Augmentin, 156 mg/5 ml suspension, 100 ml

Augmentin is a broad-spectrum antibacterial, bactericidal.

Pharmacodynamics

Amoxicillin is a semi-synthetic broad-spectrum antibiotic with activity against many Gram-positive and Gram-negative microorganisms.

Amoxicillin, however, is susceptible to degradation 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 that are resistant to penicillins and cephalosporins. Clavulanic acid is sufficiently effective against plasmid beta-lactamases that most often cause bacterial resistance and is less effective against chromosomal beta-lactamases of type 1 that are not inhibited by clavulanic acid.

The presence of clavulanic acid in Augmentin^® protects amoxicillin from degradation by beta-lactamase enzymes, which broadens the antibacterial spectrum of amoxicillin.

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

Bacteria generally sensitive to the combination of amoxicillin with clavulanic acid

Grampositive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus spp., including. Streptococcus pyogenes^1,2, Streptococcus agalactiae^1,2 (other beta-hemolytic streptococci)^1,2, Staphylococcus aureus (sensitive to methicillin)¹, Staphylococcus saprophyticus (sensitive to methicillin), coagulazonegative staphylococci (sensitive to methicillin).

Grampositive anaerobes: Clostridium spp., Peptococcus niger, Peptostreptococcus spp. including Peptostreptococcus magnus, Peptostreptococcus micros.

Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae¹, Helicobacter pylori, Moraxella cafarrhalis¹, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Gram-negative anaerobes: Bacteroides spp. including Bacteroides fragilis, Capnocytophaga spp., Eikenella corrodens, Fusobacterium spp. including Fusobacterium nucleatum, Porphyromonas spp., Prevotella spp.

Others: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Bacteria for which acquired resistance to the combination of amoxicillin with clavulanic acid is likely

Gram-negative aerobes: Escherichia coli¹, Klebsiella spp., including Klebsiella oxytoca, Klebsiella pneumoniae¹, Proteus spp. including Proteus mirabilis, Proteus vulgaris, Salmonella spp.

Grampositive aerobes: Corynebacterium spp., Enterococcus faecium, Streptococcus pneumoniae^1,2, Streptococcus group Viridans.

Bacteria naturally resistant to the combination of amoxicillin with 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.

Others: Chlamydia spp. including Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, Mycoplasma spp.

¹ For these bacteria, the clinical effectiveness of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical trials.

² Strains of these bacterial species do not produce beta-lactamase. The sensitivity with amoxicillin monotherapy suggests similar sensitivity to a combination of amoxicillin and clavulanic acid.

Pharmacokinetics

absorption

The two active ingredients in the drug Augmentin<^® – amoxicillin and clavulanic acid – are rapidly and completely absorbed from the gastrointestinal tract after oral administration. Absorption of the active ingredients of Augmentin^® is optimal if the drug is taken at the beginning of a meal.

The pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in different studies when healthy volunteers aged 2-12 years took 40 mg+10 mg/kg/day of the drug on an empty stomach in three doses are shown belowi>Augmentin^®, powder for preparation of oral suspension, 125 mg+31.25 mg in 5 ml (156.25 mg).

Indications

The combination of amoxicillin with clavulanic acid is indicated for treatment of bacterial infections of the following localizations caused by microorganisms sensitive to amoxicillin-clavulanic acid combination:

sup>1, Streptococcus pyogenes and species of the genus Bacteroides1;

– Bone and joint infections such as osteomyelitis, usually caused by Staphylococcus aureus1, long term therapy may be necessary;

– odontogenic infections such as periodontitis, odontogenic maxillary sinusitis, severe dental abscesses with spreading cellulitis (only for tablet forms of Augmentin, dosages 500 mg/125 mg, 875 mg/125 mg);

– other mixed infections (e.g., septic abortion, postpartum sepsis, intra-abdominal sepsis) as part of staged therapy (only for tablet forms of Augmentin in doses of 250 mg/125 mg, 500 mg/125 mg, 875 mg/125 mg).

