Composition, form of production and packaging
Powder for the preparation of a suspension for ingestion from white to almost white, with a faint fruity odor; prepared suspension from almost white to light yellow color, with a fruity smell.
5 ml of finished couscous.
amoxicillin (in the form of trihydrate) 125 mg
clavulanic acid (in the form of potassium clavulanate) 31.25 mg
Auxiliary substances: lactulose - 200 mg, aspartame - 5.5 mg, silicon dioxide colloid (aerosil) - 16.885 mg, xanthan gum - 10 mg, crospovidone (collidone CL-M) - 28.1 mg, citric acid anhydrous - 2.165 mg, sodium citrate dihydrate - 8.335 mg, sodium benzoate - 2.085 mg, talc - 25 mg, orange flavor - 4 mg, mannitol (mannitol) - up to 1.25 g.
25 g - bottles of dark glass with a volume of 125 ml (1) complete with a dosing double-spoon (2.5 ml and 5 ml) - packs of cardboard.
Powder for the preparation of a suspension for ingestion from white to almost white, with a faint fruity odor; prepared suspension from almost white to light yellow color, with a fruity smell.
5 ml of finished couscous.
amoxicillin (in the form of trihydrate) 250 mg
clavulanic acid (in the form of potassium clavulanate) 62.5 mg
Auxiliary substances: lactulose - 400 mg, aspartame 5.5 mg, silicon dioxide colloid (aerosil) 16.885 mg, xanthan gum 10 mg, crospovidone (collidone CL-M) 28.1 mg, anhydrous citric acid 2.165 mg, sodium citrate dihydrate - 8.335 mg, sodium benzoate - 2.085 mg, talc - 25 mg, orange flavor - 4 mg, mannitol (mannitol) - up to 1.25 g.
25 g - bottles of dark glass with a volume of 125 ml (1) complete with a dosing double-spoon (2.5 ml and 5 ml) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2010.
PHARMACHOLOGIC EFFECT
The combined preparation of amoxicillin and clavulanic acid is a beta-lactamase inhibitor. Amoxicillin is a semisynthetic broad-spectrum antibiotic; acts bactericidal, inhibiting the synthesis of the protein of the cell wall 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 with beta-lactamases is prevented, and the bactericidal activity of the antibiotic is preserved. Clavulanic acid inhibits beta-lactamase II-V types 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 and clinical trials is active against the following microorganisms :
Gram-positive aerobic microorganisms:
Staphylococcus aureus (strains producing and non-producing beta-lactamases);
Gram-negative aerobic microorganisms:
Enterobacter spp. (despite the fact that most Enterobacter strains are resistant in vitro, the efficacy of the drug has been clinically proven in the treatment of infectious diseases caused by this pathogen of the urinary system);
Escherichia coli (strains producing and non-producing beta-lactamases);
Haemophilus influenzae (strains producing and non-producing beta-lactamases);
Klebsiella spp. (all known strains produce beta-lactamases);
Moraxella catarrhalis (strains producing and non-producing beta-lactamases).
The results of in vitro studies have shown the sensitivity to a combination of amoxicillin and clavulanic acid of the following microorganisms:
Gram-positive aerobic microorganisms:
Enterococcus faecalis **;
Staphylococcus epidermidis (strains producing and non-producing beta-lactamases);
Staphylococcus saprophyticus (strains producing and non-producing beta-lactamases);
Streptococcus pneumoniae ** (beta-lactamase does not produce);
Streptococcus pyogenes ** (beta-lactamase does not produce);
Streptococcus spp. group viridans ** (beta-lactamase does not produce).
Gram-negative aerobic microorganisms:
Eikenella corrodens (strains producing and non-producing beta-lactamases);
Neisseria gonorrhoeae ** (strains producing and non-producing beta-lactamases);
Proteus mirabilis ** (strains producing and non-producing beta-lactamases).
Anaerobic microorganisms:
Bacteroidesspp., Including Bacteroides fragilis (strains producing and not producing beta-lactamases);
Fusobacterium spp. (strains producing and non-producing beta-lactamases);
Peptostreptococcus spp. (beta-lactamase does not produce).
NOTE: ** - (clinically proven the effectiveness of amoxicillin in the treatment of a number of infections caused by these pathogens).
Lactulose, which is part of the Ecoclave as a bifidogenic factor, is a synthetic disaccharide, the molecule of which consists of the remnants of galactose and fructose.Lactulose in the stomach and upper intestine is not absorbed and not hydrolyzed. Released from Ecoclav tablets Lactulose as a substrate is fermented by the normal microflora of the large intestine, stimulating the growth of bifidobacteria and lactobacilli. As a result of hydrolysis of lactulose in the large intestine, organic acids are formed - lactic, acetic and formic, suppressing the growth of pathogenic microorganisms and thereby reducing the production of nitrogen-containing toxic substances.
Thus, lactulose as part of Ecoclav reduces the damaging effect of the antibiotic on the normal intestinal microflora and the risks of side effects associated with dysbiosis.
PHARMACOKINETICS
Suction. After oral administration, both components of the drug are rapidly absorbed from the gastrointestinal tract. Absorption of active ingredients of the drug is optimal in case of its intake at the beginning of the meal.
