Gastrointestinal disorders and water-electrolyte balance disorders may occur.
Symptoms: there may be symptoms from the gastrointestinal tract and violations of the water-electrolyte balance. Amoxicillin crystalluria is described, which in some cases led to the development of renal failure (see "Special instructions").
Seizures may occur in patients with impaired renal function, as well as in those who receive high doses of the drug.
Treatment: symptoms from the gastrointestinal tract-symptomatic therapy, paying special attention to the normalization of the water-electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis. The results of a prospective study, which was conducted with 51 children in a toxicology center, showed that the administration of amoxicillin at a dose of less than 250 mg / kg did not lead to significant clinical symptoms and did not require gastric lavage.
hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins) in the anamnesis,
previous episodes of jaundice or impaired liver function when using a combination of amoxicillin with clavulanic acid in the anamnesis,
children under 3 months of age,
impaired renal function (Creatinine Cl <30 ml / min),
phenylketonuria.
With caution: the drug Augmentin® EC should be used with caution in patients with impaired liver function.
Simultaneous use of the drug Augmentin® The EU and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of the drug Augmentin® EC and probenecid can lead to an increase and persistence in the blood concentration of amoxicillin, but not clavulanic acid.
Concomitant use of allopurinol and amoxicillin may increase the risk of skin allergic reactions. Currently, there is no data in the literature on the simultaneous use of a combination of amoxicillin with clavulanic acid and allopurinol.
Penicillins are able to slow the elimination of methotrexate from the body by inhibiting its tubular secretion, so the simultaneous use of the drug Augmentin® EC and methotrexate may increase the toxicity of methotrexate.
Like other antibacterial drugs, the drug Augmentin® EC can affect the intestinal microflora, leading to a decrease in the absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives.
The literature describes rare cases of increased INR in patients with the combined use of acenocumarol or warfarin and amoxicillin. If necessary, simultaneous administration of the drug Augmentin® Patients with anticoagulants PV or INR should be carefully monitored when prescribing or discontinuing Augmentin® For example, you may need to adjust the dose of anticoagulants for oral administration.
Powder: almost white in color with a characteristic strawberry smell. When diluted with water, a suspension of almost white color is formed.
The adverse events presented below are listed depending on the anatomical and physiological classification and frequency of occurrence. The frequency of occurrence is defined as follows: very often - ≥1/10, often - ≥1/100 and <1/10, not often - ≥1/1000 and <1/100, rarely - ≥1/10000 and <1/1000, very rarely - <1/10000, including individual cases.
Frequency categories were formed based on clinical trials of the drug and post-registration follow-up.
Frequency of occurrence of adverse events
Infectious and parasitic diseases: often-candidiasis of the skin and mucous membranes.
Disorders of the blood and lymphatic system: rarely-reversible leukopenia (including neutropenia) and reversible thrombocytopenia, very rarely-reversible agranulocytosis and reversible hemolytic anemia, prolongation of PV and bleeding time, anemia, eosinophilia, thrombocytosis.
Disorders of the immune system: very rarely-angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.
Disorders of the nervous system: infrequently-dizziness, headache, very rarely-reversible hyperactivity, seizures (seizures can be observed in patients with impaired renal function, as well as in those who receive high doses of the drug), insomnia, agitation, anxiety, behavior changes.
Disorders of the gastrointestinal tract: often-diarrhea, nausea, vomiting. Nausea is more common with high-dose oral administration. If gastrointestinal disorders are confirmed, they can be eliminated if you take the drug at the beginning of a meal, infrequently-digestive disorders, very rarely-antibiotic-associated colitis induced by taking antibiotics (including pseudomembranous colitis and hemorrhagic colitis), black "hairy" tongue. In children, very rarely there was a change in the color of the surface layer of tooth enamel. Oral care helps to prevent discoloration of the tooth enamel, as it is enough to brush your teeth.
Disorders of the liver and biliary tract: rarely, a moderate increase in the activity of AST and/or ALT. This phenomenon is observed in patients receiving therapy with beta-lactam antibiotics, but its clinical significance is unknown, very rarely — hepatitis and cholestatic jaundice (observed with concomitant therapy with other penicillins and cephalosporins), an increase in the concentration of bilirubin and alkaline phosphatase. 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 rarely observed in children. The listed signs and symptoms usually occur during or immediately after the end of therapy, but in some cases they may not appear for several weeks after the end of therapy. Adverse events are usually reversible. Adverse events from the liver can be severe, in extremely rare cases, there have been reports of fatal outcomes. In almost all cases, these were individuals with serious comorbidities or individuals receiving potentially hepatotoxic drugs at the same time
Disorders of the skin and subcutaneous tissues: infrequently-rash, itching, urticaria, rarely-erythema multiforme, very rarely — Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis. In case of skin allergic reactions, treatment with Augmentin® The EU needs to stop.
