Instructions for use AMOCLAV-625 (AMOCLAV-625)
Before starting treatment with Amoclav-625, it is necessary to collect a detailed history regarding previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam drugs.
Serious and occasionally fatal hypersensitivity reactions (anaphylactoid reactions) have been observed during penicillin therapy. They are most likely to develop in patients with hypersensitivity reactions to penicillins and a history of atopy. If an allergic reaction occurs, treatment with the amoxicillin/clavulanic acid combination should be discontinued and alternative therapy initiated.
If the infection is confirmed to be caused by amoxicillin-susceptible organisms, a switch from amoxicillin/clavulanic acid combination therapy to amoxicillin therapy should be considered in accordance with official guidelines. This dosage form should not be used in the treatment of infections caused by penicillin-resistant strains of Streptococcus pheumoniae.
In patients with impaired renal function or when taking the drug in high doses, seizures may occur.
The use of a combination of amoxicillin/clavulanic acid is not recommended for suspected infectious mononucleosis, since such patients experience a morbilliform rash after taking amoxicillin.
The combined use of allopurinol and amoxicillin increases the risk of allergic skin reactions.
Long-term treatment may lead to excessive proliferation of insensitive microorganisms.
The appearance of pustules on erythematous areas of the skin 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 further use of amoxicillin.
The amoxicillin/clavulanic acid combination should be used with caution in patients with signs of liver failure.
Adverse liver events have been observed primarily in men and elderly patients and may be associated with long-term therapy. These adverse events are very rarely observed in children. Signs and symptoms of liver dysfunction usually occur during or immediately after completion of therapy, but in some cases may not appear until several weeks after completion of therapy. As a rule, they are reversible. Liver side effects may be severe. In extremely rare cases, there have been reports of deaths. In almost all cases, these were patients with serious comorbidities or patients receiving concomitantly potentially hepatotoxic drugs.
Antibiotic-associated colitis has been reported with virtually all antibacterial drugs. This adverse reaction 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. If antibiotic-associated colitis occurs, the drug should be discontinued immediately. The patient should consult a doctor who will prescribe appropriate treatment. In such a situation, the use of drugs that inhibit peristalsis is contraindicated.
During long-term therapy with Amoclav-625, 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, prolongation of prothrombin time has been observed in rare cases. When co-prescribing a combination of amoxicillin and clavulanic acid with anticoagulants, appropriate monitoring should be carried out. To maintain the desired level of anticoagulation, dose adjustment of the anticoagulant may be necessary.
In patients with impaired renal function, the dose of Amoclav-625 should be adjusted according to the degree of impairment.
In patients with reduced diuresis, the development of crystalluria has been reported in very rare cases, mainly with parenteral use of amoxicillin. While taking high doses of amoxicillin, it is recommended to drink enough fluids and maintain adequate diuresis to reduce the chance of amoxicillin crystal formation. In patients with urinary catheters, catheter patency should be checked regularly.
During treatment with amoxicillin, if tests for the presence of glucose in urine are necessary, 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 drug may cause nonspecific binding of IgG and albumin to red blood cell membranes, which may lead to a false-positive Coombs test result.
Patients taking the combination of amoxicillin and clavulanic acid may have a false-positive Platelia Aspergillus EIA test result for Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses have been reported in the Platelia Aspergillus EIA test. Therefore, positive test results in patients taking the combination of amoxicillin and clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.
Impact on the ability to drive vehicles and machinery
No special studies have been conducted, but adverse reactions may occur (allergic reactions, dizziness, convulsions), which may affect the ability to drive vehicles and other mechanisms.
Amoxiclav Quiktab (dispersible tablet 625 mg No. 14)
A country
Slovenia
The country of production may vary depending on the batch of goods. Please check with the operator for detailed information when confirming your order.
Active substance
Amoxicillin + Clavulanic acid
Compound
1 tablet contains: amoxicillin trihydrate 574 mg, potassium clavulanate 148.87 mg. Excipients: tropical mixture flavor, sweet orange flavor, aspartame, colloidal anhydrous silicon dioxide, iron (III) oxide yellow (E172), talc, hydrogenated castor oil, microcrystalline cellulose silicon-containing. Dispersible tablets are light yellow in color with brown inclusions, oblong, octagonal, with a fruity odor.
pharmachologic effect
Broad-spectrum antibiotic; contains semisynthetic penicillin amoxicillin and irreversible β-lactamase inhibitor clavulanic acid. Clavulanic acid forms a stable inactivated complex with these enzymes and ensures the resistance of amoxicillin to the effects of β-lactamases produced by microorganisms. Clavulanic acid, similar in structure to beta-lactam antibiotics, has weak intrinsic antibacterial activity. Amoxiclav® is active against strains sensitive to amoxicillin, including strains producing β-lactamases, incl. aerobic gram-positive bacteria: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus bovis, Enterococcus spp., Staphylococcus aureus (except methicillin-resistant strains), Staphylococcus epidermidis (except methicillin-resistant strains), Staphylococcus saprophyticus, Listeria spp.; aerobic gram-negative bacteria: Bordetella pertussis, Brucella spp., Campylobacter jejuni, Escherichia coli, Gardnerella vaginalis, Haemophilus ducreyi, Haemophilus influenzae, Helicobacter pylori, Klebsiella spp., Moraxella catarrhalis, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Proteus spp. , Salmonella spp., Shigella spp., Vibrio cholerae, Yersinia enterocolitica, Eikenella corrodens; gram-positive anaerobes: Peptococcus spp., Peptostreptococcus spp., Clostridium spp., Actinomyces israelii, Fusobacterium spp., Prevotella spp., gram-negative anaerobes: Bacteroides spp.
