kg of body weight.

For impaired renal function

At chronic renal failure carry out the correction of the dose and the frequency of administration depending on the CC: when CC more than 30 ml / min dose adjustment is not required; at QC 10-30 ml/min: inside - 250-500 mg / day every 12 hours; IV - 1 g, then 500 mg IV; at QC less than 10 ml / min- 1 g, then 500 mg/day IV or 250-500 mg/day orally in one dose. For children, doses should be reduced in the same way. With CC less than 30 ml / min, the use of tablets 875 mg / 125 mg is contraindicated.

Patients on hemodialysis- 250 mg or 500 mg orally in a single dose or 500 mg IV, plus 1 dose during dialysis and 1 more dose at the end of the dialysis session.

For impaired liver function

Contraindicated in episodes of jaundice or hepatic impairment as a result of the use of amoxicillin / clavulanic acid in history.

With caution: severe liver failure