Buy Augmentin powder for oral suspension 125mg+31.25mg/5ml 11.5g 100ml in pharmacies

Buy Augmentin powder for oral suspension 125mg+31.25mg/5ml 11.5g 100ml in pharmacies

Augmentin Buy Augmentin in DOSAGE FORMS powder for the preparation of oral suspension 125mg+31 25mg/5ml powder for the preparation of suspension for oral administration 125mg+31 25mg/5ml

MANUFACTURERS Smithkline Beacham (Great Britain) Smithkline Beacham PLC (Great Britain)

GROUP Combined antimicrobial agents

COMPOSITION Active substance: amoxicillin + clavulanic acid.

INTERNATIONAL NON-PROPENTED NAME Amoxicillin + Clavulanic acid

SYNONYMS Amoxiclav, Amoxiclav Quiktab, Arlet, Augmentin EU, Augmentin SR, Clamosar, Medoclav, Panclave, Ranclave, Rapiclav, Sinulox, Sinulox RTU, Flemoclav Solutab, Ecoclave

PHARMACOLOGICAL ACTION Broad spectrum antibacterial. Blocks the synthesis of peptidoglycan of the membrane of microbial cells (amoxicillin), inhibits beta-lactamases (clavulanic acid). Clavulanic acid forms a stable inactivated complex with these enzymes and protects amoxicillin from the loss of antibacterial activity caused by the production of beta-lactamases by the main pathogens and opportunistic microorganisms. Active against gram-positive aerobes: Streptococcus pneumoniae, S.pyogenes, S.viridans, S.bovis, Staphylococcus aureus (except methicillin-resistant strains), S.epidermidis (except methicillin-resistant strains), Listeria spp., Enterococcus spp. Gram-negative aerobes: Bordetella pertussis, Brucella spp., Campylobacter jejuni, E.coli, Gardnerella vaginalis, H.influenzae, H.ducreyi, Klebsiella spp., Moraxella catarrhalis, N.gonorrhoeae, N.meningitidis, Pasteurella multocida, Proteus spp., Salmonella spp., Shigella spp., Vibrio cholerae, Yersinia enterocolitica. Anaerobes: Peptococcus spp., Peptostreptococcus spp., Clostridium spp., Bacteroides spp., Actinomyces israelii. Rapidly absorbed after oral administration (food intake does not affect absorption). The maximum concentration is reached 1 hour after administration. The maximum plasma concentration after a bolus injection of 1.2 g is 105.4 mg/l (for amoxicillin) and 28.5 mg/l (for clavulanic acid). It has a large volume of distribution - high concentrations are found in body fluids and tissues (lungs, pleural, peritoneal, synovial fluid, tonsils, bronchial secretions, prostate gland, peritoneal abscess, muscle tissue, adipose tissue, paranasal sinus secretions, middle ear, etc. .). Peak concentrations in body fluids are observed 1 hour after peak plasma concentrations are reached. Does not pass through the BBB when the meninges are not inflamed, passes through the placental barrier and penetrates into breast milk in trace concentrations. Weakly binds to plasma proteins. Amoxicillin is partially metabolized, clavulanic acid undergoes intensive metabolism. Amoxicillin is excreted by the kidneys almost unchanged by tubular secretion and glomerular filtration; clavulanic acid - by glomerular filtration, partly in the form of metabolites. Small amounts are excreted by the intestines and lungs. The half-life is 1-1.5 hours, with severe renal failure it increases to 7.5 (for amoxicillin) and 4.5 hours (for clavulanic acid). It is removed during hemodialysis, and slightly - during peritoneal dialysis.

INDICATIONS FOR USE Infectious diseases of the upper (acute and chronic sinusitis, acute and chronic otitis media, retropharyngeal abscess, tonsilopharyngitis) and lower respiratory tract (acute and chronic bronchitis, pneumonia, pleural empyema); urinary tract infections (including cystitis, urethritis, pyelonephritis), gynecological infections (including salpingitis, salpingoophoritis, endometritis, septic abortion, pelvioperitonitis); biliary tract (cholecystitis, cholangitis), bone and connective tissue (including chronic osteomyelitis), skin and soft tissue (phlegmon, wound infection), odontogenic infections (periodontitis); sexually transmitted infections (gonorrhea, chancroid).

CONTRAINDICATIONS Hypersensitivity; history of allergic reactions to antibiotics of the penicillin and cephalosporin group; cholestatic jaundice, hepatitis caused by taking penicillin antibiotics (in history); liver failure; infectious mononucleosis, lymphocytic leukemia. Use during pregnancy and breastfeeding: possible if the expected effect of therapy exceeds the potential risk to the fetus. Breastfeeding should be stopped during treatment.

SIDE EFFECTS In most cases, side effects are weak and transient, most often affecting the gastrointestinal tract: loss of appetite, nausea, vomiting, diarrhea. Possible development of superinfection, stomatitis, vaginitis; in rare cases - pseudomembranous colitis with severe diarrhea. Allergic reactions may occur: itching, skin rashes; in sensitive patients, immediate hypersensitivity reactions may develop (angioedema, bronchospasm, rarely - anaphylactic shock). It is extremely rare that a transient increase in the level of transaminases in the blood plasma can be observed. There are isolated reports of cholestatic jaundice, hepatitis, and liver dysfunction.