Indications for use
Treatment of infectious and inflammatory diseases caused by microorganisms sensitive to the drug: - infections of the upper respiratory tract and ENT organs (including acute and chronic sinusitis, acute and chronic otitis media, retropharyngeal abscess, tonsillitis, pharyngitis); - infections of the lower respiratory tract (including acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia); - urinary tract infections; - gynecological infections; - skin and soft tissue infections, including human and animal bites; - bone and connective tissue infections; - biliary tract infections (cholecystitis, cholangitis); - odontogenic infections.
Mode of application
Inside. The tablets must be dissolved in half a glass of water (at least 30 ml) and mixed thoroughly and drunk. It is possible to hold the tablets in your mouth until completely dissolved, then swallow. In order to reduce the risk of developing side effects from the gastrointestinal tract, the drug should be taken at the beginning of a meal. Adults and children over 12 years of age (with body weight >40 kg) with mild or moderate infection are prescribed 1 tablet. (625 mg) every 12 hours, in case of severe infection and respiratory tract infections - 1 tablet. (625 mg) every 8 hours or 1 tablet. (1000 mg) every 12 hours. Duration of treatment is up to 14 days. If treatment is started with parenteral administration of the drug, therapy may be continued by taking Amoxiclav® Quiktab tablets orally. In accordance with the severity of renal functional disorders, the dose of the drug should be reduced and/or the interval of use should be increased . For moderate renal failure (creatinine clearance 10-30 ml/min), 1 tablet is prescribed. (625 mg) every 12 hours. In case of severe renal failure (CC Interaction, when using the drug Amoxiclav® Quiktab simultaneously with antacids, glucosamine, laxatives, aminoglycosides, absorption slows down, with ascorbic acid it increases. Diuretics, allopurinol, phenylbutazone, NSAIDs and other drugs agents that block tubular secretion increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration). When used simultaneously, Amoxiclav® Quiktab increases the toxicity of methotrexate. When using Amoxiclav® Quiktab with allopurinol, the incidence of exanthema increases. Simultaneous use of Amoxiclav should be avoided. ® Kviktab with disulfiram. In some cases, taking the drug may prolong the prothrombin time, therefore caution should be exercised when prescribing anticoagulants and the drug Amoxiclav® Kviktab simultaneously. The combination of amoxicillin with rifampicin is antagonistic (mutual weakening of the antibacterial effect is noted). Amoxiclav® Kviktab should be used several hours before taking bacteriostatic antibiotics (macrolides, tetracyclines), sulfonamides. Probenecid reduces the excretion of amoxicillin, increasing its serum concentration. Amoxiclav® Quiktab reduces the effectiveness of oral contraceptives.
Side effect
Side effects in most cases are weak and transient. From the digestive system: - loss of appetite, nausea, vomiting, diarrhea; - rarely - increased activity of liver enzymes (ALT, AST), increased alkaline phosphatase levels, liver dysfunction; - in isolated cases - cholestatic jaundice, hepatitis, pseudomembranous colitis. From the central nervous system: - dizziness, headache; - very rarely - convulsions (may occur in patients with impaired renal function when taking the drug in high doses). From the hematopoietic system: - rarely - reversible leukopenia (including neutropenia), thrombocytopenia; - very rarely - hemolytic anemia, reversible increase in prothrombin time (when used together with anticoagulants). From the urinary system: - very rarely - interstitial nephritis, crystalluria. Allergic reactions: - erythematous rash , itching, urticaria; - very rarely - exudative erythema multiforme, angioedema, anaphylactic shock, allergic vasculitis; - in isolated cases - exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalized exanthematous pustulosis. Others: - rarely - development superinfections (incl. candidiasis).
Contraindications
- a history of indications of cholestatic jaundice and/or other liver dysfunction caused by taking amoxicillin/clavulanic acid; - children under 12 years of age or weighing less than 40 kg; - hypersensitivity to the components of the drug; - history of hypersensitivity to any antibiotic from the group of penicillins, cephalosporins and other beta-lactam antibiotics. The drug should be used with caution in patients with a history of pseudomembranous colitis, liver failure, severe renal impairment, and during lactation. Due to the fact that a large number of In patients suffering from infectious mononucleosis and lymphocytic leukemia who received ampicillin, the appearance of an erythematous rash was observed; the use of antibiotics from the ampicillin group is not recommended for such patients.
Overdose
There are no reports of death or life-threatening side effects due to an overdose of the drug. Symptoms: gastrointestinal disorders - abdominal pain, diarrhea, vomiting, possibly also anxiety, insomnia, dizziness; in some cases - convulsive seizures. Treatment: symptomatic, in case of recent use of the drug (less than 4 hours), it is necessary to perform gastric lavage and prescribe activated charcoal to reduce the absorption of the drug. The patient must be under medical supervision. Amoxicillin/potassium clavulanate is removed by hemodialysis.
special instructions
During a course of treatment, the functions of the hematopoietic organs, liver and kidneys should be monitored. In patients with severely impaired renal function, adequate adjustment of the dosage regimen or an increase in the intervals between doses of the drug is required. In order to reduce the risk of developing adverse reactions from the gastrointestinal tract, the drug should be taken at the beginning of meals. When using Amoxiclav Kviktab, a false positive reaction is possible when determining the level of glucose in urine using Benedict's reagent or Felling's solution (it is recommended to use enzymatic reactions with glucosidase). Impact on the ability to drive vehicles and operate machinery Data on the negative effect of the drug Amoxiclav® Kviktab in recommended doses on the ability no to driving vehicles and operating machinery.
