Bacteria for which acquired resistance is likely 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, tnterosoccus faecium, Streptococcus pneumoniae 1,2, group streptococci 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 a combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.
2 strains of these types of bacteria 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 to healthy volunteers at a dosage of 500 mg + 100 mg (0.6 g) or 1000 mg + 200 mg (1.2 g) 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);
• lower respiratory tract infections (exacerbation of chronic bronchitis, lobar pneumonia and bronchopneumonia);
• urinary tract infections (cystitis, urethritis, pyelonephritis);
• infections in gynecology;
• infections of the skin and soft tissues, including human and animal bites;
• bone and joint infections (eg, osteomyelitis);
• infections of the abdominal cavity, incl. biliary tract (cholecystitis, cholangitis);
• sexually transmitted infections (gonorrhea, chancre);
• prevention of infections after surgery.

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

Application 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 necrotizing entercolitis in newborns. 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 oral mucous membranes associated with the penetration of trace amounts of the active ingredients of this drug into breast milk, no other adverse reactions were observed in breastfed infants. However, during breastfeeding, the drug Amoxiclav ® is used only if the intended benefit to the mother outweighs the potential risk to the fetus and child. In case of adverse reactions, breastfeeding should be discontinued.

Interaction with other medicinal products
Combined use with probenecid is not recommended. Probenecid reduces the 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, nonsteroidal 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 medicines ( 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 the prothrombin index). In some cases, taking the drug can lengthen the prothrombin time, therefore, care should be taken with the simultaneous use of anticoagulants and the drug Amoxiclav ®.
Indirect anticoagulants and antibiotics of the penicillin series 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 it is necessary to use it simultaneously with anticoagulants, the prothrombin time or INR should be carefully monitored when prescribing or discontinuing the drug; a dose adjustment of anticoagulants may be required.
In patients receiving mycophenolate mofetil, after starting the use of a 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 general changes in mycophenolic acid exposure.
The simultaneous use of allopurinol and amoxicillin may increase the risk of allergic skin reactions. Currently, there are 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.
Simultaneous use with disulfiram should be avoided.
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 aminoglycosides lose their activity under such conditions.
Avoid mixing with dextrose, dextran, sodium bicarbonate solutions.

special instructions

Release form

Storage conditions

Shelf life

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

Conditions of dispensing from pharmacies

Manufacturer

Latin name:
Amoxycillinum + Acidum clavulanicum
ATX code: J01CR02
Active substance:
amoxicillin and clavulanic acid
Manufacturer: Sandoz, Switzerland
Condition for dispensing from the pharmacy: On prescription

Amoxicillin and clavulanic acid have antibacterial properties. Amoxicillin is an antibiotic of significant application, and clavulanic acid is an inhibitor of beta-lactamases of microorganisms. The drug is effective against bacteria that are particularly susceptible to it. Due to the pharmacokinetic parameters, both substances do not affect the properties of each other. The drug has excellent absorption when taken orally. The highest plasma saturation is found one hour after administration.

Indications for use

The instructions for use must be strictly followed. Indications for use can be:

• Bacterial infections
• Bronchitis, pneumonia, lung abscess
• Infectious diseases of ENT organs
• Diseases of the genitourinary system and pelvic organs (pyelitis, urethritis, prostatitis, salpingitis, endomeritis, bacterial vaginitis, sepsis, septic abortions, gonorrhea, etc.)
• Soft tissue and skin infections
• Postoperative infections.

Composition of the preparation

Basic substances: amoxicillin in the form of trihydrate, clavulinic acid in the form of potassium salt.

Additional substances: colloidal silicon dioxide, crospovidone, croscarmellose magnesium stearate, microcrystalline cellulose, hypromellose, titanium dioxide, talc, triethyl citrate, polysorbate.

Medicinal properties

Active substances act as irritants for bacteria, neutralizing and destroying them. Amoxicillin and clavulanic acid are very effective in combination, since they are complementary substances, which only enhances the effect.

Clavulanic acid is excreted by the kidneys, but partly through exhaled air and feces. Amoxicillin - directly through urine during the first hours after injection.