Active ingredient

Composition

5 ml of the finished suspension contains:

Active substance:

amoxicillin (in trihydrate form) 125 mg;

clavulanic acid (in potassium salt form) 31.25 mg.

Auxiliary substances:

xanthan gum – 12.5 mg,

aspartame – 12.5 mg,

succinic acid – 0.84 mg,

colloidal silica – 25 mg,

hypromellose – 150 mg,

p> orange flavoring 1 – 15 mg,

orange flavoring 2 – 11.25 mg,

Raspberry flavoring – 22.5 mg,

Light molasses flavoring – 23.75 mg,

Silica dioxide – 125 mg.

How to take, the dosage

The dosing regimen is adjusted individually depending on the patient’s age, body weight, kidney function, and the severity of the infection. For optimal absorption and reduction of possible side effects on the digestive system Augmentin® is recommended to be taken at the beginning of meals. The minimum course of antibiotic therapy is 5 days.

The treatment should not be continued for more than 14 days without a review of the clinical situation.

If necessary, step therapy (parenteral administration of the drug at the beginning of therapy followed by switch to oral administration) is possible.

Adults and children over 12 years of age or with a body weight of 40 kg or more

1 tablet 250 mg/125 mg 3 times/day (for mild to 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 of 400 mg/57 mg/5 ml suspension 2 times/day (equivalent to 1 tablet 875 mg/125 mg).

Two 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 oral suspension. Calculation of the dose is made depending on age and body weight, stated in mg/kg body weight/day (calculation for amoxicillin) or in ml of suspension.

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

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

The recommended dosing regimen and dosing frequency are as follows:

The dosing frequency is 3 times/day; 4:1 suspension (125 mg/31.25 mg in 5 ml):

The frequency of administration is 2 times/day; 7:1 suspension (200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml):

Low doses of Augmentin® are used to treat skin and soft tissue infections and recurrent tonsillitis.

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

There is insufficient clinical evidence to recommend the use of Augmentin® at doses greater than 40 mg/kg/day in 3 doses (4:1 suspension) in children younger than 2 years of age.

Children from birth to 3 months

In view of immature renal excretory function, the recommended dose ofi>Augmentin® (amoxicillin calculation) is 30 mg/kg/day in 2 doses as a suspension 4:1. The use of 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 dosing recommendations.

Elderly patients

No dose adjustment of the drug 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 based on CK values.

Adults

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

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

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

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

Patients on hemodialysis

Dose adjustments are based on the maximum recommended dose of amoxicillin: 2 tablets. 250 mg/125 mg at a single dose every 24 hours, or 1 tablet. 500 mg/125 mg at a single dose every 24 hours, or 15 mg/3.75 mg/kg suspension once daily.

Tablets: During a hemodialysis session an additional dose (one tablet) and another 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 a hemodialysis session. A second additional dose of 15 mg/3.75 mg/kg should be administered after hemodialysis to restore the blood concentrations of the active components of Augmentin®.

Patients with hepatic impairment

Treatment with caution; regular monitoring of liver function is indicated. There is insufficient data to perform dosing adjustments in this category of patients.

Regulations for preparing the suspension

The suspension is prepared immediately before the first use.

The suspension (125 mg/31.25 mg in 5 ml): in a vial with the powder add approximately 60 ml of boiled water, cooled to room temperature, then close the vial with the lid and shake until the powder is completely diluted, letting the vial stand for 5 minutes to ensure complete dilution. Then add water to the mark on the bottle and shake the bottle again. In total, about 92 ml of water is required to prepare the suspension. The bottle should be shaken well before each use. For precise dosage of the drug the measuring cap should be used, which should be well washed with water after each use. After dilution the suspension should be stored no more than 7 days in the refrigerator, but not frozen.

