Clavulanic acid instructions for use. Amoxicillin Clavulanic acid is a combined antibacterial agent. Application and dosage

Active ingredients:

Amoxicillin 250 mg/500 mg/875 mg (as amoxicillin trihydrate 286.70 mg/573.40 mg/1003.44 mg).

Clavulanic acid 125 mg (as potassium clavulanate 277.77 mg)

Excipients: microcrystalline cellulose 80.58 mg / 118.83 mg / 110.74 mg, sodium carboxymethyl starch 6.65 mg / 10 mg / 14.35 mg, colloidal silicon dioxide 6.65 mg / 10 mg / 14.35 mg, magnesium stearate 6.65 mg / 10 mg / 14.35 mg, opadry white 06B58855 (hypromellose-5cP 14.62 mg / 21.49 mg / 30.96 mg, hypromellose-15cP 1.36 mg / 1.99 mg /2, 88 mg, macrogol-400 2.18 mg/3.21 mg/4.62 mg, titanium dioxide 6.12 mg/8.99 mg/12.96 mg).

Dosage 250 mg + 125 mg: biconvex, oval shape white or almost white film-coated tablets white, engraved with "A" on one side and "63" on the other side.

Dosage 500 mg +125 mg: biconvex, oval-shaped, white or almost white film-coated tablets, engraved with “A” on one side and “64” on the other side.

Cross section: core light yellow color, surrounded by a film shell of white or almost white color.

Dosage 875 mg +125 mg: biconvex, oval-shaped tablets, film-coated, white or almost white, with an engraving “A” on one side and a line between the engravings “6” and “5” on the other side.

On a cross section: the core is light yellow, surrounded by a filmy shell of white or almost white color.

Mechanism of action

Amoxicillin- a semisynthetic broad-spectrum antibiotic with activity against many gram-positive and gram-negative microorganisms. At the same time, it 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 is sufficiently effective against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against type 1 chromosomal beta-lactamases, which are not inhibited by clavulanic acid.

The presence of clavulanic acid in the drug protects against destruction by enzymes - beta-lactamases, which allows expanding antibacterial spectrum amoxicillin.

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

Bacteria usually susceptible to the combination of amoxicillin and clavulanic acid

Gram-positive aerobes

Bacillus anthracis

Enterococcus faecalis

Listeria monocytogenes

Nocardia asteroides

Streptococcus pyogenes 1,2

Streptococcus agalactiae 1,2

Streptococcus spp. (other beta-hemolytic streptococci) 1.2

Staphylococcus aureus (methicillin sensitive) 1

Staphylococcus saprophyticus (methicillin sensitive) Coagulase-negative staphylococci (methicillin sensitive)

Gram-positive anaerobes

Clostridium spp.

Peptococcus niger

Peptostreptococcus magnus

Peptostreptococcus micros

Peptostreptococcus spp.

Gram-negative aerobes

Bordetella pertussis

Haemophilus influenzae 1

Helicobacter pylori

Moraxella catarrhalis 1

Neisseria gonorrhoeae

Pasteurella multocida

Vibrio cholerae

Gram-negative anaerobes

Bacteroides fragilis

Bacteroides spp.

Capnocytophaga spp.

Eikenella corrodens

Fusobacterium nucleatum

Fusobacterium spp.

Porphyromonas spp.

Prevotella spp.

Others

Borrelia burgdorferi

Leptospira icterohaemorrhagiae

Treponema pallidum

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

Gram-negative aerobes

Escherichia col i 1

Klebsiella oxytoca

Klebsiella pneumoniae 1

Klebsiella spp.

Proteus mirabilis

Proteus vulgaris

Proteus spp.

Salmonella spp.

Shigella spp.

Gram-positive aerobes

Corynebacilium spp.

Enterococcus faecium

Streptococcus pneumoniae 1.2

Streptococcus group Viridans

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

Others

Chlamydia pneumoniae

Chlamydia psittaci

Chlamydia spp.