Forms of issue

• Mixture for suspension (bubbles) 156 mg, 312.5 mg. (293-345 rubles)
• Coated tablets 375 mg, 500 mg, 625 mg. (220-420 rubles)
• Mixture for intravenous administration 0.6 mg and 1.2 mg. (RUB 49-835)

Method of administration and dosage

Suspension

Be sure to shake the bottle before use to dissolve the powder mixture. For two doses of the drug, about 86 ml of water is added to the bottle. One scoop holds 5 ml of medication. For children, the dose of the suspension is calculated based on body weight.

Newborns and children under 3 years of age should take 30mg per kg of body weight in 24 hours. The dose is divided in half and drunk after the same number of hours. In case of moderate infectious diseases, the doctor prescribes 20 mg per 1 kg of body weight per day, but in especially difficult situations, 45 mg is allowed - this is a boundary dose for children within 24 hours.

Parenteral administration

30 mg contains 25 mg of amoxicillin and 5 mg of clavulanic acid. The closest analogue "Augmentin" contains high concentrations of active ingredients.

In order to prepare an intravenous solution, you must mix the vial fluid and water for injection. For 600mg packaging, 10 ml of water will be required, for 1.2g - 20 ml. The liquid is usable for only 20 minutes. It is prohibited to freeze the medicine.

Adults and children over 12 years of age should be given 1.2 mg every 8 hours, but if complications occur, the drug is injected every 6 hours. Premature babies - 30 mg per 1 kg of body weight every 11-12 hours.

Having achieved a therapeutic effect, the transition to oral administration is allowed. It should be followed for two weeks.

Prevention of purulent processes before surgery

Injected intravenously at 1.2 mg before anesthesia. If the operation lasts more than one hour, another dose may be required. You cannot inject more than 4 times, 1.2 mg per day. In case of possible complications, intravenous or oral administration should be continued postoperatively.

Renal failure

Admission should be adjusted for adults and children depending on creatinine clearance. In the case of hemodialysis, 85% of the substance is excreted from the body, therefore 600 mg intravenously is assigned after it. During peritoneal dialysis, clavulanic acid is not excreted, therefore, the dosage does not need to be changed.

Pills

Crush the tablet in a container with water (volume not less than 100 ml) and wait for complete dissolution. You can also chew a tablet and drink plenty of water before eating. Tablets are prescribed for adults and children from 12 years old, weighing 40 kg. Depending on the course of the disease, the patient consumes about 3 tablets per day after an equal number of hours. In some situations, 4 tablets are allowed. The powder can be white or yellowish.

The solution should be injected very slowly - within 3-4 minutes.

During pregnancy and breastfeeding

Any infectious disease should be taken very seriously when carrying or feeding a baby. Treatment should begin immediately.

The drug is prescribed for pregnant and lactating women in the case of:

• Respiratory system diseases
• ENT organs
• Gynecological abnormalities
• Diseases of the kidneys and genitourinary system.

The danger of an antibiotic is that a small concentration of it can penetrate the placenta. The main rule of safe administration of the drug for pregnant women is strict adherence to the doctor's instructions and the exact dosage.

Contraindications

It is highly undesirable to combine the medicine with the intake of other medicines. People who suffer from kidney failure should be treated with special care when taking pills.

• High susceptibility to beta-lactam antibiotics
• Intolerance to the main substance
• Lymphocytic leukemia
• Infectious mononucleosis.

Precautionary measures

Only after consultation in the doctor's office, the drug is assigned to patients with a predicted allergy to cephalosporins and beta-lactam antibiotics, since there may be a risk of increased cross-sensitivity of ampicillin. In case of impaired liver and kidney function, the dose is significantly adjusted. Taking a similar drug "Augmentin" in this case is not recommended due to the increased content of active substances.

Cross-drug interactions

The antibiotic can be taken with other medications after consulting a doctor, but in no case should it be combined with beta-lactam drugs (Augmentin).

Side effects

Side effects of acid include:

• Nausea and vomiting
• Dizziness
• Decreased appetite
• Stomach pain and diarrhea
• Anxiety and nervousness
• Convulsions
• Failure of the kidneys, liver and intestines
• Various allergic reactions
• Disorder of blood properties.