After oral administration at a dose of 125 mg + 31.25 mg:
- Cmax amoxicillin - 1.96 Ојg / ml, clavulanic acid - 0.77 Ојg / ml;
- Tmax amoxicillin - 1.5 h, clavulanic acid - 1.0 h;
- AUC amoxicillin - 9.19 mg • h / l, clavulanic acid - 2.69 mg • h / l.
When the drug is used, concentrations of amoxicillin in the blood serum are similar to those for oral administration of equivalent doses of one amoxicillin.
Distribution. Both components of the preparation 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 gland, uterus, ovaries), skin; fatty, bone and muscle tissues; pleural, synovial and peritoneal fluids; plasma, bile, purulent discharge, sputum, bronchial secretion.
Amoxicillin and clavulanic acid have a moderate degree of binding to plasma proteins, respectively, by 18% and 25%.
Both components of the drug penetrate the placental barrier, but there is no published data on the negative effect on the fetus.
Amoxicillin and clavulanic acid in low concentrations are found in breast milk.
Metabolism, excretion. Approximately 60-70% of amoxicillin is excreted by the kidneys: by tubular secretion and glomerular filtration in an unchanged form, about 10-25% in the form of inactive penicillic acid. Clavulanic acid is actively metabolized in the liver and is excreted by glomerular filtration (40-65%), partially in the form of metabolites. The smaller part is excreted by the intestine. With renal failure, the clearance of amoxicillin with clavulanic acid decreases, so dose adjustment is required.
Lactulose, which is part of Ecoclav, does not affect the main pharmacokinetic parameters characterizing the bioavailability of amoxicillin and clavulanic acid.
INDICATIONS
Infectious-inflammatory diseases caused by drug-susceptible pathogens:
- 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, salpingoophoritis, endometritis, bacterial vaginitis, septic abortion, chancroid, gonorrhea);
- skin and soft tissue infections (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection);
- infections of bones and joints (osteomyelitis).
DOSING MODE
Inside. The dosage regimen is set individually depending on the patient's body weight, severity of the course and localization of the infectious process, as well as the sensitivity of the pathogen.
The minimum course of antibiotic therapy is from 5 days. Treatment should not be continued for more than 14 days without reviewing the clinical situation. The duration of treatment of acute uncomplicated otitis media is 5-7 days, in children under 2 years - 7-10 days.
A single dose is established depending on the age and body weight (calculation for amoxicillin):
Children under 3 months - 30 mg / kg / day in 2 divided doses;
Children from 3 months and older:
- low doses (for treatment of skin and soft tissue infections, as well as chronic tonsillitis) - 20 mg / kg / day in 3 divided doses;
- high doses (for treatment of otitis media, sinusitis, lower respiratory tract infections, urinary tract infections) - 40 mg / kg / day in 3 divided doses.
Children weighing 40 kg or more should be given doses as adults.
The suspension can be used in adults with difficulty swallowing.
Recommended dosing regimen for adults: 20 ml of suspension in a dosage of 125 mg + 31.25 mg / 5 ml or 10 ml of suspension at a dosage of 250 mg + 62.5 mg / 5 ml 2-3 times / day.
The 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.
The maximum daily dose of clavulanic acid for adults and children over 12 years is 600 mg, for children under 12 years, 10 mg / kg.
Patients with impaired renal function:
Correction of doses is based on the maximum recommended dose of amoxicillin and the value of creatinine clearance.
Children
Creatinine clearance more than 30 ml / min dose adjustment is not required;
Creatinine clearance 10-30 ml / min - 15 mg / 3.75 mg / kg 2 times / day, maximum dose of 500 mg + 125 mg (20 ml of suspension at a dosage of 125 mg + 31.25 mg / 5 ml or 10 ml of suspension in a dosage of 250 mg +62.5 mg / 5 ml) 2 times / day;
Creatinine clearance less than 10 ml / min - 15 mg / 3.75 mg / kg 1 time / day, maximum daily dose of 500 mg + 125 mg (20 ml of suspension at a dosage of 125 mg + 31.25 mg / 5 ml or 10 ml of suspension at a dosage of 250 mg +62.5 mg / 5 ml);
Adults
Creatinine clearance more than 30 ml / min dose adjustment is not required;
Creatinine clearance 10-30 ml / min - 500 mg + 125 mg (20 ml suspension at a dosage of 125 mg + 31.25 mg / 5 ml or 10 ml suspension at a dosage of 250 mg + 62.5 mg / 5 ml) 2 times / day;
Creatinine clearance less than 10 ml / min - 500 mg + 125 mg (20 ml suspension at a dosage of 125 mg + 31.25 mg / 5 ml or 10 ml suspension at a dosage of 250 mg + 62.5 mg / 5 ml) 1 time / day;
Patients on hemodialysis:
Correction of doses is based on the maximum recommended dose of amoxicillin
Children - 15 mg / 3.75 mg / kg 1 time / day.
Before the hemodialysis session, one additional dose of 15 mg / 3.75 mg / kg should be taken. To restore the concentration of active components of the drug in the blood, a second additional dose of 15 mg / 3.75 mg / kg should be taken after a hemodialysis session.