Coxiella burnetii

Mycoplasma spp..

1 - for these bacteria, the clinical effectiveness 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. Sensitivity during amoxicillin monotherapy suggests similar sensitivity to the combination of amoxicillin and clavulanic acid.

Suction

Both active ingredients and the drug, and clavulanic acid, are quickly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of the active ingredients of the drug is optimal if the drug is taken at the beginning of a meal.

The following shows the pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in different studies when healthy volunteers took it on an empty stomach:

1 tablet of a drug containing a combination of amoxicillin with clavulanic acid, 250 mg + 125 mg (375 mg); 2 tablets of a drug containing a combination of amoxicillin with clavulanic acid, 250 mg + 125 mg (375 mg); 1 tablet of a drug containing a combination of amoxicillin with clavulanic acid, 500 mg + 125 mg (625 mg);

500 mg amoxicillin;

125 mg clavulanic acid;

2 tablets of a drug containing a combination of amoxicillin and clavulanic acid, 875 mg + 125 mg (1000 mg).

Main pharmacokinetic parameters

C max - maximum concentration in blood plasma.

Tmax is the time to reach the maximum concentration in the blood plasma.

AUC is the area under the concentration-time curve.

T 1/2 - half-life.

When using a drug containing a combination of amoxicillin with clavulanic acid, plasma concentrations of amoxicillin are similar to those after oral administration of equivalent doses of amoxicillin.

Distribution

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

The combination of amoxicillin with clavulanic acid has weak degree binding to blood plasma proteins. Studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin in the blood plasma is bound to plasma proteins.

In animal studies, no accumulation of the components of the combination of amoxicillin and clavulanic acid was found in any organ. , like most penicillins, penetrates breast milk.

Trace amounts of clavulanic acid may also be found in breast milk. With the exception of the possibility of sensitization, diarrhea and candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of breastfed children are known.

Animal reproductive studies have shown that clavulanic acid also crosses the placental barrier. However, it was not revealed negative influence for the fruit.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic acid).

Clavulanic acid is extensively metabolized to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and is excreted by the kidneys. through the gastrointestinal tract, as well as with exhaled air in the form of carbon dioxide.

Removal

Elderly patients

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

Patients with impaired renal function

Correction of the dosage regimen is based on the maximum recommended dose of amoxicillin and the creatinine clearance value.

Tablets 875 mg + 125 mg should be used only in patients with creatinine clearance more than 30 ml/min, and no dosage adjustment is required. In most cases, whenever possible, parenteral therapy should be preferred.

Patients on hemodialysis

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

2 tablets 250 mg + 125 mg in one dose every 24 hours.

1 tablet 500 mg + 125 mg in one dose every 24 hours.

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

Patients with liver dysfunction

Treatment is carried out with caution; regularly monitor liver function.

Adverse reactions, presented below, are listed in accordance with the damage to organs and organ systems and the frequency of occurrence.

The frequency of occurrence is determined as follows: Often (≥ 1/10), often (≥ 1/100 And< 1 / 10 ), infrequently (≥ 1/1 000 And< 1 / 100 ), rarely (≥ 1/10 000 And< 1/1 000 ), very rarely (< 1/10 000, включая отдельные случаи).

Frequency of occurrence of adverse reactions

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.

Violations by nervous system

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, adverse reactions from the gastrointestinal tract are observed, they can be eliminated if the drug 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.

Disorders of the liver and biliary tract

Uncommon: moderate increase in aspartate aminotransferase and/or alanine aminotransferase (AST and/or ALT) activity. This phenomenon 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.

If allergic skin reactions occur, treatment with the drug must be discontinued.

Kidney disorders and urinary tract

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

Symptoms : Gastrointestinal symptoms and water and electrolyte imbalance may occur.

Amoxicillin crystalluria has been described, in some cases leading to the development renal failure(see section "Special instructions").

Convulsions may occur in patients with impaired renal function, as well as in those receiving high doses of the drug.

