Augmentin EC powder for suspension 600 mg + 42.9 mg/5 ml, 100 ml
Registration Certificate Holder
GlaxoSmithKline Trading (Russia)
Dosage form
Medicine - Augmentin® ES (Augmentin® ES)
Description
Powder for suspension for oral administration
almost white in color, with a characteristic strawberry smell; When diluted with water, an almost white suspension is formed.
5 ml ready suspension 1
amoxicillin trihydrate2 697.65 mg, which corresponds to the content of amoxicillin 600 mg potassium clavulanate3 52.31 mg, which corresponds to the content of clavulanic acid 42.9 mg
Excipients
: xanthan gum - 3 mg, aspartame - 12.5 mg, colloidal silicon dioxide - 35 mg, sodium carmellose - 30 mg, strawberry flavor - 26 mg, silicon dioxide4 - up to 1009.96 mg.
12.85 g (50 ml of ready-made suspension) - glass bottles (1) complete with a measuring spoon - cardboard packs. 23.13 g (100 ml of ready-made suspension) - glass bottles (1) complete with a measuring spoon - cardboard packs.
1 The quantities of all substances are indicated without excess. During the production of the drug, the amount of excipients is added with an 8.8% excess, which is: xanthan gum - 3.26 mg, aspartame - 13.6 mg, colloidal silicon dioxide - 38.08 mg, carmellose sodium - 32.64 mg, strawberry flavor - 28.29 mg, silicon dioxide - up to 1098.84 mg. The total mass of dry powder, including excess, is 1098.84 mg. 2 in the production of amoxicillin trihydrate is supplied with an 8.8% excess, which is 759.04 mg (in terms of amoxicillin 652.8 mg). The amount of amoxicillin trihydrate varies depending on the purity of the substance. 3 in the production of potassium clavulanate is added with an 8% excess at the initial stage of mixing the active components and with 8.8% at the stage of mixing all components, which is 61.48 mg (in terms of clavulanic acid - 50.41 mg). The amount of potassium clavulanate varies depending on the purity of the substance. 4 the amount of silicon dioxide is adjusted taking into account changes in the amounts of amoxicillin trihydrate and a mixture of potassium clavulanate and silicon dioxide.
Indications
Treatment of infections caused by sensitive microorganisms in children:
- ENT infections (recurrent or persistent acute otitis media caused by Streptococcus pneumoniae (MIC ≤4 μg/ml), Haemophilus influenzae* and Moraxella catarrhalis*);
- tonsillopharyngitis and sinusitis, usually caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis* and Streptococcus pyogenes;
- lower respiratory tract infections (lobar pneumonia and bronchopneumonia) caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis*;
- infections of the skin and soft tissues, usually caused by Staphylococcus aureus* and Streptococcus pyogenes.
* Some strains of these bacterial species produce β-lactamases, which makes them insensitive to amoxicillin monotherapy.
Infections caused by microorganisms sensitive to amoxicillin can be treated with Augmentin® EC, 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 microorganisms producing β-lactamase, sensitive to the combination of amoxicillin with clavulanic acid.
The sensitivity of bacteria to the combination of amoxicillin and clavulanic acid varies regionally and over time. Where possible, local sensitivity data should be taken into account. If necessary, microbiological samples should be collected and bacteriological susceptibility testing should be carried out.
Contraindications for use
- history of hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins);
- history of previous episodes of jaundice or impaired liver function when using a combination of amoxicillin and clavulanic acid;
- children up to 3 months;
- impaired renal function (creatinine clearance less than 30 ml/min);
- phenylketonuria.
Carefully:
liver dysfunction.
pharmachologic effect
Mechanism of action
Amoxicillin
is a semisynthetic broad-spectrum antibiotic with activity against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by β-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce this enzyme.
Clavulanic acid
- a β-lactamase inhibitor, structurally related to penicillins, has the ability to inactivate a wide range of β-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is quite effective against plasmid β-lactamases, which most often determine bacterial resistance, and is less effective against type 1 chromosomal β-lactamases, which are not inhibited by clavulanic acid.
The presence of clavulanic acid in Augmentin® EC protects amoxicillin from destruction by enzymes - β-lactamases, which allows expanding the antibacterial spectrum of amoxicillin.
Below is the activity of the combination of amoxicillin and clavulanic acid in vitro.
Bacteria usually susceptible to the combination of amoxicillin and clavulanic acid
Gram-positive aerobes:
Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pneumoniae1,2, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, Viridans group Streptococcus2, Streptococcus spp. (other beta-hemolytic streptococci)1,2, Staphylococcus aureus (methicillin sensitive)1, Staphylococcus saprophyticus (methicillin sensitive), Staphylococcus spp. (coagulase-negative, methicillin-sensitive).