Dispensing conditions in pharmacies
On prescription
Amoxiclav recipe in Latin step by step
So, we’ve figured out the release forms and dosages, now let’s move on to the rules for writing a prescription.
- The Latin recipe for amoxiclav begins, like any other recipe, with the Latin word Rp. – Recipe – “take it”.
- Next, after the colon, it is necessary to indicate the dosage form of amoxiclav that we need (tablets or powder), with a capital letter, in the genitive case, singular and in Latin.
- Then we indicate “Amoxiclav”, put it in quotes as we are writing out the commercial name.
- Then in the same line you need to write the dosage and how much to give (after N - Numero).
- And, on a new line, we write DS - Da Signa - issue and designate - fill in the signature.
Prescription for amoxiclav in tablet form
For example, let’s write out a prescription for amoxiclav in Latin in the form of tablets with a dosage of 250/125 mg. Read more here - recipe for tablets in Latin.
Rp.: Tab. “Amoxiclav” 250/125 mg N 15 DS Orally, 1 tablet 4 times a day.
You can write the dosage as a sum, for example, not 250/125, but 375 mg. The pharmacist will understand too.
Amoxiclav recipe in Latin in powder form
For example, let’s write out a prescription for amoxiclav in powder form with a dosage of 500/100 mg. We will prescribe it intramuscularly. Read more - the recipe for the powder is in Latin and, since the powders are given in bottles, the recipe for the bottles is in Latin.
Rp.: Pulv. “Amoxiclav” 500/100 mg N 6 DS Dilute in saline solution. Intramuscularly 2 times a day.
Let's write out a recipe for amoxiclav in Latin in the form of a powder for preparing a suspension with a dosage of 125 mg + 31.25 mg/5 ml. Let's appoint inside.
Rp.: Pulv. “Amoxiclav” 125+31.25 mg /5 ml DS Add water to the mark. Inside, 1 spoon 4 times a day.
Amoksiklav®
Before starting treatment, it is necessary to interview the patient to identify a history of hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics. In patients who are hypersensitive to penicillins, cross-allergic reactions with cephalosporin antibiotics are possible.
Serious and sometimes fatal hypersensitivity reactions (anaphylactic as well as 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, as well as atopy. If allergic reactions occur, treatment with the drug should be discontinued and appropriate alternative therapy should be initiated.
If the infection is proven to be caused by microorganisms sensitive to amoxicillin, the advisability of switching from amoxicillin/clavulanic acid to amoxicillin should be considered.
During a course of treatment, it is necessary to monitor the state of the function of the hematopoietic organs, liver, and kidneys. In patients with impaired renal function, the dose should be adjusted according to the degree of impairment.
In order to reduce the risk of developing side effects from the gastrointestinal tract, the drug should be taken at the beginning of a meal.
In patients receiving a combination of amoxicillin and clavulanic acid together with indirect (oral) anticoagulants, an increase in prothrombin time 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. To maintain the desired effect of oral anticoagulants, their dose may require adjustment.
In some cases, prolonged use may lead to overgrowth of non-susceptible microorganisms. Superinfection may develop due to the growth of microflora insensitive to amoxicillin, which requires a corresponding change in antibacterial therapy.
In patients with impaired renal function, as well as when taking high doses of the drug, seizures may occur.
If infectious mononucleosis is suspected, the drug should not be used, since amoxicillin can cause a measles-like skin rash in patients with this disease, which makes diagnosing the disease difficult.
Taking allopurinol during treatment with amoxicillin may increase the likelihood of allergic skin reactions.
The appearance at the beginning of treatment of generalized erythema with pustules, accompanied by an increase in body temperature, may be a symptom of acute generalized exanthematous pustulosis. If such a reaction occurs, you should stop taking the drug and refuse further therapy with amoxicillin.
Amoxiclav® should be used with caution in patients with signs of liver failure.
Hepatic side effects were observed predominantly in men and elderly patients and may be associated with prolonged treatment. In children, these phenomena were observed very rarely. In all groups of patients, signs and symptoms usually appear during or shortly after the end of treatment, but in some cases they may appear several weeks after the end of treatment. They are usually reversible. Liver side effects can be severe, and deaths have been reported very rarely. In almost all cases, they were observed in patients with a severe underlying disease or during the simultaneous use of other drugs that can affect the liver.
Antibiotic-associated colitis has been observed during therapy with almost all antibacterial drugs, including amoxicillin, and the severity can range from mild to life-threatening. Therefore, it is important to consider this diagnosis in patients with diarrhea that occurs during or after administration of any of the antibiotics. If antibiotic-associated colitis develops, Amoxiclav® should be immediately discontinued, consult a doctor and begin appropriate treatment. In this situation, drugs that inhibit intestinal motility are contraindicated.
Crystalluria very rarely occurs in patients with reduced diuresis. During the use of large doses of amoxicillin, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.
In patients with a catheterized bladder, regular checks of catheter patency are necessary.
Lab tests
: High concentrations of amoxicillin give a false-positive reaction to urine glucose when using Benedict's reagent or Fehling's solution.
It is recommended to use enzymatic reactions with glucosidase.
Clavulanic acid may cause nonspecific binding of immunoglobulin G (IgG) and albumin to red blood cell membranes, resulting in false-positive Coombs test results.
There have been cases of positive test results using the Bio-Rad Laboratories Platelia Aspergillus enzyme immunoassay in patients receiving amoxicillin/clavulanic acid who were subsequently free of Aspergillus
. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses have been reported using the Platelia Aspergillus test. Therefore, caution should be used when interpreting positive test results in patients receiving amoxicillin/clavulanic acid, and they should also be confirmed using other diagnostic methods.
