Instructions for use AUGMENTIN® tablets

Pharmacological properties of the drug Augmentin™

Pharmacodynamics . Amoxicillin is a semisynthetic penicillin antibiotic with a wide spectrum of antibacterial activity against many gram-positive and gram-negative microorganisms. Amoxicillin is sensitive to the action of beta-lactamase and breaks down under its influence, therefore the spectrum of activity of amoxicillin does not include microorganisms that synthesize this enzyme. Clavulanic acid has a beta-lactam structure similar to that of penicillins, and also has the ability to inactivate beta-lactamase enzymes produced by microorganisms resistant to penicillins and cephalosporins. In particular, it has pronounced activity against clinically important plasmid beta-lactamases, which are often responsible for the occurrence of cross-resistance to antibiotics. The presence of clavulanic acid in Augmentin protects amoxicillin from degradation by beta-lactamase enzymes and expands the spectrum of antibacterial action of amoxicillin, including many microorganisms resistant to amoxicillin and other penicillins and cephalosporins. Thus, Augmentin has the properties of a broad-spectrum antibiotic and beta-lactamase inhibitor. Augmentin has a bactericidal effect against a wide range of microorganisms, including: gram-positive aerobes: Bacillus anthracis *, Corynebacterium spp., Enterococcus faecalis *, Enterococcus faecium *, Listeria monocytogenes, Nocardia asteroides, Staphylococcus aureus *, coagulase-negative staphylococci (including Staphylococcus epidermidis), Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus species, Streptococcus viridans; gram-positive anaerobes: Clostridium spp. , Peptococcus spp. , Peptostreptococcus spp.; gram-negative aerobes: Bordetella pertussis, Brucella spp., Escherichia coli*, Gardnerella vaginalis, Haemophilus influenzae*, Helicobacter pylori, Klebsiella spp. *, Legionella spp., Moraxella catarrhalis* (Branhamella catarrhalis), Neisseria gonorrhoeae*, Neisseria meningitidis*, Pasteurella multocida, Proteus mirabilis*, Proteus vulgaris *, Salmonella spp.*, Shigella spp.*, Vibrio cholerae, Yersinia enterocolitica*; gram-negative anaerobes: Bacteroides (including Bacteroides fragilis ) , Fusobacterium species; other microorganisms: Borrelia burgdorferi , Chlamydia species , Leptospira icterohaemorrhagiae, Treponema pallidum. *Some strains of these bacterial species produce β-lactamase, which makes them insensitive to amoxicillin monotherapy. Pharmacokinetics . Absorption . Both components of Augmentin (amoxicillin and clavulanic acid) are completely soluble in aqueous solutions at physiological pH values. Both components are well and quickly absorbed when administered orally. Augmentin absorption improves when taken at the beginning of a meal. Distribution . When administered orally, therapeutic concentrations of amoxicillin and clavulanic acid are determined in tissues and interstitial fluid. Therapeutic concentrations of both substances are detected in the gall bladder, abdominal tissue, skin, adipose and muscle tissue, as well as in synovial and peritoneal fluids, bile and pus. Amoxicillin and clavulanic acid are weakly bound to plasma proteins; Studies have found that protein binding rates are 25% for clavulanic acid and 18% for amoxicillin of their total concentration in blood plasma. Animal studies have not shown the accumulation of any of these components in any organ. Amoxicillin, like other penicillins, passes into breast milk. Trace amounts of clavulanic acid are also found in breast milk. Animal reproductive studies have shown that both amoxicillin and clavulanic acid can cross the placental barrier. However, no data have been identified regarding reproductive dysfunction or harmful effects on the fetus. Excretion. As with other penicillins, the main route of elimination for amoxicillin is renal excretion, whereas clavulanate is eliminated through both the kidney and extrarenal mechanisms. About 60–70% of amoxicillin and 40–65% of clavulanic acid are excreted unchanged in the urine during the first 6 hours after a single dose of tablets. Amoxicillin is also partially excreted in the urine as inactive penicillic acid in amounts equivalent to 10–25% of the dose taken. Clavulanic acid is extensively metabolized in humans to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrol-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and is excreted in urine and feces, as well as in the form of carbon dioxide in exhaled air. Augmentin (BD) Pharmacokinetic parameters were studied in studies in which Augmentin (BD) tablets 625 mg 500/125 mg (compared to the separate administration of both components) were administered on an empty stomach in groups of healthy volunteers and the results of which are shown below:

