Ecoclav^® (Tablets, Powder) Instructions for Use

ATC Code

J01CR02 (Amoxicillin and beta-lactamase inhibitor)

Active Substances

Amoxicillin (Rec.INN registered by WHO)

Clavulanic acid (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Broad-spectrum penicillin antibiotic with a beta-lactamase inhibitor

Pharmacotherapeutic Group

Systemic antibacterial agents; beta-lactam antibacterial agents, penicillins; combinations of penicillins, including combinations with beta-lactamase inhibitors

Pharmacological Action

Amoxicillin is a broad-spectrum semi-synthetic antibiotic; it acts bactericidally by inhibiting the synthesis of the cell wall protein of susceptible bacteria during the growth stage.

Clavulanic acid has a high affinity for bacterial β-lactamases and forms a stable complex with them. Thus, the biodegradation of amoxicillin by β-lactamases is prevented, and the bactericidal activity of the antibiotic is preserved. Clavulanic acid inhibits β-lactamases of types II-V according to the Richmond-Sykes classification and is not active against type I β-lactamases produced by Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp.

Based on the results of in vitro tests and clinical studies, the combination of amoxicillin and clavulanic acid is active against the following microorganisms gram-positive aerobic microorganisms – Staphylococcus aureus (strains producing and not producing β-lactamases); gram-negative aerobic microorganisms – Enterobacter spp. (despite the fact that most strains of Enterobacter are resistant in vitro, the clinical efficacy of the drug in the treatment of urinary system infections caused by this pathogen has been proven), Escherichia coli (strains producing and not producing β-lactamases), Haemophilus influenzae (strains producing and not producing β-lactamases), Klebsiella spp. (all known strains produce β-lactamases), Moraxella catarrhalis (strains producing and not producing β-lactamases).

Based on in vitro studies, the following microorganisms have shown sensitivity to the combination of amoxicillin and clavulanic acid: gram-positive aerobic microorganisms – Enterococcus faecalis**, Staphylococcus epidermidis (strains producing and not producing β-lactamases), Staphylococcus saprophyticus (strains producing and not producing β-lactamases), Streptococcus pneumoniae** (does not produce β-lactamases), Streptococcus pyogenes** (does not produce β-lactamases), Streptococcus viridans** (does not produce β-lactamases); gram-negative aerobic microorganisms – Eikenella corrodens (strains producing and not producing β-lactamases), Neisseria gonorrhoeae** (strains producing and not producing β-lactamases), Proteus mirabilis** (strains producing and not producing β-lactamases); anaerobic microorganisms – Bacteroides spp., including Bacteroides fragilis (strains producing and not producing β-lactamases), Fusobacterium spp. (strains producing and not producing β-lactamases), Peptostreptococcus spp. (does not produce β-lactamases).

** The clinical efficacy of amoxicillin in the treatment of a number of infections caused by these pathogens has been proven.

Pharmacokinetics

Absorption

After oral administration, both components are rapidly absorbed from the gastrointestinal tract. Absorption of the active substances is optimal when taken at the beginning of a meal. After oral administration of a dose of 250 mg+125 mg, the C_max of amoxicillin is 3.7 µg/ml, of clavulanic acid – 2.2 µg/ml; T_max of amoxicillin – 1.1 h, of clavulanic acid – 1.2 h; AUC of amoxicillin – 10.9 mg×h/l, of clavulanic acid – 6.2 mg×h/l. After oral administration of a dose of 500 mg+125 mg, the C_max of amoxicillin is 6.5 µg/ml, of clavulanic acid – 2.8 µg/ml; T_max of amoxicillin – 1.5 h, of clavulanic acid – 1.3 h; AUC of amoxicillin – 23.2 mg×h/l, of clavulanic acid – 7.3 mg×h/l. After oral administration of a dose of 875 mg+125 mg, the C_max of amoxicillin is 8.8 µg/ml, of clavulanic acid – 2.07 µg/ml; T_max of amoxicillin – 1.5 h, of clavulanic acid – 1.5 h; AUC of amoxicillin – 25.4 mg×h/l, of clavulanic acid – 6.1 mg×h/l.

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

Distribution

Both components of the drug are characterized by a good V_d – therapeutic concentrations of amoxicillin and clavulanic acid are achieved in various organs and tissues, interstitial fluid: lungs, middle ear, abdominal organs, pelvic organs (prostate, uterus, ovaries), skin; adipose, 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 cross the placental barrier, but no data on negative effects on the fetus have been published.

