Ecoclave, 1 piece, 25 g, 250 mg+62.5 mg/5 ml, powder for the preparation of suspension for oral administration

Composition and release form

in contour cell packages of 5 or 7 pcs; in a cardboard pack 1, 2 or 3 packages (for tablets of 250+125 mg and 500+125 mg) and 1 or 2 packages (for tablets of 875+125 mg) or in polymer bottles of 14 or 15 tablets. dosage 250+125 and 500+125 mg and 5, 7, 10 or 14 tablets. dosage 875+125 mg; 1 bottle in a cardboard pack.

Side effects

The drug is well tolerated. Side effects occur rarely, are mostly mild and transient in nature.

From the digestive system:

nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, cholestatic jaundice, hepatitis, liver failure (more often in the elderly, men, with long-term therapy), colitis (including pseudomembranous), black “hairy” tongue, darkening of tooth enamel, increased activity “ liver" transaminases, increased bilirubin content and alkaline phosphatase activity.

From the hematopoietic organs:

reversible increase in prothrombin time and bleeding time, thrombocytopenia, thrombocytosis, eosinophilia, leukopenia, agranulocytosis, hemolytic anemia.

From the central nervous system:

dizziness, headache, hyperactivity, anxiety, behavior changes, convulsions.

Allergic reactions:

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

From the kidneys and urinary tract:

interstitial nephritis, crystalluria, hematuria.

Others:

candidiasis, development of superinfection.

Directions for use and doses

Inside.

The dosage regimen is set individually depending on the age and body weight of the patient, the severity and localization of the infectious process, as well as the sensitivity of the pathogen.

The minimum course of antibacterial therapy is 5 days. Treatment should not be continued for more than 14 days without reviewing the clinical situation.

Adults and children over 12 years of age or weighing more than 40 kg:

Mild to moderate infections

— 1 table. 250+125 mg 3 times a day or 1 tablet. 500+125 mg 2 times a day.

Severe or lower respiratory tract infections

— 1 table. 875+125 mg 2 times a day or 1 tablet. 500 mg + 125 mg 3 times a day.

Since the tablets contain the same amount of clavulanic acid (125 mg), it should be noted that 2 tablets. 250+125 mg are not equivalent to 1 tablet. 500+125 mg each.

The maximum daily dose of amoxicillin for adults and children over 12 years of age is 6 g, clavulanic acid is 600 mg.

In case of chronic renal failure, the dose and frequency of administration are adjusted depending on creatinine clearance:

— when creatinine Cl >30 ml/min, no dose adjustment is required;

— with creatinine Cl 10–30 ml/min — 1 tablet of 250+125 mg 2 times a day (for mild and moderate infections) or 1 tablet. 500+125 mg 2 times a day (for severe infections or lower respiratory tract infections);

— with Cl creatinine <10 ml/min — 1 table. 250+125 mg 1 time per day (for mild and moderate infections) or 1 table. 500+125 mg 1 time per day (for severe infections or lower respiratory tract infections);

- patients on hemodialysis - 1 table. 500+125 mg or 2 tablets. 250+125 mg every 24 hours in combination with 1 dose during hemodialysis and 1 dose after hemodialysis, since the concentration of amoxicillin and clavulanic acid decreases.

Description

Oval biconvex tablets, film-coated, white or almost white. On a cross section, the kernel is almost white to light yellow with a brown tint; inclusions from white to yellow are acceptable.

Pharmacotherapeutic group

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

ATX code:

J01CR02

Pharmacological properties

A combination drug of amoxicillin and clavulanic acid, a beta-lactamase inhibitor. Amoxicillin is a semisynthetic broad-spectrum antibiotic; acts bactericidal, inhibiting the synthesis of cell wall protein of sensitive bacteria at the growth stage. Clavulanic acid has a high affinity for bacterial beta-lactamases and forms a stable complex with them. Thus, the biodegradation of amoxicillin by beta-lactamases is prevented, and the bactericidal activity of the antibiotic is maintained. Clavulanic acid inhibits type II-V beta-lactamases according to the Richmond-Sykes classification and is not active against type I beta-lactamases produced by Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp.

The combined preparation of amoxicillin and clavulanic acid, according to the results of in vitro tests and clinical studies, is active against the following microorganisms:

Gram-positive aerobic microorganisms:

Staphylococcus aureus (strains producing and not producing beta-lactamases);

Gram-negative aerobic microorganisms:

• Enterobacter spp. (despite the fact that most Enterobacter are resistant in vitro , the effectiveness of the drug in the treatment of infectious diseases of the urinary system caused by this pathogen has been clinically proven);
• Escherichia coli (strains producing and not producing beta-lactamases);
• Haemophilus influenzae (strains producing and not producing beta-lactamases);
• Klebsiella spp. (all known strains producing beta-lactamases);
• Moraxella catarrhalis (strains producing and not producing beta-lactamases).

Based on the results of in vitro studies, the following microorganisms are sensitive to the combination of amoxicillin and clavulanic acid:

Gram-positive aerobic microorganisms:

• Enterococcus faecalis**;
• Staphylococcus epidermidis (strains producing and not producing beta-lactamases);
• Staphylococcus saprophyticus (strains producing and not producing beta-lactamases);
• Streptococcus pneumoniae ** (strains that do not produce beta-lactamases);
• Streptococcus pyogenes** (strains that do not produce beta-lactamases);
• Streptococcus viridans group** (strains that do not produce beta-lactamases).

