Augmentin powder for suspension for oral administration (200mg / 28.5mg) / 5ml No. 1

Name:
Augmentin.
Description:
Free flowing powder of white or almost white color. When diluted, a suspension of white or almost white color is formed. On standing, a white precipitate slowly forms. The main active ingredient is amoxicillin + clavulanic acid. Release form Tablets. Dosage 200mg + 28.5mg. Pharmacological action Beta-lactam antibiotics-penicillins. Combinations of penicillins, including beta-lactamase inhibitors. ATX code: J01CR02. Pharmacodynamics Mechanism of action Amoxicillin is a semi-synthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (known as penicillin-binding proteins) during the biosynthesis of bacterial peptidoglycan, which is the unifying structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to thinning of the cell wall, which subsequently leads to cell lysis and death. Amoxicillin is destroyed by the action of β-lactamases produced by resistant bacteria, and therefore the spectrum of activity of amoxicillin itself does not include microorganisms that produce these enzymes. Clavulanic acid is a β-lactamase inhibitor structurally related to penicillins. Clavulanic acid blocks the action of some β-lactamase enzymes, thereby preventing the inactivation of amoxicillin. Clavulanic acid alone does not show a clinically significant antibacterial effect. The relationship of pharmacokinetics / pharmacodynamics The main factor determining the effectiveness of amoxicillin is the time of exceeding the minimum inhibitory concentration (T> MIC). Mechanism of resistance formation There are two main mechanisms for the formation of resistance to amoxicillin/clavulanic acid: this action target. In addition, changes in the permeability of the microorganism envelope as well as the expression of efflux pumps can induce or promote the development of bacterial resistance, especially in Gram-negative bacteria. Bacteriological susceptibility to antibiotics varies by region and over time. It is desirable to take into account local data on sensitivity, especially when it comes to the treatment of severe infections. Experts should be consulted if local resistance data call into question the efficacy of a medicinal product in the treatment of certain types of infections. Susceptible microorganisms Aerobic gram-positive microorganisms: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus, methicillin-susceptible*, coagulase-negative staphylococci (methicillin-susceptible), Streptococcus agalactiae, Streptococcus pneumoniae1, Streptococcus pyogenes and other beta-hemolytic streptococci, Gram-negative virid aerobicus group microorganisms: Capnocytophaga spp., Eikenella corrodens, Haemophilus influenzae2, Moraxella catarrhalis, Pasteurella multocida Anaerobic microorganisms: Bacteroides fragilis, Fusobacterium nucleatum, Prevotella spp. Microorganisms for which acquired resistance may exist Aerobic gram-positive microorganisms: Enterococcus faecium** Aerobic gram-negative microorganisms: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris Naturally resistant microorganisms Aerobic gram-negative microorganisms Acinetobacter sp., Enterobacter sp., Citrobacter sp. , Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas sp., Serratia sp., Stenotrophomonas maltophilia Other organisms Chlamydophilia pneumoniae, Chlamodophila psittaci, Coxiella burnetii, Mycoplasma pneumoniae * All methicillin-resistant staphylococci are resistant to amoxicillin/clavulanic acid. ** Natural moderate sensitivity in the absence of an acquired resistance mechanism. Amoxicillin/clavulanic acid tablets 875 mg/125 mg and 500 mg/125 mg are not suitable for the treatment of infections caused by penicillin-resistant Streptococcus pneumoniae (see sections “Method of administration and dosage” and “Precautions”). In some countries, strains with reduced susceptibility have been reported at rates greater than 10%. Pharmacokinetics Absorption Amoxicillin and clavulanic acid are completely soluble in aqueous solutions at physiological pH. Both components are rapidly and well absorbed from the gastrointestinal tract (GIT) after oral administration. After oral administration, the bioavailability of amoxicillin and clavulanic acid is 70%. The pharmacokinetic parameters of both components are similar, the time to reach the maximum plasma concentration (Tmax) is about 1 hour. Below are the pharmacokinetic results of a study in which amoxicillin/clavulanic acid tablets (875 mg/125 mg dosage) were taken by healthy volunteers 2 times a day on an empty stomach and at a dosage of 500 mg/125 mg were taken by healthy volunteers 3 times a day on an empty stomach. Mean value of pharmacokinetic parameters (± relative deviation) Amoxicillin/clavulanic acid Dose (mg) Cmax (mcg/ml) Tmax* (h) AUC(0-24h) (mcg×h/ml) T1/2 (h) Amoxicillin 875 mg /125 mg 875 11.64 ± 2.78 1.50 (1.0-2.5) 53.52 ± 12.31 1.19 ± 0.21 500 mg/125 mg 500 7.19 ± 2.26 1.5 (1.0-2.5) 53.5 ± 8.87 1.15 ± 0.20 Clavulanic acid 875 mg/125 mg 125 2.18 ± 0.99 1.25 (1.0-2 .0) 10.16 ± 3.04 0.96 ± 0.12 500 mg/ 125 mg 125 2.40 ± 