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.

Carefully

Ecoclave® should be used with caution in patients with impaired liver function.

Use during pregnancy and breastfeeding

Pregnancy

In animal reproductive studies, oral and parenteral administration of a combination of ammoxicillin and clavulanic acid did not cause teratogenic effects.

In a single study in women with premature rupture of membranes, it was found that prophylactic therapy with the drug may be associated with an increased risk of developing necrotizing enterocolitis in newborns. Like all medications, Ecoclave® is not recommended for use during pregnancy, unless the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding period

Ecoclave® can be used during breastfeeding. With the exception of the possibility of sensitization, diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active ingredients of this drug into breast milk, no other adverse effects were observed in breastfed children. If adverse effects occur in breastfed infants, breastfeeding should be discontinued.

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

White to almost white powder with a faint fruity odor. After dissolution in water, an almost white to light yellow suspension with a fruity odor is formed.

Pharmacotherapeutic group:

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

ATX code:

J01CR02

Pharmacological properties

Pharmacodynamics

Mechanism of action

Amoxicillin is a semisynthetic broad-spectrum antibiotic that is active against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by beta-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce this enzyme.

Clavulanic acid is a beta-lactamase inhibitor, structurally related to penicillins, and has the ability to inactivate a wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is sufficiently effective against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against type 1 chromosomal beta-lactamases, which are not inhibited by clavulonic acid.

The presence of clavulonic acid in Ecoclave® protects amoxicillin from destruction by enzymes - beta-lactamases, which allows expanding the antibacterial spectrum of amoxicillin.

in vitro activity of the combination of amoxicillin and clavulanic acid :

Bacteria usually susceptible to the combination of amoxicillin and clavulonic acid

Gram-positive
aerobes

• Bacillus anthracis
• Enterococcus faecalis
• Listeria monocytogenes
• Nocardia asteroidеs
• Streptococcus pyogenes1,2
• Streptococcus agalactiae1,2
• Streptococcus spp. (other beta-hemolytic streptococci)1,2
• Staphylococcus aureus (methicillin sensitive)1
• Staphylococcus saprophyticus (methicillin sensitive)
• Coagulase-negative staphylococci (methicillin sensitive)

Gram-positive anaerobes

• Clostridium spp.
• Peptococcus niger
• Peptostreptococcus magnum
• Peptostreptococcus micros
• Peptostreptococcus spp.

Gram-negative aerobes

• Bordetella pertussis
• Haemophilus influenzae1
• Helicobacter pylori
• Moraxella catarrhalis1
• Neisseria gonorrhoeae
• Pasteurella multocida
• Vibrio cholerae

Gram-negative
anaerobes

• Bacteroides fragilis
• Bacteroides spp.
• Capnocytophaga spp.
• Eikenella corrodens
• Fusobacterium nucleatum
• Fusobacterium spp.
• Porphyromonas spp.
• Prevotella spp.

Others

• Borrelia burgdorferi
• Leptospira icterohaemorrhagiae
• Treponema pallidum

Bacteria for which acquired resistance to the combination of amoxicillin and clavulonic acid is likely

Gram-negative aerobes

• Escherichia coli1
• Klebsiella oxytoca
• Klebsiella pneumoniae1
• Klebsiella spp.
• Proteus mirabilis
• Proteus vulgaris
• Proteus spp.
• Salmonella spp.
• Shigella spp.

Gram-positive
aerobes

• Corynebacterium spp.
• Enterococcus faecium
• Streptococcus pneumoniae1,2
• Streptococci of the Viridians group

Bacteria that are naturally resistant to the combination of amoxicillin and clavulonic acid

Gram-negative aerobes

• Acinetobacter spp.
• Citrobacter freundii
• Enterobacter spp.
• Hafnia alvei
• Legionella pneumophila
• Morganella morganii
• Providencia spp.
• Pseudomonas spp.
• Serratia spp.
• Stenotrophomonas maltophilia
• Yersinia enterocolitica

Others

• Chlamydia pneumoniae
• Chlamydia psittaci
• Chlamydia spp.
• Coxiella burnetii
• Mycoplasma spp.

1 – for these bacteria, the clinical effectiveness of the combination of amocricillin with clavulonic acid has been demonstrated in clinical studies.

2 – strains of these types of bacteria do not produce beta-lactamases. Sensitivity during monotherapy with amoxicillin suggests similar sensitivity to the combination of amoxicillin with clavulonic acid.

Pharmacokinetics

Suction

Both active ingredients of Ecoclave®, amoxicillin and clavulanic acid, are quickly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of the active ingredients of the drug Ecoclave® is optimal if the drug is taken at the beginning of a meal.

The following shows the pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in different studies in which healthy volunteers aged 2-12 years took 40 mg/10 mg/kg per day on an empty stomach in three divided doses of amoxicillin with clavulanic acid, powder for the preparation of suspension for administration. orally, 125 mg/31.25 mg in 5 ml.