In children under 2 years of age the measured single dose of Augmentin® suspension can be doubled with water.

The suspension (200 mg/28.5 mg in 5 ml or 400 mg/57 mg in 5 ml): in a vial with the powder add approximately 40 ml of boiled water which has been cooled to room temperature, close the vial with the cap and shake until the powder is completely diluted, letting the vial stand for 5 minutes to ensure complete dilution. Then add water to the mark on the bottle and shake the bottle again. In total, about 64 ml of water is required to prepare the suspension. The bottle should be shaken well before each use. For precise dosage of the drug a measuring cap or a dosing syringe should be used, which should be well washed with water after each use. After dilution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.

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

Interaction

The concomitant use of Augmentin® and probenecid is not recommended. Probenecid decreases the tubular secretion of amoxicillin, and therefore concomitant use of Augmentin® and probenecid may result in increased and persistent blood concentrations of amoxicillin but not clavulanic acid.

The concomitant use of allopurinol and amoxicillin may increase the risk of skin allergic reactions. There are currently no data in the literature on the simultaneous use of the combination of amoxicillin with clavulanic acid and allopurinol.

Penicillins can slow down excretion of methotrexate by inhibiting its tubular secretion, therefore concomitant use of Augmentin® and methotrexate may increase toxicity of methotrexate.

As with other antibacterials, Augmentin® may have an effect on the gut flora, resulting in decreased gastrointestinal absorption of estrogen and decreased efficacy of combined oral contraceptives.

The literature describes rare cases of increased international normalized ratio (MHO) in patients when coadministering acenocoumarol or warfarin and amoxicillin. If concomitant administration of Augmentin® with anticoagulants is necessary, prothrombin time or MHO should be closely monitored when prescribing or withdrawing Augmentin®, oral anticoagulants may need to be adjusted.

Special Instructions

Before starting treatment with Augmentin®, a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins or other allergens should be taken.

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. In case of allergic reactions, the treatment with Augmentin® should be discontinued and an appropriate alternative therapy should be started. In severe hypersensitivity reactions, epinephrine should be administered immediately. Oxygen therapy, intravenous GCS and airway management including intubation may also be necessary.

The use of Augmentin® is not recommended in patients with suspected infectious mononucleosis because in patients with this disease amoxicillin may cause a rash which makes it difficult to diagnose the disease.

Long treatment with Augmentin® sometimes leads to overgrowth of insensitive microorganisms. In general, Augmentin® is well tolerated and of low toxicity common to all penicillins. During prolonged therapy with Augmentin® it is recommended to periodically monitor renal, hepatic and hematopoietic function.

In order to decrease the risk of gastrointestinal side effects, the drug should be taken at the beginning of meals.

In patients who received a combination of amoxicillin with clavulanic acid together with indirect (oral) anticoagulants, in rare cases an increase in prothrombin time (increase in MHO) has been reported. When co-administration of indirect (oral) anticoagulants with the combination of amoxicillin with clavulanic acid it is necessary to monitor the corresponding indicators. To maintain the desired effect of oral anticoagulants may require adjustment of their dose.

In patients with impaired renal function the dose of Augmentin® should be reduced according to the degree of impairment.

In patients with decreased urine output very rarely crystalluria has been reported, mainly with parenteral administration of the drug. During administration of high doses of amoxicillin it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of formation of amoxicillin crystals.

The oral administration of drug Augmentin® causes high content of amoxicillin in urine that may lead to false positive results in determining glucose in urine (e.g., Benedict test, Felling test). In this case it is recommended to use glucose-oxidant method of determining the concentration of glucose in urine.

Mouth care can help prevent discoloration of the teeth, because brushing is sufficient.

The tablets must be used within 30 days of opening the laminated aluminum foil package.

Abuse and drug dependence

There have been no drug dependence, addiction, or euphoric reactions associated with the use of Augmentin®.

Impact on driving and operating machinery

As the drug may cause dizziness, patients should be advised about caution when driving or operating moving machinery.