Treatment : carrying out symptomatic therapy, correction of water and electrolyte balance. removed from the blood by hemodialysis.

The simultaneous use of the drug and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of the drug and probenecid may lead to an increase and persistence in the blood concentration of amoxicillin, but not clavulanic acid.

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

Penicillins can slow down the elimination of methotrexate from the body by inhibiting its tubular secretion, so simultaneous use of the drug and methotrexate may increase the toxicity of methotrexate.

Like others antibacterial drugs, the drug may have an effect on intestinal microflora, leading to a decrease in the absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives.

The literature describes rare cases of an increase in the international normalized ratio (INR) in patients with joint use acenocoumarol or warfarin and amoxicillin. If it is necessary to prescribe the drug simultaneously with anticoagulants, the prothrombin time or INR should be carefully monitored when prescribing or discontinuing the drug; dose adjustment of oral anticoagulants may be required.

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

Before starting treatment with the drug, it is necessary to collect a detailed history regarding previous hypersensitivity reactions to penicillins, cephalosporins or other substances that cause an allergic reaction in the patient.

Serious and sometimes fatal hypersensitivity reactions (anaphylactic reactions) to penicillins have been described. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. If an allergic reaction occurs, treatment with the drug should be discontinued and appropriate alternative therapy should be initiated.

In case of serious anaphylactic reactions, the drug should be administered to the patient immediately. Oxygen therapy, intravenous corticosteroids, and airway management, including intubation, may also be required.

In case of suspected infectious mononucleosis, the drug should not be used, since in patients with this disease it can cause a measles-like skin rash, which makes diagnosing the disease difficult.

Long-term treatment with the drug may lead to excessive proliferation of insensitive microorganisms.

Since the combination of amoxicillin and clavulanic acid may cause dizziness, caution should be exercised when driving or operating machinery.

Film-coated tablets, 250 mg+125 mg, 500 mg+125 mg and 875 mg+125 mg.

7 tablets in a blister made of three-layer PA/Aluminium/PVC film and aluminum foil.

2 blisters along with instructions for use in a cardboard box.

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

Keep out of the reach of children.

Do not use too late expiration date indicated on the packaging.

Amoxicillin + Clavulanic acid is a broad-spectrum antibiotic.

Release form and composition

Dosage forms Amoxicillin + Clavulanic acid:

• film-coated tablets: oval, biconvex, almost white or white, engraved “A” on one side, “63” (250 mg + 125 mg tablets) or “64” (500 mg + 125 mg tablets) on the other ), or engraving separated by a line – “6|5” (tablets 875 mg + 125 mg); a cross-section shows a light yellow core surrounded by a white or almost white shell (7 pieces in blisters, 2 blisters in a cardboard box);
• powder for the preparation of suspension for oral administration (strawberry): granulated, almost white or white (at a dosage of 125 mg + 31.25 mg/5 ml - 7.35 g each in translucent bottles of 150 ml, at a dosage of 250 mg + 62 .5 mg/5 ml – 14.7 g in translucent bottles of 150 ml; each bottle in a cardboard box);
• powder for preparing a solution for intravenous (IV) administration: from white to white with a yellowish tint (in 10 ml bottles, 1 or 10 bottles in a cardboard box; packaging for hospitals - from 1 to 50 bottles in a cardboard box) .

Composition of 1 tablet:

• active ingredients: amoxicillin (in the form of trihydrate) – 250 mg, or 500 mg, or 875 mg, clavulanic acid (in the form of potassium clavulanate) – 125 mg;
• auxiliary (inactive) components: sodium carboxymethyl starch, microcrystalline cellulose, magnesium stearate, colloidal silicon dioxide, opadry white 06B58855 (titanium dioxide, macrogol, hypromellose-15cP, hypromellose-5cP).

