Amoxicilina Acido Clavulánico Vitalis

For all dosage forms

Infections caused by sensitive strains of microorganisms:

upper respiratory tract and ENT organs (including acute and chronic sinusitis, acute and chronic otitis media, pharyngeal abscess, tonsillitis, pharyngitis),

lower respiratory tract (including acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia),

urinary tract infections (e.g. cystitis, urethritis, pyelonephritis),

in gynecology,

skin and soft tissue, including human and animal bites,

bone and connective tissue,

bile ducts (cholecystitis, cholangitis),

odontogenic.

Amoxiclav^®

For powder for preparation of solution for intravenous administration in addition

abdominal infections,

sexually transmitted infections (gonorrhea, mild chancre),

prevention of infections after surgical interventions.

The drug Augmentin^® CP is indicated for the treatment of bacterial infections of the following localizations caused by microorganisms sensitive to the combination of amoxicillin with clavulanic acid:

respiratory tract infections, such as community-acquired pneumonia, exacerbation of chronic bronchitis, acute bacterial sinusitis, usually caused by Streptococcus pneumoniae (including penicillin-resistant strains), Haemophilus influenzae¹, Moraxella catarrhalis¹ and Streptococcus pyogenes,

prevention of local infections after surgery in dentistry.

¹ Some strains of these bacteria produce beta-lactamases, which makes them insensitive to amoxicillin monotherapy.

Infections caused by amoxicillin-sensitive microorganisms can be treated with Augmentin^® CP, since amoxicillin is one of its active ingredients. The drug Augmentin^® CP is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as beta-lactamase-producing microorganisms sensitive to the combination of amoxicillin with clavulanic acid.

The drug Augmentin^® CP demonstrated efficacy against strains S. pneumoniae, resistant to penicillin (strains with MPC ≥2 mg/l).

Preparations containing a combination of amoxicillin with clavulanic acid should be used in accordance with the Russian guidelines for antibiotic therapy and regional data on the sensitivity of pathogens to the combination of amoxicillin with clavulanic acid.

The sensitivity of bacteria to the combination of amoxicillin with clavulanic acid varies depending on the region and over time. Where possible, local sensitivity data should be taken into account. If necessary, microbiological samples should be collected and analyzed for bacteriological sensitivity.

It is also used for the prevention of infections that are associated with major surgical operations on the gastrointestinal tract, in the pelvis, head and neck, on the heart, kidneys, and bile ducts.

Amoxiclav^®

Film-coated tablets

Inside. 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.

The drug Amoxiclav^® it is recommended to take it at the beginning of a meal for optimal absorption and to reduce possible side effects from the digestive system.

The course of treatment is 5-14 days. The duration of the course of treatment is determined by the attending physician. Treatment should not last more than 14 days without a second medical examination.

Children under 12 years old

The dose is prescribed depending on the age and body weight. The recommended dosage regimen is 40 mg / kg / day in 3 doses.

Children with a body weight of 40 kg or more should be prescribed the same doses as adults. For children aged less than 6 years, it is more preferable to take a suspension of the drug Amoxiclav^®.

Adults and children over 12 years of age (or >40 kg of body weight)

The usual dose in the case of mild and moderate infection is 1 tab. 250 125 mg every 8 hours or 1 tab. 500 125 mg every 12 hours, in the case of severe infection and respiratory tract infections-1 tab. 500 125 mg every 8 hours or 1 tab. 875 125 mg every 12 hours.

Since the tablets of the combination of amoxicillin and clavulanic acid of 250 125 mg and 500 125 mg contain the same amount of clavulanic acid-125 mg, then 2 tables of 250 125 mg are not equivalent to 1 table of 500 125 mg.

Dosage for odontogenic infections

1 tab. 250 125 mg every 8 hours or 1 tab. 500 125 mg every 12 hours for 5 days.

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 Cl creatinine:

- adults and children over 12 years of age (or ≥40 kg of body weight) (Table 2),

- with anuria, the interval between dosing should be increased to 48 hours or more,

- tablets 875 125 mg should only be used in patients with creatinine Cl >30 ml / min.

Table 2

Patients with impaired liver function

Taking the drug Amoxiclav^® it should be carried out with caution. It is necessary to conduct regular monitoring of liver function.

Powder for preparation of suspension for oral administration

Inside

The daily dose of suspensions is 125 31.25 mg/5 ml and 250 62.5 mg/5 ml (to facilitate correct dosing, a 5-ml graduated pipette with a 0.1-ml scale or a 5-ml dosing spoon with a 2.5-ml ring mark in the cavity is inserted into each package of suspensions 125 31.25 mg/5 ml and 250 62.5 mg/5 ml).

Newborns and children up to 3 months old — 30 mg / kg / day (according to amoxicillin), divided into 2 doses (every 12 hours).

Dosage of Amoxiclav^® dosage pipette-calculation of single doses for the treatment of infections in newborns and children up to 3 months (Table 3).

Table 3

Children older than 3 months — from 20 mg / kg for mild and moderate infections to 40 mg / kg for severe infections and lower respiratory tract infections, otitis media, sinusitis (amoxicillin) per day, divided into 3 doses (every 8 hours).

Dosage of Amoxiclav^® dosage pipette-calculation of single doses for the treatment of mild and moderate infections in children older than 3 months (at the rate of 20 mg/kg/day (according to amoxicillin) (Table 4).

Table 4

Dosage of Amoxiclav^® dosage pipette-calculation of single doses for the treatment of severe infections in children older than 3 months (at the rate of 40 mg / kg / day (according to amoxicillin) (Table 5).

Table 5

Dosage of Amoxiclav^® dosage spoon (in the absence of a dosage pipette) - recommended doses of suspensions depending on the child's body weight and the severity of the infection (Table 6).