INTERACTION When used simultaneously with methotrexate, the toxicity of methotrexate increases, with allopurinol - the incidence of exanthema, and with anticoagulants - the prothrombin time is prolonged. Reduces the effectiveness of oral contraceptives. Concomitant use with disulfiram should be avoided. The effectiveness of Amoxiclav is weakened by combination with bacteriostatic antibiotics (macrolides, tetracyclines); combination with rifampicin is antagonistic. Probenecid reduces the excretion of amoxicillin, increasing its serum concentration. Pharmaceutically 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.

DOSAGE AND ADMINISTRATION The dose of the drug depends on age, body weight and kidney function.

OVERDOSE Symptoms: in most cases nausea, diarrhea, vomiting, possible agitation, insomnia, dizziness, and in some cases seizures. There are no reports of deaths or life-threatening side effects. Treatment: symptomatic, in case of recent use (less than 4 hours), remove the drug from the gastrointestinal tract (gastric lavage, taking activated charcoal to reduce absorption), hemodialysis is effective.

SPECIAL INSTRUCTIONS Prescribe with caution to patients prone to allergic reactions to cephalosporins and other beta-lactam antibiotics (risk of cross-sensitivity), with severe impairment of liver and kidney function (dosage regimen adjustment is necessary). High concentrations give a false positive reaction for glucose in urine when using Benedict's reagent or Felling's solution (it is recommended to use enzymatic reactions with glucose oxidase).

STORAGE CONDITIONS List B. At room temperature.

Augmentin 250mg+125mg 20 pcs. film-coated tablets

pharmachologic effect

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

Clavulanic acid is a β-lactamase inhibitor, structurally related to penicillins, and has the ability to inactivate a wide range of β-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is quite effective against plasmid β-lactamases, which most often cause bacterial resistance.

The two main mechanisms of resistance to the combination of amoxicillin and clavulanic acid are:

• Inactivation by bacterial β-lactamases that are not themselves inhibited by clavulanic acid, including various amino acid sequences classified as Ambler classes B, C, and D.
• Changes in penicillin-binding proteins that reduce the affinity of the antibacterial agent for the target. Reduced outer membrane permeability and efflux pump mechanisms may cause or contribute to resistance, especially among Gram-negative microorganisms.

The presence of clavulanic acid in Augmentin® protects amoxicillin from destruction by enzymes - β-lactamases, which allows expanding the antibacterial spectrum of amoxicillin.

Pharmacodynamic effects

Below is a classification of microorganisms according to their in vitro sensitivity to the combination of amoxicillin and clavulanic acid.

Bacteria usually susceptible to the combination of amoxicillin and clavulanic acid

Gram-positive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, Streptococcus spp. (other β-hemolytic streptococci)1,2, Staphylococcus aureus (methicillin sensitive)1, Staphylococcus saprophyticus (methicillin sensitive), Staphylococcus spp. (coagulase-negative, methicillin-sensitive).

Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Gram-positive anaerobes: Clostridium spp., Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus spp.

Gram-negative anaerobes: Bacteroides fragilis, Bacteroides spp., Capnocytophaga spp., Eikenella corrodens, Fusobacterium nucleatum, Fusobacterium spp., Porphyromonas spp., Prevotella spp.

Other: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Bacteria for which acquired resistance to the combination of amoxicillin and clavulanic 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, Streptococcus of the Viridans group2.

Bacteria that are naturally resistant to the combination of amoxicillin and clavulanic 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.

Other: Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia spp., Coxiella burnetti, Mycoplasma spp.

• For these bacterial species, the clinical effectiveness of the combination of amoxicillin and clavulanic acid has been demonstrated in clinical studies.
• Strains of these bacterial species do not produce β-lactamases. Sensitivity during amoxicillin monotherapy suggests similar sensitivity to the combination of amoxicillin and clavulanic acid.

Composition and release form Augmentin 250mg+125mg 20 pcs. film-coated tablets

White to almost white, oval, film-coated tablets with the inscription “AUGMENTIN” imprinted on one side; at the fracture - from yellowish-white to almost white.

1 tab.

• Active ingredients: amoxicillin (in the form of trihydrate) - 250 mg; clavulanic acid (in the form of potassium salt) - 125 mg;
• Excipients: magnesium stearate - 6.5 mg, sodium carboxymethyl starch - 13 mg, colloidal silicon dioxide - 6.5 mg, microcrystalline cellulose - 650 mg.

Film shell composition: titanium dioxide - 9.63 mg, hypromellose (5cP) - 7.39 mg, hypromellose (15cP) - 2.46 mg, macrogol 4000 - 1.46 mg, macrogol 6000 - 1.46 mg, dimethicone - 0.013 mg, purified water (removed during production ).

10 pieces. - blisters (1) with a bag of silica gel - packages of laminated aluminum foil (2) - cardboard packs.

White to almost white, film-coated tablets, oval, with embossed inscription “AC” and a score line on one side.

1 tab.

• Active ingredients: amoxicillin (in the form of amoxicillin trihydrate) - 500 mg; clavulanic acid (in the form of potassium clavulanate) - 125 mg;
• Excipients: magnesium stearate - 7.27 mg, sodium carboxymethyl starch - 21 mg, colloidal silicon dioxide - 10.5 mg, microcrystalline cellulose - up to 1050 mg.

