Amoxiclav 2x powder for suspension for oral administration (400mg + 57mg) / 5ml 17.5g №1

Name:
Amoxiclav 2X por.d/prep.susp. d / ext. (400mg+57mg)/5ml per vial. 17.5 g in pack No. 1
Description:
Crystal powder from white to yellowish-white color Main active ingredientAmoxicillin + clavulanic acid Form of releasePowder DosageEach 5 ml of suspension for internal use (1 dosing syringe) contains 400 mg of amoxicillin in the form of trihydrate and 57 mg of clavulanic acid in form of potassium salt. Pharmacological properties Pharmacodynamics Amoxicillin is a semi-synthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often called penicillin-binding proteins) during the biosynthesis of peptidoglycan, a structural component of the bacterial cell wall. Suppression of peptidoglycan synthesis leads to a loss of cell wall strength, which usually leads to cell death. Amoxicillin is destroyed by the action of beta-lactamases produced by resistant bacteria, so it is inactive against microorganisms that produce these enzymes. Clavulanic acid is a beta-lactam structurally similar to penicillins. It inhibits some beta-lactamases and thus prevents the inactivation of amoxicillin. By itself, clavulanic acid does not have a clinically useful antibacterial effect. The time to maintain the concentration above the minimum inhibitory (T> MIC) is recognized as the main determining factor in the effectiveness of amoxicillin. Mechanisms of resistance There are two main mechanisms for the development of resistance to amoxicillin/clavulanic acid: Inactivation by bacterial beta-lactamases that are insensitive to the inhibitory effect of clavulanic acid, including class B, C and D beta-lactamases; A change in penicillin-binding proteins (PBPs) that causes a decrease in the affinity of the antibacterial drug for the target. Bacterial impermeability or active drug transport mechanisms out of the bacterial cell can directly cause or contribute to resistance, especially in Gram-negative bacteria. Limits of sensitivity The minimum inhibitory concentrations (MICs) for amoxicillin/clavulanic acid correspond to the limits of sensitivity established by the European Committee for the Evaluation of Antibiotic Susceptibility (EUCAST) Organism Limits of Detection (µg/ml) Sensitive Intermediate Resistant Haemophilus influenzae1 ? 1->1 Moraxella catarrhalis1 ? 1->1 Staphylococcus aureus2 ? 2 – > 2 Coagulase-negative staphylococci2 ? 0.25 > 0.25 Enterococcus1? 4 8 > 8 Streptococcus A, B, C, G5 ? 0.25 – > 0.25 Streptococcus pneumoniae3 ? 0.5 1-2 > 2 Enterobacteria1.4 – – > 8 Gram-negative anaerobes1 ? 4 8 > 8 Gram-positive anaerobes1 ? 4 8 > 8 Non-species-specific limits1 ? 2 4-8 > 8 1 The obtained values correspond to the concentrations of amoxicillin. For the purpose of sensitivity assessment, a fixed concentration of clavulanic acid is used – 2 mg / l. 2 The values obtained correspond to the concentrations of oxacillin. 3 Limit values in the table are based on ampicillin susceptibility limits. 4 The resistance limit, R > 8 mg/l, guarantees the antibiotic resistance of all isolated strains with resistance mechanisms. 5 Limit values in the table are based on sensitivity limits for benzylpenicillin. The prevalence of resistance in individual species is geographically and temporally dependent, and therefore, before starting therapy, it is desirable to obtain local information on antibiotic resistance, especially in the case of severe infections. If local indicators of antibiotic resistance cast doubt on the effectiveness of the drug in at least some types of infections, you should seek the help of appropriate expert specialists. Generally susceptible species Gram-positive aerobes: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus (methicillin-susceptible strains)?, Streptococcus agalacticae, Streptococcus pneumoniae1, Streptococcus pyogenes and other beta-hemolytic streptococci, Streptococcus viridans group Gram-negative aerobes: Capnocytophaga spp., Eikenella corrodens, Haemophilus influenzae2, Moraxella catarrhalis, Pasteurella multocida Anaerobes: Bacteroides fragilis, Fusobacterium nucleatum, Prevotella spp. Species with possible development of acquired resistance Gram-positive aerobes: Enterococcus faecium$ Gram-negative aerobes: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris Species with natural resistance Gram-negative aerobes: Acinetobacter sp., Citrobacter freundii, Enterobacter sp., Legionella pneumophila, Morganela morganii, Providencia spp, Pseudomonas sp., Serratia sp., Stenotrophomonas maltophilia Other organisms: Chlamydophila pneumoniae, Clamydophila psittaci, Coxiella burnetti, Mycoplasma pneumoniae $Naturally intermediate susceptibility in the absence of an acquired resistance mechanism. All methicillin-resistant staphylococci are resistant to amoxicillin/clavulanic acid. 2Strains with reduced susceptibility have been identified in some EU countries, occurring at frequencies above 10%. Pharmacokinetics Amoxicillin and clavulanic acid are completely soluble in water at physiological pH. Both components are rapidly and well absorbed after oral