Table 6

Daily dose of suspension 400 mg 57 mg/5 ml

The dose is calculated per kg of body weight, depending on the severity of the infection. From 25 mg / kg - for mild and moderate infections to 45 mg/kg-for severe infections and lower respiratory tract infections, otitis media, sinusitis (in terms of amoxicillin) per day, divided into 2 doses.

To facilitate correct dosing, a dosing pipette is inserted into each package of 400 mg 57 mg/5 ml suspension, graduated simultaneously into 1, 2, 3, 4, 5 ml and into 4 equal parts.

Suspension 400 mg 57 mg/5 ml is used in children older than 3 months.

Table 7

The recommended dose of the suspension depends on the child's body weight and the severity of the infection

The exact daily doses are calculated based on the child's body weight, not their age.

The maximum daily dose of amoxicillin is 6 g for adults and 45 mg/kg for children.

The maximum daily dose of clavulanic acid (in the form of potassium salt) is 600 mg for adults and 10 mg/kg for children.

In patients with impaired renal function, the dose should be adjusted based on the maximum recommended dose of amoxicillin.

Patients with creatinine Cl >30 ml / min do not require any dose adjustment.

Adults and children weighing more than 40 kg (the specified dosage regimen is used for moderate and severe infections)

Patients with creatinine Cl 10-30 ml / min — 500/125 mg 2 times a day.

When creatinine Cl <10 ml / min, the recommended dose is 500/125 mg once a day.

For patients on hemodialysis, the recommended dose is 500/125 mg every 24 hours, plus 500/125 mg during dialysis and another dose at the end of dialysis (since serum concentrations of amoxicillin and clavulanic acid are reduced).

Children weighing less than 40 kg

With a creatinine Cl of 10-30 ml / min, the recommended dose is 15/3. 75 mg / kg 2 times a day (maximum 500/125 mg 2 times a day).

When creatinine Cl <10 ml / min, the recommended dose is 15/3. 75 mg / kg once a day (maximum 500/125 mg).

For hemodialysis, the recommended dose is 15/3. 75 mg / kg once a day. Before hemodialysis — 15/3. 75 mg/kg. To restore the appropriate concentrations of the drug in the blood,it is necessary to take another dose of 15/3. 75 mg/kg after hemodialysis.

The course of treatment is 5-14 days. The duration of the course of treatment is determined by the attending physician. Treatment should not last more than 14 days without a second medical examination.

Instructions for preparing the suspension

Powder for suspension preparation 125 31.25 mg/5ml - shake the bottle vigorously, add 86 ml of water in two doses (up to the mark), each time shaking well until the powder is completely dissolved.

Powder for suspension preparation 250 62.5 mg/5ml - shake the bottle vigorously, add 85 ml of water in two doses (up to the mark), shaking well each time until the powder is completely dissolved.

Suspension preparation powder 400 mg 57 mg/5 ml - shake the bottle vigorously, add water in two steps (up to the label) in the amount indicated on the label and shown in the table, each time shaking well until the powder is completely dissolved.

Table 8

Shake vigorously before use!

To prepare the suspension, it is recommended to dilute the powder with boiled water at room temperature. It is recommended to place the finished suspension in the refrigerator.

It is not recommended to heat the suspension before use (it is necessary to bring the suspension to room temperature).

After taking the drug, it is recommended to rinse the dosage pipette with boiled water.

Powder for preparation of solution for intravenous administration

In/in.

Children: with a body weight of less than 40 kg-the dose is calculated depending on the body weight.

Under 3 months with a body weight of less than 4 kg - 30 mg / kg (in terms of the entire drug Amoxiclav^®) every 12 hours.

Under 3 months with a body weight of more than 4 kg - 30 mg / kg (in terms of the entire drug Amoxiclav^®) every 8 hours.

In children younger than 3 months, the drug Amoxiclav^® it should be administered only slowly by infusion for 30-40 minutes.

Children from 3 months to 12 years old - 30 mg / kg (in terms of the entire drug Amoxiclav^®) at intervals of 8 hours, in the case of severe infection - at intervals of 6 hours.

Children with impaired renal function

The dose adjustment is based on the maximum recommended dose of amoxicillin. In patients with creatinine Cl values above 30 ml/min, dose adjustment is not necessary.

Children weighing <40 kg:

Every 30 mg of Amoxiclav^® they contain 25 mg of amoxicillin and 5 mg of clavulanic acid.

Adults and children over 12 years of age or weighing more than 40 kg - 1.2 g of the drug (1000-200 mg) at an interval of 8 hours, in case of severe infection - at an interval of 6 hours.

Prophylactic doses for surgical interventions: 1.2 g for introductory anesthesia (if the duration of the operation is less than 2 hours). For longer operations-1.2 g up to 4 times during the day.

For patients with renal insufficiency, the dose and / or interval between injections of the drug should be adjusted depending on the degree of insufficiency:

Since 85% of the drug is removed by hemodialysis, the usual dose of Amoxiclav should be administered at the end of each hemodialysis procedure^®. In peritoneal dialysis, dose adjustment is not required.

The course of treatment is 5-14 days. The duration of the course of treatment is determined by the attending physician. With a decrease in the severity of symptoms, it is recommended to switch to oral forms of the drug Amoxiclav to continue therapy^®.

Preparation of solutions for intravenous injection. Dissolve the contents of the vial in water for injection: 600 mg (500 100 mg) - in 10 ml of water for injection or 1.2 g (1000 200 mg) - in 20 ml of water for injection. In/in enter slowly (within 3-4 minutes).

The drug Amoxiclav^® it should be administered within 20 minutes after the preparation of solutions for intravenous administration.