0.83 1.5 (1.0-2.0) 15.72 ± 3.86 0 .98 ± 0.12 *Median (range) Cmax – maximum plasma concentration. Tmax is the time to reach the maximum plasma concentration. AUC is the area under the concentration-time curve. T1 / 2 – half-life. Serum concentrations of amoxicillin and clavulanic acid when using the combined drug are similar to those achieved when ingesting equivalent doses of amoxicillin or clavulanic acid alone. Distribution Plasma proteins bind 25% of the total amount of clavulanic acid and 18% of amoxicillin. The volume of distribution is about 0.3-0.4 l/kg of amoxicillin and about 0.2 l/kg of clavulanic acid. After intravenous administration, both amoxicillin and clavulanic acid are found in the gallbladder, abdominal tissues, skin, adipose and muscle tissues, synovial and peritoneal fluids, bile and purulent discharge. Amoxicillin does not penetrate into the cerebrospinal fluid in a significant way. In animal studies, no accumulation of drug components in any tissues was found. Amoxicillin, like most penicillins, passes into breast milk. Trace amounts of clavulanic acid are also found in breast milk. Both amoxicillin and clavulanic acid cross the placental barrier. Biotransformation Amoxicillin is partially excreted in the urine as an inactive metabolite of penicillic acid in an amount equivalent to 10-25% of the initial dose. Clavulanic acid is extensively metabolized and excreted by the kidneys and intestines, as well as in the form of carbon dioxide with exhaled air. Excretion Amoxicillin is excreted primarily by the kidneys, while clavulanic acid is eliminated by both renal and non-renal mechanisms. The mean half-life for the amoxicillin/clavulanic acid combination is about 1 hour, and the mean total clearance is about 25 L/h in healthy volunteers. Approximately 60-70% of amoxicillin and approximately 40-65% of clavulanic acid are excreted unchanged by the kidneys within 6 hours after taking one tablet of Augmentin at a dosage of 250 mg + 125 mg or 500 mg + 125 mg. Various studies indicate that 50-85% of amoxicillin and 27-60% of clavulanic acid are excreted by the kidneys within 24 hours. With regard to clavulanic acid, the maximum amount of the active substance is excreted within the first two hours after administration. Simultaneous reception of probenecid slows down the excretion of amoxicillin, but does not slow down the excretion of clavulanic acid (see section “Interaction with other drugs”). Age The elimination half-life of amoxicillin is similar in children aged three months to two years, as well as in older children and adults. For very young children (including premature babies) in the first week of life, the drug should not be used more than twice a day due to the immaturity of the renal elimination pathway. Since there is an increased likelihood of decreased renal function in elderly patients, care should be taken when choosing a dose. In addition, monitoring of renal function may be required. Gender Ingestion of the amoxicillin/clavulanic acid combination by healthy men and women showed no significant effect of gender on the pharmacokinetics of amoxicillin or clavulanic acid. Renal insufficiency The total clearance of amoxicillin/clavulanic acid in serum decreases in proportion to the decrease in renal function. The decrease in drug clearance is more pronounced for amoxicillin than for clavulanic acid, since most of the amoxicillin is excreted by the kidneys. The dosage regimen of the drug in patients with renal insufficiency should prevent the accumulation of amoxicillin, but at the same time maintain an adequate level of clavulanic acid. Hepatic insufficiency The drug should be used with caution in patients with hepatic insufficiency with constant monitoring of liver function. Indications for use Augmentin is indicated for the treatment of the following infections in adults and children: Acute bacterial sinusitis Acute otitis media Exacerbations of chronic bronchitis Community-acquired pneumonia Cystitis Pyelonephritis Infections of the skin and soft tissues, in particular phlegmon, animal bites, severe dental abscess with spreading phlegmon. Infections of bones and joints, in particular osteomyelitis Official guidelines on the prudent use of antibacterial agents should be taken into account. Contraindications for use Hypersensitivity to any of the components of the drug or penicillins. History of a severe immediate hypersensitivity reaction (eg, anaphylaxis) to previous administration of beta-lactam antibiotics (cephalosporins, carbapenems, or monobactams). A history of jaundice or impaired liver function that developed against the background of the use of a combination of amoxicillin / clavulanic acid (see section “Side Effects”). Route of administration and doses Dose calculation is based on amoxicillin and clavulanic acid, except for cases when dosing is carried out for each component separately. When selecting a dose, the following factors should be considered: likely pathogens and their expected sensitivity to antibacterial drugs (see section “Precautions”); the severity and localization of