Augmentin, 400mg+57mg/5ml suspension, vial 12.6g

Composition

5 ml of the finished suspension contains:

Active ingredient:

amoxicillin (in the form of trihydrate) 400 mg;

clavulanic acid (in the form of potassium salt) 57 mg.

Auxiliary substances:

xanthan gum – 12.5 mg,

aspartame – 12.5 mg,

succinic acid – 0.84 mg,

silicon dioxide colloid – 25 mg,

hypromellose – 79.65 mg,

orange flavor 1 – 15 mg,

orange flavor 2 – 11.25 mg,

flavoring raspberry – 22.5 mg,

flavoring “in Light syrup” – 23.75 mg,

silicon dioxide, up to 900 mg.

Pharmacological action

Amoxicillin is a semi-synthetic broad-spectrum 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 penicillin-and cephalosporin-resistant microorganisms.

Clavulanic acid is sufficiently effective against plasmid beta-lactamases, which are most often responsible for bacterial resistance, and less effective against chromosomal type 1 beta-lactamases, which are not inhibited by clavulanic acid.

The presence of clavulanic acid in Augmentin® protects amoxicillin from destruction by beta — lactamase enzymes, which allows you to expand the antibacterial spectrum of amoxicillin.

The activity of the combination of amoxicillin with clavulanic acid in vitro is shown below.

Bacteria usually sensitive to the combination of amoxicillin and clavulanic acid

Gram-positive aerobes:  Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pyogenes1,2, Streptococcus agalactiae1,2, Streptococcus spp. (other beta-hemolytic streptococci)1,2, Staphylococcus aureus (methicillin-sensitive)1, Staphylococcus saprophyticus (sensitive to methicillin), Staphylococcus spp. (coagulase-negative, sensitive to methicillin).

Gram-negative aerobes:  Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Other services:  Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Gram-positive anaerobes:  Clostridium spp., Peptococcus niger, Peplostreptococcus 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 develop resistance to the combination of amoxicillin and 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 aerobes:  Corynebacterium spp., Enterococcus faecium, Streptococcus pneumoniae1,2, Streptococcus groups Viridans2.

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 services:  Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia spp., Coxiella burnetti, Mycoplasma spp.

1-for these types of microorganisms, the clinical efficacy 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. The sensitivity of amoxicillin monotherapy suggests a similar sensitivity to the combination of amoxicillin with clavulanic acid.

Indications

The combination of amoxicillin with clavulanic acid is indicated for the treatment of bacterial infections of the following locations caused by microorganisms sensitive to the combination of amoxicillin with clavulanic acid: Upper respiratory tract infections (including ENT infections), such as recurrent tonsillitis, sinusitis, and otitis media, usually caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes.

Lower respiratory tract infections, such as exacerbations of chronic bronchitis, lobar pneumonia, and bronchopneumonia, usually caused by Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Infections of the genitourinary tract, such as cystitis; urethritis, pyelonephritis, infections of the female genital organs, usually caused by species of the family Enterobacteriaceae (mainly Escherichia coli), Staphylococcus saprophytics and species of the genus Enterococcus, as well as gonorrhea caused by Neisseria gonorrhoeae. Skin and soft tissue infections, usually caused by Staphylococcus aureus*. Streptococcus pyogenes and species of the genus Bacteroides#.

Infections of the bones and joints, such as osteomyelitis, usually caused by Staphylococcus aureus#, if necessary, long-term therapy is possible. Other mixed infections (for example, septic abortion, postpartum sepsis, intraabdominal sepsis, sepsis, peritonitis, postoperative infections) as part of step therapy.

Augmentin®in a dosage of 1000 mg + 200 mg is also indicated for the prevention of postoperative infections, for surgical interventions on the gastrointestinal tract, pelvic organs, head and neck, heart, kidneys, biliary tract, as well as for the implantation of artificial joints.

Use during pregnancy and lactation

In studies of reproductive function in animals, oral and parenteral use of Augmentin® 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 developing necrotizing enterocolitis in newborns. As with all medications, Augmentin® is not recommended for use during pregnancy, except in cases where the expected benefit to the mother exceeds the potential risk to the fetus.

Augmentin® can be used during breastfeeding. With the exception of the possibility of developing diarrhea or candidiasis of the oral mucosa associated with the penetration of trace amounts of active substances of this drug into breast milk, no other adverse effects were observed in children who are breastfed. In case of adverse effects in children who are breastfed, it is necessary to stop breastfeeding.

Contraindications

• 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 12 years of age and weighing less than 40 kg (for tablets 250 mg / 125 mg or 500 mg/125 mg, or 875 mg/125 mg).
• Children under 3 months of age (for oral suspension powder 200 mg/28.5 mg and 400 mg/57 mg).
• Impaired renal function (creatinine clearance < 30 ml/min) – (for tablets 875 mg / 125 mg, for powder for preparation of suspension for oral use 200 mg/28.5 mg and 400 mg/57 mg).
• Phenylketonuria (for powder preparation of suspension for oral use).