The plasma concentration of amoxicillin achieved with Augmentin (BD) is similar to that achieved with oral administration of amoxicillin alone in equivalent doses. Concomitant use of probenecid inhibits the excretion of amoxicillin, but does not affect the renal excretion of clavulanic acid. Augmentin tablets 1 g (875/125 mg) Pharmacokinetic parameters when taking Augmentin tablets 875/125 mg (1 g) 2 times a day are as follows: AUC - 53.52 mcg/h/ml for amoxicillin and 10.16 mcg/h/ ml for clavulanic acid, half-life - 1.19 hours for amoxicillin and 0.96 hours for clavulanic acid, maximum serum concentration - 11.64 µg/ml for amoxicillin and 2.18 µg/ml for clavulanic acid. Augmentin powder for the preparation of injection solution. Pharmacokinetic studies of Augmentin for intravenous use were carried out using a group of healthy volunteers who used the drug at a dose of 500/100 (600) mg or 1000/200 mg (1.2 g) intravenously. The obtained data are presented in tables. Average pharmacokinetic parameters for the constituent components of Augmentin 600 mg and 1.2 g. Amoxicillin:

Clavulanic acid:

The pharmacokinetic parameters of Augmentin ES when used to treat children at a dose of 45 mg/kg every 12 hours are shown in the table.

Augmentin during pregnancy: can it be taken and what are the risks for the fetus?

Augmentin is a semisynthetic antibiotic of the penicillin group that is resistant to beta-lactamases (a bacterial enzyme).
It contains amoxicillin and clavulanic acid (clavulanate). The drug acts bactericidal (kills microbes) due to the fact that it inhibits the synthesis of mucopeptides in the cell wall of microorganisms. Augmentin is also called a beta-lactam antibiotic, since its molecule contains a beta-lactam ring. Augmentin has been classified as pregnancy category B by the US Food and Drug Administration (FDA), meaning that animal studies have not found any evidence of teratogenicity (developmental defects), and there is no well-controlled data on the effects in humans during pregnancy. The results of the study suggest an increased risk of necrotizing enterocolitis (death of tissue of the intestinal wall) in newborns when Augmentin is administered prophylactically to women with premature rupture of membranes. In a study of birth defects conducted by the Michigan Medicaid program, it was found that many pregnant women who were exposed to penicillin derivatives, specifically amoxicillin, in the first trimester of pregnancy did not show a significant increase in the risk of birth defects in the fetus.

However, the Michigan Medicaid Birth Defects Study found several cases of adverse effects of clavulanate in the first trimester of pregnancy resulting in birth defects, including spina bifida in the infant.

To summarize, it should be noted that Augmentin should be prescribed by a doctor during pregnancy only when the need for it is clearly established, and also after comparing that the expected benefits for the mother clearly prevail over the manifestation of all kinds of risks for the fetus.

Indications for use of the drug Augmentin™

The drug is intended for short-term treatment of bacterial infections caused by microorganisms sensitive to the drug:

• upper respiratory tract infections (including infections of the ENT organs), including recurrent tonsillitis, sinusitis, otitis media;
• lower respiratory tract infections, including chronic bronchitis in the acute phase, lobar pneumonia and bronchopneumonia;
• infections of the urinary system, including cystitis, urethritis, pyelonephritis;
• infections of the skin and soft tissues, including burns, abscesses, inflammation of the subcutaneous tissue, wound infections, animal bites;
• infections of bones and joints, including osteomyelitis;
• other infections, including septic abortion, postpartum sepsis, intra-abdominal sepsis;
• dental infections, including dentoalveolar abscesses.

The use of Augmentin tablets 1 g (875/125 mg) is also indicated for infections of the female genital organs and gonorrhea. The use of Augmentin 1000/200 mg (in injection form) is also indicated for infections of the female genital organs and gonorrhea, for the prevention of infectious complications during surgical interventions, for most types of surgical interventions on the gastrointestinal tract, pelvic organs, head and neck area, heart, kidneys, joint replacement and bile duct surgery. Infections caused by amoxicillin-sensitive microorganisms are effectively treated with Augmentin, given the amoxicillin content in it. Mixed infections caused by amoxicillin-insensitive microorganisms in combination with augmentin-sensitive microorganisms that produce beta-lactamase can thus be treated with Augmentin. Augmentin ES: treatment of bacterial infections in children caused by microorganisms sensitive to Augmentin: infections of the upper respiratory tract (including ENT organs), including recurrent or persistent otitis media (children's patients, usually with at least experience in antibiotic therapy for otitis media 3 months or under 2 years of age or attending preschool institutions); tonsillopharyngitis or sinusitis; lower respiratory tract infections, including lobar and bronchopneumonia; skin and soft tissue infections.