Preparation of solutions for intravenous infusions. For infusion administration of the drug Amoxiclav^® further dilution is necessary: prepared solutions containing 600 mg (500 100 mg) or 1.2 g (1000 200 mg) of the drug should be diluted in 50 or 100 ml of the infusion solution, respectively. The duration of the infusion is 30-40 minutes.

When using the liquids listed below in the recommended volumes, the necessary concentrations of the antibiotic are preserved in the infusion solutions:

Solution of the drug Amoxiclav^® do not mix with dextrose, dextran, or sodium bicarbonate solutions.

Only clear solutions should be used. Prepared solutions should not be frozen.

Amoxiclav^® Quicktab

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

The tablets should be dissolved in half a glass of water (at least 30 ml) and thoroughly mixed, then drink or hold the tablets in your mouth until completely dissolved, then swallow.

In order to reduce the risk of side effects from the gastrointestinal tract, you should take the drug at the beginning of a meal.

Dispersible tablets of the drug Amoxiclav^®Quicktab 500 mg/125 mg:

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

For the treatment of mild and moderate infections — 1 tablet (500 mg/125 mg) every 12 hours (2 times a day).

For the treatment of severe infections and respiratory infections — 1 tablet (500 mg/125 mg) every 8 hours (3 times a day).

Maximum daily dose of Amoxiclav^®Quicktab is 1500 mg of amoxicillin/375 mg of clavulanic acid.

Patients with impaired renal function. In patients with a creatinine Cl above 30 ml/min, there is no need for dose adjustment.

Adults and children over 12 years of age with a body weight of ≥40 kg (the indicated dosage regimen is used for moderate and severe infections):

Dispersible tablets of the drug Amoxiclav^®Quicktab 875 mg/125 mg:

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

For severe infections and respiratory infections — 1 table (875 mg / 125 mg) every 12 hours (2 times a day).

Daily dose of Amoxiclav^®Quicktab when used 2 times a day is 1750 mg of amoxicillin/250 mg of clavulanic acid.

Patients with impaired renal function. In patients with a creatinine Cl of more than 30 ml/min, there is no need for dose adjustment.

Patients with creatinine Cl less than 30 ml / min using dispersible tablets of Amoxiclav^®Quicktab, 875 mg/125 mg is contraindicated.

Such patients should take the drug at a dosage of 500 mg/125 mg after a dose adjustment corresponding to the level of Cl creatinine.

Patients with impaired liver function. When taking the drug Amoxiclav^®Quicktab should be careful. It is necessary to conduct regular monitoring of liver function. In the case of starting treatment with parenteral administration of the drug, therapy can be continued by taking tablets of the drug Amoxiclav^®Quicktab.

The duration of the course of treatment is determined by the attending physician!

The minimum course of antibacterial therapy is 5 days. Treatment should not last more than 14 days without reviewing the clinical situation.

Inside, drinking water, at the beginning of a meal (in order to reduce the risk of side effects from the gastrointestinal tract), 2 times a day, strictly observing the interval between meals of 12 hours.

Film-coated tablets

Adults and children over 12 years of age (body weight ≥40 kg)

Take 1 tablet. 2 times a day, every 12 hours.

The maximum daily dose of amoxicillin for adults is 6 g, for children-45 mg / kg / day.

The maximum daily dose of clavulanic acid for adults (in the form of potassium clavulanate) is 600 mg, for children-10 mg/kg / day.

The course of treatment is 5-14 days, set individually, taking into account the characteristics of the pathogen, localization and severity of the infection. Treatment should not last more than 14 days without a second medical examination.

Dosage for renal failure

Tablets 875/125 mg should be used only in patients with a creatinine Cl of more than 30 ml / min, and dose adjustment is not required.

Patients on peritoneal dialysis do not need to adjust the dose. Patients on hemodialysis may need to adjust the dose of the drug.

Powder for preparation of suspension for oral administration

Dose with a measuring spoon, taking into account that 5 ml of the finished suspension contains amoxicillin 400 mg/clavulanic acid 57 mg. Drink 0.5-1 cup of water.

The dose of Panclav 2X is prescribed by a doctor, taking into account the characteristics of the pathogen, localization and severity of the infection. The dosage regimen is set individually, depending on age, body weight (for children) and kidney function. The course of treatment is 5-14 days, set individually.

For infections that require a long course of therapy (for example, osteomyelitis), exceeding the maximum recommended course of therapy of 14 days is possible only after a thorough assessment by the doctor of the patient's condition, the achieved and expected therapeutic effects and risks.

The maximum daily dose of amoxicillin for adults is 6 g, for children-45 mg / kg / day. The maximum daily dose of clavulanic acid for adults (in the form of potassium clavulanate) is 600 mg, for children-10 mg/kg / day.

Adults and children over 12 years of age (body weight ≥40 kg)

Standard dosage regimen for all indications:

2 scoops (800/114 mg) 2 times a day, every 12 hours.

Children from 2 to 12 years (body weight ≥40 kg)

Children from 3 months to 3 years old

The daily dose for children older than 3 months and up to 12 years (body weight ≥40 kg) is 25-45 mg/kg / day (based on amoxicillin), divided into two doses, every 12 hours.Low doses of the drug (25 mg/kg/day) are used to treat skin and soft tissue infections, as well as recurrent tonsillitis. High doses of the drug (45 mg / kg / day) are used to treat diseases such as otitis media, sinusitis, lower respiratory tract and urinary tract infections. The duration of treatment of acute uncomplicated otitis media is 5-7 days, in children-7-10 days.

Children and adults with renal insufficiency

With a creatinine Cl of less than 30 ml / min, the drug at this dose is not recommended, with a creatinine Cl of more than 30 ml/min, there is insufficient evidence to develop special recommendations for the dosage regimen. It is allowed both to reduce the dose of the drug, and to increase the interval between doses.