Contraindications

Hypersensitivity.

Side effects

The undesired phenomena presented below are listed according to organ and organ system involvement and frequency of occurrence. The frequency is defined as follows: very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), rare (≥1/10 000, < 1/1000), very rare (< 1/10 000).

The frequency categories were derived from clinical studies of the drug and post-registration surveillance.

Infectious and parasitic diseases: frequently, 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.

Injury to the immune system:very rarely – angioedema, anaphylactic reactions, serum-like syndrome, allergic vasculitis.

Nervous system disorders: infrequent – dizziness, headache; very rare – reversible hyperactivity, seizures (seizures may be seen in patients with impaired renal function and those receiving high doses of the drug), insomnia, agitation, anxiety, behavior changes.

Gastrointestinal disorders: adults: very common – diarrhea, common – nausea, vomiting; children – common – diarrhea, nausea, vomiting; all population: nausea is most common when taking high doses of the drug. If unwanted gastrointestinal reactions are observed after starting the drug, they can be eliminated if the drug is taken at the beginning of meals.

Infrequent – digestive disorders; very rare – antibiotic-associated colitis induced by taking antibiotics (including pseudomembranous colitis and hemorrhagic colitis), black “hairy” tongue, gastritis, stomatitis. In children, very rare changes in the coloration of the surface layer of tooth enamel have been observed when using the suspension. Oral care can help prevent discoloration of tooth enamel by simply brushing.

Liver and biliary tract side: infrequent – moderate increase in ASTi and/or ALT activity (observed in patients receiving therapy with beta-lactam antibiotics, but its clinical significance is unknown); very rare – hepatitis and cholestatic jaundice (these phenomena have been reported with therapy with other penicillins and cephalosporins), increased bilirubin and alkaline phosphatase concentrations.

Hepatic adverse events have been observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse events are very rarely seen in children.

The signs and symptoms listed usually occur during or immediately after completion of therapy, but in some cases may not occur for several weeks after completion of therapy. The adverse events are generally reversible. Liver adverse events can be severe, and in exceptionally rare cases deaths have been reported. In almost all cases, these were individuals with serious comorbidities or individuals receiving concomitant potentially hepatotoxic medications.

Skin and subcutaneous tissues: frequent – rash, pruritus, urticaria; rare – erythema multiforme; very rare – Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

In case of skin allergic reactions the treatment with Augmentin® must be stopped.

Recreational and urinary tract disorders:very rarely – interstitial nephritis, crystalluria, hematuria.

Overdose

Symptoms:Gastrointestinal symptoms and water-electrolyte imbalances may occur. Amoxicillin crystalluria has been described, in some cases leading to renal failure.

There may be seizures in patients with impaired renal function and in those who receive high doses of the drug.

Treatment:Gastrointestinal symptoms – symptomatic therapy, with special attention to normalization of water-electrolyte balance. In case of overdose, amoxicillin and clavulanic acid may be removed from the bloodstream by hemodialysis.

The results of a prospective study, which involved 51 children in a toxicology center, showed that administration of amoxicillin at a dose of less than 250 mg/kg did not result in significant clinical symptoms and did not require gastric lavage.

Pregnancy use

In animal reproductive studies, oral and parenteral administration of Augmentin® did not cause teratogenic effects.

In a single study in women with premature rupture of fetal membranes, prophylactic therapy with the drug was found to be associated with an increased risk of necrotizing enterocolitis in newborns.

As with all drugs, Augmentin® is not recommended for use during pregnancy unless the expected benefit to the mother exceeds the potential risk to the fetus.

The drug Augmentin® can be used during breastfeeding. Except for possible development of diarrhea or oral candidiasis due to leaking of trace amounts of active principles of the drug into breast milk, no other adverse effects have been observed in breastfed infants.

Breastfeeding should be stopped if adverse effects occur in breastfed infants.

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