Gram-negative aerobic microorganisms:

• Eikenella corrodens (strains producing and not producing beta-lactamases);
• Neisseria gonorrhoeae ** (strains producing and not producing beta-lactamases);
• Proteus mirabilis** (strains producing and not producing beta-lactamases).

Anaerobic microorganisms:

• Bacteroides spp., including Bacteroides fragilis (beta-lactamase-producing and non-beta-lactamase producing strains);
• Fusobacterium spp. (strains producing and not producing beta-lactamases);
• Peptostreptococcus spp. (does not produce beta-lactamase).

NOTE: ** - (amoxicillin has been clinically proven to be effective in treating a number of infections caused by these pathogens).

Pharmacokinetics

Suction.

After oral administration, both components of the drug are quickly absorbed from the gastrointestinal tract. Absorption of the active ingredients of the drug is optimal if taken at the beginning of a meal.

After oral administration at a dose of 250 mg + 125 mg:

• maximum concentration (Cmax) of amoxicillin – 3.7 µg/ml, clavulanic acid – 2.2 µg/ml;
• time to reach maximum concentration (Tmax) of amoxicillin – 1.1 hours, clavulanic acid – 1.2 hours;
• the area under the concentration-time curve (AUC) of amoxicillin is 10.9 mg∙h/l, clavulanic acid is 6.2 mg∙h/l.

After oral administration at a dose of 500 mg + 125 mg:

• Cmax of amoxicillin – 6.5 µg/ml, clavulanic acid – 2.8 µg/ml;
• Tmax of amoxicillin – 1.5 hours, clavulanic acid – 1.3 hours;
• AUC of amoxicillin – 23.2 mg∙h/l, clavulanic acid – 7.3 mg∙h/l.

After oral administration at a dose of 875 mg + 125 mg:

• Cmax of amoxicillin – 8.8 µg/ml, clavulanic acid – 2.07 µg/ml;
• Tmax of amoxicillin – 1.5 hours, clavulanic acid – 1.5 hours;
• AUC of amoxicillin – 25.4 mg∙h/l, clavulanic acid – 6.1 mg∙h/l.

When using the drug, concentrations of amoxicillin in the blood serum are similar to those after oral administration of equivalent doses of amoxicillin alone.

Distribution

Both components of the drug are characterized by a good volume of distribution - therapeutic concentrations of amoxicillin and clavulanic acid are created in various organs and tissues, interstitial fluid: lungs, middle ear, abdominal organs, pelvic organs (prostate, uterus, ovaries), skin; fat, bone and muscle tissues; pleural, synovial and peritoneal fluids; plasma, bile, purulent discharge, sputum, bronchial secretions.

Amoxicillin and clavulanic acid have a moderate degree of binding to plasma proteins, 18% and 25%, respectively.

Both components of the drug penetrate the placental barrier, but no data on negative effects on the fetus have been published.

Amoxicillin and clavulanic acid are found in low concentrations in breast milk.

Metabolism, excretion

Approximately 60-70% of amoxicillin is excreted by the kidneys: by tubular secretion and glomerular filtration. Clavulanic acid is actively metabolized in the liver and excreted by glomerular filtration (40-65%), partly in the form of metabolites. A smaller part is excreted by the intestines.

In case of renal failure, the clearance of amoxicillin with clavulanic acid is reduced, so dose adjustment is required.

Interaction with other drugs

It is not recommended to use a combination drug of amoxicillin and clavulanic acid simultaneously with probenecid. Probenecid reduces the tubular secretion of amoxicillin, so their joint administration may lead to an increase and persistence of amoxicillin concentrations in the serum, while the serum concentration of clavulanic acid does not change.

Antacids, glucosamine, laxatives slow down and reduce the absorption of amoxicillin; ascorbic acid - increases.

Allopurinol increases the risk of skin rashes.

Diuretics, allopurinol, phenylbutazone, non-steroidal anti-inflammatory drugs and other drugs that block tubular secretion increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).

Like other broad-spectrum antibiotics, the combination drug of amoxicillin and clavulanic acid may reduce the effectiveness of oral contraceptives, and patients should be informed about this.

The literature describes rare cases of an increase in the international normalized ratio (INR) in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe a combination drug of amoxicillin and clavulanic acid with indirect anticoagulants, the prothrombin time or INR should be carefully monitored when prescribing or discontinuing the drug.

special instructions

The severity of gastrointestinal symptoms decreases when taking the drug at the beginning of a meal.

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

The development of superinfection is possible due to the selection of resistant forms of the pathogen.

False-positive results may be detected when determining glucose in urine. In this case, it is recommended to use the glucose oxidant method for determining the concentration of glucose in urine.

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

If infectious mononucleosis is suspected, the drug should not be used, since amoxicillin can cause a measles-like skin rash in patients with this disease, which makes diagnosing the disease difficult.

Given the likelihood of developing side effects from the central nervous system, caution should be exercised when driving vehicles and operating machinery.