Disorders of the kidneys and urinary tract: very rarely-interstitial nephritis, crystalluria (see "Overdose"), hematuria.
According to the recipe.
Before starting treatment with Augmentin® A detailed history of previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens should be collected by the EC.
Serious and sometimes fatal hypersensitivity reactions (including anaphylactic reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. In the event of an allergic reaction, it is necessary to stop treatment with Augmentin® EC. In case of serious hypersensitivity reactions, epinephrine should be administered immediately. Oxygen therapy, intravenous administration of corticosteroids, and airway patency, including intubation, may also be required.
It is not recommended to prescribe the drug Augmentin® EU if infectious mononucleosis is suspected, because in patients with this disease, amoxicillin can cause a skin rash, which makes it difficult to diagnose the disease.
Long-term treatment with Augmentin® EC sometimes leads to excessive reproduction of insensitive microorganisms.
In general, the drug Augmentin® EC is well tolerated and has the low toxicity characteristic of all penicillins. During long-term therapy with Augmentin® The EC is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis.
In order to reduce the risk of side effects from the gastrointestinal tract, you should take the drug at the beginning of a meal.
In patients treated with a combination of amoxicillin and clavulanic acid together with indirect (oral) anticoagulants, an increase in PV (an increase in INR) was rarely reported. When co-prescribing indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, it is necessary to monitor the appropriate parameters. To maintain the desired effect of oral anticoagulants, it may be necessary to adjust their dose.
In patients with reduced diuresis, the development of crystalluria has been reported in very rare cases, mainly with parenteral use of the drug. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain adequate diuresis to reduce the likelihood of amoxicillin crystals forming.
Taking the drug Augmentin® Ingestion leads to a high content of amoxicillin in the urine, which can lead to false positive results when determining glucose in the urine (for example, the Benedict test, the Fehling test). In this case, it is recommended to use a glucose oxidant method for determining the concentration of glucose in the urine.
Oral care helps to prevent discoloration of the teeth, as it is enough to brush your teeth.
Abuse and drug addiction
There was no drug dependence, addiction, or euphoric reactions associated with the use of the drug Augmentin® EU.
Influence on the ability to drive vehicles, mechanisms. Since the drug can cause dizziness, it is necessary to warn patients about precautions when driving a vehicle or working with moving mechanisms.
The drug Augmentin® EC is used for the short-term treatment of infections caused by sensitive microorganisms in children.
upper respiratory tract infections: recurrent or persistent acute otitis media caused by Streptococcus pneumoniae (minimum inhibitory concentration <4 mcg / ml), Haemophilus influenzae1 and Moraxella catarrhalis1,
tonsillo-pharyngitis and sinusitis, usually caused by Streptococcus pneumoniae, Haemophilus influenzae1, Moraxella catarrhalis1 and Streptococcus pyogenes,
lower respiratory tract infections: lobar pneumonia and bronchopneumonia caused by Streptococcus pneumoniae, Haemophilus influenzae1, Moraxella catarrhalis1,
skin and soft tissue infections, usually caused by Staphylococcus aureus1 and Streptococcus pyogenes.
1 Some strains of these bacterial species produce beta-lactamases, which makes them insensitive to amoxicillin monotherapy (see also "Pharmacodynamics").
Infections caused by amoxicillin-sensitive microorganisms can be treated with Augmentin® EU, since amoxicillin is one of its active ingredients. The drug Augmentin® EC is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as beta-lactamase-producing microorganisms sensitive to the combination of amoxicillin with clavulanic acid. The sensitivity of bacteria to the combination of amoxicillin with clavulanic acid varies by region and over time. Where possible, local sensitivity data should be taken into account. If necessary, microbiological samples should be collected and analyzed for bacteriological sensitivity.
Mechanism of action
Amoxicillin is a broad-spectrum semi-synthetic antibiotic with activity 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, a beta-lactamase inhibitor structurally related to penicillins, has the ability to inactivate a wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid has sufficient efficacy against plasmid beta-lactamases, which most often cause bacterial resistance, and is less effective against type 1 chromosomal beta-lactamases, which are not inhibited by clavulanic acid. The presence of clavulanic acid in the preparation Augmentin® The EC protects amoxicillin from destruction by beta — lactamase enzymes, which makes it possible to expand the antibacterial spectrum of amoxicillin.