Amoxiclav 625 mg No. 15 tablet p.p.o.
Instructions for medical use of the drug Amoxiclav Trade name Amoxiclav International nonproprietary name No Dosage form Film-coated tablets, 375 mg and 625 mg Composition One tablet contains active substances: amoxicillin in the form of amoxicillin trihydrate 250 mg, clavulanic acid in the form of potassium clavulanate 125 mg (for a dosage of 375 mg) or amoxicillin in the form of amoxicillin trihydrate 500 mg, clavulanic acid in the form of potassium clavulanate 125 mg (for a dosage of 625 mg), excipients: colloidal silicon dioxide, crospovidone, croscarmellose sodium, magnesium stearate, talc, microcrystalline cellulose, film shell composition: hydroxypropyl cellulose, ethyl cellulose, polysorbate, triethyl citrate, titanium dioxide (E 171), talc. Description White or almost white film-coated tablets, octagonal in shape with a biconvex surface, engraved “250/125” on one side and “AMC” on the other side (for dosage 250 mg + 125 mg). White or almost white, film-coated tablets, oval in shape with a biconvex surface (for a dosage of 500 mg + 125 mg). Pharmacotherapeutic group Antibacterial drugs for systemic use. Beta-lactam antibacterial drugs - Penicillins. Penicillins in combination with beta-lactamase inhibitors. Clavulanic acid + amoxicillin. ATC code J01CR02 Pharmacological properties Pharmacokinetics Amoxicillin and clavulanic acid are completely dissolved in an aqueous solution at the pH environment of the body. Both components are well absorbed after oral administration. It is optimal to take amoxicillin/clavulanic acid during or at the beginning of a meal. After oral administration, the bioavailability of amoxicillin and clavulanic acid is approximately 70%. The dynamics of drug concentration in plasma of both components are similar. Maximum serum concentrations are achieved 1 hour after administration. Serum concentrations of amoxicillin and clavulanic acid when taking the amoxicillin/clavulanic acid combination are similar to those observed when an equivalent dose of amoxicillin and clavulanic acid is taken orally separately. About 25% of the total amount of clavulanic acid and 18% of amoxicillin are bound to proteins in the blood plasma. The volume of distribution for oral administration of the drug is approximately 0.3-0.4 l/kg amoxicillin and 0.2 l/kg clavulanic acid. After intravenous administration, both amoxicillin and clavulanic acid were detected in the gallbladder, abdominal tissue, skin, fat, muscle tissue, synovial and peritoneal fluid, bile and pus. Amoxicillin penetrates poorly into the cerebrospinal fluid. Amoxicillin and clavulanic acid penetrate the placental barrier. Both components also pass into breast milk. Amoxicillin is partially excreted in the urine as inactive penicillic acid in quantities equivalent to 10 - 25% of the original dose. Clavulanic acid is metabolized in the body and excreted in urine and feces, as well as in the form of carbon dioxide in exhaled air. The average half-life of amoxicillin/clavulanic acid is approximately 1 hour, and the average total clearance is approximately 25 L/h. Approximately 60 - 70% of amoxicillin and 40 - 65% of clavulanic acid are excreted unchanged from the body in the urine during the first 6 hours after taking a single dose of amoxicillin/clavulanic acid tablets. During various studies, it was found that 50-85% of amoxicillin and 27-60% of clavulanic acid are excreted in the urine within 24 hours. The largest amount of clavulanic acid is excreted during the first 2 hours after use. Concomitant use of probenecid slows down the release of amoxicillin, but this drug does not affect the excretion of clavulanic acid through the kidneys. The half-life of amoxicillin is similar in children aged 3 months to 2 years, as well as in older children and adults. When prescribing the drug to very young children (including premature newborns) in the first weeks of life, the drug should not be administered more than twice a day, which is associated with the immaturity of the renal excretion pathway in children. Due to the fact that elderly patients are more likely to suffer from renal dysfunction, caution should be exercised when prescribing the drug to this group of patients, but if necessary, monitoring of renal function should be carried out. The total plasma clearance of amoxicillin/clavulanic acid decreases in direct proportion to the decrease in renal function. The decrease in clearance of amoxicillin is more pronounced compared to clavulanic acid, since a larger amount of amoxicillin is excreted through the kidneys. Therefore, when prescribing the drug to patients with renal failure, dose adjustment is necessary to prevent excessive accumulation of amoxicillin and maintain the required level of clavulanic acid. When prescribing the drug to patients with liver failure, care should be taken when choosing the dose and regularly monitor liver function. Pharmacodynamics Amoxicillin is a semisynthetic antibiotic from the penicillin group (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin binding proteins) involved in the biosynthesis of peptidoglycan, which is an important structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis results in weakening of the cell wall, which is usually followed by cell lysis and death. Amoxicillin is destroyed by beta-lactamases produced by resistant bacteria, and therefore the spectrum of activity of amoxicillin alone does not include microorganisms that produce these enzymes. Clavulanic acid is a beta-lactam, structurally related to penicillins. It inhibits some beta-lactamases, thereby preventing the inactivation of amoxicillin and expanding its spectrum of activity. Clavulanic acid itself does not have a clinically significant antibacterial effect. The time it takes to exceed the minimum inhibitory concentration (T > MIC) is considered the main determinant of the effectiveness of amoxicillin. The two main mechanisms of resistance to amoxicillin and clavulanic acid are: - inactivation by bacterial beta-lactamases that are not inhibited by clavulanic acid, including classes B, C and D. - changes in penicillin binding proteins, which reduces the affinity of the antibacterial agent for the target pathogen. Bacterial impermeability or efflux pump mechanisms (transport systems) can cause or maintain bacterial resistance, especially Gram-negative bacteria. The MIC breakpoints for amoxicillin/clavulanic acid are those defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Strains Limits of sensitivity (µg/ml) Sensitive Moderately resistant 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 Enterobacteriaceae5-> 8 gram-negative anaerobes1 ≤ 4 8> 8 Grampose anaerobes1 ≤ 4 8> 8 Borderline without a specific connection1 ≤ 2 4-8> 8 1 published values are for amoxicillin concentration. To determine sensitivity, the concentration of clavulanic acid is fixed at 2 mg/l. 2 Published values are oxacillin concentrations. 