Composition of 5 ml suspension (made from powder for preparing the suspension):

• active ingredients: amoxicillin (in the form of trihydrate) - 125 mg and clavulanic acid (in the form of potassium clavulanate) - 31.25 mg, or amoxicillin - 250 mg and clavulanic acid - 62.5 mg;
• auxiliary components: xanthan gum, silicon dioxide, hypromellose, aspartame, succinic acid, colloidal silicon dioxide, strawberry flavor.

Active ingredients in 1 bottle of powder for preparing a solution for intravenous administration: amoxicillin - 500 mg and clavulanic acid - 100 mg, or amoxicillin - 1000 mg and clavulanic acid - 200 mg.

Pharmacological properties

Pharmacodynamics

The effect of the drug Amoxicillin + Clavulanic acid is due to the properties of the active substances included in its composition.

Amoxicillin is a semi-synthetic antibiotic. It has a wide spectrum of action and is active against many gram-negative and gram-positive microorganisms. It has no effect on microorganisms producing beta-lactamase enzymes, since it is destroyed under their action.

Clavulanic acid is a beta-lactamase inhibitor, structurally related to penicillins. It has the ability to inactivate most beta-lactamases found in microorganisms resistant to cephalosporins and penicillins. Clavulanic acid is quite effective against plasmid beta-lactamases, which most often have resistance, but is not active against type 1 chromosomal beta-lactamases.

Clavulanic acid in the drug protects amoxicillin from the destructive effects of beta-lactamases and expands the spectrum of its activity, including against bacteria that are usually resistant to amoxicillin.

The following microorganisms are sensitive to the combination of amoxicillin + clavulanic acid:

• gram-positive aerobes: Streptococcus agalactiae 1, 2, Listeria monocytogenes, Bacillus anthracis, Nocardia asteroids, Enterococcus faecalis, Streptococcus pyogenes 1, 2, methicillin-sensitive Staphylococcus aureus, methicillin-sensitive coagulase-negative Staphylococcus spp., Staphylococcus saprophytic us, other beta-hemolytic streptococci Streptococcus spp. 12 ;
• gram-positive anaerobes: Clostridium spp., Peptostreptococcus magnus, Peptostreptococcus spp., Peptococcus niger, Peptostreptococcus micros;
• gram-negative aerobes: Neisseria gonorrhoeae, Haemophilus influenzael, Vibrio cholerae, Pasteurella multocida, Moraxella catarrhalisl (Branhamella catarrhalis), Helicobacter pylori, Bordetella pertussis;
• gram-negative anaerobes: Porphyromonas spp., Capnocytophaga spp., Prevotella spp., Eikenella corrodens, Bacteroides spp. (including Bacteroides fragilis), Fusobacterium spp., Fusobacterium nucleatum;
• others: Leptospira icterohaemorrhagiae, Treponema pallidum, Borrelia burgdorferi.

For the following microorganisms, acquired resistance to the drug Amoxicillin + Clavulanic acid is likely:

• gram-negative aerobes: Proteus spp. (including Proteus vulgaris and Proteus mirabilis), Escherichia coli 1, Salmonella spp., Klebsiella spp. (including Klebsiella pneumoniae 1 and Klebsiella oxytoca), Shigella spp.;
• gram-positive aerobes: Enterococcus faecium, Streptococcus pneumonia 1, 2, Corynebacterium spp., Streptococcus spp. groups

The following microorganisms are naturally resistant to the action of amoxicillin in combination with clavulanic acid:

• gram-negative aerobes: Stenotrophomonas maltophilia, Pseudomonas spp., Enterobacter spp., Yersinia enterocolitica, Legionella pneumophila, Hafnia alvei, Citrobacter freundii, Serratia spp., Providencia spp., Morganella morganii, Acinetobacter spp.;
• other: Mycoplasma spp., Chlamydia psittaci, Chlamydia spp., Coxiella burnetii, Chlamydia pneumoniae.

Notes:

1 For these bacteria, clinical studies have established the effectiveness of amoxicillin in combination with clavulanic acid.