Overdose

An excess of clavulanic acid causes the following symptoms:

• Nausea
• Diarrhea
• Gagging
• Insomnia
• Dizziness
• Convulsions.

There is no information on death or health hazardous consequences. Having taken a large dose, it is necessary to flush the gastrointestinal tract and drink activated charcoal to weaken the absorption.

Conditions and shelf life

The safe storage period is 2 years from the date of manufacture. Fresh suspension is allowed to be saved for only a week.

Analogs

SmithKline Beecham Pharmaceuticals, UK
Price fluctuates in the range of 220 -835 rubles.

Augmentin is the closest in composition and principle of action to the original drug. Augmentin is available in tablets, powder for injection and suspension

pros:

• Fast healing
• Higher safety of active ingredients
• Lower price

Minuses

• Low bioavailability

It is a combined preparation of clavulanic acid (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-lactamloccus): Staphyus. 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 meninglophilis duct, Hacreemyrhoea jejuni, Yersinia multocida. Clavulanic acid inhibits beta-lactamases (types 3, 2, 5, 4) and in relation to type 1 beta-lactamase, which form Serratia spp., Pseudomonas aeroginosa, Acinetobacter spp., Is inactive. Clavulanic acid to penicillinases has a high tropism, therefore, it forms a stable complex with the enzyme, which is the prevention of enzymatic degradation of amoxicillin under the action of beta-lactamases.

When taken orally, both active ingredients of the drug are absorbed quickly in the gastrointestinal tract. The drug binds to plasma proteins as follows: clavulanic acid binds by 22 - 30%, amoxicillin binds by 17 - 20%. Joint intake 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 content 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 content of amoxicillin is 5.09 - 7.91 μg / ml, the maximum plasma content of clavulanic acid is 1.19 - 2.41 μg / ml, when the drug is taken every 8 hours in doses of 500/125 mg, the maximum plasma concentration of amoxicillin is 4.94 - 9.46 μg / ml, the maximum plasma concentration of clavulanic acid is 1.57 - 3.23 μg / 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 the drug is administered intravenously at 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 it takes to reach the maximum inhibitory concentration of 1 μg / ml is similar for amoxicillin when used after 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 in 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) in this way: 25 - 40% and 50 - 78% of the administered dose of clavulanic acid and amoxicillin, respectively, are excreted unchanged within the first 6 hours after administration ...

Indications

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

Method of application of amoxicillin + clavulanic acid and doses

The drug is taken orally, injected intravenously. Doses and regimen of taking the drug are set individually 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 old or weighing more than 40 kg: 3 times a day 250 mg or 2 times a day 500 mg. With infections of the respiratory system, as well as with 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 divided 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 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 body weight.
It is recommended to use the suspension in adults with difficulty swallowing.
When preparing syrup, suspension and drops, water must be used as a solvent.
When administered intravenously to patients over 12 years of age, 1 g (for amoxicillin) is administered 3 times a day, possibly, if necessary, 4 times a day. The maximum daily dose is 6 grams. Children 3 months - 12 years old - 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 post-perinatal 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.
Prophylaxis 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 of 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 the creatinine clearance, the frequency of administration and the dose are adjusted: if the creatinine clearance is more than 30 ml / min, there is no need to adjust the dose; with creatinine clearance 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 by mouth in one dose or then by 500 mg per day intravenously. For children, the dose must be reduced as well. Patients on hemodialysis - 500 mg or 250 mg orally at one time or 500 mg intravenously, one additional dose during dialysis and one dose at the end of dialysis.

During 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 in the determination of glucose in the urine can give a false positive result. Therefore, it is recommended to use the glucose oxidant method for determining the glucose content in urine. After the suspension is diluted, it must be stored in the refrigerator for no more than 1 week, but not frozen. In patients who are hypersensitive to penicillins, with cephalosporin antibiotics, cross-allergic reactions may develop. There are cases of neonatal development 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), you need to know that two 250 mg tablets (for amoxicillin) 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 measles-like rash), a history of liver dysfunction or episodes of jaundice when using amoxicillin with clavulanic acid; creatinine clearance less than 30 ml / min (for tablets 875 mg / 125 mg).

Restrictions on use

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.