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

Metabolism and Excretion

Approximately 60-70% of amoxicillin is excreted by the kidneys via tubular secretion and glomerular filtration.

Clavulanic acid is actively metabolized in the liver and excreted by glomerular filtration (40-65%), partially in the form of metabolites. A smaller part is excreted through the intestines.

Pharmacokinetics in Special Clinical Cases

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

Indications

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

• Infections of the lower respiratory tract (bronchitis, pneumonia);
• Infections of the ENT organs (sinusitis, tonsillitis, otitis media);
• Infections of the genitourinary system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, bacterial prostatitis, cervicitis, salpingitis, salpingo-oophoritis, endometritis, bacterial vaginitis, septic abortion, chancroid, gonorrhea);
• Infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection);
• Infections of bones and joints (osteomyelitis).

ICD codes

Dosage Regimen

Tablets

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

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

Powder

Doses are given in terms of amoxicillin. The dosage regimen is set individually depending on the patient’s age, the severity and location of the infection, and the sensitivity of the pathogen.

Children under 12 years: 20-40 mg/kg/day in 2-3 doses.

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

Maximum daily dose of amoxicillin for adults and children over 12 years is 6 g, for children under 12 years – 45 mg/kg of body weight.

Adverse Reactions

Side effects occur rarely, are mostly mild and transient.

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 of liver transaminases, increased bilirubin content and alkaline phosphatase activity.

From the hematopoietic system 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, convulsions.

From the urinary system interstitial nephritis, crystalluria, hematuria.

Allergic reactions urticaria, erythematous rashes, multiform exudative erythema, anaphylactic shock, angioedema, exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), allergic vasculitis, serum sickness-like syndrome, acute generalized exanthematous pustulosis.

Other candidiasis, development of superinfection.

Contraindications

• Hypersensitivity (including to cephalosporins and other beta-lactam antibiotics);
• Infectious mononucleosis;
• History of episodes of jaundice or impaired liver function as a result of the use of amoxicillin/clavulanic acid;
• Chronic renal failure (creatinine clearance less than 30 ml/min) for tablets with a dosage of 875 mg+125 mg.

With caution the drug should be prescribed for severe liver failure, gastrointestinal diseases (including a history of colitis associated with the use of penicillins), chronic renal failure.

Use in Pregnancy and Lactation

This combination is recommended to be prescribed during pregnancy only in cases where the expected benefit of its use to the mother outweighs the potential risk to the fetus.

The drug can be used during breastfeeding. Except for the risk of sensitization associated with the penetration of trace amounts of the active ingredients of this drug into breast milk, no other adverse effects have been identified in breastfed infants.

Use in Hepatic Impairment

The drug should be prescribed with caution in severe liver failure.

Use is contraindicated in case of a history of episodes of jaundice or impaired liver function as a result of the use of amoxicillin/clavulanic acid.

Use in Renal Impairment

The drug should be prescribed with caution in chronic renal failure.

Contraindicated in chronic renal failure (creatinine clearance less than 30 ml/min) for tablets with a dosage of 875 mg+125 mg.

Pediatric Use

The drug is prescribed to children from 12 years of age or with a body weight over 40 kg.

Special Precautions

The severity of gastrointestinal symptoms decreases when this combination is taken at the beginning of a meal.

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

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

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

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

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

Effect on ability to drive vehicles and mechanisms

Given the possibility of side effects from the central nervous system, caution should be exercised in situations requiring increased concentration, including when driving vehicles and working with mechanisms.

Drug Interactions

It is not recommended to use this combination simultaneously with probenecid. Probenecid reduces the tubular secretion of amoxicillin, so their co-administration may lead to an increase and persistence of the concentration of amoxicillin 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 it.

Allopurinol increases the risk of skin rash.

Diuretics, allopurinol, phenylbutazone, NSAIDs 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, this combination may reduce the effectiveness of oral contraceptives; patients should be informed about this.

Rare cases of increased INR in patients with the combined use of acenocoumarol or warfarin and amoxicillin are described in the literature. If it is necessary to prescribe this combination simultaneously with indirect anticoagulants, prothrombin time or INR should be carefully monitored when prescribing or discontinuing the drug.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.