Augmentin during breastfeeding: effect on the newborn

It has been established that amoxicillin is excreted into breast milk in small quantities, and clavulanic acid is not found in breast milk.
Since side effects are unlikely in an infant, the American Academy of Pediatrics (AAP) considers taking Augmentin compatible with breastfeeding. However, there are still studies that indicate that there is a connection between the occurrence of candidiasis (fungal infection) of the oral mucosa, the presence of diarrhea, or the manifestation of an allergic reaction in an infant who is breastfed by a mother taking Augmentin. Therefore, the prescription of this drug during lactation should be strictly handled by a doctor, if such a need exists. In some cases, it may be necessary to stop breastfeeding while treating bacterial infections with Augmentin.

Sources

• Augmentin / State register of medicinal products
• Amoxicillin / clavulanate Pregnancy and Breastfeeding Warnings / Drugs.com (English)
• Use of antibiotics during pregnancy and the risk of major congenital malformations: a population based cohort study / PubMed (English)
• Augmentin / Drugs.com
• Amoxicillin and Clavulanic Acid / MedlinePlus (English)
• Amoxicillin / DrugBank (English)
• Clavulanic acid / DrugBank (English)
• Use of penicillin antibiotics / Best use of medicines in pregnancy (BUMPS) (English)

Use of Augmentin™

Augmentin (ВD) tablets 625 mg (500/125 mg) For the treatment of mild to moderate infections in adults and children over 12 years of age: 1 tablet of Augmentin (ВD) 2 times a day. For severe infections (including chronic and recurrent urinary tract infections and bronchopulmonary infections), 1-2 tablets of Augmentin (BD) are prescribed 3 times a day. The recommended dosage for dentoalveolar abscesses is 1 tablet 2 times a day for 5 days.

Dosage for renal impairment:

Dosage for hemodialysis: 1 tablet per day + 1 tablet during and at the end of dialysis (taking into account the decrease in the concentrations of amoxicillin and clavulanic acid in the blood plasma). Dosing for liver dysfunction : use with caution, regular monitoring of liver function is necessary. Insufficient data to make dosage recommendations. Dosing for elderly patients: no dose adjustment is necessary; if necessary, the dose is adjusted depending on renal function. For optimal absorption and to reduce possible undesirable effects from the gastrointestinal tract, the drug should be taken at the beginning of a meal. Treatment should not be continued for 14 days without assessing the patient's condition. Treatment can be started parenterally and then continued orally. Augmentin tablets 1 g (875/125 mg) Dosage depends on the age and body weight of the patient, kidney function, and the severity of the infection. Dose for the treatment of mild to moderate infections in adults and children over 12 years of age: 1 tablet of Augmentin 875/125 mg 2 times a day. For severe infections (including chronic and recurrent urinary tract infections and bronchopulmonary infections) - 1 Augmentin tablet 3 times a day. Augmentin 1 g tablets are not recommended for use in children under 12 years of age. Dosing for renal impairment: Augmentin tablets 1 g (875/125 mg) are used only in patients with a creatinine clearance of 30 ml/min. In case of renal failure with creatinine clearance ≤30 ml/min, Augmentin 875/125 mg is not used. Dosing for liver dysfunction: Use with caution and regular monitoring of liver function is necessary. There are insufficient data regarding dosing recommendations. Dosing for elderly patients: There is no need for dose adjustment in elderly patients; if necessary, the dose is adjusted depending on the state of renal function. In order to reduce undesirable effects on the gastrointestinal tract, the drug should be taken at the beginning of a meal, which improves the absorption of Augmentin; treatment should not be continued for more than 14 days without assessing the patient’s condition. Treatment can be started parenterally and then continued orally. Augmentin suspension 228.5 mg/5 ml Recommended daily doses:

• 25/3.6 mg/kg/day for mild to moderate infections (infections of the ENT organs, for example, recurrent tonsillitis, respiratory tract infections, skin and soft tissue infections);
• 45/6.4 mg/kg/day for the treatment of more severe infections (infections of the ENT organs, for example, otitis media and sinusitis, respiratory tract infections, for example, bronchopneumonia and urinary tract infections).

Recommendations regarding dosing for use in children are given in the table.