Application 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, an increase in the activity of liver transaminases, diarrhea, in isolated cases - the development of hepatitis and liver failure (usually in elderly men with prolonged treatment), cholestatic jaundice, hemorrhagic and pseudomembranous colitis (can 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 administration;
allergic reactions: erythematous rash, urticaria, rarely - the development of angioedema, exudative erythema multiforme, anaphylactic shock, very rarely - malignant exudative erythema, exfoliative dermatitis, allergic vasculitis, acute generalized exanthematous pustules-like syndrome;
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 down absorption; ascorbic acid increases absorption. Bacteriostatic drugs (chloramphenicol, macrolides, tetracyclines, lincosamides, sulfonamides) act antagonistically. Increases the effectiveness of indirect anticoagulants (by suppressing intestinal microflora, reducing the prothrombin index and vitamin K synthesis). When used together with anticoagulants, it is necessary to monitor blood clotting parameters. Reduces the effectiveness of oral contraceptives, drugs, during the metabolism of which PABA is formed. When used together with ethinyl estradiol, the risk of developing breakthrough bleeding increases. Allopurinol increases the likelihood of developing skin rashes. Diuretics, phenylbutazone, allopurinol, nonsteroidal 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. It is necessary to carry out symptomatic treatment; hemodialysis is effective.

Clavulanic acid was first discovered in 1974-1975 in the UK. It is produced by bacteria Streptomyces clavuligerus... Chemically, it is a bicyclic beta-lactam that does not contain either a penicillin or a cephalosporin nucleus. Clavulanic acid is active against certain bacteria, including chlamydia, neisseria, streptococci,. However, it is not used as a stand-alone antibiotic. The most important property of clavulanic acid is the ability to inhibit beta-lactamase. These are enzymes that protect bacteria from action. They break down beta-lactams before they can damage the bacterial cell wall. It is beta-lactamases that provide bacteria resistance to penicillins and cephalosporins. They are produced by both gram-positive and gram-negative bacteria.

Clavulanic acid is used in combination with beta-lactams. With their help, meningitis, endocarditis, sepsis, bronchitis and pneumonia, peritonitis, bacterial diseases of the kidneys, urinary tract and reproductive system, skin infections are treated. In addition, combined agents are also used for the prevention of diseases, for example, before surgery. Of these, the most famous is "Amoxiclav" ("Panklav", "Augmentin", "Verklav", "Amovikomb"), which contains amoxicillin. In veterinary medicine, "Amoxiclav" is used to treat infections in dogs and cats, as well as pigs, sheep, cows and poultry. It should not be used on rabbits, hamsters, guinea pigs and laying hens whose eggs are intended for food.

In addition to reducing the activity of beta-lactamases, clavulanic acid enhances the immune response to infection, which increases the effectiveness of combined drugs. So, in studies of penicillin-resistant Staphylococcus aureus, amoxicillin reduced the degree of its phagocytosis - the absorption and digestion of bacteria by cells of the immune system. On the other hand, the addition of clavulanic acid stimulated this process. However, this is true only for bacteria resistant to beta-lactams: studies on strains that do not produce beta-lactamases did not reveal significant differences in the intensity of phagocytosis under the action of amoxicillin alone and its combination with clavulanic acid.

When taken orally, clavulanic acid is absorbed in the digestive tract and then rapidly excreted in the urine. It is also removed from tissues quickly, including after injections. In small amounts, clavulanic acid is excreted in milk.

Clavulanic acid is used in combination with other drugs. Therefore, side effects are usually considered for the drug as a whole, rather than for individual substances. Combination therapy with beta-lactams and clavulanic acid has been associated with an increased risk of cholestasis and drug-induced hepatitis that occurs during or shortly after treatment. These conditions are usually not life threatening. There are known cases of allergic reactions caused by clavulanic acid.

The LD50 of clavulanic acid for rats and mice exceeds 2000 mg / kg body weight, which means little toxicity for mammals. In case of poisoning with this substance, nausea, diarrhea and abdominal pain are observed. Rarely, rash, hyperactivity, or drowsiness have been reported in addition to these symptoms. Clavulanic acid does not show genotoxic and carcinogenic properties. However, experiments in rats and mice have shown reproductive toxicity.