Main pharmacokinetic parameters

Amoxicillin

Clavulanic acid

Cmax – maximum concentration in blood plasma.

Tmax – time to reach maximum concentration in blood plasma.

AUC is the area under the concentration-time curve.

T1/2 – half-life

Distribution

As with intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulonic acid are found in various tissues and interstitial fluid (gallbladder, abdominal tissue, skin, adipose and muscle tissue, synovial and peritoneal fluids, bile, purulent discharge) .

Amoxicillin and clavulanic acid have a weak degree of binding to plasma proteins. Studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin in the blood plasma is bound to plasma proteins.

In animal studies, no accumulation of the components of the combination of amoxicillin and clavulanic acid was found in any organ. Amoxocillin, like most penicillins, passes into breast milk. Trace amounts of clavulanic acid may also be found in breast milk. With the exception of the possibility of sensitization, development of diarrhea and candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of breastfed children are known.

Animal reproductive studies have shown that amoxicillin and clavulanic acid cross the placental barrier. However, no negative effects on the fetus were detected.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicylic acid). Clavulanic acid is extensively metabolized to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and is excreted by the kidneys. through the gastrointestinal tract, as well as with exhaled air in the form of carbon dioxide.

Removal

Like other penicillins, amoxicillin is eliminated primarily by the kidneys, while clavulanic acid is eliminated through both renal and extrarenal mechanisms. Approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted unchanged by the kidneys in the first 6 hours after administration of 1 tablet 250 mg/125 mg or 1 tablet 500 mg/125 mg. Simultaneous administration of probenecid slows down the elimination of amoxicillin, but not clavulanic acid (see section “Interaction with other drugs”)

Method of preparing the suspension

The suspension is prepared immediately before the first use.

Add approximately 60 ml of boiled water, cooled to room temperature, to the bottle with the powder, then close the bottle with a lid and shake until the powder is completely diluted, let the bottle stand for 5 minutes to ensure complete dilution. Then add water up to the mark on the bottle and shake the bottle again. In total, about 92 ml of water is required to prepare the suspension.

The bottle should be shaken well before each use. For precise dosing of the drug, you should use a double-sided dosing spoon, which should be rinsed well with water after each use. After dilution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.

For children under 2 years of age, a measured single dose of Ecoclave® suspension can be diluted twice with water.

special instructions

Before starting treatment with Ecoclave®, it is necessary to collect a detailed history regarding previous hypersensitivity reactions to penicillins, cephalosporins or other substances that cause an allergic reaction in the patient.

Serious and sometimes fatal hypersensitivity reactions (anaphylactic reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. If an allergic reaction occurs, treatment with Ecoclav® should be discontinued and appropriate alternative therapy should be initiated. In case of serious anaphylactic reactions, the patient should be given epinephrine immediately. Oxygen therapy, intravenous corticosteroids, and airway management, including intubation, may also be required.

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

Long-term treatment with Ecoclave® may lead to excessive proliferation of insensitive microorganisms.

In general, Ecoclave® is well tolerated and has the low toxicity characteristic of all penicillins. During long-term therapy with Ecoclave®, it is recommended to periodically evaluate renal, liver and hematopoietic function.

Cases of pseudomembranous colitis have been described with the use of antibiotics, the severity of which can vary from mild to life-threatening. Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after antibiotic use. If diarrhea is prolonged and severe or the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be examined.

In patients receiving a combination of amoxicillin and clavulanic acid together with indirect (oral) anticoagulants, an increase in prothrombin time (increase in INR) has been reported in rare cases. When co-prescribing indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, monitoring of relevant indicators is necessary. Dosage adjustments may be required to maintain the desired effect of oral anticoagulants.

In patients with impaired renal function, the dose of Ecoclave® should be reduced according to the degree of impairment (see Section "Dosage and Administration" - Patients with impaired renal function

).

In patients with reduced diuresis, crystalluria very rarely occurs, mainly during parenteral therapy. During administration of high doses of amoxicillin, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation. (see section "Overdose")

Taking Ecoclave® orally leads to a high level of amoxicillin in the urine, which can lead to false-positive results when determining glucose in urine (for example, Benedict's test, Fehling's test). In this case, it is recommended to use the glucose oxidant method for determining the concentration of glucose in the urine.

Clavulanic acid may cause nonspecific binding of immunoglobulin G and albumin to red blood cell membranes, leading to false-positive Coombs test results.

Oral care helps prevent tooth discoloration associated with taking Ecoclave® by simply brushing your teeth.

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Antibiotic Ecoclave has a broad bactericidal effect.

Amoxicillin , which is part of it, inhibits the production of protein in the cell wall of bacteria sensitive to it.

Clavulanic acid is related to bacterial lactamases and forms a stable compound with them, preventing the biodegradation of amoxicillin by beta-lactamases, while maintaining the bactericidal activity of the antibiotic. The drug is active against a wide range of gram-positive and gram-negative aerobic and anaerobic microorganisms.