Children aged 2 months to 2 years. The dosage regimen is set depending on the child’s body weight. There are no clinical data regarding the use of Augmentin in the form of a suspension for the treatment of children under 2 months of age, therefore there are no dosage recommendations. For information on dosing of the drug in this age group, please refer to the Instructions for Medical Use of the parenteral form of Augmentin. Renal dysfunction. Dosage adjustments are based on the maximum recommended doses of amoxicillin and depend on the glomerular filtration rate (GFR). For children with GFR 30 ml/min, the dose does not need to be changed. For the treatment of children with GFR ≤30 ml/min, Augmentin 228.5 mg/5 ml suspension is not recommended. In most cases, parenteral therapy should be given preference. Liver dysfunction. Use with caution and monitor liver function at regular intervals. The available data are insufficient to make dosage recommendations. For optimal absorption and to reduce possible gastrointestinal side effects, the drug should be taken at the beginning of a meal. Treatment should not be continued for more than 14 days without consulting a doctor. You can start treatment with parenteral administration of the drug, and continue with the oral form of the drug. Instructions for preparing the suspension: Dilute the powder contained in the bottle to form a suspension, as described below. Pour boiled water into a bottle with powder to the lower level indicated by a line with an arrow, close the lid and shake the bottle until a suspension is formed. Let the suspension stand for 5 minutes until completely dispersed. Add water to the upper level indicated by the arrow line and shake again. When diluted, a white suspension with a yellowish or slightly grayish tint is formed. After preparing the suspension, it should be stored in the refrigerator at a temperature of 2 to 8 °C for 7 days. When treating children under 2 years of age, Augmentin syrup can be diluted by half with water. Augmentin powder for the preparation of injection solution. Dosage is based on the patient's age, weight, and kidney function, as well as the severity of the infection. Doses are given in amoxicillin/clavulanate units. Augmentin is administered intravenously (slow stream, over 3-4 minutes) or drip (infusion time - 30-40 minutes). This form of Augmentin is not used for intramuscular injection. Treatment cannot last more than 14 days without assessing the results of use and the clinical picture. Dosage for adults: standard dose - 1000/200 mg every 8 hours, severe infections - 1000/200 mg every 4-6 hours. Prevention of complications during surgical interventions. Duration of surgery ≤1 hour - 1000/200 mg of the drug is administered before anesthesia. The duration of the operation is 1 hour - as indicated above, and up to 4 doses of 1000/200 mg of the drug are administered according to the instructions over 24 hours. The purpose of using Augmentin during surgical interventions is to reduce the risk of developing a postoperative infectious complication. In case of clinical signs of infection during surgery, it is necessary to carry out a full course of intravenous or oral use of Augmentin after surgery. Renal dysfunction . Dose adjustments are based on the maximum recommended doses of amoxicillin. Creatinine clearance ≤30 ml/min: no dose adjustment required. Creatinine clearance 10–30 ml/min: 1000/200 mg, then 500/100 mg 2 times a day. Creatinine clearance ≤10 ml/min: 1000/200 mg, then 500/100 mg every 24 hours. Hemodialysis . Dose adjustments are based on the maximum recommended doses of amoxicillin. The initial dose is 1000/200 mg, then 500/100 mg every 24 hours. Taking into account the need to maintain effective concentrations, another dose should be administered after the end of hemodialysis. Liver dysfunction . Care should be taken when dosing; continuous monitoring of liver function at regular intervals. The available data are insufficient to make dosage recommendations. Elderly patients . No dose adjustment is needed. Dosing is used for adults; if necessary, the dose is adjusted depending on renal function. Dosing for children . Dosing for children weighing ≤40 kg is based on body weight; the minimum interval between doses is 4 hours. Children under 3 months of age: child body weight ≤4 kg - 25/5 mg/kg every 12 hours; child's body weight is 4 kg - up to 25/5 mg/kg every 8 hours, depending on the course of the infection. Children aged 3 months to 12 years: 25/5 mg/kg every 6–8 hours, depending on the course of the infection. Renal dysfunction . Dose adjustments are based on the maximum recommended doses of amoxicillin. Creatinine clearance ≤30 ml/min - no dose adjustment required. Creatinine clearance 10–30 ml/min - 25/5 mg/kg 2 times a day. Creatinine clearance ≤10 ml/min - 25/5 mg/kg once a day. Hemodialysis . Dose adjustment is based on the maximum recommended doses of amoxicillin - 25/5 mg/kg 1 time per day. Taking into account the need to restore the effective concentration of the drug, another dose should be administered after the end of hemodialysis (25/5 mg/kg/day). Preparation of the solution. 600 mg vial: dissolve contents in 10 ml water for injection (final volume 10.5 ml). 1.2 g bottle: dissolve contents in 20 ml water for injection (final volume 20.9 ml). During dissolution, a temporary pink color may or may not appear, which disappears. Augmentin solutions are usually colorless or have a pale straw color. IV injection . The stability of Augmentin solution is concentration dependent, so Augmentin solution should be used immediately after dissolution and administered slowly over 3-4 minutes. Augmentin can be injected directly into a vein or through a catheter as a drip. IV infusion . Augmentin can be administered intravenously as an infusion, dissolved in water for injection or in 0.9% sodium chloride solution for injection. Add 600 mg solution to 50 ml of infusion fluid or 1.2 g solution to 100 ml of infusion fluid (it is better to use a mini-container or burette). Carry out the infusion over 30–40 minutes within a 4-hour period after dissolution. The solutions are brought to the full volume, which is introduced, immediately after dissolving the powder. The remaining antibiotic solutions cannot be used. Stability of the prepared solution . To dissolve Augmentin for intravenous infusion, various intravenous solutions can be used. A satisfactory concentration of the antibiotic is maintained at 5 °C at room temperature (25 °C) in the recommended volumes of the infusion solutions indicated below. When the drug is dissolved and stored at room temperature, the infusion should be carried out for the time indicated below