Film shell composition: titanium dioxide - 11.6 mg, hypromellose (5 cps) - 8.91 mg, hypromellose (15 cps) - 2.97 mg, macrogol 4000 - 1.76 mg, macrogol 6000 - 1.76 mg, dimethicone 500 (silicone oil) - 0.013 mg.

7 pcs. - blisters (1) with a bag of silica gel - packages of laminated aluminum foil (2) - cardboard packs. 10 pieces. - blisters (1) with a bag of silica gel - packages of laminated aluminum foil (2) - cardboard packs.

White to almost white, oval, film-coated tablets, debossed with “AC” on both sides and a score line on one side.

1 tab.

• Active ingredients: amoxicillin trihydrate - 1004.43 mg (corresponds to the content of amoxicillin - 875 mg); potassium clavulanate - 148.91 mg (corresponds to the content of clavulanic acid - 125 mg);
• Excipients: magnesium stearate - 14.5 mg, sodium carboxymethyl starch - 29 mg, colloidal silicon dioxide - 10 mg, microcrystalline cellulose - 243.16 mg.

Composition of the film shell Opadry OY-S-7300 white: titanium dioxide - 43%, hypromellose 5 cP - 33%, hypromellose 15 cP - 11%, macrogol 4000 - 6.5%, macrogol 6000 - 6.5%.

7 pcs. - blisters (1) with a desiccant package - packaging made of laminated aluminum foil (2) - cardboard packs.

Directions for use and doses

The drug is taken orally.

The dosage regimen is set individually depending on the age, body weight, kidney function of the patient, as well as the severity of the infection.

For optimal absorption and reduction of possible side effects from the digestive system, Augmentin® is recommended to be taken at the beginning of a meal.

The minimum course of antibacterial therapy is 5 days.

Treatment should not continue for more than 14 days without reviewing the clinical situation.

If necessary, it is possible to carry out stepwise therapy (initially, intravenous administration of the drug Augmentin® in powder dosage form for the preparation of a solution for intravenous administration, followed by a transition to the drug Augmentin® in dosage forms for oral use).

It must be remembered that 2 tablets of 250 mg/125 mg are not equivalent to 1 tablet of 500 mg/125 mg.

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

1 tab. 250 mg/125 mg 3 times/day for mild to moderate infections.

For severe infections (including chronic and recurrent urinary tract infections, chronic and recurrent lower respiratory tract infections), other dosages of Augmentin® are recommended - 1 tablet. 500 mg/125 mg 3 times a day or 1 tablet. 875 mg/125 mg 2 times/day.

Special patient groups

Children under 12 years of age weighing less than 40 kg

It is recommended to use other dosage forms of Augmentin®.

Elderly patients

No dose adjustment is required. In elderly patients with impaired renal function, the dose should be adjusted as indicated below for adults with impaired renal function.

Patients with impaired renal function

Dose adjustments are based on the maximum recommended dose of amoxicillin and are carried out taking into account QC values.

In most cases, whenever possible, parenteral therapy should be preferred.

Tablets 875 mg + 125 mg should be used only in patients with CC 30 ml/min, and no dosage adjustment is required.

Patients on hemodialysis

Dose adjustment is based on the maximum recommended dose of amoxicillin: 2 tablets. 250 mg/125 mg or 1 tablet. 500 mg/125 mg in one dose every 24 hours. During a hemodialysis session, an additional 1 dose (1 tablet) and another 1 dose (1 tablet) at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

Patients with liver dysfunction

Treatment is carried out with caution; regularly monitor liver function. There is insufficient data to adjust the dosage regimen in this category of patients.

Pharmacokinetics

Suction

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

The following are pharmacokinetic data for amoxicillin and clavulanic acid obtained from separate studies when administered to healthy volunteers on an empty stomach:

• 1 tablet of Augmentin® 250 mg/125 mg (375 mg);
• 2 tablets of Augmentin® 250 mg/125 mg (375 mg);
• 1 tablet of Augmentin® 500 mg/125 mg (625 mg);
• 500 mg amoxicillin;
• 125 mg clavulanic acid;
• 2 tablets of Augmentin® 875 mg/125 mg (1000 mg).

Main pharmacokinetic parameters

Distribution

As with the intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are created in various organs and tissues, interstitial fluid (abdominal organs, adipose, bone and muscle tissues, synovial and peritoneal fluids, skin, bile, purulent separable).

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 are bound to plasma proteins.

In animal studies, accumulation of the ingredients of Augmentin® was not detected.

Amoxicillin, like most penicillins, passes into breast milk. Trace amounts of clavulanic acid have also been found in breast milk. With the exception of the possibility of developing sensitization, 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, with no evidence of adverse effects on the fetus.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic 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, whereas clavulanic acid is eliminated through both renal and extrarenal mechanisms. Studies have shown that, on average, 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 the drug.