With caution:  liver function disorders.

Side effects

The adverse events listed below are listed according to the lesion of organs and organ systems and frequency of occurrence. The frequency of occurrence is defined as follows: very common (≥1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10 000, < 1/1000), very rare (

Frequency categories were formed based on clinical studies of the drug and post-marketing surveillance.

Infectious and parasitic diseases:  often-candidiasis of the skin and mucous membranes.

Blood and lymphatic system disorders:  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.

Nervous system disorders:  infrequently – dizziness, headache; very rarely-reversible hyperactivity, seizures (seizures can occur in patients with impaired renal function, as well as in those who receive high doses of the drug), insomnia, agitation, anxiety, behavior changes.

Gastrointestinal disorders: adults:  very common-diarrhea, often-nausea, vomiting; children-often-diarrhea, nausea, vomiting; whole population: nausea is most often observed when taking high doses of the drug. If after the start of taking the drug there are undesirable reactions from the gastrointestinal tract, 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 antibiotics (including pseudomembranous colitis and hemorrhagic colitis), black “hairy” tongue, gastritis, stomatitis. In children, when using the suspension, very rarely there was a change in the color of the surface layer of tooth enamel. Oral care helps prevent discoloration of the tooth enamel, as it is enough to brush your teeth.

Liver and biliary tract disorders: infrequently-a moderate increase in the activity of A and / or ALT (observed in patients receiving beta-lactam antibiotics, but its clinical significance is unknown); very rarely – hepatitis and cholestatic jaundice (these phenomena were observed during 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 rare in children.

These 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, and in extremely rare cases, fatal outcomes have been reported. In almost all cases, these were people with serious comorbidities or those receiving potentially hepatotoxic drugs at the same time.

Skin and subcutaneous tissue disorders: infrequently-rash, pruritus, urticaria; rarely-erythema multiforme; very rarely-Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

In case of allergic skin reactions, treatment with Augmentin® should be discontinued.

From the side of the kidneys and urinary tract: very rarely – interstitial nephritis, crystalluria, hematuria.

Interaction

Concomitant use of Augmentin and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of Augmentin® 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 the elimination of methotrexate from the body by inhibiting its tubular secretion, therefore, the simultaneous use of Augmentin® and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, Augmentin® 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 an increase in the international normalized ratio (MHO) in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If it is necessary to co-administer Augmentin® with anticoagulants, prothrombin time or MHO should be carefully monitored when prescribing or discontinuing Augmentin®, and dose adjustment of oral anticoagulants may be required.

How to take, course of use and dosage

The dosage regimen is set individually depending on the age, body weight, kidney function of the patient, as well as the severity of the infection.

For optimal absorption and reduction of possible side effects from the digestive system, Augmentin® is recommended to be taken at the beginning of a meal.

The minimum course of antibacterial therapy is 5 days.

Treatment should not be continued for more than 14 days without reviewing the clinical situation.

If necessary, it is possible to conduct step therapy (at the beginning of therapy, parenteral use of the drug with subsequent transition to oral use).

Adults and children over 12 years of age or weighing 40 kg or more

1 tablet 250 mg / 125 mg 3 times / day (for mild and moderate infections), or 1 tablet 500 mg/125 mg 3 times/day, or 1 tablet 875 mg/125 mg 2 times/day, or 11 ml suspension 400 mg/57 mg/5 ml 2 times/day (equivalent to 1 tablet 875 mg/125 mg).

2 250 mg/125 mg tablets are not equivalent to 1 500 mg/125 mg tablet.

Children from 3 months to 12 years of age with a body weight of less than 40 kg

The drug is prescribed in the form of a suspension for oral use.

The dose is calculated depending on age and body weight, indicated in mg / kg of body weight/day (calculated according to amoxicillin) or in ml of suspension.

The frequency of taking the suspension 125 mg / 31.25 mg in 5 ml is 3 times / day every 8 hours.

The frequency of taking the suspension 200 mg / 28.5 mg in 5 ml or 400 mg/57 mg in 5 ml is 2 times / day every 12 hours.

The recommended dosage regimen and frequency of use are presented below:

Frequency of use-3 times / day; suspension 4: 1 (125 mg / 31.25 mg in 5 ml):

• Low doses – 20 mg / kg / day.
• High doses – 40 mg / kg / day.

Dose rate-2 times / day; suspension 7: 1 (200 mg / 28.5 mg in 5 ml or 400 mg/57 mg in 5 ml):

• Low doses – 25 mg / kg / day.
• High doses – 45 mg / kg / day.

Low-dose Augmentin® is used to treat skin and soft tissue infections, as well as recurrent tonsillitis.

High doses of Augmentin® are used to treat diseases such as otitis media, sinusitis, lower respiratory and urinary tract infections, bone and joint infections.

There are insufficient clinical data to recommend the use of Augmentin® at a dose of more than 40 mg / kg / day in 3 doses (suspension 4:1) in children under 2 years of age.