The stability of Augmentin solutions depends on the concentration. If the solution is prepared at a higher concentration, the stability period of the solution increases proportionally. When stored at 5 °C, 1000/200 mg and 500/100 mg solutions can be added to a pre-cooled infusion solution (in a sterile plastic container) and the resulting drug can be stored at this temperature for up to 8 hours.

When warmed to room temperature, the solution should be used immediately. Augmentin is less stable in solutions of glucose, dextran and bicarbonate. Solutions on this basis must be used within 3–4 minutes after dissolution. Any unused solution should be destroyed. Augmentin is not designed for multi-dose use. Augmentin ES. Children aged 3 months and older: the recommended dose is 90/6.4 mg/kg/day in 2 divided doses at 12-hour intervals for 10 days (see table below). There is no experience of use for the treatment of children weighing 40 kg and adults. There is also no experience of clinical use for the treatment of children under 3 months of age.

Augmentin ES does not contain the same amount of clavulanic acid (as the potassium salt) as other forms of Augmentin suspension. Augmentin ES contains 42.9 mg clavulanic acid per 5 ml suspension, while Augmentin 200 mg/5 ml suspension contains 28.5 mg clavulanic acid per 5 ml, and 400 mg/5 ml suspension contains 57 mg clavulanic acid per 5 ml. Therefore, Augmentin ES cannot be replaced by any other form of Augmentin suspension. Liver dysfunction . Use cautiously and monitor liver function at regular intervals. The available data are insufficient to make dosage recommendations. Renal dysfunction . There are no recommendations regarding the use of the drug for the treatment of this group of patients. In order to minimize the risk of undesirable effects of Augmentin ES on the gastrointestinal tract, the drug is taken at the beginning of a meal, while the absorption of Augmentin ES is optimal. Treatment can be started with parenteral administration of the drug, and continued with an oral form of the drug. Preparation of the suspension Add 90 ml of water to the bottle with the powder. Water is added in 2 additions. First, add approximately 2/3 of the specified amount of water so that the powder in the bottle is freely covered with water, close the lid and shake the bottle until a suspension is formed. Then add the rest of the water and shake again. When diluting the first time, the suspension should be allowed to stand for 5 minutes until completely dispersed. When diluted, a white suspension with a yellowish or grayish tint is formed. Store the prepared suspension in the refrigerator at a temperature of 2 to 8 °C and use for 10 days.

Instructions for use AUGMENTIN

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 to reduce possible side effects from the digestive system, Augmentin is recommended to be taken 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 (at the beginning of intravenous administration of the drug, followed by switching to oral administration).

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

1 tablet (875 mg + 125 mg) 2 times a day or 1 tablet (500 mg + 125 mg) 3 times a day.

Children under 12 years old

The dose, depending on age and body weight, is indicated in mg/kg body weight per day or in ml of suspension.

Recommended dosage regimen:

• 45 mg/kg/day in 2 divided doses or 40 mg/kg/day in 3 divided doses. The frequency of administration depends on the form of release.

Children weighing 40 kg or more

the drug should be prescribed in the same doses as for adults.

Single doses of Augmentin depending on age and body weight are presented in the table.

* for amoxicillin.