the infection; age, body weight and renal function status of the patient. If necessary, the possibility of prescribing other dosage forms of the drug Augmentin (including those with a higher content of amoxicillin and / or a different ratio of amoxicillin / clavulanic acid) should be considered. For children weighing <40 kg, subject to the dosage regimen indicated below, taking Augmentin in this dosage form provides a maximum daily dose of 1000-2800 mg of amoxicillin / 143-400 mg of clavulanic acid. If a higher daily dose of amoxicillin is required, it is recommended to choose a different dosage form in order to avoid taking an excessive daily dose of clavulanic acid (see sections "Precautions" and "Pharmacodynamics"). The duration of treatment is determined by the clinical picture. Some infections (such as osteomyelitis) require longer treatment. Treatment should not be continued for longer than 14 days without a review of the clinical situation (see section "Precautions"). For the treatment of adults and children ≥ 40 kg, other dosage forms of Augmentin intended for adults should be used. Children < 40 kg For the treatment of children, Augmentin can be used in the form of tablets, powder for oral suspension in vials or sachets. For the treatment of children under the age of 6 years, inclusive, it is preferable to use Augmentin in the form of a powder for the preparation of a suspension for oral administration in vials or sachets. Recommended dosage regimen in children: 25 mg/3.6 mg/kg/day to 45 mg/6.4 mg/kg/day in 2 doses for the treatment of a number of infections (acute otitis media, sinusitis, lower respiratory tract infections) may apply a dose of up to 70 mg / 10 mg / kg / day in 2 divided doses. Data on the use of dosage forms of the drug Augmentin with a ratio of active ingredients of 7: 1 at the age of up to two months and at a dose of more than 45 mg / 6.4 mg / kg / day in children under two years of age are not available. In this regard, it is not possible to make recommendations on dosing in this group of patients. Elderly patients This dosage form of Augmentin is not used to treat elderly patients. Patients with impaired renal function Dosing regimen adjustment is not required for creatinine clearance of more than 30 ml / min. In patients with creatinine clearance less than 30 ml / min, it is not recommended to use Augmentin dosage forms with an amoxicillin / clavulanic acid ratio of 7: 1, due to the lack of recommendations on the dosing regimen for this group of patients. Patients with impaired liver function Treatment should be carried out with caution, with regular monitoring of liver function (see sections "Contraindications for use" and "Precautions"). Use during pregnancy and lactation Pregnancy Animal studies have not revealed a direct or indirect negative effect of the drug on the course of pregnancy, embryonic / fetal development, childbirth or postpartum development. Limited data on the use of amoxicillin/clavulanic acid in women during pregnancy have not shown an increased risk of congenital anomalies. One study in women with preterm rupture of the membranes found that prophylactic therapy with the combination amoxicillin/clavulanic acid may be associated with an increased risk of neonatal necrotizing enterocolitis. The drug should be avoided during pregnancy, unless the doctor considers it necessary. Lactation Both active substances of the drug pass into breast milk (the effect of clavulanic acid on breastfed children is not known). In this regard, there is a possibility of developing diarrhea or a fungal infection of the mucous membranes in children who are breastfed, so it may be necessary to stop lactation. The possibility of sensitization should be taken into account. The amoxicillin/clavulanic acid combination may only be used during breastfeeding after a benefit/risk assessment by the treating physician. Precautions Before starting treatment with amoxicillin/clavulanic acid, a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam antibiotics should be taken (see sections "Contraindications for Use" and "Side Effects"). Serious, sometimes fatal, hypersensitivity reactions (including anaphylactoid and severe skin adverse reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins and in individuals with atopy. If an allergic reaction occurs, amoxicillin/clavulanic acid treatment should be discontinued and alternative therapy initiated. If the infection has been confirmed to be caused by amoxicillin-susceptible organisms, consideration should be given to switching from amoxicillin/clavulanic acid therapy to amoxicillin therapy in accordance with official guidelines. Augmentin 875 mg / 125 mg and 500 mg / 125 mg tablets are not suitable for use in cases where there is a high risk that suspected pathogens have reduced sensitivity or resistance to beta-lactams, which is not mediated by beta-lactamases inhibited by clavulanic acid. These dosage forms should not be used in the treatment of infections caused by penicillin-resistant S. pneumoniae. In patients with impaired renal function or when taking