In the European Union, the maximum permissible levels of clavulanic acid in food of animal origin are limited by law. So, in pork, beef and fat of these animals, more than 100 μg / kg of this substance should not be present. The content of clavulanic acid in pork and beef liver should not exceed 200 μg / kg, in kidneys - 400 μg / kg, in cow's milk - 200 μg / kg. In the Russian Federation and the EAEU countries, the maximum permissible levels of clavulanic acid in food products have not been established.

Literature

1. Amoxicillin + Clavulanic acid. Register of medicines of the Russian Federation.
2. Clavulanic acid. PubChem.
3. Clavulanic Acid. Summary Report (2). Committee For Veterinary Medicinal Products. EMEA / MRL / 776/01-FINAL. February 2001
4. Finlay J, Miller L, Poupard JA. A review of the antimicrobial activity of clavulanate. J Antimicrob Chemother. 2003 Jul; 52 (1): 18-23. Epub 2003 May 29.
5. Dufour V, Millon L, Faucher JF, Bard E, Robinet E, Piarroux R, Vuitton DA, Meillet D. Effects of a short-course of amoxicillin / clavulanic acid on systemic and mucosal immunity in healthy adult humans. Int Immunopharmacol. 2005 May; 5 (5): 917-28.
6. Tortajada Girbés M, Ferrer Franco A, Gracia Antequera M, Clement Paredes A, García Muñoz E, Tallón Guerola M (2008). Hypersensitivity to clavulanic acid in children. Allergol Immunopathol (Madr). 36 (5): 308-10.

INN: Amoxicillin, Clavulanic acid

Manufacturer: Kraspharma OJSC

Anatomical-therapeutic-chemical classification: Amoxicillin in combination with beta-lactamase inhibitors

Registration number in the RK: No. RK-LS-5 No. 020148

Registration period: 30.09.2013 - 30.09.2018

Instructions

Tradename

Amoxicillin + Clavulanic Acid

International non-proprietary name

Dosage form

Powder for the preparation of a solution for intravenous administration 0.5 g + 0.1 g; 1.0 g +0.2 g.

Composition

One bottle contains

active substances: amoxicillin sodium in terms of amoxicillin - 0.5 g; 1.0 g

potassium clavulanate in terms of clavulanic acid - 0.1 g; 0.2 g

Description

Powder from white to white with a yellowish sheen.

Pharmacotherapeutic group

Beta-lactam antibacterial drugs - Penicillins. Penicillins in combination with beta-lactamase inhibitors. Clavulanic acid +

Amoxicillin

ATX code J01СR02

Pharmacological properties

Pharmacokinetics

After intravenous administration of the drug at doses of 1.2 and 0.6 g, the average values ​​of the maximum plasma concentration (Cmax) of amoxicillin are 105.4 and 32.2 μg / ml, of clavulanic acid - 28.5 and 10.5 μg / ml, respectively. Both components are characterized by a good volume of distribution in body fluids and tissues (lungs, middle ear, pleural and peritoneal fluids, uterus, ovaries). Amoxicillin also penetrates into the synovial fluid, liver, prostate gland, palatine tonsils, muscle tissue, gallbladder, sinuses, bronchial secretions. Amoxicillin and clavulanic acid do not cross the blood-brain barrier in non-inflamed meninges.

Active substances penetrate the placental barrier and are excreted in trace concentrations in breast milk.

Plasma protein binding is 17-20% for amoxicillin, and 22-30% for clavulanic acid.

Both components are metabolized in the liver. Amoxicillin is partially metabolized - 10% of the administered dose, clavulanic acid undergoes intensive metabolism - 50% of the administered dose.

After intravenous administration of the drug amoxicillin + clavulanic acid at doses of 1.2 and 0.6 g, the half-life (T1 / 2) for amoxicillin is 0.9 and 1.07 hours, for clavulanic acid 0.9 and 1.12 hours.

Amoxicillin is excreted by the kidneys (50-78% of the administered dose) practically unchanged by tubular secretion and glomerular filtration. Clavulanic acid is excreted by the kidneys by glomerular filtration unchanged, partly in the form of metabolites (25-40% of the administered dose) within 6 hours after taking the drug.

Small amounts can be excreted through the intestines and lungs.