For correct dosing of the volume of suspension in children under 3 months

It is recommended to use a graduated syringe.

For ease of use in children under 2 years of age

the suspension can be diluted by half with water.

In the treatment of skin and soft tissue infections, as well as recurrent tonsillitis

the drug can be prescribed at a dose of 20 mg/kg/day in 3 doses (suspension 4:1) and 25 mg/kg/day in 2 doses (suspension 7:

• 1).

If the frequency of isolation of pneumococcus with a high level of penicillin resistance (with a penicillin MIC of 2-4 mg/l) in the region (or closed institution) exceeds 10%, it is necessary to use amoxicillin/clavulanate (Augmentin) at a dose of 80-90 mg/kg/day, divided for 3 doses.

The optimal dosage form of Augmentin for children from 6 to 12 years old

are tablets 500 mg + 125 mg, taken 2 times a day.

Patients with impaired renal function

Dose adjustments are based on the maximum recommended dose of amoxicillin and are carried out taking into account QC values.

Adults

Tablets 875 mg + 125 mg should be used only in patients with CC >30 ml/min.

Children

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

Patients on hemodialysis

Dose adjustments are based on the maximum recommended dose of amoxicillin.

For adults

prescribe 1 tablet. (500 mg+125 mg) every 24 hours.

Additionally, 1 dose is prescribed during the dialysis session and another 1 dose at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

For children

Prescribe 15 mg+3.75 mg/kg 1 time/day.

Before a hemodialysis session, one additional dose of 15 mg + 3.75 mg/kg should be administered. To restore the concentrations of the active ingredients 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 liver dysfunction

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

Elderly patients

There is no need to reduce the dose of Augmentin; doses are the same as for adults. In elderly patients with impaired renal function

the dose should be adjusted as above for adults with impaired renal function.

Method of application of the suspension

The suspension is prepared immediately before the first use. The powder should be dissolved with boiled water cooled to room temperature, gradually shaking and adding water to the mark on the bottle. Then let stand for about 5 minutes to ensure complete dissolution. The bottle should be shaken well before each use. For an accurate dosage of the drug, you should use a measuring cap, which should be rinsed well with water after each use. After dilution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.

Side effects of Augmentin™

Side effects were classified by organs and systems and by frequency of occurrence. According to the frequency of occurrence, they are divided into the following categories: very often (≥1/10), often (≥1/100 and ≤1/10), infrequently (≥1/1000 and ≤1/100), rarely (≥1/10 000 and ≤1/1000), very rare (≤1/10,000). Infections and infestations Often: candidiasis of the skin and mucous membranes. Blood and lymphatic systems Rare: reversible leukopenia (including neutropenia) and thrombocytopenia. Very rare: reversible agranulocytosis and hemolytic anemia, increased bleeding time and prothrombin index. Immune system Very rare: angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis. Nervous system Uncommon : dizziness, headache. Very rare : reversible hyperactivity and convulsions. Convulsions may occur in patients with impaired renal function or in patients receiving the drug in high doses. Vascular disorders Rare: thrombophlebitis at the injection site. Gastrointestinal tract Very often: diarrhea (when using tablet forms). Often: diarrhea (when using suspension and injection forms), nausea, vomiting. Uncommon : indigestion. Nausea is more often noted when using the drug in high doses. The above gastrointestinal symptoms can be reduced by taking the drug at the beginning of a meal. Very rare : antibiotic-associated colitis, including pseudomembranous and hemorrhagic colitis (the likelihood of its development is much lower with parenteral administration of the drug), black and “hairy” tongue. Hepatobiliary reactions Uncommon: Moderate increases in liver transaminases have been detected in patients taking beta-lactam antibiotics, but the clinical significance of this has not been established. Very rare : hepatitis and cholestatic jaundice. The same phenomena were noted with the use of other penicillins or cephalosporins. Hepatitis occurred mainly in men and elderly patients; their occurrence may be associated with prolonged treatment with the drug. In children, such manifestations occurred very rarely. Signs and symptoms occur during or immediately after treatment, but in some cases may appear several weeks after stopping treatment. These phenomena are usually reversible. Extremely rare (less than 1 report in approximately 4 million prescriptions) deaths occur, which always occur in patients with a severe underlying disease or while taking drugs that have a negative effect on the liver. Skin and subcutaneous tissues Uncommon: skin rash, itching and urticaria. Rare : erythema multiforme. Very rare : Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis and acute generalized exanthematous pustulosis. If any allergic dermatitis occurs, treatment should be discontinued. Kidneys and urinary system Very rare: interstitial nephritis, crystalluria (see OVERDOSE).