Gram-negative aerobes:
Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.
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.
Other:
Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.
Bacteria for which acquired resistance to the combination of amoxicillin and clavulanic acid is likely
Gram-negative aerobes:
Escherichia coli1, Klebsiella oxytoca, Klebsiella pneumoniae1, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Proteus spp., Salmonella spp., Shigella spp.
Gram-positive aerobes:
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 burnetti, Mycoplasma spp.
1 For these types of microorganisms, the clinical effectiveness of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.
2 Strains of these bacterial species do not produce β-lactamases. Sensitivity during amoxicillin monotherapy suggests similar sensitivity to the combination of amoxicillin and clavulanic acid.
Drug interactions
The simultaneous use of Augmentin® EC and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of Augmentin® EC and probenecid may 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 allergic skin reactions. Currently, there is no data in the literature on the simultaneous use of a combination of amoxicillin with clavulanic acid and allopurinol.
Penicillins can slow down the elimination of methotrexate from the body by inhibiting its tubular secretion, therefore, the simultaneous use of Augmentin® EC and methotrexate may increase the toxicity of methotrexate.
Like other antibacterial drugs, Augmentin® EC may 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 MHO in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe Augmentin® EC with anticoagulants, prothrombin time or MHO should be carefully monitored when prescribing or discontinuing Augmentin® EC; dose adjustment of anticoagulants for oral administration may be required.
In patients receiving mycophenolate mofetil, after starting the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite, mycophenolic acid, was observed before taking the next dose of the drug by approximately 50%. Changes in this concentration may not accurately reflect overall changes in mycophenolic acid exposure.
Dosage regimen
Dosing of the drug Augmentin® EC is carried out in accordance with the age of the child, the dose is calculated in mg per kg per day or in ml of the finished suspension. Dosage calculations are based on amoxicillin and clavulanic acid, except in cases where dosing 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 carry out stepwise therapy (initially, intravenous administration of the drug Augmentin® in dosage form - powder for the preparation of a solution for intravenous administration, followed by a transition to the drug Augmentin® in dosage forms for oral administration).
Children
Augmentin® EC is recommended for children aged 3 months and older
.
There is no experience with the use of Augmentin® EC in children under 3 months
.
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 weighing more than 40 kg
Other dosage forms of Augmentin® are recommended.
In terms of the content of clavulanic acid, Augmentin® EC differs from other suspensions containing amoxicillin and clavulanic acid. The drug Augmentin® EC contains 600 mg of amoxicillin and 42.9 mg of clavulanic acid in 5 ml of reconstituted suspension, while preparations containing 200 mg and 400 mg of amoxicillin in 5 ml of suspension contain, respectively, 28.5 mg and 57 mg of clavulanic acid in 5 ml of suspension . 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® EC are not interchangeable.
Special patient groups
No dosage adjustment required for CC ≥30 ml/min
.
The drug is contraindicated for use with CC <30 ml/min
.
In patients with impaired liver function
treatment is carried out with caution; regularly monitor liver function. There is insufficient data to change the recommended dosage regimen in these patients.
Method of preparing the suspension
The suspension is prepared immediately before the first use.
Add approximately 2/3 of the volume of boiled water, cooled to room temperature, to the bottle with the powder, 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 up to the mark on the bottle and shake the bottle again.
The bottle should be shaken well before each use.
To accurately dose the drug, use a measuring spoon, which must be rinsed well with water after each use. After dilution, the suspension should be stored for no more than 10 days in the refrigerator, but not frozen. Approximate volume of water for preparing the suspension
Volume of the bottle Volume of water for preparing the suspension
50 ml50 ml100 ml90 ml
Overdose
Symptoms:
Gastrointestinal symptoms and water-electrolyte imbalance may occur.
Amoxicillin crystalluria has been described, in some cases leading to the development of renal failure. Convulsions may occur in patients with impaired renal function, as well as in those receiving high doses of the drug. Treatment:
symptoms from the gastrointestinal tract - symptomatic therapy, paying special attention to the normalization of water and electrolyte balance. In case of overdose, amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.
The results of a prospective study that was conducted in 51 children at a poison control center showed that amoxicillin administered at a dose of less than 250 mg/kg did not lead to significant clinical symptoms and did not require gastric lavage.
Side effect
The adverse reactions presented below are listed according to the damage to organs and organ systems and the frequency of occurrence. The frequency of occurrence is determined as follows: very often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10,000, < 1/1000), very rare (<1/10,000, including isolated reports).