Adults -500 mg + 125 mg (20 ml suspension at a dosage of 125 mg + 31.25 mg / 5 ml or 10 ml suspension at a dosage of 250 mg + 62.5 mg / 5 ml) once every 24 hours.
In addition, 1 dose during the dialysis session and another dose at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid)
Method of preparation of the suspension:
Suspension is prepared immediately before use.
The powder in the vial is pre-shaken, then, adding a small amount of boiled and chilled to room temperature water, mix to obtain a uniform suspension, then add water to the label on the vial. To accurately dispense the suspension, you should use a dosage two-way spoon, which should be rinsed well with water after each use.After reconstitution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.
SIDE EFFECT
The drug is well tolerated. Side effects occur rarely, are mostly mildly expressed and are transient in nature.
From the side of the digestive system: nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, cholestatic jaundice, hepatitis, hepatic insufficiency (more often in the elderly, men, with prolonged therapy), colitis (including pseudomembranous), black hairy tongue, darkening of the dental enamel, increased activity of "liver" transaminases, an increase in the bilirubin content and activity of alkaline phosphatase.
On the part of the hematopoiesis : reversible increase in prothrombin time and bleeding time, thrombocytopenia, thrombocytosis, eosinophilia, leukopenia, agranulocytosis, hemolytic anemia.
From the side of the central nervous system : dizziness, headache, hyperactivity, anxiety, behavior change, convulsions.
Allergic reactions : urticaria, erythema eruptions, multiforme exudative erythema, 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 side of the kidneys and urinary tract : interstitial nephritis, crystalluria, hematuria.
Other : Candidiasis, development of superinfection.
CONTRAINDICATIONS
- hypersensitivity (including to cephalosporins and other beta-lactam antibiotics);
- Infectious mononucleosis;
- episodes of jaundice or impaired liver function as a result of amoxicillin / clavulanic acid in history;
- phenylketonuria (contains aspartame).
Carefully:
Severe hepatic insufficiency, diseases of the gastrointestinal tract (including colitis in history, associated with the use of penicillins), chronic renal failure.
PREGNANCY AND LACTATION
The combined preparation of amoxicillin and clavulanic acid during pregnancy is recommended to be prescribed only in cases when the expected benefit from its administration for the mother exceeds the potential risk for 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 preparation into breast milk, no other adverse effects were found in infants fed breastfeeding.
APPLICATION FOR FUNCTIONS OF THE LIVER
Precautions should be taken in chronic renal failure.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in the presence of episodes of jaundice or a violation of liver function as a result of the use of amoxicillin / clavulanic acid in the anamnesis.
With caution appoint with severe hepatic insufficiency.
APPLICATION FOR CHILDREN
The application is possible according to the dosing regimen.
SPECIAL INSTRUCTIONS
The severity of gastrointestinal symptoms decreases when taking the drug at the beginning of the meal.
At course treatment it is necessary to monitor the status of the functions of the organs of hematopoiesis, liver and kidneys.
It is possible to develop superinfection by selecting the resistant forms of the pathogen.
There may be false-positive results in determining the glucose level in urine. In this case, it is recommended to use a glucose oxidase method to determine the concentration of glucose in the urine.
In patients who are hypersensitive to penicillins, there may be cross-allergic reactions with cephalosporin antibiotics.
In case of suspected infectious mononucleosis, the drug should not be used, as in patients with this disease, amoxicillin can cause a skinlike skin rash, which makes it difficult to diagnose the disease.
Given the likelihood of side effects from the central nervous system, care should be taken when driving vehicles and working with moving mechanisms.
OVERDOSE
Symptoms: a violation of the function of the gastrointestinal tract and water-electrolyte balance.
Treatment: symptomatic. Hemodialysis is effective.
DRUG INTERACTION
It is not recommended to use a combined preparation of amoxicillin and clavulanic acid simultaneously with probenecid. Probenecid reduces the tubular secretion of amoxicillin, so their combined use can lead to an increase and persistence of amoxicillin concentration in the serum, while the serum concentration of clavulanic acid does not change.
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).
Antacids, glucosamine, laxatives slow down and reduce the absorption of amoxicillin; ascorbic acid - increases.
Allopurinol increases the risk of skin rashes.
Like other broad-spectrum antibiotics, the combination drug amoxicillin and clavulanic acid may reduce the effectiveness of oral contraceptives, and patients should be informed about this.
In the literature, rare cases of an increase in the international normalized ratio (INR) in patients with the joint use of acenocoumarol or warfarin and amoxicillin are described. If it is necessary to simultaneously use a combination drug amoxicillin and clavulanic acid with indirect anticoagulants, prothrombin time or INR should be carefully monitored when the drug is prescribed or withdrawn.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
Storage conditions
In a dry, protected from light place at a temperature of no higher than 25 В° C.
The finished suspension is stored at a temperature of 2 В° C to 8 В° C in a tightly closed vial.
Keep out of the reach of children.
Shelf life
2 years.
The finished suspension is 7 days.
Do not use after the expiration date.