2 Strains of these types of microorganisms do not produce beta-lactamases and are sensitive to amoxicillin, and therefore, presumably, to the combination of amoxicillin + clavulanic acid.

Pharmacokinetics

After taking the drug Amoxicillin + Clavulanic acid orally, the active substances are quickly and completely absorbed from the gastrointestinal tract. Maximum concentrations are reached after 1–2 hours. Optimal absorption was observed when taking the drug at the beginning of a meal.

When taken orally and intravenously, the active substances have a moderate degree of binding to plasma proteins: amoxicillin - 17-20%, clavulanic acid - 22-30%.

Both components are characterized by a good volume of distribution in body fluids and tissues. Found in the lungs, middle ear, pleural and peritoneal fluids, uterus, and ovaries. Getting into the secret paranasal sinuses nose, palatine tonsils, synovial fluid, bronchial secretions, muscle tissue, prostate gland, gallbladder and liver. Amoxicillin can pass into breast milk, as do most penicillins. Trace amounts of clavulanic acid have also been found in breast milk.

Amoxicillin and clavulanic acid penetrate the placental barrier. They do not penetrate the blood-brain barrier provided that the meninges are not inflamed.

Both components are metabolized in the liver: amoxicillin - about 10% of the dose, clavulanic acid - about 50% of the dose.

Amoxicillin (50–78% of the dose) is excreted almost unchanged by the kidneys by glomerular filtration and tubular secretion. Clavulanic acid (25–40% of the dose) is excreted by glomerular filtration by the kidneys, partly in the form of metabolites and unchanged. Both components are eliminated within the first 6 hours. Small quantities can be excreted through the lungs and intestines.

In severe renal failure, the half-life increases: for amoxicillin - up to 7.5 hours, for clavulanic acid - up to 4.5 hours.

Both active substances of the antibiotic are removed by hemodialysis, and in small quantities by peritoneal dialysis.

Indications for use

According to the instructions, Amoxicillin + Clavulanic acid is used for the treatment of infectious and inflammatory diseases caused by microorganisms sensitive to the combination of active ingredients:

• infections of the ENT organs and upper respiratory tract: acute and chronic sinusitis, recurrent tonsillitis, acute and chronic otitis media, pharyngitis and retropharyngeal abscess, usually caused by Streptococcus pyogenes, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis;
• lower respiratory tract infections: exacerbation of chronic bronchitis, acute bronchitis with bacterial superinfection, bronchopneumonia, pneumonia, usually caused by Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis;
• infections of bone and connective tissue and joints, including osteomyelitis, usually caused by Staphylococcus aureus;
• infections biliary tract: cholangitis, cholecystitis;
• genitourinary tract infections: pyelitis, pyelonephritis, urethritis, cystitis, chancroid, prostatitis, gonorrhea (caused by Neisseria gonorrhoeae), infections of the female genital organs, usually caused by species of the family Enterobacteriaceae (mainly Escherichia coli), species of the genus Enterococcus, Staphylococcus saprophyticus, such as bacterial vaginitis, salpingitis, endometritis, salpingoophoritis, cervicitis, tubo-ovarian abscess, septic abortion;
• skin and soft tissue infections: secondary infected dermatoses, cellulitis, erysipelas, abscess, impetigo and wound infections, usually caused by species of the genus Bacteroides, Streptococcus pyogenes, Staphylococcus aureus;
• meningitis, peritonitis, endocarditis, sepsis;
• odontogenic infections;
• other mixed infections, for example, intra-abdominal infections, post-abortion or postpartum sepsis (as part of stepwise therapy).

In surgery, antibiotics are used to prevent postoperative infections.

Contraindications

• infectious mononucleosis (including with the appearance of a measles-like rash);
• impaired liver function and cholestatic jaundice associated with the use of a combination of amoxicillin and clavulanic acid or penicillin in the anamnesis;
• children under 12 years of age (for tablets);
• phenylketonuria (for suspension);
• creatinine clearance less than 30 ml/min (for tablets 875 mg + 125 mg);
• hypersensitivity to the components of the drug, beta-lactam antibiotics, cephalosporins or penicillins.

