Amoxiclav 2X tablets p/o 1000mg(875mg/125mg) №7×2

Name:
Amoxiclav 2X tab. 1000mg (875mg/125mg) in bl. No. 7×2
Description:
White or almost white, oval, biconvex tablets with beveled edges, film-coated, on one side a notch and “875/125” is squeezed out, on the other side “AMC” is squeezed out Main active ingredient Amoxicillin + clavulanic acid Release form Tablets Dosage Each tablet contains 875 mg amoxicillin trihydrate and 125 mg clavulanic acid potassium salt (7:1 ratio) peptidoglycan is an integral component of the bacterial cell wall. Inhibition of peptidoglycan synthesis results in a loss of cell wall strength, which usually results in cell lysis and 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 concentrations above the minimum inhibitory (T> MIC) is recognized as the main determinant of the effectiveness of amoxicillin. Mechanisms of resistance There are two main mechanisms of bacterial resistance to amoxicillin/clavulanic acid: inactivation by bacterial beta-lactamases that are insensitive to the inhibitory effects of clavulanic acid, including class B, C, and D beta-lactamases; a change in penicillin-binding proteins, as a result of which the affinity of antibacterial drugs for target structures decreases. 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 Minimum inhibitory concentrations 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 sensitivity (μg / ml) Sensitivity Intermediate sensitivity Resistance Haemophilus influenzae1 ? 1->1 Moraxella catarrhalis1 ? 1->1 Staphylococcus aureus2 ? 2 – > 2 Coagulase-negative staphylococcus aureus2 ? 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, so it is desirable to obtain local information on antibiotic resistance before starting therapy, especially in the case of severe infections. In cases where local indicators of antibiotic resistance cast doubt on the appropriateness of the drug for at least some types of infections, you should seek the help of appropriate specialists. Usually susceptible species Gram-positive aerobes: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus (methicillin-susceptible strains)?, Coagulase-negative Staphylococci (methicillin-susceptible strains)?, Streptococcus agalactiae, Streptococcus pneumoniae1, Streptococcus pyogenes and other beta-hemolytic streptococci, group Streptococcus viridans 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, Morganella morganii, Providencia spp, Pseudomonas sp., Serratia sp., Stenotrophomonas maltophilia Other organisms: Chlamydophyla pneumoniae, Chlamydophyla psittaci, Coxiella burnetti, Mycoplasma pneumoniae $ Natural intermediate susceptibility in the absence of an acquired resistance mechanism. ? All methicillin-resistant staphylococci are resistant to amoxicillin/clavulanic acid. 1 Infections caused by penicillin-resistant strains of Streptococcus pneumoniae should not be treated with this dosage form of the drug, if there is a high risk that the alleged pathogens are resistant, due not to the production of beta-lactamase sensitive to clavulanic acid inhibition, but to a change in penicillin-binding proteins (see “Doses and method of application” and “Special instructions and precautions”). 2 In some EU countries, strains with reduced sensitivity have been identified, occurring at a frequency above 10%. Pharmacokinetics Amoxicillin and clavulanic acid are completely soluble in water at physiological pH. Both components are quickly and well absorbed after oral administration. Their absorption improves if the drug is taken immediately before meals. When administered orally, the bioavailability of amoxicillin and clavulanic acid reaches approximately 70%. The plasma concentration profiles of both components are similar, the time to peak concentration (Tmax) for each substance is approximately one hour. When groups of healthy volunteers took the 875 mg/125 mg combination tablet twice daily on an empty stomach, peak serum concentrations (Cmax) were 11.64 ± 2.78 μg/mL for amoxicillin and 2.18 ± 0.99 μg /ml for clavulanic acid. The time to reach maximum serum concentration (Tmax) was 1.5 hours (range 1.0-2.5) for amoxicillin and 1.25 hours (range 1.0-2.0) for clavulanic acid. Mean T1/2 values were 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 of the combined preparation are similar to those obtained by oral administration of equivalent doses of amoxicillin or clavulanic acid alone. About 25% of the total plasma clavulanic acid and 18% of the total plasma amoxicillin 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 only slightly 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 Breastfeeding). Both 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 in the human body, excreted in urine and feces, as well as in the form of carbon dioxide with exhaled air. The main route of excretion of amoxicillin is the kidneys, while clavulanic acid is excreted from the body using renal and extrarenal mechanisms. The amoxicillin/clavulanic acid combination has a mean half-life of about one hour and a mean total clearance of about 25 L/h in healthy subjects. 