Preparation of suspension for oral administration

In the bottle with the powder, gradually add water to the mark (distilled water or boiled and cooled) and shake until the powder is evenly wet (about 30 c). If the level of the prepared suspension is below the label on the bottle label, re-add water to the label and shake.

The finished suspension must be shaken before each meal.

Important! If the drug is missed, you should take the tablet (or suspension) as soon as possible, without waiting for the time of the next dose. Then observe equal intervals of time between meals — 12 hours. You should never take a double dose to make up for a missed medication!

Inside.

To optimize absorption, the drug should be taken at the beginning of a meal.

Treatment should not last more than 14 days without reviewing the clinical situation.

Tablets of the drug Augmentin^® The SRS have a dividing groove that allows them to be broken in half for ease of ingestion, but not to reduce the dose: both halves must be taken simultaneously. The recommended dose of the drug is 2 tablets. 2 times a day.

Adults (16 years and older). Respiratory tract infections: 2 table. 2 times a day for 7-10 days, including the following diseases:

- community-acquired pneumonia — 2 tables. 2 times a day for 7-10 days,

- exacerbation of chronic bronchitis — 2 tables. 2 times a day for 7 days,

- acute sinusitis of bacterial etiology — 2 tables. 2 times a day for 10 days.

Prevention of local infections after surgical dental interventions: 2 tables. 2 times a day for 5 days starting 3 hours after the intervention.

Special patient groups

Children under 16. Not applicable.

Elderly patients. No dosage adjustment is required.

Patients with impaired renal function. No dosage adjustment is required for creatinine Cl ≥30 ml/min. It is not recommended to prescribe the drug to patients with creatinine Cl <30 ml/min.

Patients on hemodialysis. Not recommended.

Impaired liver function. Treatment is carried out with caution, liver function is regularly monitored. There is insufficient data to recommend a dosage regimen for this group of patients.

In/in. Enter slowly, for 3-4 minutes, no later than 20 minutes after dissolution. For the infusion, 600 mg of the substance is dissolved in 50 ml of the infusion solution or 1.2 g of the substance in 100 ml of the solution. The duration of the drip infusion is 30-40 minutes. The drug can be administered in various infusion solutions, except for glucose (dextrose) solution.

Adults and children over 12 years of age: 1.2 g every 8 hours, with more severe infections, the interval between injections is reduced to 6 hours.

Children from 3 months to 12 years: 30 mg / kg every 8 hours, with more severe infections, the interval between injections is reduced to 6 hours.

Children under 3 months: 30 mg / kg every 12 hours in premature infants and newborns, then the interval between injections is reduced to 8 hours.

30 mg of the intravenous drug contains 25 mg of amoxicillin and 5 mg of clavulanic acid.

In surgical practice, Amoxicilina Acido Clavulánico Vitalis is used to protect against infection during surgery. Adults are given 1.2 g intravenously before anesthesia, if the intervention lasts more than an hour. The course of treatment can be extended for several days if the risk of infection was increased during the intervention. The drug should also be used in postoperative treatment.

With reduced renal function: adults with mild insufficiency (creatinine Cl > 30 ml / min) there is no need to reduce the dosage, with moderate insufficiency (Cl creatinine — 10-30 ml/min), treatment begins with the introduction of 1.2 g / in, then 600 mg / in every 12 hours, with severe renal insufficiency (Cl creatinine < 10 ml / min), treatment begins with the introduction of 1.2 g / in, then continue with 600 mg / in every 24 hours, dialysis reduces the concentration in the serum, so the drug is prescribed at a dosage of 600 mg / in during or after dialysis. The dosage for children is also reduced.

Treatment of adults and children can last 14 days, after which it is necessary to decide whether to continue antibacterial therapy or cancel it.

Inside, before or during a meal. Adults and children over 12 years of age: moderate infections-375 mg (1 table) 3 times a day, severe infections-625 mg 3 times a day. The duration of the course of treatment-no more than 14 days.

In case of impaired renal function, adults:

hypersensitivity to the components of the drug,

hypersensitivity to penicillins, cephalosporins and other beta-lactam antibiotics in the anamnesis,

a history of cholestatic jaundice and/or other liver disorders caused by amoxicillin/clavulanic acid,

infectious mononucleosis and lymphocytic leukemia,

For Amoxiclav dispersible tablets^® Quicktab optional

children under 12 years of age or with a body weight of less than 40 kg.

phenylketonuria,

renal insufficiency (creatinine Cl <30 ml / min) (for dispersible tablets 875 mg 125 mg)

With caution: pseudomembranous colitis in the anamnesis, gastrointestinal diseases, liver failure, severe renal impairment, pregnancy, lactation, concomitant use with anticoagulants.

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.

With caution: liver function disorders.

Hypersensitivity to penicillin antibiotics, infectious mononucleosis, lymphocytic leukemia.

Amoxiclav^® film-coated tablets and powder for the preparation of a solution for intravenous administration

From the digestive system: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, gastritis, stomatitis, glossitis, black "hairy" tongue, darkening of tooth enamel, hemorrhagic colitis (also can develop after therapy), enterocolitis, pseudomembranous colitis, impaired liver function, increased ALT, AST, ALP and/or bilirubin levels in blood plasma, liver failure (more often in the elderly, men, with long-term therapy), cholestatic jaundice, hepatitis.

Allergic reactions: itching, urticaria, erythematous rashes, multiform exudative erythema, angioedema, anaphylactic shock, allergic vasculitis, exfoliative dermatitis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, a syndrome similar to serum sickness, toxic epidermal necrolysis.