Pharmacokinetics

Ecoclave, after ingestion, is quickly absorbed from the gastrointestinal tract. Tmax of the drug is about one hour. Both components of Ecoclave are well distributed in various organs and tissues, quickly creating the required therapeutic concentration. The degree of binding to blood proteins is moderate: 18% for amoxicillin and 25% for clavulanic acid. Metabolism occurs in the liver, is excreted through the kidneys and partially through the intestines.

Interaction with other drugs

The simultaneous use of Ecoclave® and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, therefore the simultaneous use of Ecoclave® and probenecid may lead to an increase and persistence in the blood level of amoxicillin, but not clavulanic acid.

Concomitant 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.

Penicillins can slow down the elimination of methotrexate from the body by inhibiting its tubular secretion, therefore the simultaneous use of Ecoclave® and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, Ecoclave® can affect the intestinal flora, leading to a decrease in the absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives.

The literature describes rare cases of an increase in the international normalized ratio (INR) in patients with simultaneous use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe Ecoclave® with anticoagulants, prothrombin time or INR should be carefully monitored when prescribing or discontinuing Ecoclave®; Dosage adjustment of oral anticoagulants may be required.

In patients taking mycophenolate mofetil, after starting 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.

Side effects

The adverse reactions presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is defined as follows: “very often” (>10), “often” (>1/100, <1/10), “infrequently” (>1/1000, <1/100), “rarely” (> 1/10,000, <1/1000), “very rare” (<10,000), “frequency unknown.”

Infectious and parasitic diseases

Often

: candidiasis of the skin and mucous membranes.

From the hematopoietic and lymphatic system

:

Rarely

: reversible leukopenia (including neutropenia) and reversible thrombocytopenia.

Very rarely

: reversible agranulocytosis and reversible hemolytic anemia, prolongation of prothrombin time and bleeding time, anemia, eosinophilia, thrombocytosis.

Immune system disorders

:

Very rarely

: angioedema, anaphylactic reactions; syndrome similar to serum sickness, allergic vasculitis.

Disorders of the skin and subcutaneous tissues:

Infrequently

: skin rash, itching, urticaria.

Rarely

: erythema multiforme.

Very rarely

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

If any allergic skin reactions develop, you should stop using the drug.

Nervous system disorders:

Infrequently

: dizziness, headache.

Very rarely

: seizures (may occur in patients with impaired renal function, as well as in those receiving high doses of the drug), insomnia, agitation, anxiety, behavioral changes, reversible hyperactivity.

Gastrointestinal disorders:

Adults:

Often

: diarrhea.

Often

: nausea, vomiting.

Children:

Often

: diarrhea, nausea, vomiting.

Whole population:

nausea most often occurred when using high doses of the drug. If, after starting to take the drug, undesirable reactions from the gastrointestinal tract are observed, they can be eliminated by taking Ecoclave® at the beginning of the meal.

Infrequently

: digestive disorders.

Very rarely

: antibiotic-associated colitis (including pseudomembranous and hemorrhagic), gastritis, stomatitis, black “hairy” tongue, discoloration of the surface layer of tooth enamel in children.

Disorders of the liver and biliary tract:

Infrequently

: Moderate increase in aspartate aminotransferase activity. This reaction has been observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown.

Very rarely

: hepatitis and cholestatic jaundice (these reactions are observed in patients receiving therapy with penicillin antibiotics and cephalosporins), increased alkaline phosphatase activity and/or bilirubin concentration.

Adverse reactions from the liver were observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse reactions are very rarely observed in children. The listed signs and symptoms very rarely occur during or immediately after completion of therapy, but in some cases they may not appear for several weeks after completion of therapy. Adverse reactions are usually reversible. Adverse reactions from the liver can be severe, and deaths have been reported in extremely rare cases. In almost all cases, these were patients with serious comorbidities or patients receiving concomitantly potentially hepatotoxic drugs.

Renal and urinary tract disorders:

Very rarely

: interstitial nephritis, crystalluria, hematuria.

Ecoclave price, where to buy

The price of Ecoclave tablets 250 mg + 125 mg No. 15 varies within 170 rubles per pack. The cost of Ecoclave powder for suspension 125 mg + 31.25 mg / 5 ml in a bottle is about 140 rubles per package. You can easily purchase the drug in the pharmacy chain of Moscow and other cities.

• Online pharmacies in RussiaRussia

ZdravCity

• Ecoclave por.
  d/prig. susp. for oral administration 250 mg + 62.5 mg/5 ml vial. 25g No. 1 JSC "AVVA RUS" 254 rub. order
• Ecoclave por. d/prig. susp. for oral administration 125 mg + 31.25/5 ml vial. 25g No. 1 JSC "AVVA RUS"

  RUB 137 order