Indications for use Augmentin 250mg+125mg 20 pcs. film-coated tablets

Bacterial infections caused by microorganisms sensitive to the drug:

• infections of the upper respiratory tract and ENT organs (for example, recurrent tonsillitis, sinusitis, otitis media), usually caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis*, Streptococcus pyogenes;
• lower respiratory tract infections (for example, exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia), usually caused by Streptococcus pneumoniae, Haemophilus influenzae* and Moraxella catarrhalis* (except 250 mg/125 mg tablets);
• genitourinary tract infections: cystitis, urethritis, pyelonephritis, infections of the female genital organs, usually caused by species of the Enterobacteriaceae family (mainly Escherichia coli*), Staphylococcus saprophyticus and species of the genus Enterococcus;
• gonorrhea caused by Neisseria gonorrhoeae* (except 250 mg/125 mg tablets);
• infections of the skin and soft tissues, usually caused by Staphylococcus aureus*, Streptococcus pyogenes and species of the genus Bacteroides*;
• infections of bones and joints (for example, osteomyelitis, usually caused by Staphylococcus aureus*), if long-term therapy is necessary;
• odontogenic infections (for example, periodontitis, maxillary sinusitis, severe dental abscesses with spreading cellulitis) - for tablets 500 mg/125 mg or 875 mg/125 mg;
• other mixed infections (for example, septic abortion, postpartum sepsis, intra-abdominal sepsis) as part of stepwise therapy.

* Some representatives of this genus of microorganisms produce β-lactamase, which makes them insensitive to amoxicillin.

Infections caused by microorganisms sensitive to amoxicillin can be treated with Augmentin®, since amoxicillin is one of its active ingredients.

Augmentin® is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as β-lactamase-producing microorganisms sensitive to the combination of amoxicillin with clavulanic acid.

The sensitivity of bacteria to the combination of amoxicillin and clavulanic acid varies regionally and over time. Where possible, local sensitivity data should be taken into account. If necessary, microbiological samples should be collected and bacteriological susceptibility testing should be carried out.

Contraindications

• history of hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins);
• history of previous episodes of jaundice or impaired liver function when using a combination of amoxicillin and clavulanic acid;
• children under 12 years of age and body weight less than 40 kg;
• impaired renal function (creatinine clearance ≤30 ml/min) - (for tablets 875 mg/125 mg).

With caution: liver dysfunction.

Application Augmentin 250mg+125mg 20 pcs. film-coated tablets during pregnancy and breastfeeding

In studies of reproductive function in animals, oral and parenteral administration of Augmentin® 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, Augmentin® is not recommended for use during pregnancy, unless the expected benefit to the mother outweighs the potential risk to the fetus.

Augmentin® 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.

The use of the drug is contraindicated in children under 12 years of age and with a body weight of less than 40 kg.

Overdose

Symptoms: Gastrointestinal symptoms and fluid and electrolyte imbalance may occur. Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure. Convulsions may occur in patients with impaired renal function, as well as in those receiving high doses of the drug.

Treatment: symptoms from the gastrointestinal tract - symptomatic therapy, paying special attention to the normalization of water and electrolyte balance. In case of overdose, amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

The results of a prospective study that was conducted in 51 children at a poison control center showed that amoxicillin administered at a dose of less than 250 mg/kg did not lead to significant clinical symptoms and did not require gastric lavage.

Side effects Augmentin 250mg+125mg 20 pcs. film-coated tablets

Adverse reactions presented below are listed according to damage to organs and organ systems and frequency of occurrence. The frequency of occurrence is determined as follows: very often (≥1/10), often (≥1/100,

Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.

Infectious and parasitic diseases: often - candidiasis of the skin and mucous membranes.

From the hematopoietic 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.

From the immune system: very rarely - angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.

From the nervous system: infrequently - dizziness, headache; very rarely - reversible hyperactivity, convulsions (convulsions can be observed in patients with impaired renal function, as well as in those receiving high doses of the drug), insomnia, agitation, anxiety, behavior changes.

From the digestive system: adults: very often - diarrhea, often - nausea, vomiting; children: often - diarrhea, nausea, vomiting; entire population: nausea is most often observed when taking high doses of the drug. If, after starting to take the drug, adverse reactions from the gastrointestinal tract are observed, they can be eliminated if the drug is taken at the beginning of the meal. Uncommon: digestive disorders; very rarely - antibiotic-associated colitis induced by antibiotics (including pseudomembranous colitis and hemorrhagic colitis) (see section "Special Instructions"), black "hairy" tongue, gastritis, stomatitis.

From the liver and biliary tract: uncommon - moderate increase in AST and/or ALT activity (observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown); very rarely - hepatitis and cholestatic jaundice (these reactions were observed during therapy with other penicillins and cephalosporins), increased concentrations of bilirubin and alkaline phosphatase. 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 usually 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 persons with serious comorbidities or persons receiving concomitantly potentially hepatotoxic drugs.

From the skin and subcutaneous tissues: infrequently - rash, itching, urticaria; rarely - erythema multiforme; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

If allergic skin reactions occur, treatment with Augmentin® should be discontinued.

From the urinary system: very rarely - interstitial nephritis, crystalluria, hematuria.

Drug interactions

The simultaneous use of Augmentin® and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of Augmentin® and probenecid may lead to an increase and persistence in the blood concentration 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 Augmentin® and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, Augmentin® can affect the intestinal microflora, 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 increased MHO in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe Augmentin® with anticoagulants, prothrombin time or MHO should be carefully monitored when prescribing or discontinuing Augmentin®, and dose adjustment of oral anticoagulants may be required.

In patients receiving mycophenolate mofetil, after starting the combination of amoxicillin and clavulanic acid, there was a decrease in the concentration of the active metabolite, mycophenolic acid, 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.

Precautionary measures

Before starting treatment with Augmentin®, 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 Augmentin® should be discontinued and appropriate alternative therapy should be initiated. For severe hypersensitivity reactions, epinephrine should be administered immediately. Oxygen therapy, intravenous administration of corticosteroids, and airway management, including intubation, may also be required.