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 250 mg/125 mg or 500 mg/125 mg tablets. The level of excretion 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 the elderly, the dose is selected with caution due to the possible decrease in kidney function and, if necessary, regularly check the work of the kidneys. 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 and 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 “Doses and method of administration”). Hepatic insufficiency In patients with hepatic insufficiency, the drug is prescribed with caution and regularly monitor liver function. Indications for use Amoxiclav 2x is indicated for the treatment of the following infections in adults and children: acute bacterial sinusitis); acute otitis media; acute exacerbations 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 the bones and joints, in particular osteomyelitis. Consideration should be given to official guidelines on the appropriate use of antibacterial agents. Route of administration and doses Doses reflect the content of amoxicillin / clavulanic acid. 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. The use of other dosage forms of the drug (for example, with higher doses of amoxicillin and / or with a different dose ratio of amoxicillin / clavulanic acid) is considered as necessary. When taking the drug, 1 tablet 2 times a day at the doses recommended below, adults and children weighing ? 40 kg will receive a total daily dose of 1750 mg amoxicillin / 250 mg clavulanic acid, and when taken 1 tablet 3 times a day – 2625 mg amoxicillin / 375 mg clavulanic acid. If you need a higher daily dose of amoxicillin, it is recommended to choose a different dosage form of the drug in order to avoid taking excessively high daily doses of clavulanic acid. The duration of therapy is determined by the response to treatment. Some infections (such as osteomyelitis) require longer treatment. The duration of treatment should not exceed 14 days without revision (see information on long-term therapy in the section “Special instructions and precautions”). Adults and children weighing ? 40 kg Recommended doses: standard dose (for all indications) – one tablet twice a day; a higher dose (especially for the treatment of infections such as otitis media, sinusitis, infections of the lower respiratory tract and urinary tract) – one tablet three times a day. Elderly patients (>65 years) Dose adjustment is not required. Patients with impaired renal function Patients with a creatinine clearance of more than 30 ml / min dose adjustment is not required. Amoxiclav 2x is not used for the treatment of patients with creatinine clearance <30 ml/min, since no dose recommendations have been developed for these patients. Patients with impaired liver function Use with caution. Monitor liver function regularly. (see "Contraindications" and "Special instructions and precautions"). Children weighing less than 40 kg Amoxiclav 2x is not intended for use in children weighing less than 40 kg. If the patient has forgotten to take the prescribed dose of the drug, it should be taken as soon as possible. In this case, the interval before taking the next dose after this should be more than 4 hours. Then you should return to the previous dosing regimen. Do not take a double dose. Method of application For oral administration. Take immediately before meals to minimize possible gastrointestinal side effects. Use during pregnancy and lactation 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. The use of the drug during pregnancy should be avoided 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. The possibility of sensitization should be considered. Therapy with the drug during breastfeeding is possible only after assessing the benefit-risk ratio by the attending physician. Precautions Before starting therapy with the drug, a thorough history is taken for hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam drugs. There have been reports of the development of serious hypersensitivity reactions, sometimes fatal, (including anaphylactoid and severe skin adverse reactions) in patients receiving penicillin therapy. They are most likely to develop in patients with hypersensitivity reactions to penicillins and a history of atopy. In the event of an allergic reaction, Amoxiclav 2x therapy is stopped, and other suitable antibacterial drugs are prescribed instead. In cases of proven susceptibility of infectious agents to amoxicillin, a switch from Amoxiclav 2x to amoxicillin is considered in accordance with official guidelines. This dosage form of the drug is not suitable for use if there is a high risk that the alleged pathogens are resistant, due not to the production of beta-lactamase sensitive to clavulanic acid inhibition, but to a change in penicillin-binding proteins (including resistant S. pneumoniae). In patients with impaired renal function or receiving high-dose therapy, seizures may develop (see "Side Effects"). Therapy with Amoxiclav 2x should be avoided 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 potentially increases the likelihood of allergic skin reactions. Prolonged use of Amoxiclav 2x may lead to overgrowth 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 is 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 