AUGMENTIN

Side effects

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 defined as follows: very common (≥ 1/10), common (≥ 1/100 and < 1/10), uncommon (≥ 1/1,000 and <1/100), rare (≥ 1/10,000 and <1/1,000), very rare (<1/10,000, including isolated cases). Frequency categories were formed based on clinical studies of the drug and post-registration surveillance. Frequency of occurrence of adverse reactions

Infectious and parasitic diseases

Common: candidiasis of the skin and mucous membranes.

Blood and lymphatic system disorders

Rare: reversible leukopenia (including neutropenia), reversible thrombocytopenia. Very rare: reversible agranulocytosis and reversible hemolytic anemia, prolongation of bleeding time and prothrombin time, anemia, eosinophilia, thrombocytosis.

Immune system disorders

Very rare: angioedema, anaphylactic reactions, serum sickness-like syndrome, allergic vasculitis.

Nervous system disorders

Uncommon: dizziness, headache. Very rare: reversible hyperactivity, seizures. Seizures may occur in patients with impaired renal function, as well as in 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.

Whole population

Nausea was most often associated with the use of high doses of the drug. If, after starting to take the drug, undesirable reactions from the gastrointestinal tract are observed, they can be eliminated if Augmentin® is taken at the beginning of the meal.

Uncommon: indigestion. Very rare: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis) (see section "Special Instructions"), black "hairy" tongue, gastritis, stomatitis. Changes in the color of the surface layer of tooth enamel in children.

Disorders of the liver and biliary tract

Uncommon: moderate increase in aspartate aminotransferase and/or alanine aminotransferase (AST and/or ALT) activity. This reaction has been observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown. Very rare: hepatitis and cholestatic jaundice. These reactions are observed in patients receiving therapy with penicillin antibiotics 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 patients with serious comorbidities or patients receiving concomitantly potentially hepatotoxic drugs.

Skin and subcutaneous tissue disorders

Uncommon: rash, itching, urticaria. Rarely: erythema multiforme. Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

Renal and urinary tract disorders

Very rare: interstitial nephritis, crystalluria (see section “Overdose”), hematuria.

Special instructions for the use of Augmentin™

Before starting Augmentin therapy, it is necessary to exclude a history of hypersensitivity reactions to penicillins and cephalosporins or other allergens. Severe, sometimes fatal hypersensitivity reactions (anaphylactoid reactions) have occurred in patients during penicillin therapy. Such reactions are more likely in patients with a history of hypersensitivity to penicillins (see CONTRAINDICATIONS). If allergic reactions occur, treatment with Augmentin should be discontinued and alternative therapy should be prescribed. Severe anaphylactic reactions require emergency treatment with adrenaline, oxygen therapy, intravenous administration of corticosteroids and provision of pulmonary function, including intubation. Augmentin should not be prescribed if infectious mononucleosis is suspected, since cases of measles-like rash have been reported with the use of amoxicillin for this pathology. Long-term use of the drug may cause excessive growth of microflora insensitive to Augmentin. Augmentin is usually well tolerated and exhibits low toxicity typical of penicillin antibiotics. With prolonged use, the functions of organs and systems, including the functions of the kidneys, liver and hematopoiesis, should be periodically monitored. Occasionally, patients taking Augmentin experience an increase in prothrombin time. When taking anticoagulants concomitantly, appropriate monitoring is necessary. Augmentin should be used with caution in patients with impaired liver function. In patients with impaired renal function, the dose must be adjusted according to the severity of renal failure. If parenteral administration of high doses of the drug is necessary, the sodium concentration in solutions administered to patients on a sodium-controlled diet should be taken into account. In patients with reduced diuresis, crystalluria very rarely occurs, mainly with parenteral use of the drug. Therefore, to reduce the risk of its occurrence during treatment with the drug in high doses, it is recommended to ensure an adequate balance between drunk and excreted fluid (see OVERDOSE). Augmentin ES contains aspartame (every 5 ml of suspension contains 7 mg of phenylalanine), so this form of the drug should be used with caution when treating patients with phenylketonuria. During pregnancy and breastfeeding . Pregnancy (category B) . Reproductive studies in animals (using doses 10 times higher than human doses) of oral and parenteral forms of Augmentin did not reveal teratogenic effects. One study in women with premature rupture of membranes reported that prophylactic use of Augmentin during pregnancy may be associated with an increased risk of necrotizing enterocolitis in the newborn. Prescribing the drug during pregnancy, especially in the first trimester, should be avoided, unless the benefit of the drug outweighs the potential risk. Breastfeeding period. Augmentin can be used during breastfeeding. Excluding the risk of hypersensitivity associated with the excretion of trace amounts of Augmentin in breast milk, no harmful effects on a breastfed child have been identified. Children . Augmentin (BD) (this dosage) is not recommended for use in children under 12 years of age. No negative effects on the ability to drive vehicles or operate other mechanisms , however, the possibility of developing such a side effect as dizziness should be taken into account.