Frequency categories were formed based on clinical studies of the drug and post-registration surveillance.
Infectious and parasitic diseases:
often - candidiasis of the skin and mucous membranes.
From the hematopoietic system:
rarely - reversible leukopenia (including neutropenia) and reversible thrombocytopenia; very rarely - reversible agranulocytosis and reversible hemolytic anemia, prolongation of prothrombin time and bleeding time, anemia, eosinophilia, thrombocytosis.
From the immune system:
very rarely - angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.
From the nervous system:
infrequently - dizziness, headache; very rarely - reversible hyperactivity, convulsions (convulsions can be observed in patients with impaired renal function, as well as in those receiving high doses of the drug), insomnia, agitation, anxiety, behavior changes.
From the digestive system:
often - diarrhea, nausea, vomiting (nausea is more often observed when taking high doses orally. If gastrointestinal disorders are confirmed, they can be eliminated if the drug is taken at the beginning of meals); infrequently - digestive disorders; very rarely - antibiotic-associated colitis induced by taking antibiotics (including pseudomembranous colitis and hemorrhagic colitis, black “hairy” tongue. In children, discoloration of the surface layer of tooth enamel was very rarely observed.
From the liver and biliary tract:
uncommon - moderate increase in AST and/or ALT activity (observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown); very rarely - hepatitis and cholestatic jaundice (these reactions were observed during therapy with other penicillins and cephalosporins), increased concentrations of bilirubin and alkaline phosphatase. Adverse reactions from the liver were observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse reactions are very rarely observed in children.
The listed signs and symptoms usually occur during or immediately after completion of therapy, but in some cases they may not appear for several weeks after completion of therapy. Adverse reactions are usually reversible. Adverse reactions from the liver can be severe, and deaths have been reported in extremely rare cases. In almost all cases, these were persons with serious comorbidities or persons receiving concomitantly potentially hepatotoxic drugs.
For the skin and subcutaneous tissues:
uncommon - rash, itching, urticaria;
rarely - erythema multiforme; very rarely - Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis. If allergic skin reactions occur, treatment with Augmentin® EC should be discontinued.
From the urinary system:
very rarely - interstitial nephritis, crystalluria, hematuria.
special instructions
Before starting treatment with Augmentin® EC, 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 (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. If an allergic reaction occurs, you must stop treatment with Augmentin® EC. For severe hypersensitivity reactions, epinephrine should be administered immediately. Oxygen therapy, intravenous administration of corticosteroids, and airway management, including intubation, may also be required.
It is not recommended to prescribe Augmentin® EC for suspected infectious mononucleosis, since amoxicillin can cause a measles-like rash in patients with this disease, which makes diagnosing the disease difficult.
Long-term treatment with Augmentin® EC sometimes leads to excessive proliferation of insensitive microorganisms.
In general, Augmentin® EC is well tolerated and has the low toxicity characteristic of all penicillins. During long-term therapy with Augmentin® EC, 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 MHO) 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 reduced diuresis, the development of crystalluria has been reported in very rare cases, mainly with parenteral use of the drug. During high-dose amoxicillin administration, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.
Taking Augmentin® EC orally leads to a high level of amoxicillin in the urine, 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.
Oral care helps prevent tooth discoloration by simply brushing your teeth.
Drug abuse and dependence
There was no drug dependence, addiction, or euphoric reactions associated with the use of Augmentin® EC.
Effect on the ability to drive vehicles and operate machinery
Since the drug can cause dizziness, it is necessary to warn patients about precautions when driving or working with moving mechanisms.
Storage conditions
The drug should be stored out of the reach of children at a temperature not exceeding 25°C.
Best before date
Shelf life: 2 years. Do not take the drug after the expiration date indicated on the package.
The prepared suspension should be stored in the refrigerator at a temperature of 2-8°C in a tightly closed bottle. The shelf life of the prepared suspension is 10 days.
Use during pregnancy and breastfeeding
Restrictions during pregnancy - With caution. Restrictions when breastfeeding - With caution.
In studies of reproductive function in animals, oral and parenteral administration of Augmentin® did not cause teratogenic effects.
In a single study in women with premature rupture of membranes, it was found that prophylactic therapy with the drug may be associated with an increased risk of developing necrotizing enterocolitis in newborns. Like all medicinal products, Augmentin® EC is not recommended for use during pregnancy, unless the expected benefit to the mother outweighs the potential risk to the fetus.
Augmentin® EC can be used during breastfeeding. With the exception of the possibility of sensitization, diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active ingredients of this drug into breast milk, no other adverse effects were observed in breastfed children. If adverse effects occur in breastfed infants, breastfeeding should be discontinued.