administration. Their absorption improves if the drug is taken immediately at the beginning of a meal. When administered orally, the bioavailability of amoxicillin and clavulanic acid reaches approximately 70%. The plasma concentration profiles of both components are similar and the time to peak concentration (Tmax) for each substance is approximately one hour. In a group of healthy volunteers, when taking the combined drug at a dose of 875 mg / 175 mg in the form of tablets twice a day on an empty stomach, the maximum serum concentrations were 11.64 ± 2.78 μg / ml for amoxicillin and 2.18 ± 0.99 μg / ml for clavulanic acid. The time to peak concentration was 1.5 hours (range 1.0–2.5) for amoxicillin and 1.25 hours (range 1.0–2.0) for clavulanic acid. AUC(0-24) values were 53.52 ± 12.31 μg h/mL for amoxicillin and 10.16 ± 3.04 μg h/mL for clavulanic acid. And the half-life (T?) was 1.19 ± 0.21 h for amoxicillin and 0.96 ± 0.12 h for clavulanic acid. Serum concentrations of amoxicillin and clavulanic acid achieved by oral administration are similar to those obtained by oral administration of equivalent doses of amoxicillin or clavulanic acid alone. Approximately 25% of the total content of clavulanic acid and 18% of the total content of amoxicillin in plasma is in a protein-bound state. The apparent volume of distribution is about 0.3 – 0.4 l / kg for amoxicillin and about 0.2 l / kg for clavulanic acid. After intravenous administration, amoxicillin and clavulanic acid are found in the gallbladder, abdominal wall tissues, skin, adipose tissue, muscle tissue, synovial and peritoneal fluids, bile and pus. Amoxicillin poorly (not sufficiently) penetrates into the cerebrospinal fluid. Amoxicillin, like most penicillins, passes into breast milk. Trace amounts of clavulanic acid are also found in breast milk (see “Pregnancy and lactation”). Amoxicillin and clavulanic acid cross the placental barrier. Amoxicillin is partially excreted in the urine in the form of inactive penicillic acid in volumes equivalent to no more than 10-25% of the initial dose. Clavulanic acid is extensively metabolized, excreted in urine and feces, and also in the form of carbon dioxide with exhaled air. Amoxicillin is excreted mainly by the kidneys, while clavulanic acid is excreted from the body through both renal and extrarenal mechanisms. The amoxicillin/clavulanic acid combination in healthy individuals has a mean half-life of about one hour and a mean total clearance of about 25 L/h. Approximately 60-70% of amoxicillin and approximately 40-65% of clavulanic acid are excreted unchanged in the urine in the first 6 hours after a single dose of amoxicillin / clavulanic acid in the form of tablets with a dose of 250/125 mg or 500/125 mg. Removal in the urine within a 24-hour period is 50-85% for amoxicillin and 27-60% for clavulanic acid. The maximum amount of clavulanic acid is excreted in the first two hours after taking the drug. Age The half-life of amoxicillin in children aged three months to two years, older children and adults is similar. In very young children (including premature newborns) in the first week of life, the drug should not be given more than twice a day due to the immaturity of the renal excretion pathway. Since the elderly are more likely to have decreased renal function, caution should be exercised in dose selection in this population, and monitoring of renal function may also be required. Gender The pharmacokinetics of amoxicillin or clavulanic acid does not depend on the gender of the patient. Impaired renal function The total plasma clearance of amoxicillin / clavulanic acid decreases in proportion to the decrease in renal function. The decrease in clearance is more pronounced for amoxicillin than for clavulanic acid, since the proportion of amoxicillin excreted by the kidneys is higher. In renal insufficiency, doses are selected so as to avoid excessive accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see “Dosage and Administration”). Liver failure Treatment of patients with liver failure is carried out with caution, regular monitoring of liver function is required. Amoxiclav 2x is indicated for the treatment of the following infections in children weighing <40 kg: acute bacterial sinusitis; acute otitis media; exacerbation of chronic bronchitis; community-acquired pneumonia; cystitis; pyelonephritis; infections of the skin and soft tissues, in particular inflammation of the subcutaneous tissue, wounds from animal bites, severe tooth abscess with widespread phlegmon; infections of bones and joints, in particular osteomyelitis. Consideration should be given to official guidelines on the appropriate use of antibacterial drugs. Route of administration and dosesDoses reflect the content of amoxicillin / clavulanic acid, unless indicated that the dose corresponds to the content of the individual component. When choosing a dose for the treatment of specific infections, the following factors should be considered: suspected pathogens and their possible susceptibility to antibacterial drugs; the severity and location of the infection; age, weight, and kidney function, as listed below. For children weighing < 40 kg, Amoxiclav 2x, when taken according to the recommendations below, provides a maximum daily dose of 1000-2800 mg amoxicillin/143-400 mg clavulanic acid. If it is necessary to use a higher daily dose of amoxicillin, it is recommended to use a different form of the drug in order to avoid taking an excessively high daily dose of clavulanic acid. The duration of therapy is determined by the effectiveness of treatment. Some infections (eg, osteomyelitis) require longer therapy. The duration of treatment should not exceed 14 days without revision (see information on long-term therapy in the Precautions section). For the treatment of children with body weight ? 