From the hematopoietic system and the lymphatic system: reversible leukopenia (including neutropenia), thrombocytopenia, hemolytic anemia, reversible increase in PV (when combined with anticoagulants), reversible increase in bleeding time, eosinophilia, pancytopenia, thrombocytosis, agranulocytosis.

From the central nervous system: dizziness, headache, convulsions (may occur in patients with impaired renal function when taking high doses of the drug).

From the urinary system: interstitial nephritis, crystalluria, hematuria.

Other: candidiasis and other types of superinfection.

Amoxiclav^®

For film-coated tablets, powder for the preparation of a suspension for oral administration, powder for the preparation of a solution for intravenous administration in addition

From the central nervous system: hyperactivity. Anxiety, insomnia, behavior change, arousal.

Amoxiclav^®

Amoxiclav^® Quicktab

Amoxiclav^® Quicktab and Amoxiclav^® powder for preparation of suspension for oral administration

From the organs of hematopoiesis and the lymphatic system: rarely-reversible leukopenia (including neutropenia), thrombocytopenia, very rarely-eosinophilia, thrombocytosis, reversible agranulocytosis, increased bleeding time and reversible increase in PV, anemia, including reversible hemolytic anemia.

On the part of the immune system: the frequency is unknown — angioedema, anaphylactic reactions, allergic vasculitis, a syndrome similar to serum sickness.

From the nervous system: infrequently-dizziness, headache, very rarely-insomnia, agitation, anxiety, behavior changes, reversible hyperactivity, convulsions, convulsions can be observed in patients with impaired renal function, as well as in those who receive high doses of the drug.

From the gastrointestinal tract: often - loss of appetite, nausea, vomiting, diarrhea. Nausea is more common when ingested at high doses. If gastrointestinal disorders are confirmed, they can be eliminated if you take the drug at the beginning of a meal, infrequently-digestive disorders, very rarely-antibiotic-associated colitis induced by taking antibiotics (including pseudomembranous and hemorrhagic colitis), black "hairy" tongue, gastritis, stomatitis. In children, 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.

From the skin: infrequently-skin rash, itching, urticaria, rarely-multiform exudative erythema, frequency unknown-Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

From the urinary system: very rarely — crystalluria, interstitial nephritis, hematuria.

From the liver and biliary tract: infrequently-increased activity of ALT and / or AST (this phenomenon is observed in patients receiving beta-lactam antibiotics, but its clinical significance is unknown), Adverse events from the liver were observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse events are very rarely observed in children.

The listed signs and symptoms usually occur during or immediately after the end of therapy, but in some cases they may not appear for several weeks after the end of therapy. Adverse events are usually reversible. Adverse events from the liver can be severe, in extremely rare cases, there have been reports of fatal outcomes. In almost all cases, these were patients with serious comorbidities or patients receiving potentially hepatotoxic drugs at the same time. Very rarely-an increase in the activity of alkaline phosphatase, an increase in the level of bilirubin, hepatitis, cholestatic jaundice (observed with concomitant therapy with other penicillins and cephalosporins)

Other: often-candidiasis of the skin and mucous membranes, the frequency is unknown-the growth of insensitive microorganisms.

The adverse events presented below are listed according to the lesion of organs and organ systems and the frequency of occurrence. The frequency of occurrence is defined as follows: very often - ≥1/10, often - ≥1/100 and <1/10, infrequently - ≥1/1000 and <1/100, rarely - ≥1/10000 and <1/1000, very rarely - <1/10000, including individual cases. Frequency categories were formed based on clinical trials of the drug and post-registration follow-up.

Infectious and parasitic diseases: often-genital moniliasis, cutaneous-mucosal candidiasis.

From the blood and lymphatic system: rarely-reversible leukopenia (including neutropenia) and thrombocytopenia, very rarely-reversible agranulocytosis and hemolytic anemia, increased bleeding time and PV.

On the part of 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.

From the gastrointestinal tract: very often-diarrhea, often-nausea, abdominal pain, infrequently-vomiting, digestive disorders, very rarely-colitis induced by taking antibiotics (including pseudomembranous colitis and hemorrhagic colitis), black "hairy" tongue.

From the liver and biliary tract: infrequently-moderate increase in the activity of ACT and / or ALT. This phenomenon is observed in patients receiving beta-lactam antibiotics, but its clinical significance is unknown, very rarely — hepatitis and cholestatic jaundice. This phenomenon is observed in patients receiving therapy with penicillin-type antibiotics and cephalosporins.

Adverse events from the liver are observed mainly in men and elderly patients and may be associated with long-term therapy.

The listed signs and symptoms usually occur during or immediately after the end of therapy, but in some cases they may not appear for several weeks after the end of therapy. Adverse events are usually reversible. Adverse events from the liver can be severe, in extremely rare cases, there have been reports of fatal outcomes. In almost all cases, these were patients with serious comorbidities or patients receiving potentially hepatotoxic drugs at the same time.

From the skin and subcutaneous tissues: infrequently-rash, itching, urticaria, rarely-erythema multiforme, very rarely — Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis. In case of any allergic reactions, treatment with Augmentin^® The CP must be stopped.

From the kidneys and urinary tract: very rarely — interstitial nephritis, crystalluria.

Dyspeptic phenomena (nausea, vomiting, diarrhea), allergic reactions (erythema, rash).

There are no reports of fatal or life-threatening side effects due to an overdose of the drug.

Symptoms: in most cases — disorders of the gastrointestinal tract (abdominal pain, diarrhea, vomiting), possibly also anxiety, insomnia, dizziness, in some cases — convulsive seizures.

Treatment: in case of overdose, the patient should be under the supervision of a doctor, treatment is symptomatic.