3 Breakpoint values in the table are based on ampicillin breakpoints. 4 A resistance breakpoint of R > 8 mg/L ensures that all strains with resistance mechanisms are reported as resistant. 5 Breakpoint values in the table are based on benzylpenicillin breakpoints. The prevalence of resistance may vary geographically and temporally for selected species, and local information on resistance is desirable, especially when treating severe infections. Susceptible strains Aerobic gram-positive microorganisms Enterococcus faecalis Gardnerella vaginalis Staphylococcus aureus (methicillin sensitive) Streptococcus agalacticae Streptococcus pneumoniae Streptococcus pyogenes and other beta-hemolytic streptococci Streptococcus viridans group Aerobic gram-negative microorganisms Capnocyptophaga spp. Eikenella corrodens Haemophilus influenzae Moraxella catarrhalis Pasteurella multocida Anaerobic microorganisms Bacteroides fragilis Fusobacterium nucleatum Prevotella spp. Strains in which acquired resistance may be problematic Aerobic gram-positive microorganisms Enterococcus faecium Aerobic gram-negative microorganisms Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Proteus vulgaris Resistant strains Aerobic gram-negative microorganisms Acinetobacter sp. Citrobacter freundii Enterobacter sp. Legionella pneumophila Morganella morganii Providencia spp. Pseudomonas sp. Serratia sp. Stenotrophomonas maltophilia Other strains Chlamydophila pneumoniae Chlamydophila psitacci Coxiella burnetti Mycoplasma pneumoniae Indications for use - acute bacterial sinusitis - acute otitis media - exacerbation of chronic bronchitis - bronchopneumonia - cystitis - pyelonephritis - skin and soft tissue infections (including phlegmon, animal bites, periodontal abscess , phlegmon of the maxillofacial area) - infections of bones and joints (in particular osteomyelitis) Method of administration and dosage Doses are calculated taking into account the content of amoxicillin/clavulanic acid. When choosing the dose of Amoxiclav® for the treatment of individual infections, the following should be taken into account: - the sensitivity of the pathogen to the antibiotic - the severity and location of the infection - the age, weight and renal function of the patient, as shown below. It is also necessary to consider other ways of using the drug Amoxiclav®, for example, using higher doses of amoxicillin and/or prescribing amoxicillin and clavulanic acid in different ratios. The tablets should be taken orally before meals to reduce possible gastrointestinal disturbances and increase the absorption of amoxicillin/clavulanic acid. Adults and children weighing more than 40 kg: Prescribe 1 tablet of 375 mg 3 times a day or 1 tablet of 625 mg 2-3 times a day. The duration of treatment depends on the patient's response. Some infections (such as osteomyelitis) require a longer period of treatment. The maximum duration of therapy should not exceed 14 days. The maximum daily dose for a dosage of 375 mg is 750 mg amoxicillin/375 mg clavulanic acid, for a dosage of 625 mg is 1500 mg amoxicillin/375 mg clavulanic acid. Children weighing less than 40 kg should be prescribed the drug in a different dosage form (suspension). Elderly patients do not require dose adjustment. In case of renal failure, dose adjustment is made taking into account the maximum recommended level of amoxicillin. Dose adjustment is not required when prescribing the drug to patients with creatinine clearance (CrCl) more than 0.5 ml/sec. (30 ml/min.). Adults and children weighing more than 40 kg Creatinine clearance: 0.17-0.5 ml/sec. (10-30ml/min) 375 mg and 625 mg twice a day. Creatinine clearance: <0.17 ml/sec (10 ml/min) 375 mg and 625 mg once daily. Hemodialysis 375 mg and 625 mg every 24 hours and additionally at the end of dialysis 375 mg and 625 mg (as the concentration of amoxicillin and clavulanic acid in the serum decreases). In case of liver failure, it should be used with caution. Liver function should be checked regularly. Side effects When assessing the frequency of occurrence of various adverse reactions, the following gradations were used: “very often” – ³ 1/10, “often” – from ³ 1/100 to < 1/10, “infrequently” – from ³ 1/1000 to < 1 /100, “rare” – from ³ 1/10000 to < 1/1000, “very rare” – < 1/10000, unknown (available data are insufficient to make an assessment). Very often: - diarrhea Often: - candidiasis (skin and mucous membranes) - nausea3 - vomiting Uncommon: - dizziness, headache - indigestion - increased levels of AST and/or ALT5 - skin rash7, itching7, urticaria7 Rarely: - transient leukopenia ( including neutropenia), thrombocytopenia - erythema multiforme7 Unknown: - growth of non-susceptible organisms - transient agranulocytosis, hemolytic anemia, increased bleeding time and prothrombin time1 - angioedema10, anaphylaxis10, serum-like syndrome10, allergic vasculitis10 - transient hyperactivity, convulsions2 - antibiotic-associated colitis4 , black “villous” tongue, tooth discoloration11 - hepatitis6, cholestatic jaundice6 - Stevens-Johnson syndrome7, toxic epidermal necrolysis7, bullous exfoliative dermatitis7, acute generalized exanthematous pustulosis (AGEP)9 - interstitial nephritis - crystalluria8 1 see section Special instructions. 2 see section Special instructions. 3 Nausea is more common with higher oral doses. It is possible to reduce gastrointestinal reactions by taking amoxicillin/clavulanic acid at the beginning of meals. 4 Including pseudomembranous colitis and hemorrhagic colitis (see section Special instructions). 5 Moderate increases in AST and/or ALT levels have been noted in patients treated with beta-lactam antibiotics, but the significance of these findings is unknown. 6 These complications have been noted when using the drug in combination with other penicillins and cephalosporins (see section Special instructions). 