Below is the activity of the combination of amoxicillin with clavulanic acid in vitro.
Bacteria usually sensitive to the combination of amoxicillin with clavulanic acid
Gram-positive airbags — Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pneumoniae1,2, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, Group streptococci Viridans Streptococcus spp. (other beta-hemolytic streptococci)1, 2, Staphylococcus aureus (sensitive to methicillin)1, Staphylococcus saprophyticus (sensitive to methicillin), 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 — Clostridium spp., Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, Peptostreptococcus spp.
Gram-negative anaerobes — Bacteroides fragilis, Bacteroides spp., Capnocytophaga spp., Eikenella corrodens, Fusobacterium nucleatum, Fusobacterium spp., Porphyromonas spp., Prevotella spp.
Bacteria that are likely to have acquired resistance to the combination of amoxicillin with clavulanic acid
Gram-negative aerobes — Escherichia coli1, Klebsiella oxytoca, Klebsiella pneumoniae1, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Proteus spp., Salmonella spp., Shigella spp.
Gram-positive airbags — Corynebacterium spp., Enterococcus faecium.
Bacteria that are naturally resistant to the combination of amoxicillin and clavulanic acid
Gram-negative aerobes — Acinetobacter spp. Citrobacter freundii, Enterobacter spp., Hafnia alvei, Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas spp., Serratia spp., Stenotrophomonas maltophilia, Yersinia enterocolitica.
Other — Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia spp., Coxiella burnetii, Mycoplasma spp.
1For these bacteria, the clinical efficacy of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies,
2strains of these types of bacteria do not produce beta-lactamases. The sensitivity of amoxicillin monotherapy suggests a similar sensitivity to the combination of amoxicillin with clavulanic acid.
Suction
Active ingredients of the drug Augmentin® EC — amoxicillin and clavulanic acid-are rapidly and completely absorbed from the gastrointestinal tract after oral administration. The absorption of active substances is optimal in the case of taking the drug Augmentin® EU along with the meal.
Below are the pharmacokinetic parameters of amoxicillin and clavulanic acid after administration at a dose of 45 mg / kg every 12 hours in patients under 12 years of age.
Table 2
Average values of pharmacokinetic parameters
| Medication | Cmax, mg/l | Tmax, h | AUC, mg * h/ml | T1/2, h |
| Amoxicillin | ||||
| Augmentin® EU | 15,7 | 2 | 59,8 | 1,4 |
| Clavulanic acid | ||||
| Augmentin® EU | 1,7 | 1,1 | 4 | 1,1 |
Distribution
As with the 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 (in the gallbladder, abdominal tissues, skin, adipose and muscle tissues, 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 binds to plasma proteins. In animal studies, no accumulation of the components of the drug Augmentin was found® The EU in any body.
Amoxicillin, like most penicillins, can be detected in breast milk. Trace amounts of clavulanic acid may also be found in breast milk. With the exception of the possibility of diarrhea and candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of infants fed with breast milk are known. Studies of reproductive function in animals have shown that amoxicillin and clavulanic acid penetrate the placental barrier. However, there was no negative effect on the fetus.
Metabolism
10-25% of the initial dose of amoxicillin is excreted by the kidneys as an inactive metabolite (penicillic acid). Clavulanic acid undergoes intensive metabolism to 2,5-dihydro-4 - (2-hydroxyethyl) - 5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butane-2-one and is excreted by the kidneys, through the gastrointestinal tract, and with exhaled air in the form of carbon dioxide.
Output
Like other penicillins, amoxicillin is mainly excreted by the kidneys, while clavulanic acid is excreted by both the renal and extrarenal mechanisms. Approximately 60-70% of amoxicillin and about 40-65 % of clavulanic acid are excreted unchanged by the kidneys in the first 6 hours after administration of 1 table 250/125 mg or 1 table 500/125 mg. Simultaneous administration of probenecid slows down the removal of amoxicillin but not of clavulanic acid (see "Interaction").
At a temperature not exceeding 25 °C. The prepared suspension is stored in the refrigerator at a temperature of 2-8 oC in a tightly closed bottle.
Keep out of reach of children.