40 kg and adults, other forms of release of Amoxiclav should be used. Children weighing <40 kg Children can take the drug in the form of a suspension or tablets. Recommended doses: 25 mg / 3.6 mg to 45 mg / 6.4 mg / kg of body weight per day, divided into two doses; in the treatment of some infections, a dose of up to 70 mg / 10 mg / kg body weight per day, divided into two doses, can be used (for example, for otitis media, sinusitis and lower respiratory tract infections). Clinical data on the use of dosage forms of the drug with a ratio of active ingredients 7:1 in doses above 45 mg / 6.4 mg / kg of body weight per day for the treatment of children under two years of age are not available. There are no clinical data on use in children under two months of age. Therefore, for this group of patients it is impossible to provide recommendations on the dosage of the drug. Elderly patients Dose adjustment is not required. Patients with renal insufficiency Patients with creatinine clearance above 30 ml / min dose adjustment is not required. This drug (with a ratio of amoxicillin to clavulanic acid 7:1) is not recommended for the treatment of patients with creatinine clearance less than 30 ml / min (0.5 ml / sec), since there are no dose adjustment recommendations for them. Patients with hepatic impairment Use with caution. Regular monitoring of liver function is required (see "Contraindications" and "Precautions"). If you forget to take Amoxiclav 2x If you forget to take a dose, take it as soon as you remember. Do not take the next dose shortly after this one, wait about 4 hours before taking the next dose. Method of application For oral administration. Take immediately at the start of a meal to minimize the potential for gastrointestinal intolerance. Treatment can be started with the parenteral form of the drug, following the instructions attached to it, and continue with the oral dosage form. Suspension preparation Before use, check that the sealing of the cap is not broken. Shake the bottle to loosen the powder. Add 59 ml of water in two portions (first 2/3, then up to the mark) and shake the suspension well each time. Shake well before each use! Dispose of unused product in accordance with local regulations. Use during pregnancy and lactation In animal studies, neither direct nor indirect harmful effects on the course of pregnancy, development of the embryo / fetus, the process of childbirth and the development of the newborn have been shown. Limited data on the use of the drug during pregnancy do not indicate an increased risk of congenital anomalies. In women with preterm preterm rupture of membranes, prophylactic treatment with amoxicillin/clavulanic acid has been potentially associated with an increased risk of neonatal necrotizing enterocolitis. Do not take the drug during pregnancy, unless the doctor considers treatment necessary. Both active ingredients are excreted in breast milk (data on the effect of clavulanic acid on breastfed children are not available). Breastfed babies may develop diarrhea and fungal infections of the mucous membranes, which may require stopping breastfeeding. Possible sensitization should be considered. Taking the drug during breastfeeding is possible only after assessing the benefits and risks by the attending physician. Precautions Before starting therapy with Amoxiclav 2x, a thorough history should be taken for hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam drugs. Serious and sometimes fatal hypersensitivity reactions (including anaphylactoid and severe skin adverse reactions) have been observed during penicillin therapy. They are most likely to develop in patients with hypersensitivity reactions to penicillins in the past and in individuals prone to developing allergic reactions. In the event of an allergic reaction, Amoxiclav 2x therapy should be discontinued and other suitable antibacterial drugs prescribed. In cases of proven susceptibility of infectious agents to amoxicillin, the option of switching from Amoxiclav 2x to amoxicillin should be considered in accordance with current official guidelines. This dosage form of the drug is not suitable for use at a high risk of resistance of suspected pathogens to beta-lactam drugs, due not to the production of beta-lactamase sensitive to clavulanic acid suppression, but to a change in penicillin-binding