Pharmacodynamics

The drug is a combination of a semi-synthetic penicillin amoxicillin and a beta-lactamase inhibitor - clavulanic acid. Acts bactericidal, inhibits the synthesis of the bacterial wall.

Active against:

aerobic gram-positive bacteria(including strains producing beta-lactamases): Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus spp, Corynebacterium spp., Listeria monocytogenes;

anaerobic gram-positive bacteria: Clostridium spp., Peptococcus spp., Peptostreptococcus spp .;

aerobic gram-negative bacteria(including strains producing beta-lactamases) : Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella spp., Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria Haophilus ), Campylobacter jejuni;

anaerobic gram-negative bacteria(including strains producing beta-lactamases): Bacteroides spp., including Bacteroides fragilis.

Clavulanic acid inhibits types II, III, IV and V beta-lactamases, is inactive against type I beta-lactamases produced by Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high tropism 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.

Indications for use

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

Upper respiratory tract infections (including ENT organs):

acute and chronic sinusitis, acute and chronic otitis media,

retropharyngeal abscess, tonsillitis, pharyngitis

Lower respiratory tract infections: acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia

Infections of the genitourinary system: pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, chancre, gonorrhea

Infections in gynecology: cervicitis, salpingitis, salpingo-oophoritis, tubo-ovarian abscess, endometritis, bacterial vaginitis, septic abortion

Skin and soft tissue infections: erysipelas, impetigo, secondary-infected dermatoses, abscess, phlegmon, wound infection

Bone and connective tissue infections

Biliary tract infections: cholecystitis, cholangitis

Odontogenic infections, post-surgical infections, prevention of infections caused by sensitive microorganisms in the surgical treatment of gastrointestinal tract pathologies

Method of administration and dosage

The dosage regimen is set individually, depending on age, body weight, renal function, as well as the severity of the infection. Treatment should not be continued for more than 14 days without re-evaluating the patient's condition.

Adults and children over 12 years of age: the drug is prescribed at a dose of 1.2 g every 8 hours 3 times a day, in case of severe infection - every 6 hours, 4 times a day. The maximum daily dose is 6 g.

Children

In children weighing less than 40 kg, dosage is applied based on the child's body weight. It is recommended to maintain a 4-hour interval between injections of Amoxicillin + Clavulanic acid to prevent an overdose of clavulanic acid.

Children under 3 months old

Children weighing less than 4 kg: 50 / 5mg / kg every 12 hours

Children weighing more than 4 kg: 50/5 mg / kg every 8 hours, depending on the severity of the infection

Children from 3 months to 12 years old

50 / 5mg / kg every 6-8 hours, depending on the severity of the infection

For patients with renal insufficiency, the dose and / or the interval between injections of the drug should be adjusted depending on the degree of insufficiency: when creatinine clearance is more than 30 ml / min, dose reduction is not required; with a creatinine clearance of 10-30 ml / min, treatment begins with the introduction of 1.2 g, then 0.6 g every 12 hours; with creatinine clearance less than 10 ml / min - 1.2 g, then 0.6 g / day.

For children with creatinine levels less than 30 ml / min, the use of this form of Amoxicillin + Clavulanic acid is not recommended. Since 85% of the drug is removed by hemodialysis, the usual dose of the drug must be administered at the end of each hemodialysis procedure.

No dose adjustment is required with peritoneal dialysis.

Preparation and administration of solutions for intravenous injection: dissolve the contents of the vial 0.6 g (0.5 g + 0.1 g) in 10 ml of water for injection or 1.2 g (1.0 g + 0.2 g) - in 20 ml of water for injection.

Introduce IV slowly (within 3-4 minutes)

Preparation and administration of solutions for intravenous infusion: prepared solutions for intravenous injection containing 0.6 g (0.5 g + 0.1 g) or 1.2 g (1.0 g + 0.2 g) of the drug should be diluted in 50 ml or 100 ml of solution for infusion, respectively. The duration of the infusion is 30-40 minutes.

When using the infusion solutions listed below in the recommended volumes, they retain the required antibiotic concentrations.

As a solvent for intravenous infusion, infusion solutions can be used: sodium chloride solution 0.9%, Ringer's solution, potassium chloride solution.