Children from birth to 3 months

Due to immaturity of the excretory function of the kidneys, the recommended dose of Augmentin® (calculated according to amoxicillin) is 30 mg / kg / day in 2 doses in the form of a 4:1 suspension.

The use of a 7: 1 suspension (200 mg / 28.5 mg in 5 ml or 400 mg/57 mg in 5 ml) is not recommended in this population.

Children born prematurely

There are no recommendations regarding the dosage regimen.

Elderly patients

No dose adjustment is required. In elderly patients with impaired renal function, the dose should be adjusted as indicated below for adults with impaired renal function.

Patients with impaired renal function

Dose adjustment is based on the maximum recommended dose of amoxicillin and is carried out taking into account the values of creatinine clearance.

Adults

Tablets 250 mg+125 mg or 500 mg+125 mg:

• Creatinine clearance > 30 ml / min – no dosage adjustment is required.
• Creatinine clearance 10-30 ml / min – 1 tab. 250 mg+125 mg 2 times/day or 1 tab. 500 mg+125 mg (for mild and moderate infection) 2 times / day.
• QC 250 mg+125 mg 1 time/day or 1 tab. 500 mg+125 mg (for mild and moderate infection) 1 time/day.

4: 1 suspension (125 mg / 31.25 mg in 5 ml):

• Creatinine clearance > 30 ml / min – no dosage adjustment is required.
• Creatinine clearance 10-30 ml / min – 15 mg / 3.75 mg / kg 2 times / day, maximum dose-500 mg / 125 mg 2 times/day.
• Creatinine clearance < 10 ml / min – 15 mg / 3.75 mg / kg 1 time / day, the maximum daily dose is 500 mg/125 mg.

875 mg+125 mg tablets and 7:1 suspension (200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml) should only be used in patients with creatinine clearance > 30 ml / min, and no dose adjustment is required.

In most cases, if possible, parenteral therapy should be preferred.

Patients undergoing hemodialysis

Dose adjustments are based on the maximum recommended dose of amoxicillin: 2 tablets. 250 mg / 125 mg in one dose every 24 hours, or 1 tab. 500 mg / 125 mg in one dose every 24 hours, or suspension at a dose of 15 mg/3.75 mg / kg 1 time / day.

Tablets: during the hemodialysis session, an additional 1 dose (one tablet) and another 1 dose (one tablet) at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

Suspension: One additional dose of 15 mg/3.75 mg/kg should be administered before the hemodialysis session. To restore the concentration of the active components of Augmentin® in the blood, a second additional dose of 15 mg/3.75 mg/kg should be administered after a hemodialysis session.

Patients with impaired liver function

Treatment is carried out with caution; liver function is regularly monitored. There is insufficient data to correct the dosage regimen in this category of patients.

Suspension preparation rules

The suspension is prepared immediately before the first application.

Suspension (125 mg / 31.25 mg in 5 ml): add approximately 60 ml of boiled water cooled to room temperature to the powder bottle, 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. In general, about 92 ml of water is required to prepare the suspension. The bottle should be shaken well before each use. For accurate dosage of the drug, a measuring cap should be used, which should be thoroughly washed with water after each application. After dilution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.

For children under 2 years of age, the measured single dose of Augmentin® suspension can be diluted twice with water.

Suspension (200 mg / 28.5 mg in 5 ml or 400 mg/57 mg in 5 ml): add approximately 40 ml of boiled water cooled to room temperature to the powder bottle, 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. In general, about 64 ml of water is required to prepare the suspension. The bottle should be shaken well before each use. For accurate dosage of the drug, you should use a measuring cap or a dosing syringe, which must be thoroughly washed with water after each application. After dilution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.

For children under 2 years of age, the measured single dose of Augmentin® suspension can be diluted with water in a ratio of 1: 1.

Overdose

Symptoms: gastrointestinal disorders and water-electrolyte balance disorders are possible. Amoxicillin crystalluria is described, which in some cases leads to the development of renal failure.

Treatment: symptomatic therapy, correction of water and electrolyte balance. Amoxicillin and clavulanic acid are eliminated from the blood by hemodialysis.

Special instructions

With caution, the drug should be administered intravenously to patients with severe hepatic impairment.

If urticaria or erythematous rash occurs, treatment should be discontinued.

The frequency and severity of dyspeptic symptoms may decrease when taking the drug with a meal.

Form of production

Powder for the preparation of a suspension for oral use.

Storage conditions

In a dry place, at a temperature not exceeding 25 °C

Shelf life

2 years

Active ingredient

Amoxicillin, Clavulanic Acid

Conditions of release from pharmacies

By prescription

Dosage form

suspension for oral use

Purpose

For pregnant women as prescribed by a doctor, For children over 2 years of age, For adults as prescribed by a doctor, For Children as prescribed by a doctor, for nursing mothers as prescribed by a doctor

Indications

Periodontitis, Osteomyelitis, Sinusitis, Bronchitis, Skin Infections, Sore Throat, Otitis Media, Pneumonia, Urinary Tract infections