occur during or shortly after treatment, however, in some cases, they do not appear until a few weeks after cessation of therapy. They are usually reversible. Serious adverse events from the liver can develop, extremely rarely with a fatal outcome. They were almost always observed among patients with serious underlying diseases or taking concomitant drugs that can damage the liver. Cases of antibiotic-associated colitis observed during therapy with almost all antibacterial drugs, including amoxicillin, can vary in severity from mild to life-threatening. Therefore, 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 the drug, prolongation of prothrombin time was noted. When taking anticoagulants at the same time, proper monitoring of coagulation parameters is mandatory. Dose adjustment of oral anticoagulants may be required to achieve the desired level of anticoagulation. In patients with renal insufficiency, dose adjustment is mandatory in accordance with the level of insufficiency (see "Doses and method of administration"). In patients with reduced diuresis, crystalluria was observed in rare cases, mainly against the background of parenteral therapy. During therapy with high doses of amoxicillin, sufficient 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 evaluate the level of glucose in the urine during treatment with amoxicillin, enzymatic methods with glucose oxidase should be used, 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 test for Aspergillus. Positive test results in patients taking Amoxiclav 2x should be interpreted with caution and confirmed by other diagnostic methods. Interactions with other drugs Oral anticoagulants Cases of an increase in the international normalized ratio in patients receiving maintenance therapy with acenocoumarol or warfarin against the background of the prescribed course of amoxicillin are described. If necessary, the simultaneous administration of drugs carefully monitor the prothrombin time or international normalized ratio at the beginning and after stopping treatment with amoxicillin. Dose adjustment of oral anticoagulants may be required. Methotrexate Penicillins may reduce the excretion of methotrexate, which may lead to increased toxicity. Probenecid It is not recommended to use simultaneously probenecid, which reduces the secretion of amoxicillin by the renal tubules. The simultaneous use of probenecid with Amoxiclav 2x can lead to an increase and to a longer maintenance of the level of amoxicillin (but not clavulanic acid) in the blood. Mycophenolate mofetil In patients taking mycophenolate mofetil, after the start of oral amoxicillin and clavulanic acid, an approximately 50% decrease in the concentration of the active metabolite - mycophenolic acid (MPA) - was observed before taking the next dose of mycophenolate mofetil. Such a change in the concentration of MFC before taking the next dose may not indicate a change in the overall exposure of the MFC. 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 tablet contains 875 mg amoxicillin trihydrate and 125 mg clavulanic acid potassium salt (7:1 ratio). Excipients Core: anhydrous colloidal silicon dioxide, crospovidone, croscarmellose sodium, magnesium stearate, microcrystalline cellulose; shell: hydroxypropyl cellulose, ethyl cellulose, polysorbate 80, triethyl citrate, talc, titanium dioxide E 171. Overdose Gastrointestinal symptoms may develop, as well as water and electrolyte imbalance. There have been cases of amoxicillin-associated crystalluria, sometimes leading to renal failure. Convulsions may develop 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 potassium clavulanate can be excreted from the body by hemodialysis. Side effects The following categories were used to classify the incidence of adverse reactions: 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 to the drug 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 syndrome, allergic vasculitis. Nervous system disorders Uncommon: dizziness, headache. Unknown frequency: reversible hyperactivity, convulsions, aseptic meningitis. Gastrointestinal disorders Very common: diarrhoea. Common: Nausea (often associated with high oral doses; gastrointestinal reactions can be minimized if the drug is taken at the start of a meal), vomiting. Uncommon: indigestion. Unknown frequency: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis, see section "Special instructions and precautions"), "black" tongue. 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, see "Special instructions and precautions"). Skin and subcutaneous tissue disorders Treatment should be discontinued if any allergic skin reaction develops. Uncommon: skin rash, itching, urticaria. Rare: erythema multiforme. Unknown frequency: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome). Renal and urinary disorders Unknown frequency: interstitial nephritis, crystalluria. If you notice any side effects, including those not mentioned in this leaflet, please tell your doctor. Storage conditions Keep out of the reach of children. Store in a place protected from moisture at a temperature not exceeding 25? Buy Amoxiclav 2X tablets po 1000mg(875mg/125mg) №7x2