Side effects

Often (≥1 / 100,<1/10)

Candidiasis

Infrequently (≥1 / 1000,<1/100)

Dizziness, headache

Nausea, vomiting, dyspepsia

Moderate increase in liver enzymes

Skin rash, itching, urticaria

Rarely (≥1 / 10000,<1/1000)

Reversible leukopenia (including neutropenia), thrombocytopenia

Erythema multiforme

Thrombophlebitis at the injection site

Very rarely(<1/10000)

Reversible agranulocytosis and hemolytic anemia, increased bleeding time and prothrombin time index

Angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis

Reversible hyperactivity and seizures

Pseudomembranous or hemorrhagic colitis

Change in color of the surface layer of tooth enamel

Hepatitis, cholestatic jaundice

Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous

pustulosis

Interstitial nephritis, crystalluria

Contraindications

Hypersensitivity to penicillins or to any component of the drug

Known hypersensitivity to other beta-lactam antibiotics (cephalosporins, carbapenems, monobactams)

Jaundice or abnormal liver function that developed with the use of Amoxicillin + Clavulanic acid or beta-lactam antibiotics

Infectious mononucleosis (including when a bark of a similar rash appears).

Drug interactions

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

The drug increases the effectiveness of indirect anticoagulants (suppressing the intestinal microflora, reduces the synthesis of vitamin K and the prothrombin index). With the simultaneous administration of the drug with anticoagulants, it is necessary to monitor the indicators of blood clotting.

Amoxicillin + clavulanic acid reduces the effectiveness of oral contraceptives. With the simultaneous use of the drug with ethinyl estradiol or with drugs, in the process of metabolism of which para-aminobenzoic acid (PABA) is formed, there is a risk of "breakthrough" bleeding.

Diuretics, allopurinol, phenylbutazone, nonsteroidal anti-inflammatory drugs 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 skin rashes.

With the simultaneous use of the drug with methotrexate, the toxicity of the latter increases.

Simultaneous use with disulfiram should be avoided.

Pharmaceutical incompatible with solutions containing blood, proteins, lipids, glucose, dextran, bicarbonate. Do not mix in a syringe or infusion bottle with other drugs. Incompatible with aminoglycosides.

special instructions

Before starting treatment with Amoxicillin + Clavulanic acid, it is necessary to collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics.

Serious and sometimes fatal hypersensitivity reactions (anaphylactic shock) to penicillins have been described. In the event of an allergic reaction, it is necessary to discontinue treatment and begin alternative therapy. If serious hypersensitivity reactions develop, adrenaline should be administered to the patient immediately. Oxygen therapy, intravenous steroids, and airway management, including intubation, may be required.

Amoxicillin + Clavulanic acid should not be prescribed if infectious mononucleosis is suspected, since in patients with this disease, amoxicillin can cause a skin rash, making it difficult to diagnose the disease.

Long-term treatment with Amoxicillin + Clavulanic acid may be accompanied by an excessive growth of microorganisms insensitive to it.

Carefully Amoxicillin + Clavulanic acid should be used in patients with impaired liver function.

In patients receiving Amoxicillin + Clavulanic acid, an increase in prothrombin time is occasionally observed, therefore, with the simultaneous use of Amoxicillin + Clavulanic acid and anticoagulants, appropriate monitoring should be carried out.

Crystalluria may occur in rare cases in patients with reduced urine output. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of fluids and maintain adequate urine output to reduce the likelihood of amoxicillin crystal formation.

Lab tests: High concentrations of amoxicillin give a false positive reaction to urine glucose when using Benedict's reagent or Fehling's solution. It is recommended to use enzymatic reactions with glucosidase.

Pregnancy and lactation

Amoxicillin + Clavulanic acid passes into breast milk, which can cause diarrhea and fungal infections of the mucous membranes in breastfed babies. The decision to suspend breastfeeding is made after careful assessment of the benefit / risk ratio by the attending physician.

Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

Unknown.

Overdose

Symptoms: possible gastrointestinal disorders and disturbances in water and electrolyte balance. Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure.

Treatment: symptomatic therapy, correction of water and electrolyte balance. Amoxicillin + clavulanic acid is removed from the blood by hemodialysis.

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