Amoxicillin + Clavulanic acid should be used with caution in the following cases:

• heavy liver failure;
• chronic renal failure;
• diseases of the gastrointestinal tract (including a history of colitis caused by the use of penicillins);
• pregnancy and lactation period.

Instructions for use Amoxicillin + Clavulanic acid: method and dosage

Film-coated tablets

In tablet form, the drug is indicated for oral use. For optimal absorption and reduced risk of developing side effects For the digestive system, it is recommended to take tablets at the beginning of a meal.

If necessary, step-down therapy is carried out: first, the drug Amoxicillin + Clavulanic acid is administered intravenously, then switched to oral administration.

• mild infections and moderate severity: 250 mg + 125 mg every 8 hours or 500 mg + 125 mg every 12 hours;
• severe infections, respiratory infections: 500 mg + 125 mg 3 times a day or 875 mg + 125 mg 2 times a day.

The maximum daily dose of amoxicillin should not exceed 6000 mg, clavulanic acid - 600 mg.

The minimum duration of treatment is 5 days, the maximum is 14 days. 2 weeks after the start of the therapeutic course, the doctor assesses the clinical situation and, if necessary, decides to continue treatment. The duration of therapy for uncomplicated acute otitis media is 5–7 days.

It is important to consider that 2 tablets of 250 mg + 125 mg are not equivalent in clavulanic acid content to 1 tablet of 500 mg + 125 mg.

If renal function is impaired, the dose of amoxicillin is adjusted depending on creatinine clearance (CC):

• QC >
• CC 10–30 ml/min: 2 times a day, 1 tablet 250 mg (for mild and moderate infections) or 1 tablet 500 mg;
• QC< 10 мл/мин: 1 раз в сутки по 1 таблетке 250 мг (при легких и среднетяжелых инфекциях) или 1 таблетке 500 мг.

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

Adults on hemodialysis are prescribed 1 tablet of 500 mg + 125 mg or 2 tablets of 250 mg + 125 mg 1 time per day. Additionally, one dose is prescribed during the dialysis session and another dose at the end of the session.

Powder for suspension for oral administration

Amoxicillin + Clavulanic acid suspension is usually prescribed to children under 12 years of age.

In this dosage form, the drug is intended for oral administration. A suspension is prepared from the powder: boiled and cooled to 2/3 is poured into the bottle. room temperature drinking water, shake well, then adjust the volume to the mark (100 ml) and shake vigorously again. The bottle must be shaken before each dose.

For precise dosing, the kit includes a measuring cap with marks of 2.5 ml, 5 ml and 10 ml. It must be washed with clean water after each use.

The doctor determines the dosage regimen individually depending on the severity infectious process, the patient's age, body weight and kidney function.

For optimal absorption of active substances and reducing the risk of side effects from the digestive system, it is recommended to take the Amoxicillin + Clavulanic acid suspension at the beginning of meals.

The duration of treatment is at least 5 days, but not more than 14 days. 2 weeks after the start of the therapeutic course, the doctor assesses the clinical situation and, if necessary, decides to continue treatment.

For children from 3 months to 12 years or weighing up to 40 kg, the suspension is prescribed at a dose of 125 mg + 31.25 mg per 5 ml or 250 mg + 62.5 mg per 5 ml three times a day at intervals of 8 hours.

The minimum daily dose of amoxicillin is 20 mg/kg, the maximum is 40 mg/kg. In low doses, the drug is used for recurrent tonsillitis, infections of the skin and soft tissues. In high doses – for sinusitis, otitis media, infections of the lower respiratory tract, urinary tract, bones and joints.

If renal function is impaired, the dose of amoxicillin is adjusted depending on QC:

• CC > 30 ml/min: no correction required;
• CC 10–30 ml/min: 15 mg + 3.75 mg per kg body weight twice a day, but not more than 500 mg + 125 mg twice a day;
• QC< 10 мл/мин: по 15 мг + 3,75 мг на кг массы тела один раз в сутки, но не более чем 500 мг + 125 мг.