If allergic skin reactions occur, treatment with Augmentin® should be discontinued.

If infectious mononucleosis is suspected, Augmentin® 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 Augmentin® sometimes leads to excessive proliferation of insensitive microorganisms.

Cases of pseudomembranous colitis have been described when taking 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 or severe or the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be examined. The use of drugs that inhibit intestinal motility is contraindicated.

In general, Augmentin® is well tolerated and has the low toxicity characteristic of all penicillins.

During long-term therapy with Augmentin®, it is recommended to periodically evaluate the function of the kidneys, liver and hematopoietic system.

In patients receiving a combination of amoxicillin and clavulanic acid together with indirect (oral) anticoagulants, an increase in prothrombin time (increase in MHO) 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 reduced diuresis, the development of crystalluria has been reported in very rare cases, mainly with parenteral use of the drug. 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.

Taking Augmentin® orally leads to a high level of amoxicillin in the urine, which can lead to false-positive results when determining glucose in the 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 urine.

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

The laminated aluminum foil package contains a desiccant pouch that is not intended for ingestion. Augmentin® must be used within 30 days of opening the laminated aluminum foil package.

Drug abuse and dependence

There was no drug dependence, addiction, or euphoric reactions associated with the use of Augmentin®.

Impact on the ability to drive vehicles and operate machinery

Since the drug may cause dizziness, patients should be warned to take precautions when driving or operating moving machinery.