7 If any hypersensitivity skin reaction occurs, treatment should be discontinued (see section Special instructions). 8 see section Special instructions. 9 see section Contraindications. 10 see section Special instructions. 11 Very rare cases of discoloration of the surface of teeth in children have been reported. Practicing good oral hygiene will help prevent this. Brushing your teeth removes the drug from your mouth. Contraindications - hypersensitivity to the active components of drugs from the penicillin group or any auxiliary component of the drug - a history of severe hypersensitivity reaction to other beta-lactam drugs (for example, cephalosporins, carbapenems or monobactams) - a history of cholestatic jaundice or other cases of liver failure (due to use of amoxicillin/clavulanic acid) - children under 12 years of age (weight less than 40 kg) Drug interactions Oral anticoagulants Oral anticoagulants and antibiotics of the penicillin group are widely used in practice without reports of interaction. However, the literature has noted an increase in the international normalized ratio in patients taking acenocoumarol or warfarin together with amoxicillin. If concomitant use of drugs is necessary, the prothrombin time or international normalized ratio should be carefully monitored when amoxicillin is instituted and discontinued. Moreover, changes in the dosage of oral anticoagulants may be required. Methotrexate Penicillin-type drugs may reduce the elimination of methotrexate, causing a potential increase in toxicity. Probenecid Concomitant use of probenecid is not recommended. Probenecid reduces the renal tubular secretion of amoxicillin. Concomitant use with Amoxiclav® may increase blood levels of amoxicillin, but not clavulanic acid. The simultaneous use of allopurinol and Amoxiclav® may increase the risk of allergic reactions. There are currently no data on the simultaneous use of allopurinol and Amoxiclav®. In patients taking mycophenolate mofetil, when used together with Amoxiclav®, the concentration of the active metabolite of mycophenolic acid when prescribed the initial dose is reduced by approximately 50%. The change in the initial dose concentration level may not correspond to the change in the total concentration of mycophenolic acid. Special instructions Before starting therapy with amoxicillin/clavulanic acid, it is necessary to carefully examine whether the patient has hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam substances. Serious and sometimes fatal (anaphylactic) hypersensitivity reactions have been reported in patients treated with penicillin. These reactions are more common in people with a penicillin hypersensitivity reaction and a history of atopy. If an allergic reaction to amoxicillin/clavulanic acid develops, discontinue therapy with this drug and switch to another alternative treatment. If the infection is resistant to amoxicillin, the use of amoxicillin/clavulanic acid instead of amoxicillin should be considered. If there is a high risk of pathogen resistance to beta-lactam antibiotics, Amoxiclav should not be used. The drug is not recommended for the treatment of penicillin-resistant S. pneumoniae. Patients with impaired renal function and taking a high dose of the drug may develop seizures. Amoxicillin/clavulanic acid should not be prescribed for infectious mononucleosis, as a morbilliform rash may occur (to amoxicillin). Concomitant use of allopurinol during treatment with amoxicillin may increase the likelihood of developing allergic skin reactions. There are currently no data on the simultaneous use of allopurinol and Amoxiclav®. Long-term use of the drug may cause excessive growth of insensitive microorganisms. The appearance at the beginning of treatment of generalized erythema with pustular rashes and fever may be a symptom of the development of acute generalized exanthematous pustulosis. If this reaction develops, you must stop using the drug Amoxiclav® and no longer use amoxicillin in the future. The drug should be prescribed with caution to patients with liver failure. Cases of the appearance of impaired liver function were registered mainly in men and elderly patients, quite rarely found in children who took the drug for a long period of time. Signs and symptoms usually develop during or immediately after the start of treatment, but in some cases they can manifest only a few weeks after the cessation of therapy. These symptoms are usually reversible. Complications from the liver can be expressed in severe form and in extremely rare cases to flow with fatal outcome. They almost always develop in patients with serious concomitant diseases or in patients taking other drugs that affect the liver. The development of antibiotic colitis is characteristic of any antibacterial drugs, including amoxicillin, and can vary by the degree of severity from moderate to life-threatening. Therefore, it is important to consider this diagnosis when prescribing the drug to patients suffering from diarrhea during or after the use of any antibiotics. In case of antibiotic colitis, the use of Amoxiclav® should immediately stop the use of the drug. After consulting a doctor, appropriate therapy must be prescribed. Preparations reducing peristalsis are contraindicated in this situation. With prolonged therapy, it is recommended to regularly evaluate the function of organs, including kidneys, liver and hematopoietic function. It is necessary to adjust the dose of oral anticoagulants to maintain the desired blood coagulation level. In patients with impaired renal function, dose adjustment is required depending on the severity of the disorders. In patients with reduced diuresis, crystalluria was very rarely observed, mainly during parenteral therapy. During treatment, the patient is recommended abundantly drinking to avoid the possible development of crystalluria. According to the received data, Amoxicillin settles in the catheter catheter (mainly with intravenous administration of large doses), in this case it is necessary to regularly monitor the patency of the catheter. During treatment using amoxicillin, enzymatic methods of glucose oxidase during analysis for glucose in the urine should be used, since false positive results are possible when using non -enzymatic methods. The presence of clavulanova acid in the drug can lead to non-specific binding of