In the case of recent administration (less than 4 hours) of the drug, gastric lavage should be performed and activated charcoal should be prescribed to reduce absorption. Amoxicillin / potassium clavulanate is removed by hemodialysis.

Symptoms: there may be symptoms from the gastrointestinal tract and violations of the water-electrolyte balance. Amoxicillin crystalluria is described, which in some cases led to the development of renal failure (see "Special instructions").

Treatment: symptoms from the gastrointestinal tract-symptomatic therapy, paying special attention to the normalization of the water-electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

Symptoms: nausea, diarrhea, vomiting.

Treatment: symptomatic, effective hemodialysis.

The drug Amoxiclav^® it is a combination of amoxicillin and clavulanic acid.

Amoxicillin is a semi-synthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PSBs) on the pathway of the biosynthesis of peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to a loss of cell wall strength, which usually causes the lysis and death of microbial cells.

Amoxicillin is destroyed by the action of beta-lactamases produced by resistant bacteria, so the spectrum of activity of amoxicillin does not include microorganisms that produce these enzymes.

Clavulanic acid is a beta-lactam structurally related to penicillins. It inhibits certain beta-lactamases, thereby preventing the inactivation of amoxicillin and expanding its range of activity, including bacteria that are usually resistant to amoxicillin, as well as other penicillins and cephalosporins. By itself, clavulanic acid does not have a clinically significant antibacterial effect.

The drug Amoxiclav^® it has a bactericidal effect in vivo for the following microorganisms:

- gram-positive airbags — Staphylococcus aureus*, Streptococcus pneumoniae, Streptococcus pyogenes,

- gram-negative aerobes — Enterobacter spp.**, Escherichia coli*, Haemophilus influenzae*, species of the genus Klebsiella*, Moraxella catarrhalis* (Branhamella catarrhalis).

The drug Amoxiclav^® it has a bactericidal effect in vitro for the following microorganisms (however, the clinical significance is still unknown):

- gram-positive airbags — Bacillis anthracis*, species of the genus Corynebacterium, Enterococcus faecalis*, Enterococcus faecium*, Listeria monocytogenes, Nocardia asteroides, coagulase-negative staphylococci* (including Staphylococcus epidermidis), Streptococcus agalactiae, other species of the genus Streptococcus, Streptococcus viridans,

- gram-positive anaerobes - species of the genus Clostridium, species of the genus Peptococcus, species of the genus Peptostreptococcus,

- gram-negative aerobes — Bordetella pertussis, species of the genus Brucella, Gardnerella vaginalis, Helicobacter pylori, species of the genus Legionella, Neisseria gonorrhoeae*, Neisseria meningitidis*, Pasteurella multocida, Proteus mirabilis*, Proteus vulgaris*, species of the genus Salmonella*, species of the genus Shigella*, Vibrio cholerae, Yersinia enterocolitica*,

- gram-negative anaerobes - species of the genus Bacteroides* (including Bacteroides fragilis), species of the genus Fusobacterium*,

- other — Borrelia burgdorferi, Chlamydia spp., Leptospira icterohaemorrhagiae, Treponema pallidum.

* Some strains of these bacterial species produce beta-lactamases, which contributes to their insensitivity to amoxicillin monotherapy.

** Most strains of these bacteria are resistant to the amoxicillin/clavulanic acid combination in vitro However, the clinical efficacy of this combination has been demonstrated in the treatment of urinary tract infections caused by these strains.

Amoxicillin is a broad-spectrum semi-synthetic antibiotic with activity against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by beta-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce this enzyme.

Clavulanic acid, a beta-lactamase inhibitor structurally related to penicillins, has the ability to inactivate a wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid has sufficient efficacy against plasmid beta-lactamases, which most often cause bacterial resistance, and is less effective against type 1 chromosomal beta-lactamases, which are not inhibited by clavulanic acid.

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

Delayed release of amoxicillin in Augmentin^® CP allows you to maintain the sensitivity of those strains S. pneumoniae, in which resistance to amoxicillin is due to penicillin-binding proteins (penicillin-resistant S. pneumoniae, or PRSP).

Below is the activity of the combination of amoxicillin with clavulanic acid in vitro.

Bacteria usually sensitive to the combination of amoxicillin with clavulanic acid

Gram-positive airbags: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pneumoniae^1,2, Streptococcus pyogenes^1,2, Streptococcus agalactiae^1,2, group streptococci Viridans², Streptococcus spp. (other beta-hemolytic streptococci)^1,2, Staphylococcus aureus (sensitive to methicillin)¹, Staphylococcus saprophyticus (sensitive to methicillin), coagulase-negative staphylococci (sensitive to methicillin).

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

Other: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Gram-positive anaerobes: Clostridium spp., Peptostreptococcus spp., incl. Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros.

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

Bacteria that are likely to have acquired resistance to the combination of amoxicillin with clavulanic acid

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

Gram-positive airbags: Corynebacterium spp., Enterococcus faecium.

Bacteria that are naturally resistant to the combination of amoxicillin and clavulanic acid

Gram-negative aerobes: Acinetobacter spp., Citrobacter freundii, Enterobacter spp., Hafnia alvei, Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas spp., Serratia spp., Stenotrophomonas maltophilia, Yersinia enterocolitica.

Other: Chlamydia spp., incl. Chlamydia pneumoniae, Chlamydia psittaci, Coxiella burnetii, 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 types of bacteria do not produce beta-lactamases. The sensitivity of amoxicillin monotherapy suggests a similar sensitivity to the combination of amoxicillin with clavulanic acid.

Resistance

Cross-resistance. Amoxicillin directly demonstrates cross-resistance with other beta-lactam antibiotics, as well as a combination of beta-lactam antibiotics with beta-lactamase inhibitors and cephalosporins.