Augmentin 125 mg/31.25 mg/5 ml 100 ml portioned/susp. for oral administration

Instructions for medical use of the drug Augmentin® Trade name Augmentin® International nonproprietary name No Dosage form Powder for the preparation of suspension for oral administration, 125 mg/31.25 mg/5 ml, 100 ml Composition 5 ml of suspension contains active substances: amoxicillin (in as amoxicillin trihydrate) 125 mg; clavulanic acid (in the form of potassium clavulanate) 31.25 mg, excipients: xanthan gum, aspartame, succinic acid, colloidal anhydrous silicon dioxide, hypromellose, dry orange flavor 610271 E, dry orange flavor 9/027108, dry raspberry flavor NN07943, flavor “Light molasses” dry 52927/AR, anhydrous silicon dioxide. Description White or almost white powder with a characteristic odor. The prepared suspension is white or almost white; When standing, a white or almost white precipitate slowly forms. Pharmacotherapeutic group Antibacterial drugs for systemic use. Penicillins in combination with beta-lactamase inhibitors. Clavulanic acid + amoxicillin. ATC code J01CR02 Pharmacological properties Pharmacokinetics Absorption Amoxicillin and clavulanate are highly soluble in aqueous solutions with a physiological pH value, quickly and completely absorbed from the gastrointestinal tract after oral administration. Absorption of amoxicillin and clavulanic acid is optimal when taken at the beginning of a meal. After taking the drug orally, its bioavailability is 70%. The profiles of both components of the drug are similar and reach peak plasma concentrations (Tmax) in approximately 1 hour. The concentration of amoxicillin and clavulanic acid in the blood serum is the same both in the case of combined use of amoxicillin and clavulanic acid, and in the case of each component separately. Distribution Therapeutic concentrations of amoxicillin and clavulanic acid are achieved in various organs and tissues, interstitial fluid (lungs, abdominal organs, gall bladder, adipose, bone and muscle tissues, pleural, synovial and peritoneal fluids, skin, bile, purulent discharge, sputum). Amoxicillin and clavulanic acid practically do not penetrate into the cerebrospinal fluid. The binding of amoxicillin and clavulanic acid to plasma proteins is moderate: 25% for clavulanic acid and 18% for amoxicillin. Amoxicillin, like most penicillins, is excreted in breast milk. Trace amounts of clavulanic acid are also found in breast milk. With the exception of the risk of sensitization, amoxicillin and clavulanic acid do not have a negative effect on the health of breastfed infants. Amoxicillin and clavulanic acid penetrate the placental barrier. Elimination Amoxicillin is eliminated primarily by the kidneys, while clavulanic acid is eliminated through both renal and extrarenal mechanisms. After a single oral dose of one tablet of 250 mg/125 mg or 500 mg/125 mg, approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted unchanged in the urine during the first 6 hours. Metabolism Amoxicillin is partially excreted in the urine as inactive penicillic acid in an amount equivalent to 10-25% of the dose taken. Clavulanic acid in the body undergoes intensive metabolism to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and is released with urine and feces, as well as in the form of carbon dioxide through exhaled air. Pharmacodynamics Augmentin® is a combined antibiotic containing amoxicillin and clavulanic acid, with a wide spectrum of bactericidal action, resistant to beta-lactamase. Amoxicillin is a semisynthetic broad-spectrum antibiotic that is active against many gram-positive and gram-negative microorganisms. Amoxicillin is destroyed by beta-lactamases and has no effect on microorganisms that produce this enzyme. The mechanism of action of amoxicillin is to inhibit the biosynthesis of peptidoglycans in the bacterial cell wall, which usually leads to cell lysis and death. Clavulanic acid is a beta-lactamate, similar in chemical structure to penicillins, which has the ability to inactivate beta-lactamase enzymes of microorganisms that are resistant to penicillins and cephalosporins, thereby preventing the inactivation of amoxicillin. Beta-lactamases are produced by many gram-positive and gram-negative bacteria. The action of beta-lactamases can lead to the destruction of some antibacterial drugs even before they begin to act on pathogens. Clavulanic acid blocks the action of enzymes, restoring the sensitivity of bacteria to amoxicillin. In particular, it is highly active against plasmid beta-lactamases, which are often associated with drug resistance, but is less effective against chromosomal type 1 beta-lactamases. The presence of clavulanic acid in Augmentin® protects amoxicillin from the destructive action of beta-lactamases and expands its spectrum of antibacterial activity to include microorganisms that are usually resistant to other penicillins and cephalosporins. Clavulanic acid as a single drug does not have a clinically significant antibacterial effect. Mechanism of resistance development There are 2 mechanisms for the development of resistance to Augmentin® - inactivation by bacterial beta-lactamases that are insensitive to the effects of clavulanic acid, including classes B, C, D - deformation of the penicillin-binding protein, which leads to a decrease in the affinity of the antibiotic towards the microorganism Impermeability bacterial wall as well as pump mechanisms can cause or contribute to the development of resistance, especially in Gram-negative microorganisms. Augmentin® has a bactericidal effect on the following microorganisms: Gram-positive aerobes: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus (sensitive to methicillin), coagulase-negative staphylococci (sensitive to methicillin), Streptococcus agalactiae, Streptococcus pneumoniae1, Streptococcus pyogenes and other beta-hemolytic bacteria eptococci , group Streptococcus viridans, Bacillius anthracis, Listeria monocytogenes, Nocardia asteroides Gram-negative aerobes: Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Eikenella corrodens, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, Pasteurella multocida anaerobic microorganisms: Bactero ides fragilis, Fusobacterium nucleatum, Prevotella spp. Microorganisms with possible acquired resistance Gram-positive aerobes: Enterococcus faecium* Gram-negative aerobes: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris Microorganisms with natural resistance: Gram-negative aerobes: Acinetobacter species, Citrobacter freundii, Enterobacter species, Legionella pneumophila, Morganella morganii , Providencia species, Pseudomonas species, Serratia species, Stenotrophomonas maltophilia; others: Chlamydia trachomatis, Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetti, Mycoplasma pneumoniae. *Natural sensitivity in the absence of acquired resistance 1 With the exception of strains of Streptococcus pneumoniae resistant to penicillins Indications for use - acute bacterial sinusitis - tonsillitis - acute otitis media - lower respiratory tract infections (exacerbation of chronic bronchitis, lobar pneumonia, bronchopneumonia, community-acquired pneumonia) - cystitis , urethritis - pyelonephritis - gynecological infections, gonorrhea - infections of the skin and soft tissues (in particular, cellulitis, animal bites, acute abscesses and phlegmon of the maxillofacial area) - infections of bones and joints (in particular, osteomyelitis) Method