Shelf life of the drug Augmentin® EU2 года. Приготовленной суспензии — 10 дней.Do not use after the expiration date indicated on the package.
| Powder for preparation of suspension for oral administration | 5 ml |
| the composition is shown in the table |
| Name of components | Quantity (mg / 5 ml) |
| Active ingredients: | |
| Amoxicillin Trihydrate1 (in terms of amoxicillin) | 697,65 (600) |
| Potassium Clavulanate2 (in terms of clavulanic acid) | 52,31 (42,9) |
| Excipients: | |
| Xanthan Gum | 3,26 |
| Aspartame | 13,6 |
| Silicon Dioxide | 153,29 |
| Colloidal silicon dioxide | 38,08 |
| Sodium carmellose | 32,64 |
| Strawberry flavor | 28,29 |
1in the production of the drug amoxicillin, trihydrate is laid with an 8.8% excess.
2in the production of the potassium preparation, clavulanate is laid with an 8% excess at the initial stage of mixing the active components and with 8.8% - at the stage of mixing all the components of the suspension.
Release formPowder for preparation of suspension for oral administration, 600 mg 42.9 mg in 5 ml. 12,85 g powder (for preparing 50 ml of the prepared suspension) or 23,13 g powder (for preparing 100 ml of the prepared suspension) in vial glass, closed screw-on aluminum lid with a strip of PVC with a tamper-evident. 1 fl together with a measuring spoon is placed in a cardboard pack.
In studies of reproductive function in animals, oral and parenteral administration of the drug Augmentin® it did not cause teratogenic effects. In a single study in women with premature rupture of the fetal membranes, it was found that preventive therapy with the drug may be associated with an increased risk of necrotizing enterocolitis in newborns. Like all medications, Augmentin® EC is not recommended for use during pregnancy, except in cases where the expected benefit to the mother exceeds the potential risk to the fetus.
The drug Augmentin® EC can be used during breastfeeding. With the exception of the possibility of diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active substances of this drug into breast milk, no other adverse effects were observed in infants who were breastfed. In the event of adverse effects in infants who are breastfed, it is necessary to stop breastfeeding.
Inside. Dosage of the drug Augmentin® EC is carried out according to the age of the child, the dose is calculated in mg/kg/day or in ml of the finished suspension. The dose is calculated based on amoxicillin and clavulanic acid, except in cases where the dosage is carried out for each component separately. To minimize potential adverse events from the gastrointestinal tract and optimize absorption, the drug should be taken orally at the beginning of a meal.
Treatment should not be continued for more than 14 days without reviewing the clinical situation. If necessary, it is possible to conduct step-by-step therapy (at the beginning — intravenous administration of the drug Augmentin® (powder for the preparation of a solution for intravenous administration), followed by the transition to oral administration).
Children
The drug Augmentin® The EU is recommended for children aged 3 months and older. No experience with the use of the drug Augmentin® EC in children under 3 months of age. The recommended daily dose is 90 mg of amoxicillin and 6.4 mg of clavulanic acid per 1 kg of body weight, divided into 2 doses every 12 hours, for 10 days.
For patients with a body weight above 40 kg, other dosage forms of the drug Augmentin are recommended®. According to the content of clavulanic acid, the drug Augmentin® EC differs from other suspensions containing amoxicillin and clavulanic acid. The drug Augmentin® The EC contains 600 mg of amoxicillin and 42.9 mg of clavulanic acid in 5 ml of reduced suspension, while the preparations containing 200 and 400 mg of amoxicillin in 5 ml of suspension contain 28.5 and 57 mg of clavulanic acid in 5 ml of suspension, respectively. Preparations in the form of suspensions with a dosage of 200 mg of amoxicillin in 5 ml, 400 mg of amoxicillin in 5 ml and the drug Augmentin® The EU is not interchangeable.
Special patient groups
Patients with impaired renal function. No dosage adjustment is required for creatinine Cl ≥30 ml/min. The drug is not recommended for use with creatinine Cl <30 ml/min.
Patients with impaired liver function. Treatment is carried out with caution, liver function is regularly monitored. There is insufficient data to change the recommended dosage regimen in these patients.
Method of preparing a suspension of
The suspension is prepared immediately before the first application. In the powder, add approximately 2/3 of the volume of boiled water indicated in the table below, cooled to room temperature, then close the bottle with a lid and shake until the powder is completely diluted, let the bottle stand for 5 minutes to ensure complete dilution. Then add water to the label on the bottle and shake the bottle again. The bottle should be shaken well before each use. For accurate dosage of the drug, you should use a measuring spoon, which should be well washed with water after each use. After dilution, the suspension should be stored for no more than 10 days in the refrigerator, but not frozen
Table 3
Approximate volume of water for suspension preparation
| Volume of the bottle, ml | Volume of water for suspension preparation, ml |
| 50 | 50 |
| 100 | 90 |
J01CR02 Amoxicillin in combination with a beta-lactamase inhibitor