Mechanisms of resistance. Clavulanic acid protects amoxicillin from the damaging effects of beta-lactamases. Delayed release of the active ingredients of the drug Augmentin^® CP increases the effectiveness of amoxicillin against microorganisms whose resistance is due to modification of penicillin-binding proteins.

Bactericidal against a wide range of gram-positive and gram-negative microorganisms, aerobic and anaerobic pathogens (including those strains that have developed resistance to beta-lactam antibiotics due to the production of beta-lactamases).

Active against aerobic gram-positive bacteria (including beta-lactamase-producing strains): Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp., Listeria monocytogenes, anaerobic gram-positive bacteria: Clostridium spp., Peptococcus spp., Peptostreptococcus spp, aerobic gram-negative bacteria (including beta-lactamase-producing strains): Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella spp., Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Moraxella catarrhalis, Haemophilus influenzae , Haemophilus ducreyi, Yersinia multocida (formerly Pasteurella), Campylobacter jejuni, anaerobic gram-negative bacteria (including beta-lactamase-producing strains): Bacteroides spp., including Bacteroides fragilis.

Clavulanic acid suppresses types II, III, IV and V of beta-lactamases, is inactive against type I beta-lactamases produced by Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high tropicity to penicillinases and forms a stable complex with the enzyme, which prevents the enzymatic degradation of amoxicillin under the influence of beta-lactamases.

The main pharmacokinetic parameters of amoxicillin and clavulanic acid are similar. Amoxicillin and clavulanic acid are well soluble in aqueous solutions with a physiological pH value and after taking the drug Amoxiclav^® inside, they are quickly and completely absorbed from the gastrointestinal tract. The absorption of the active substances-amoxicillin and clavulanic acid-is optimal in the case of taking the drug at the beginning of a meal.

The bioavailability of amoxicillin and clavulanic acid after oral administration is about 70%.

Peak plasma concentrations are reached approximately 1 h after administration. Values of C_max make up for amoxicillin (depending on the dose) 3-12 mcg/ml, for clavulanic acid-about 2 mcg/ml.

C_max in the blood plasma after bolus injection at a dose of 1.2 g (1000-200 mg) of the drug is 105.4 mg/l - for amoxicillin and 28.5 mg / l — for clavulanic acid.

When using the drug Amoxiclav^® The plasma concentrations of amoxicillin/clavulanic acid are similar to those of oral administration of the corresponding doses of amoxicillin or clavulanic acid separately at equivalent doses.

Both components are characterized by a sufficient V_d in various organs, tissues and fluid environments of the body (including in the lungs, abdominal organs, adipose, bone and muscle tissues, pleural, synovial and peritoneal fluids, in the skin, bile, urine, purulent discharge, sputum, interstitial fluid).

Plasma protein binding is moderate — 25% for clavulanic acid and 18% for amoxicillin.

V_d it is approximately 0.3–0.4 l / kg for amoxicillin and approximately 0.2 l / kg for clavulanic acid.

Amoxicillin and clavulanic acid do not penetrate the blood-brain barrier in non-inflamed meninges.

Amoxicillin (like most penicillins) is excreted in breast milk. Trace amounts of clavulanic acid were also found in breast milk. Amoxicillin and clavulanic acid penetrate the placental barrier.

Amoxicillin is mainly excreted by the kidneys, whereas clavulanic acid is excreted by both the renal and extrarenal mechanisms. After a single oral administration of one tablet 250 125 mg or 500 125 mg, approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted unchanged in the urine for the first 6 hours. About 10-25% of the initial dose of amoxicillin is excreted in the urine as inactive penicillic acid. Clavulanic acid in the human body undergoes intensive metabolism with the formation of 2,5-dihydro-4 - (2-hydroxyethyl) - 5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butane-2-one and is excreted in the urine and feces

Average T_1/2 amoxicillin/clavulanic acid is approximately 1 h, the average total clearance is approximately 25 l / h in healthy patients. In the course of various studies, it was found that the excretion of amoxicillin in the urine for 24 hours is approximately 50-85%, clavulanic acid-27-60%. The greatest amount of clavulanic acid is excreted within the first 2 hours after ingestion.

The pharmacokinetic parameters of amoxicillin and clavulanic acid are summarized in Table 1.

Table 1

Patients with impaired liver function

In patients with severe renal insufficiency T_1/2 increases to 7.5 hours for amoxicillin and 4.5 hours for clavulanic acid.

For patients with impaired liver function, the dose of the drug should be selected with caution: constant monitoring of the liver condition is necessary.

Both components are removed by hemodialysis and minor amounts are removed by peritoneal dialysis.

Suction

Both active ingredients of the drug Augmentin^® CP, amoxicillin and clavulanic acid, are well soluble in aqueous solutions with a physiological pH value, are quickly and completely absorbed from the gastrointestinal tract after oral administration. The absorption of active substances is optimal in the case of taking the drug at the beginning of a meal.

The pharmacokinetic parameters of amoxicillin and clavulanic acid after taking 2 tablets of the drug Augmentin are shown below^® CP by healthy volunteers at the beginning of a meal.

Table 1

Average values of pharmacokinetic parameters

¹ For bacteria with an MPC of 4 mg/l.

² T>MPC, h (%) — the time (as a percentage of the time interval between doses) during which the concentration of the drug in the blood is higher than the BMD for a particular pathogen.

The drug Augmentin^® CP has a unique pharmacological profile, the T>MPC index characteristic of this drug is not achieved when taking tablets with immediate release of active substances containing a combination of amoxicillin and clavulanic acid.

Distribution

As with the intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are created in various tissues and interstitial fluid (gallbladder, abdominal tissue, skin, adipose and muscle tissue, synovial and peritoneal fluid, bile, purulent discharge).