of administration and dosage Suspension for oral administration is intended for use in pediatrics. Sensitivity to Augmentin® may vary by geographic location and time. Before prescribing the drug, whenever possible, the susceptibility of strains should be assessed according to local data and sensitivity should be determined by collecting and testing samples from an individual patient, especially in the case of severe infections. The dosage regimen is set individually depending on age, body weight, kidney function, infectious agents, as well as the severity of the infection. Augmentin® is recommended to be taken at the beginning of a meal. The duration of therapy depends on the patient's response to treatment. Some pathologies (in particular, osteomyelitis) may require a longer course. Treatment should not be continued for more than 14 days without re-evaluating the patient's condition. If necessary, it is possible to carry out stepwise therapy (initially, intravenous administration of the drug, followed by switching to oral administration). Children from birth to 12 years of age or with a body weight of less than 40 kg. The dose, depending on age and weight, is indicated in mg/kg of body weight per day, or in milliliters of the finished suspension. Recommended dosage regimen From 20 mg/5 mg/kg/day to 60 mg/15 mg/kg/day, divided into 3 doses. Thus, the dosage regimen of the drug 20 mg/5 mg/kg/day - 40 mg/10 mg/kg/day is used for mild infections (tonsillitis, skin and soft tissue infections); high doses of the drug (60 mg/15 mg/kg/day) are prescribed in case of severe infections - otitis media, sinusitis, lower respiratory tract infections and genitourinary tract infections. There are no clinical data on the use of Augmentin® 125 mg/31.25 mg/5 ml over 40 mg/10 mg/kg/day in children under 2 years of age. Table for selecting a single dose of Augmentin® depending on body weight Body weight (kg) 20 mg/kg/day 40 mg/kg/day 60 mg/kg/day* 2 0.5 ml 3 times a day 1.0 ml 3 once a day 1.6 ml 3 times a day 3 0.8 ml 3 times a day 1.6 ml 3 times a day 2.4 ml 3 times a day 4 1.1 ml 3 times a day 2.1 ml 3 once a day 3.2 ml 3 times a day 5 1.3 ml 3 times a day 2.7 ml 3 times a day 4 ml 3 times a day 6 1.6 ml 3 times a day 3.2 ml 3 times a day day 4.8 ml 3 times a day 7 1.9 ml 3 times a day 3.7 ml 3 times a day - 8 2.1 ml 3 times a day 4.3 ml 3 times a day - 9 2.4 ml 3 times a day 4.8 ml 3 times a day - 10 2.7 ml 3 times a day 5.3 ml 3 times a day - * For children weighing >6 kg, use Augmentin® 200 mg/28.5 mg to avoid a single dose of more than 5 ml of the drug. For children weighing less than 40 kg, the maximum daily dose is 2400 mg amoxicillin/600 mg clavulanic acid. If it is necessary to prescribe a higher daily dose of amoxicillin, a different dosage of Augmentin® should be prescribed to avoid taking high doses of clavulanic acid unnecessarily. Patients with Impaired Renal Function Dose adjustments are based on the maximum recommended dose of amoxicillin and creatinine clearance. Children Creatinine clearance Augmentin® dosage regimen >30 ml/min No dose adjustment required 10-30 ml/min 15 mg/3.75 mg/kg (1.2 ml) 2 times a day (maximum 500 mg/125 mg (20 ml) twice daily) <10 mL/min 15 mg/3.75 mg/kg (1.2 mL) once daily (maximum 500 mg/125 mg (20 mL) once daily) Patients on hemodialysis Dose adjustments based on at the maximum recommended dose of amoxicillin. Children: 15 mg/3.75 mg/kg (1.2 ml) 1 time per day. Before a hemodialysis session, take one additional dose of 15 mg/3.75 mg/kg (1.2 ml). To restore the concentrations of the active ingredients of Augmentin® in the blood, a second additional dose of 15 mg/3.75 mg/kg (1.2 ml) should be taken after a hemodialysis session. Patients with impaired liver function Treatment is carried out with caution; regularly monitor liver function. Method of using the suspension The suspension is diluted immediately before the first use. Check the integrity of the cap before use. Shake the bottle of powder. The powder should be dissolved in 92 ml of boiled water, cooled to room temperature, gradually shaking and adding water to the mark on the bottle. The finished volume of the suspension is 100 ml. The bottle should be inverted and shaken thoroughly until completely dissolved. The prepared suspension is white or almost white; When standing, a white or almost white precipitate slowly forms. The bottle should be shaken before each use. To dose the drug, you should use a measuring cap, which should be rinsed well with water after each use. For more accurate dosing of small volumes of suspension, especially in children under 3 months, it is necessary to use a standard disposable medical syringe. When treating children under 2 years of age, the finished Augmentin® suspension can be diluted by half with water. Side effects Very often ≥ 1 in 10, often ≥ 1 in 100 and < 1 in 10, sometimes ≥ 1 in 1000 and < 1 in 100, rarely ≥ 1 in 10,000 and < 1 in 1,000, very rarely < 1 in 10,000 Often - candidiasis of the skin and mucous membranes - nausea, vomiting, diarrhea. Nausea is more common when using high doses of the drug. To reduce the degree of manifestation, it is recommended to take the suspension at the beginning of a meal. Uncommon - dizziness, headache - dyspepsia - moderate increase in the level of liver enzymes ALT/AST - skin rash, itching, urticaria Rarely - reversible leukopenia (including neutropenia), thrombocytopenia - erythema multiforme Not known - reversible agranulocytosis and hemolytic anemia, increased bleeding time and index prothrombin time - angioedema, anaphylaxis; syndrome similar to serum sickness, allergic vasculitis - reversible hyperactivity and convulsions - antibiotic-associated colitis (including pseudomembranous and hemorrhagic) - black hairy tongue (chronic hyperplasia of the filiform papillae of the tongue) - discoloration of the surface layer of tooth enamel - hepatitis, cholestatic jaundice - Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis If these symptoms develop, the drug should be discontinued. - 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 impaired liver function that developed while taking a combination of amoxicillin / clavulanic acid - phenylketonuria ( due to the presence of aspartame in the drug) - glucose-galactose malabsorption (due to the presence of maltodextrin (glucose) in the drug) Drug interactions It is not recommended to use Augmentin® simultaneously with probenecid. Probenicide reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of Augmentin® and probenecid may lead to an increase in the level of amoxicillin in the blood. Concomitant use of allopurinol and Augmentin® may increase the risk of allergic reactions. There are currently no data on the simultaneous use of allopurinol and Augmentin®. Augmentin® affects the intestinal flora and leads to a decrease in reabsorption and a decrease in the effectiveness of combined oral contraceptives. Cases of increased prothrombin time have been identified (acenocoumarol and warfarin); with the simultaneous use of Augmentin® and anticoagulants, appropriate monitoring should be carried out with dose adjustment of Augmentin® if necessary. Penicillins may reduce the elimination of methotrexate, which has a potential risk of increased toxicity. In patients taking mycophenolate mofetil, when used together with Augmentin®, the concentration of the active metabolite of mycophenolic acid at the initial dose