immunoglobulin G and albumin with erythrocyte membranes and the false and positive results of the Cumbs test. The data on positive results of the Bio-Rad Laboratories Platelia aspergillus EIA analysis were obtained in patients taking amoxicillin/acid acid, who subsequently turned out to be infected with Aspergillus infection, but there is no data on cross-andSpergillus polyphuranoses. Thus, the positive results of the tests of patients taking amoxicillin/acid -clavon acid should be interpreted with caution and confirmed by other diagnostic methods. Pregnancy of animal research does not indicate a direct or indirect harmful effect on pregnancy, the development of the embryo / fetus, childbirth or postnatal development. Currently, there is a limited amount of data on the use of amoxicillin/Acid Clavulanova during pregnancy in humans that have not revealed increased risk of congenital malformations. In a clinical study in women with a premature rupture of the fetal membrane, a causal relationship was recorded between preventive treatment using amoxicillin/ acid-acid and increased risk of necrotic enterocolitis in the innocent. It is not recommended to use the drug during pregnancy, use is possible only in case of extreme need for a doctor’s prescription. Lactation both active substances are released into breast milk (there is no data on the effect of clavulanova acid on breastfeeding). Therefore, during breastfeeding, symptoms such as diarrhea and fungal infections of the mucous membranes are possible, in these cases, breastfeeding should be stopped. Amoxicillin/ clavulanic acid is allowed to be used during breastfeeding only after evaluating the benefits/ risk of the attending physician. Features of the effect of the drug on the ability to drive a vehicle or potentially dangerous research mechanisms to identify effects affecting the ability to drive a car and technique were not carried out. Nevertheless, the amoxiclav can cause undesirable reactions such as allergic reactions, convulsions that can affect the ability to control the car and moving mechanisms. An overdose symptoms: gastrointestinal symptoms and disorders of the water-electrolyte balance are possible. Amoxicillin crystalluria in some cases leads to renal failure. In patients with impaired renal function or in patients taking high doses of the drug, seizures are possible. Treatment: symptomatic treatment, taking into account water/electrolyte balance. Amoxicillin/ acid -acid can be removed from the body using hemodialysis. The form of release and packaging of 15 tablets into a bottle of brown glass with a twisting aluminum cover with the control of the first opening. 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 at a temperature not exceeding 25 °C. Keep out of the reach of children! The shelf life of 2 years is not used after the expiration of the shelf life indicated on the package. Conditions of vacation from pharmacies according to the recipe manufacturer/ Packer Lecta Pharmasyutikals D.D., Slovenia Address: Perzonali 47, Si - 2391 Prevalje, Slovenia Owner of the Lectur Lecture Farmasyutikals D.D., Slovenia Address: Verovskova, 57, 1526 Ljubljana, Sloveneena, Sloveneena IA address Organizations receiving in the territory of the Republic of Kazakhstan claims from consumers on the quality of products (goods) representation of Sandoz Farmasyutikals JSC D.D. in the Republic of Kazakhstan, Almaty, st. Lugansk 96, phone number, fax e-mail
Amoxicillin+Clavulanic acid
Before starting treatment with Amoxicillin + Clavulanic acid, 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 Amoxicillin + Clavulanic acid should be discontinued and appropriate alternative therapy should be initiated.
In case of serious anaphylactic reactions, the patient should be given epinephrine immediately. Oxygen therapy, intravenous corticosteroids, and airway management, including intubation, may also be required.
If infectious mononucleosis is suspected, Amoxicillin + Clavulanic acid should not be used, since in patients with this disease, amoxicillin can cause a measles-like skin rash, which makes diagnosing the disease difficult.
Long-term treatment with Amoxicillin + Clavulanic acid may lead to excessive proliferation of insensitive microorganisms.
In general, the drug Amoxicillin + Clavulanic acid is well tolerated and has the low toxicity characteristic of all penicillins. During long-term therapy with Amoxicillin + Clavulanic acid, it is recommended to periodically evaluate renal, liver and hematopoietic function. 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.
In patients receiving a combination of amoxicillin and clavulanic acid together with indirect (oral) anticoagulants, an increase in prothrombin time (increase in INR) 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 impaired renal function, the dose of Amoxicillin + Clavulanic acid should be reduced according to the degree of impairment (see section "Dosage and Administration" - Patients with impaired renal function).
In patients with reduced diuresis, crystalluria very rarely occurs, mainly during parenteral therapy. 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 (see section "Overdose").
When taking the drug Amoxicillin + Clavulanic acid orally, a high level of amoxicillin in the urine is observed, 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 the urine.
Clavulanic acid may cause nonspecific binding of immunoglobulin G and albumin to red blood cell membranes, leading to false-positive Coombs test results.
Drug abuse and dependence
There was no drug dependence, addiction, or euphoric reactions associated with the use of the drug Amoxicillin + Clavulanic acid.
Amoxiclav tablet p/o film 875mg+125mg 14 pcs
Pharmacological group:
Semi-synthetic antibiotic penicillin + beta-lactamase inhibitor.
Pharmacodynamics:
Mechanism of action
Amoxicillin is a semisynthetic broad-spectrum antibiotic that is active against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by beta-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce this enzyme. Clavulanic acid is a beta-lactamase inhibitor, structurally related to penicillins, and has the ability to inactivate a wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is sufficiently effective against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against type I chromosomal beta-lactamases, which are not inhibited by clavulanic acid.