Amoxicillin and clavulanic acid have a weak degree of binding to plasma proteins. Studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin in the blood plasma binds to plasma proteins.

In animal studies, no accumulation of the components of the drug Augmentin was found^® CP in any body.

Amoxicillin, like most penicillins, penetrates into breast milk. Trace amounts of clavulanic acid were also found in breast milk. With the exception of the possibility of diarrhea and candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of infants fed with breast milk are known.

Studies of reproductive function in animals when taking the drug Augmentin^® CP showed that amoxicillin and clavulanic acid penetrate the placental barrier. However, there was no negative effect on the fetus.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys as an inactive metabolite (penicillic acid). Clavulanic acid undergoes intensive metabolism to 2,5-dihydro-4 - (2-hydroxyethyl) - 5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butane-2-one and is excreted by the kidneys, through the gastrointestinal tract, and with exhaled air in the form of carbon dioxide.

Output

Like other penicillins, amoxicillin is mainly excreted by the kidneys, while clavulanic acid is excreted through both the renal and extrarenal mechanisms.

Studies have shown that, on average, about 60-70% of amoxicillin and about 40-65% of clavulanic acid is excreted unchanged by the kidneys.

Simultaneous administration of probenecid slows the elimination of amoxicillin, but does not slow the elimination of clavulanic acid (see "Interaction").

The pharmacokinetics of amoxicillin and clavulanic acid are similar. After intravenous administration in doses of 1200 mg and 600 mg S_max amoxicillin — 105.4 mcg / ml and 32.2 mcg/ml, respectively, clavulanic acid-28.5 mcg/ml and 10.5 mcg/ml, respectively. Plasma protein binding: amoxicillin-17-20%, clavulanic acid-23-30%. Both components are metabolized in the liver: amoxicillin - 10% of the administered dose, clavulanic acid-50%. T_1/2 after intravenous administration at a dose of 1.2 g and 600 mg-0.9 and 1.07 hours for amoxicillin, 0.9 and 1.12 hours-for clavulanic acid, respectively. It is mainly excreted by the kidneys (glomerular filtration and tubular secretion): 50-78% and 25-40% of the dose of amoxicillin and clavulanic acid, respectively, is excreted unchanged during the first 6 hours after administration.

For all dosage forms

Antacids, glucosamine, laxatives, aminoglycosides slow down the absorption, ascorbic acid increases the absorption.

Diuretics, allopurinol, phenylbutazone, NSAIDs and other drugs that block tubular secretion (probenecid) increase the concentration of amoxicillin (clavulanic acid is mainly excreted by glomerular filtration).

Concomitant use of Amoxiclav^® and methotrexate increases the toxicity of methotrexate.

Administration together with allopurinol increases the frequency of exanthema. Concomitant use with disulfiram should be avoided.

Reduces the effectiveness of drugs, during the metabolism of which PABA is formed, ethinylestradiol-the risk of breakthrough bleeding.

The literature describes rare cases of increased INR in patients with the combined use of acenocumarol or warfarin and amoxicillin. If concomitant use with anticoagulants is necessary, PV or INR should be carefully monitored when prescribing or discontinuing the drug.

The combination with rifampicin is antagonistic (mutual weakening of the antibacterial effect). The drug Amoxiclav^® it should not be used simultaneously in combination with bacteriostatic antibiotics (macrolides, tetracyclines), sulfonamides due to a possible decrease in the effectiveness of the drug Amoxiclav^®.

The drug Amoxiclav^® reduces the effectiveness of oral contraceptives.

For dispersible tablets and powder for preparation of suspension for oral administration in addition

Increases the effectiveness of indirect anticoagulants (suppressing intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). In some cases, taking the drug may prolong the PV, in this regard, caution should be exercised when using anticoagulants and Amoxiclav at the same time^®Quicktab.

Probenecid reduces the excretion of amoxicillin, increasing its serum concentration.

In patients receiving mycophenolate mofetil, after the start of the combination of amoxicillin with clavulanic acid, there was a decrease in the concentration of the active metabolite — mycophenolic acid, before taking the next dose of the drug by approximately 50%. Changes in this concentration may not accurately reflect the overall changes in mycophenolic acid exposure.

For powder for preparation of solution for intravenous administration in addition

The drug Amoxiclav^® and aminoglycoside antibiotics are chemically incompatible.

The drug Amoxiclav^® do not mix in a syringe or infusion bottle with other drugs.

Avoid mixing with solutions of dextrose, dextran, sodium bicarbonate, as well as with solutions containing blood, proteins, lipids.

Simultaneous use of the drug Augmentin^® CP and probenecid are not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of the drug Augmentin^® CP and probenecid can lead to an increase and persistence in the blood concentration of amoxicillin, but not clavulanic acid.

Concomitant use of allopurinol and amoxicillin may increase the risk of skin allergic reactions. Currently, there is no data in the literature on the simultaneous use of a combination of amoxicillin with clavulanic acid and allopurinol.

Penicillins are able to slow the elimination of methotrexate from the body by inhibiting its tubular secretion, so the simultaneous use of the drug Augmentin^® CP and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, the drug Augmentin^® CP can affect the intestinal microflora, leading to a decrease in the absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives.

The literature describes rare cases of increased MHO in patients with the combined use of acenocumarol or warfarin and amoxicillin. If necessary, simultaneous administration or withdrawal of the drug Augmentin^® CP with PV or MHO anticoagulants should be carefully monitored, and the dose of anticoagulants for oral administration may need to be adjusted.

Pharmacologically incompatible with solutions containing blood, proteins, lipids, glucose, dextran, bicarbonate, simultaneous administration with allopurinol increases the risk of exanthema, avoid simultaneous administration with disulfiram.