is reduced by approximately 50%. Changes in the concentration level of the initial dose may not correspond to changes in the concentration of total exposure to mycophenolic acid. Special instructions Adults and children over 12 years of age or weighing more than 40 kg are recommended to use Augmentin® tablets. Before starting treatment with Augmentin®, it is necessary to obtain a detailed history regarding previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics. Serious and sometimes fatal hypersensitivity reactions (anaphylactic shock) to penicillins have been described, and are more common in patients with a history of hypersensitivity to penicillins. If an allergic reaction occurs, treatment with Augmentin® should be discontinued and alternative therapy initiated. If serious hypersensitivity reactions develop, the patient should be given adrenaline immediately. Oxygen therapy, intravenous steroids, and airway management including intubation may be required. If a disease caused by amoxicillin-sensitive strains is confirmed, the amoxicillin/clavulanic acid combination should be discontinued and amoxicillin should be prescribed separately. It is not recommended to use Augmentin® if there is a high risk of possible resistance to the beta-lactam component of the drug. Augmentin® should not be used to treat pathologies caused by Streptococcus pneumoniae that are resistant to penicillins. Augmentin® should not be prescribed if infectious mononucleosis is suspected, since in patients with this disease, amoxicillin can cause a skin rash, which makes diagnosing the disease difficult. When prescribing the drug to patients with a reduced kidney function or when using high doses, seizures are possible. The joint use of allopurinol and amoxicillin increases the likelihood of developing skin allergic reactions. Long -term treatment with Augmentin® may be accompanied by excessive growth of microorganisms insensitive to it. To prevent a change in the color of tooth enamel, the teeth should be brushed after each suspension. Cases of the development of pseudomembrane colitis were revealed against the background of the use of antibiotics, the severity of which varied from mild to a severe degree. Thus, it is necessary to keep in mind the possibility of this pathology in patients with diarrhea when taking antibiotics or after the end of the course of therapy. In the case of prolonged or significant diarrhea, in the presence of spasms in the abdomen, Augmentin® treatment should be immediately discontinued and patients should be sent for further examination. In general, Augmentin® is tolerated well and has low toxicity inherent by all penicillins. With prolonged treatment with Augmentin®, it is recommended to periodically evaluate the functions of the kidneys, liver, and blood formation organs. In patients receiving Augmentin®, an increase in prothrombin time is occasionally observed, therefore, with the simultaneous use of augmentin® and anticoagulants, appropriate monitoring must be carried out. Augmentin® should be used with caution in patients with impaired liver function. Signs and symptoms of liver damage usually occur during or immediately after the start of treatment, but in some cases may not appear within a few weeks after the cessation of therapy. As a rule, they are reversible. Hepatic disorders can be very serious, and in extremely rare cases, death was reported. Almost always, they were recorded in patients with a serious underlying disease or in those who simultaneously took drugs known as potentially affecting the liver. Cases of the development of antibiotic-associated colitis were reported against the background of Augmentin®, the degree of which was from a slight to threatening life. In this regard, it is necessary to consider the possibility of the development of colitis in patients with diarrhea developed during or after taking antibiotics. When confirming the diagnosis of colitis, Augmentin® should be immediately canceled; The patient must consult a doctor for the necessary therapy. In patients with renal failure, the dose of the drug should be adjusted in accordance with the severity of the disease. In patients with reduced diuresis in rare cases, crystalluria may occur. 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. Patients with a catheter need a constant assessment of their condition. During the treatment with amoxicillin, to determine the content of glucose in the urine, it is necessary to use the methods of enzymatic oxidation of glucose, so non -enzymatic methods can lead to false positive results. The presence of clavulanic acid in Augmentin® may cause non -specific binding of IgG and albumins with the erythrocyte membrane, which leads to the false positive reaction of the Cumbs. Augmentin®, a powder for the preparation of a suspension for oral administration 125 mg/31.25 mg/5 ml, contains 2.5 mg/ml of aspartam, a phenylalanine source. It is not recommended to use the drug to patients with phenylketonuria. The drug contains Maltodecstrin (glucose). It is not recommended to use the drug to patients with glucose-galactose malabsorption. Pregnancy and lactation period Suspension for oral administration is intended for use in pediatrics. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous mechanisms are not data; However, in connection with the possibility of developing adverse reactions (allergies, dizziness, cramps), care must be observed. Overdose symptoms: gastrointestinal disorders and disorders of the water-electrolyte balance are possible. Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure. When prescribing the drug to patients with a reduced kidney function or when using high doses, seizures are possible. It is possible to precipitate amoxicillin on bubble catheter, especially after the appointment of high doses by intravenous administration. Treatment: symptomatic therapy, correction of water-electrolyte balance. Augmentin® is excreted from the blood using hemodialysis. The form of release and packaging powder for preparing a suspension for oral administration, 125 mg/31.25 mg/5 ml, 100 ml. The powder for the preparation of the suspension is placed in bottles of transparent type III glass with a screw aluminum cover with an internal varnish coating with protection from the first autopsy and a polymer laying of PVC or polyolefin, equipped with a dosper cap. For 1 bottle, along with instructions for medical use in the state and Russian languages, they are placed in a pack of cardboard. Storage conditions Store in a dry place at a temperature not exceeding 25 °C. Store the prepared suspension in the refrigerator at a temperature of 2 0C to 8 0C and used for 7 days. Do not freeze! Keep out of the reach of children! The shelf life of 2 years does not accept the expiration date of the vacation condition from pharmacies according to the recipe manufacturer Smithklyain Bichch Limited, Great Britain (Clarendon Road, Worthing, West Sussex, BN 14 8QH, United Kingdom). The owner of the Smithklyain registration certificate Beach Limited, Great Britain (980 Great West Road, BrentFord, Middlesex, TW89GS, United Kingdom). The address of the organization receiving in the territory of the Republic of Kazakhstan claims from consumers on the quality of products (goods) Representative Office Govayn Klein Export LTD in Kazakhstan 050059, Almaty, ul. Furmanova, 273 phone number, fax number of email address