proteins (including if resistant S. pneumoniae is suspected). In patients with impaired renal function or receiving high-dose therapy, seizures may develop (see "Side Effects"). Amoxiclav 2x should not be taken if infectious mononucleosis is suspected, since after the use of amoxicillin against the background of this disease, a measles-like rash was observed. The concomitant use of allopurinol during treatment with amoxicillin may increase the likelihood of allergic skin reactions. Prolonged use of the drug can sometimes lead to excessive reproduction of non-susceptible microorganisms. The development of generalized erythema with fever and pustules at the beginning of therapy is a potential symptom of acute generalized exanthematous pustulosis (AGEP). Such a reaction requires discontinuation of therapy with Amoxiclav 2x and is a contraindication to the subsequent use of amoxicillin. Treatment of patients with hepatic insufficiency should be carried out with caution. Adverse events from the liver were observed mainly in men and elderly patients and are potentially associated with long-term treatment. These adverse events in very rare cases were observed in children. In all groups of patients, signs and symptoms usually develop during or shortly after treatment, but in some cases they do not appear until a few weeks after stopping therapy. They are usually reversible. Serious adverse events from the liver can develop, extremely rarely with a fatal outcome. They have almost always been observed in patients with serious underlying diseases or in people taking drugs that can damage the liver. Cases of antibiotic-associated colitis observed during therapy with almost all antibacterial drugs can vary in severity from mild to life-threatening. It is important to consider this diagnosis in patients with diarrhea during or after completion of any course of antibiotic therapy. In case of development of antibiotic-associated colitis, Amoxiclav 2x therapy should be stopped immediately, consult a doctor and start appropriate treatment. In this situation, the use of drugs that depress peristalsis is contraindicated. During long-term therapy, periodic evaluation of the functions of various organ systems, including the kidneys, liver, and hematopoietic organs, is recommended. In rare cases, while taking amoxicillin / clavulanic acid, prolongation of prothrombin time was noted. When taking anticoagulants at the same time, proper monitoring must be carried out. Dose adjustment of oral anticoagulants may be required to achieve the desired level of anticoagulation. In patients with renal insufficiency, dose adjustment is required in accordance with the level of insufficiency (see "Method of application and dose"). In patients with reduced diuresis, crystalluria was observed in rare cases, mainly against the background of parenteral therapy. During high-dose amoxicillin therapy, adequate fluid intake and diuresis control are recommended to reduce the likelihood of amoxicillin-associated crystalluria. In patients with a catheter installed in the bladder, it is imperative to regularly monitor its patency. If it is necessary to assess the level of glucose in the urine during treatment with amoxicillin, it is necessary to use enzymatic methods with glucose oxidase, since non-enzymatic methods sometimes give false positive results. The presence of clavulanic acid in Amoxiclav 2x can cause non-specific binding of IgG and albumin to erythrocyte membranes, which can lead to false positive Coombs test results. There have been cases of positive results of enzyme-linked immunosorbent assay (ELISA) for Aspergillus in patients treated with the drug, in whom the absence of infections caused by Aspergillus was subsequently determined. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses have been noted in the ELISA for Aspergillus. Positive test results in patients taking Amoxiclav 2x should be interpreted with caution and confirmed by other diagnostic methods. This medicinal product contains mannitol, which may have a mild laxative effect. Interactions with other drugs Oral anticoagulants Oral anticoagulants and penicillin antibiotics have been widely used together, and no drug interactions have been reported. However, literature sources describe cases of an increase in the international normalized ratio (INR) in patients receiving maintenance therapy with acenocoumarol or warfarin against the background of the prescribed course of amoxicillin. If necessary, simultaneous appointment should be carefully monitored prothrombin time or INR during the initiation of treatment and withdrawal of amoxicillin. Dose adjustment of oral anticoagulants may be required. Methotrexate Penicillins may reduce the excretion of methotrexate, which is accompanied by an increase in toxicity. Probenecid Concomitant use of probenecid is not recommended. It reduces the secretion of amoxicillin in the renal tubules. Simultaneous use of probenecid with Amoxiclav 2x can lead to an increase in the levels of amoxicillin (but not clavulanic acid) in the blood and their longer maintenance. Mycophenolate