The presence of clavulanic acid in the drug protects amoxicillin from destruction by enzymes - beta-lactamases, which expands the antibacterial spectrum of amoxicillin.
Below is the activity of the combination of amoxicillin and clavulanic acid in vitro.
Gram-positive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, other beta-hemolytic steptococci1,2, Staphylococcus aureus (methicillin-sensitive)1, Staphylococcus saprophyticus (methicillin-sensitive), coagulase-negative staphylococci (sensitive to methicillin).
Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.
Other: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.
Gram-positive anaerobes: Leptospira icterohaemorrhagiae, Treponema pallidum. Gram-positive anaerobes: species of the genus Clostridium, Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, species of the genus Peptostreptococcus.
Gram-negative anaerobes: Bacteroides fragilis, species of the genus Bacteroides, species of the genus Capnocytophaga, Eikenella corrodens, Fusobacterium nucleatum, species of the genus Fusobacterium, species of the genus Porphyromonas, species of the genus Prevotella.
Bacteria for which acquired resistance to the combination of amoxicillin and clavulanic acid is likely
Gram-negative aerobes: Escherichia сoli1, Klebsiella oxytoca, Klebsiella pneumoniae, species of the genus Klebsiella, Proteus mirabilis, Proteus vulgaris, species of the genus Proteus, species of the genus Salmonella, species of the genus Shigella.
Gram-positive aerobes: species of the genus Corynebacterium, Enterococcus faecium. Streptococcus pneumoniae1,2, streptococci of the Viridans group.
Bacteria that are naturally resistant to the combination of amoxicillin and clavulanic acid
Gram-negative aerobes: species of the genus Acinetobacter, Citrobacter freundii, species of the genus Enterobacter, Hafnia alvei, Legionella pneumophila, Morganella morganii, species of the genus Providencia, species of the genus Pseudomonas, species of the genus Serratia, Stenotrophomonas maltophilia, Yersinia enterocolitica Others: Chlamydia pneumoniae, Chlamydia psittaci, species of the genus Chlamydia, Coxiella burnetii, species of the genus Mycoplasma 1 for these bacteria, the clinical effectiveness of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies. 2 strains of these types of bacteria do not produce beta-lactamases. Sensitivity during amoxicillin monotherapy suggests similar sensitivity to the combination of amoxicillin and clavulanic acid.
Pharmacokinetics:
Suction
The active ingredients of the drug are quickly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of active ingredients is optimal when the drug is used with food.
Metabolism
About 10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic acid). Clavulanic acid in the human body undergoes intensive metabolism with the formation of 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxybutan-2-one and is excreted by the kidneys, through the gastrointestinal tract, and also with exhaled air in the form of carbon dioxide.
Distribution
As with intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are found in various tissues and interstitial fluid (gallbladder, abdominal tissue, skin, adipose and muscle tissue, synovial and peritoneal fluids, bile, purulent discharge) .
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 in the blood plasma is bound to plasma proteins. The volume of distribution is approximately 0.3-0.4 L/kg for amoxicillin and approximately 0.2 L/kg for clavulanic acid.
Amoxicillin and clavulanic acid do not penetrate the blood-brain barrier when the meninges are not inflamed. Amoxicillin (like most penicillins) is excreted in breast milk.
Trace amounts of clavulanic acid may also be found in breast milk. With the exception of the possibility of sensitization, diarrhea and candidiasis of the oral mucosa, there are no other known negative effects of amoxicillin and clavulanic acid on the health of breastfed infants. Animal reproductive studies have shown that amoxicillin and clavulanic acid cross the placental barrier. However, no negative effects on the fetus were detected.
Removal
Amoxicillin is eliminated primarily by the kidneys, while clavulanic acid is eliminated through both renal and extrarenal mechanisms. After a single oral dose of 875 mg/125 mg or 500 mg/125 mg, approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted unchanged by the kidneys during the first 6 hours.
The average half-life (T1/2) of amoxicillin/clavulanic acid is approximately 1 hour, and the average total clearance is approximately 25 L/h in healthy patients. In various studies, it was found that renal excretion of amoxicillin within 24 hours is approximately 50-85%, clavulanic acid - 27-60%. The largest amount of clavulanic acid is excreted during the first 2 hours after administration. The pharmacokinetics of amoxicillin/clavulanic acid does not depend on the gender of the patient.
Patients with impaired renal function
The total 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, because Most amoxicillin is excreted by the kidneys. Doses of the drug for renal failure should be selected taking into account the undesirability of amoxicillin accumulation while maintaining normal levels of clavulanic acid.
Patients with liver dysfunction
In patients with impaired liver function, the drug is used with caution; continuous monitoring of liver function is necessary.
Both components are removed by hemodialysis and minor amounts by peritoneal dialysis.
Dosages and release forms of amoxiclav
Amoxiclav can be prescribed in tablet form, as well as in powder form for the preparation of a suspension or injection solution.
- Amoxiclav tablets are available in 250/125 mg, 500/125 mg and 875/125 mg - in these dosages, the first digit is the content of amoxicillin, and the second is clavulonic acid;
- Powders for preparing the “amoxiclav” suspension (taken orally) are available in 125 mg + 31.25 mg/5 ml, 250 mg + 62.5 mg/5 ml and 400 mg + 57 mg/5 ml;
- Powders for preparing injections “amoxiclav” are available in 500/100 mg, 1000/200 mg.
You can also write out a prescription for augmentin and flemoklav in Latin, these are analogues of amoxiclav.