Use for renal impairment
Restrictions for impaired renal function - With caution. No dosage adjustment is required for CC ≥30 ml/min.
use is not recommended for
CC <30 ml/min.
Use for liver dysfunction
Restrictions for liver dysfunction - With caution.
Prescribe with caution in case of liver dysfunction
(when monitoring liver function).
Contraindicated in case of previous episodes of jaundice or impaired liver function when using a combination of amoxicillin with clavulanic acid in the anamnesis.
Use in children
Restrictions for children - With caution.
The use of the drug in children under 3 months is contraindicated.
Terms of sale
The drug is available with a prescription.
Contacts for inquiries
GlaxoSmithKline Trading JSC (Russia)
125167 Moscow Leningradsky Prospekt, 37a, bldg. 4 BC "Arcus III" Tel. Fax
Clinical studies of high-dose amoxicillin/clavulanate
The effectiveness of amoxicillin/clavulanate in children has most often been studied in patients with acute otitis media who underwent tympanocentesis before treatment and after 4–6 days of treatment. This makes it possible to assess both the type of pathogen and the degree of its resistance, as well as the bacteriological effectiveness of treatment. For drugs with a dose of 45/6.4 mg/kg/day in 2 doses, efficacy was shown (86.7% for H. influenzae), superior to that of azithromycin (10 mg/kg on the 1st day, then 5 mg/kg). kg 4 days) – 39.4%. Such doses of amoxicillin/clavulanate, while effective against susceptible and intermediately resistant S. pneumoniae, may be ineffective against about 20% of resistant strains [10, 11].
A study of the bacteriological effectiveness of “enhanced” amoxicillin/clavulanate (90/6.4 mg/kg/day in 2 doses) in a large group of children with acute otitis media showed its high effectiveness against H. influenzae (94%) and S. pneumoniae ( 96%), including in relation to its strains resistant (MIC 2–4 μg/ml) to penicillin (91%). On the 12th–15th day from the onset of the disease, 89% of children recovered [12].
In a similar study, the effectiveness of amoxicillin/clavulanate (90/6.4 mg/kg/day in 2 divided doses for 10 days) was compared with that of a 5-day course of azithromycin (10 mg/kg/day, then 5 mg/kg/day). Clinical effectiveness at the end of therapy (days 12–14 of illness) was 90.5 and 80.9%, respectively (p < 0.01). The clinical effect during therapy and at follow-up (days 21–25) for amoxicillin/clavulanate was 94.9 and 88.0% versus 80.3 and 71.1% for azithromycin. Thus, amoxicillin/clavulanate showed not only a higher percentage of recovery, but also a lower rate of clinical relapse than azithromycin. The eradication rate of the pathogen was 94.2 and 70.3%, respectively. Amoxicillin/clavulanate contributed to the eradication of 96% of all S. pneumoniae (versus 89.7% in the azithromycin group) and among them 92% of completely resistant strains (versus 54.5%). Eradication of H. influenzae was achieved in 89.7 and 80.4%, and of β-lactamose-positive strains in 92.0 and 49.1%, respectively [13].
“Strengthened” forms of amoxicillin/clavulanate are used not only for otitis media; A randomized, double-blind, placebo-controlled study of this drug (90/6.4 mg/kg/day in 2 divided doses) for the treatment of acute bacterial sinusitis in 56 children 1–10 years of age was recently published. Cure was achieved in 50% of children in the experimental group and in 14 in the placebo group; complete treatment failure occurred in 14 and 68% of children, respectively [14].
Safety
Side effects when taking amoxicillin/clavulanate are usually mild; stool disorders, rashes (hepatic dermatitis), and vomiting are more common. Published studies show a lower incidence of diarrhea with amoxicillin/clavulanate twice daily compared with three times daily [15, 16]. Consistent with this, a lower frequency of twice-daily “boosted” drug administration was noted compared with thrice-daily administration of the drug [17].
Comparison of the frequency of side effects when taking regular and “strengthened” amoxicillin/clavulanate 2 times a day did not reveal any serious differences: diarrhea (stool more than 3 times within 2 days) was observed in 11 and 8.8% of children. The average stool frequency between groups (1.5–1.6 per day), as well as the maximum frequency (2.7–2.8 per day), also did not differ [18].
In a large study (521 children), high-dose amoxicillin/clavulanate caused diarrhea (3 loose stools per day or 2 loose stools for 2 days or more) in 12.5% of children, but was a concern in only 4% of parents. Equally common are rashes (5.4%), and less common are vomiting (2.3%). Treatment was discontinued in 5% of children [12].