Instructions for use AUGMENTIN® tablets

Before starting treatment with amoxicillin/clavulanic acid, it is necessary to obtain a detailed history regarding previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics (see sections “Contraindications” and “Side effects”).

Serious, sometimes fatal, hypersensitivity reactions (anaphylactoid reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins and in individuals with atopy. If an allergic reaction occurs, treatment with amoxicillin/clavulanic acid should be discontinued and alternative therapy should be initiated.

If the infection is confirmed to be due to amoxicillin-susceptible organisms, a switch from amoxicillin/clavulanic acid therapy to amoxicillin therapy should be considered in accordance with official guidelines.

Augmentin® 875 mg/125 mg and 500 mg/125 mg tablets are not suitable for use in cases where there is a high risk that the suspected pathogens have beta-lactam resistance that is not mediated by clavulanic acid-inhibited beta-lactamases. This dosage form should not be used in the treatment of infections caused by penicillin-resistant Streptococcus pneumoniae.

In patients with impaired renal function or when taking the drug in high doses, seizures may occur (see section "Side effects").

The use 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 combination of amoxicillin/clavulanic acid should be used with caution in patients with signs of liver failure (see sections “Dosage regimen”, “Contraindications”, “Special instructions”).

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. Adverse effects from the liver can be severe, and in extremely rare cases there have been reports of death. 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 agents. This adverse reaction can vary in severity from mild to life-threatening (see section "Side effects"). Therefore, this diagnosis should be considered in patients who develop diarrhea during treatment or after administration of any antibiotics. 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 Augmentin®, it is recommended to periodically evaluate renal, liver and hematopoietic function.

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 (see section “Drug Interactions” and “Side Effects”).

In patients with impaired renal function, the dose of Augmentin® should be adjusted according to the degree of impairment (see section "Dosage regimen").

In patients with reduced diuresis, the development of crystalluria has been reported in very rare cases, mainly with parenteral use of the drug. 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 (see section "Overdose").

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 amoxicillin/clavulanic acid combination may have a false-positive test result for Aspergillus infection using the Platelia Aspergillus EIA tests. There have been reports of cross-reactions between the Platelia Aspergillus EIA test and non-Aspergillus polysaccharides and polyfuranoses. Therefore, positive test results in patients taking the combination of amoxicillin/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. However, adverse reactions may occur (allergic reactions, dizziness, convulsions), which may affect the ability to drive vehicles and other mechanisms.

Interactions of the drug Augmentin™

Concomitant use of probenecid is not recommended since probenecid reduces the tubular secretion of amoxicillin. Its simultaneous use with Augmentin can lead to an increase in the level of amoxicillin in the blood plasma for a long time; does not affect the level of clavulanic acid. Concomitant use of allopurinol during treatment with amoxicillin increases the likelihood of developing skin allergic reactions. There are no data regarding the combined use of Augmentin and allopurinol. Like other antibiotics, Augmentin can affect the intestinal flora, which leads to a decrease in estrogen reabsorption and a decrease in the effectiveness of combined oral contraceptives. The presence of clavulanic acid in Augmentin can cause nonspecific binding of IgG and albumin on red blood cell membranes, as a result of which the Coombs test may be false positive. Incompatibility. Augmentin in solution for injection should not be mixed with blood products, other liquids containing protein, in particular, with protein hydrolysates, with fat emulsions for intravenous use. If Augmentin is used simultaneously with aminoglycosides, antibiotics should not be mixed in the same syringe or other container due to inactivation of the aminoglycoside.

Overdose of Augmentin™, symptoms and treatment

May be accompanied by symptoms from the digestive tract and disturbances in water and electrolyte balance. Treatment is symptomatic, correction of water and electrolyte disturbances is carried out. Crystalluria may occur, which in some cases leads to renal failure. There are reports of amoxicillin precipitation in the urinary catheter when using IV Augmentin in high doses, so its patency should be checked regularly. Augmentin can be removed from the bloodstream by hemodialysis.