high doses of the drug, convulsions may occur (see section "Side Effects"). Amoxicillin/clavulanic acid is not recommended for suspected infectious mononucleosis, as such patients have a measles-like rash after taking amoxicillin. The combined use of allopurinol and amoxicillin increases the risk of allergic skin reactions. Prolonged treatment may lead to overgrowth of non-susceptible organisms. The appearance of pustules on erythematous skin areas with fever at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis. The occurrence of this adverse reaction requires discontinuation of the drug and is a contraindication to the further use of amoxicillin. The combination of amoxicillin / clavulanic acid should be used with caution in patients with signs of hepatic insufficiency (see sections "Method of application and dosage", "Contraindications for use", "Precautions"). Adverse events from the liver were observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse events are very rare in children. Signs and symptoms of impaired liver function usually occur during or immediately after therapy, but in some cases may not appear for several weeks after therapy is completed. They are usually reversible. Adverse events from the liver can be severe, in extremely rare cases there have been reports of deaths. In almost all cases, these were individuals with serious comorbidities or individuals receiving concomitantly potentially hepatotoxic drugs. Antibiotic-associated colitis has been reported with virtually all antibacterial agents. This adverse reaction can vary in severity from mild to life-threatening (see section "Side Effects"). Therefore, the possibility of this diagnosis should be considered in patients who develop diarrhea during treatment or after the administration of any antibiotics. If antibiotic-associated colitis occurs, the drug should be immediately discontinued. The patient needs to consult a doctor who will prescribe the appropriate treatment. In such a situation, the use of drugs that inhibit peristalsis is contraindicated. During long-term therapy with Augmentin, it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis. In patients treated with a combination of amoxicillin and clavulanic acid, prolongation of prothrombin time was observed in rare cases. When co-administering a combination of amoxicillin and clavulanic acid with anticoagulants, appropriate monitoring should be carried out. To maintain the desired level of anticoagulation, it may be necessary to adjust the dose of the anticoagulant (see the section "Interaction with other drugs" and "Side effect"). In patients with impaired renal function, the dose of Augmentin should be changed according to the degree of impairment (see section "Method of application and doses"). In patients with reduced diuresis, in very rare cases, the development of crystalluria has been reported, mainly with parenteral use of the drug. While taking high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation. In patients with urinary catheters, the patency of the catheter should be checked regularly (see section "Overdose"). During treatment with amoxicillin, if it is necessary to test for the presence of glucose in the urine, enzymatic methods for determining glucose oxidase should be used due to the possibility of obtaining a false positive result when using non-enzymatic methods. The presence of clavulanic acid in the preparation can cause non-specific binding of IgG and albumin to erythrocyte membranes, which can lead to a false-positive Coombs test result. Patients taking the amoxicillin/clavulanic acid combination may experience a false positive test result for Aspergillus infection using Platelia Aspergillus EIA tests. Cross-reactions between the Platelia Aspergillus EIA test and non-Aspergillus polysaccharides and polyfuranoses have been reported. Therefore, positive test results in patients taking the amoxicillin/clavulanic acid combination should be interpreted with caution and confirmed by other diagnostic methods. Interactions with other drugs Oral anticoagulants: oral anticoagulants and penicillin antibiotics are widely used in clinical practice without reports of their interaction. However, the literature describes cases of an increase in the international normalized ratio (INR) in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If necessary, the simultaneous use of prothrombin time or INR should be carefully monitored when prescribing or canceling amoxicillin. In addition, dose adjustment of oral anticoagulants may be required. Methotrexate: Penicillins may decrease the excretion of methotrexate, leading to a potential increase in toxicity. Probenecid: It is not recommended to use Augmentin simultaneously with probenecid. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of the drug Augmentin and probenecid can lead to a steady and prolonged increase in the blood concentration of amoxicillin, but not clavulanic acid. Mycophenolate mofetil: in patients treated with mycophenolate mofetil, after the start of oral administration of the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite, mycophenolic acid, was observed before taking the next dose of the drug by approximately 50%. Changes in this concentration may not accurately reflect overall changes in mycophenolic acid exposure. In this regard, as a rule, no dose adjustment of mycophenolate mofetil is required in the absence of clinical signs of graft dysfunction. However, careful clinical monitoring should be carried out while taking the combination of drugs, as well as shortly after the end of antibiotic treatment. Contraindications Hypersensitivity to any of the components of the drug or penicillins. History of a severe immediate hypersensitivity reaction (eg, anaphylaxis) to previous administration of beta-lactam antibiotics (cephalosporins, carbapenems, or monobactams). A history of jaundice or impaired liver function that developed against the background of the use of a combination of amoxicillin / clavulanic acid (see section "Side Effects"). Active ingredients: amoxicillin 200.0 mg or 400.0 mg (as amoxicillin trihydrate 229.58 mg or 459.17 mg, respectively), clavulanic acid 28.5 mg or 57.0 mg (as potassium clavulanate 33.95 mg or 67.90 mg, respectively). Excipients: xanthan gum, aspartame (E951), succinic acid, colloidal silicon dioxide anhydrous, hydroxypropyl methylcellulose (anhydrous), dry orange flavor 1 and 2, dry raspberry flavor, dry flavor "Light molasses", silicon dioxide (anhydrous). Overdose Symptoms and signs Gastrointestinal disorders and disturbances in water and electrolyte balance may occur. Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure (see section "Precautions"). Convulsions may occur when taking high doses of the drug or in patients with impaired renal function. There are reports of deposition of amoxicillin in urinary catheters, mainly after intravenous administration in large doses, so regular checks of the patency of the catheter should be carried out (see section "Precautions"). Treatment Symptomatic correction of disorders of the gastrointestinal tract can be carried out, with special attention to the normalization of water and electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis. Side effects The most common side effects are diarrhea, nausea and vomiting. Adverse events identified during clinical trials and post-marketing surveillance are listed by body system and according to frequency of occurrence. The frequency of occurrence is defined as follows: very often (≥ 1/10), often (≥ 1/100 and < 1/10), infrequently (≥ 1/1000 and < 1/100), rarely (≥ 1/10,000 and < 1/1000), very rare (<1/10000), frequency not known (frequency cannot be estimated from the available data). Infectious diseases Often: candidiasis of the skin and mucous membranes; frequency not known: overgrowth of non-susceptible organisms. From the side of the hematopoietic and lymphatic system Rarely: reversible leukopenia (including neutropenia), thrombocytopenia; frequency not known: reversible agranulocytosis, hemolytic anemia, prolongation of bleeding time and prothrombin time (see section "Precautions"). On the part of the immune system (see sections Precautions" and "Contraindications for use") The frequency is not known: angioedema, anaphylaxis, a syndrome similar to serum sickness, allergic vasculitis. From the nervous system Uncommon: dizziness, headache; frequency not known: reversible hyperactivity, convulsions (see section "Precautions"), aseptic meningitis. From the gastrointestinal tract Very often: diarrhea; often: nausea, vomiting; infrequently: digestive disorders; frequency not known: antibiotic-induced colitis (including pseudomembranous colitis and hemorrhagic colitis), black "hairy" tongue. Nausea is more common with high doses taken orally. Reactions from the gastrointestinal tract can be reduced when taking the drug together with food. On the part of the liver and biliary tract Infrequently: increased activity of aspartate aminotransferase (AST) and / or alanine aminotransferase (ALT). A moderate increase in the activity of AST and ALT is observed in patients receiving therapy with beta-lactam antibiotics, but the clinical significance of this phenomenon is not known. Frequency not known: hepatitis and cholestatic jaundice. These adverse reactions have been reported with other penicillins and cephalosporins. On the part of the skin and subcutaneous fat Infrequently; rash, itching, urticaria; rarely: erythema multiforme; frequency not known: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome (see sections "Contraindications for use" and "Precautions"). in the event of any allergic reactions, treatment with Augmentin should be discontinued.On the part of the kidneys and urinary tract Frequency is not known: interstitial nephritis, crystalluria (see section "Overdose"), Storage conditions 3 years.Do not use after the expiration date indicated on the package.Use within 30 days from the date of opening the aluminum package. Buy Augmentin powder for oral suspension (200mg / 28.5mg) / 5ml No. 1 1 Instructions for use for Augmentin powder for oral suspension (200mg / 28.5m d)/5ml №1