mofetil In patients taking mycophenolate mofetil, after initiation of oral amoxicillin and clavulanic acid, an approximately 50% decrease in the concentration of the active metabolite of mycophenolic acid (MPA) was observed before taking the next dose of mycophenolate mofetil. Such a change in concentration before taking the next dose may not indicate a change in the overall exposure of the MPA. Therefore, in the absence of clinical signs of graft dysfunction, there is usually no need to change the dose of mycophenolate mofetil. However, during such combination therapy and for some time after the end of antibiotic therapy, close medical supervision is necessary. Contraindications Hypersensitivity to the active or excipients of the drug, as well as to any penicillins. History of severe immediate hypersensitivity reactions (eg, anaphylaxis) to other beta-lactam drugs (eg, cephalosporins, carbapenems, or monobactams). History of jaundice or other liver damage associated with the use of amoxicillin / clavulanic acid. Ingredients: Amoxicillin and clavulanic acid. Each 5 ml oral suspension (1 dosing syringe) contains 400 mg amoxicillin trihydrate and 57 mg clavulanic acid potassium salt. Excipients: citric acid anhydrous, crushed; sodium citrate anhydrous, crushed; microcrystalline cellulose and sodium carboxymethyl cellulose, dried; xanthan gum; silicon dioxide colloidal anhydrous; silicon dioxide; strawberry flavor; saccharin sodium, dried (E 954); mannitol. Overdose: Gastrointestinal symptoms may develop, as well as a violation of the water and electrolyte balance. There have been cases of amoxicillin-associated crystalluria, sometimes leading to renal failure. Convulsions may occur in patients with impaired renal function or in those receiving high-dose therapy. Amoxicillin precipitates in urinary catheters, predominantly after intravenous administration of large doses. It is necessary to regularly monitor the patency of catheters. For gastrointestinal symptoms, symptomatic treatment can be carried out along with the restoration of fluid and electrolyte balance. Amoxicillin and clavulanic acid can be excreted from the body by hemodialysis. Side effects The following categories were used to classify the incidence of adverse effects: very common (? 1/10), frequent (from ? 1/100 to < 1/10), infrequent (from ? 1/1,000 to < 1/100), rare (from ? 1/10,000 to < 1/1,000), very rare (< 1/10,000), unknown frequency (estimation from the available data is not possible). The most common adverse reactions are diarrhea, nausea and vomiting. Infectious and parasitic diseases Frequent: candidiasis of the skin and mucous membranes. Unknown frequency: overgrowth of non-susceptible microorganisms. Blood and lymphatic system disorders Rare: reversible leukopenia (including neutropenia), thrombocytopenia. Unknown frequency: reversible agranulocytosis, hemolytic anemia, prolongation of bleeding time and prothrombin time. Immune system disorders Unknown frequency: angioedema, anaphylaxis, serum-like syndrome, allergic vasculitis. Nervous system disorders Uncommon: dizziness, headache. Unknown frequency: reversible hyperactivity, convulsions, aseptic meningitis. Gastrointestinal disorders Common: Nausea (more common with high doses of the drug orally; gastrointestinal reactions can be minimized if the drug is taken immediately before meals), vomiting, diarrhea. Uncommon: dyspepsia. Unknown frequency: Antibiotic-associated colitis (including pseudomembranous and hemorrhagic colitis), black hairy tongue, discoloration of teeth (very rare discoloration of the surface of the teeth has been observed in children. Proper oral hygiene can help prevent discoloration of the teeth, as plaque forms can usually be removed with a toothbrush). Liver and biliary tract disorders Uncommon: Elevated AST and/or ALT levels (moderate increases have been reported in patients treated with beta-lactam antibiotics, but the significance of these observations is unknown). Unknown frequency: hepatitis, cholestatic jaundice (these adverse events were observed against the background of the use of other penicillins and cephalosporins). Skin and subcutaneous tissue disorders Treatment should be discontinued if any allergic skin reaction develops. Uncommon: skin rash, itching, urticaria. Rare: erythema multiforme. Frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Renal and urinary disorders Unknown frequency: interstitial nephritis, crystalluria. If you have a side effect If the described reactions occur, as well as a reaction not indicated in the instructions, you should consult a doctor. Storage conditionsKeep out of the reach of children. Store in a dry place below 25°C. Store the prepared suspension at a temperature of 2-8 ° C for no more than 7 days. Immediately after taking the drug, close the vial tightly. Buy Amoxiclav 2x powder for oral suspension (400mg + 57mg) / 5ml 17.5g No. 1 Price for Amoxiclav 2x powder for oral suspension (400mg + 57mg) / 5ml 17, 5g №1Instruction for use for Amoxiclav 2x powder for suspension for oral administration (400mg + 57mg) / 5ml 17.5g №1