Children on hemodialysis are prescribed 15 mg + 3.75 mg per kg of body weight once a day. Additionally, one dose is prescribed before the hemodialysis session, the second - after the end of the session.

Powder for the preparation of solution for intravenous administration

A solution for intravenous injection/infusion is prepared from the powder.

To prepare a solution for intravenous injection, the contents of the bottle are dissolved in water for injection: at a dose of 500 mg + 100 mg (600 mg) - in 10 ml, at a dose of 1000 mg + 200 mg (1200 mg) - in 20 ml. Enter slowly (over 3-4 minutes).

For infusion administration, further dilution of the drug is required: the resulting solutions are diluted in 50 ml (500 mg + 100 mg) or 100 ml (1000 mg + 200 mg) infusion solution. Ringer's solutions, sodium chloride or potassium chloride can be used as a solvent. The duration of the infusion is 30–40 minutes.

The doctor determines the dosage regimen individually depending on the sensitivity of the pathogen, the severity and location of the infection, the patient’s age, body weight and kidney function.

Adults and adolescents over 12 years of age are prescribed 1200 mg 3 times a day (at intervals of 8 hours), for severe infections - 4 times a day (at intervals of 6 hours).

The maximum permissible daily dose is 6000 mg.

Children from 3 months to 12 years are prescribed 30 mg/kg (based on the entire drug) 3 times a day, in case of severe infection - 4 times a day.

Children under 3 months of age are prescribed 30 mg/kg (based on the entire drug): in the postperinatal period - 3 times a day, in premature and perinatal period - 2 times a day.

Duration of treatment is 5–14 days.

For the prevention of postoperative infections, the drug Amoxicillin + Clavulanic acid is prescribed in a dose of 1200 mg during induction of anesthesia for an operation lasting less than 1 hour, 1200 mg every 6 hours during the day - for more than long operations. If there is a high risk of infection, the drug may be used for several days.

For patients with renal failure, the dose and/or interval between doses is adjusted depending on QC:

• CC 10–30 ml/min: initial dose – 1200 mg, then – 600 mg every 12 hours;
• QC< 10 мл/мин: начальная доза – 1200 мг, далее – по 600 мг 1 раз в сутки.

For children, doses and frequency of administration are reduced in the same way.

For patients undergoing hemodialysis, an additional dose is indicated at the end of each session.

For peritoneal dialysis, no dose adjustment is required.

Side effects

• from the central nervous system: infrequently – headache, dizziness; very rarely - agitation, insomnia, anxiety, confusion, behavioral changes, reversible hyperactivity and convulsions (convulsions are possible in patients receiving the drug in high doses and in patients with impaired renal function);
• from the gastrointestinal tract: very often – diarrhea; often – nausea and vomiting; infrequently – dyspepsia; very rarely - glossitis, black “hairy” tongue, stomatitis, enterocolitis, gastritis, antibiotic-associated pseudomembranous or hemorrhagic colitis;
• from the hematopoietic system: rarely - reversible thrombocytopenia, reversible leukopenia (including neutropenia); very rarely - eosinophilia, anemia, reversible hemolytic anemia, thrombocytosis, thrombocytopenic purpura, reversible agranulocytosis, increased prothrombin time and bleeding time;
• from the skin and subcutaneous tissues: infrequently – urticaria, itching, skin rash; rarely - erythema multiforme; very rarely - erythematous rashes, erythema, allergic vasculitis, a syndrome similar to serum sickness, bullous exfoliative dermatitis, anaphylactic reactions, anaphylactic shock, angioedema, toxic epidermal necrolysis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis;
• from the kidneys and urinary tract: very rarely - hematuria, crystalluria, interstitial nephritis;
• from the liver*: infrequently - moderate increase in the activity of alanine aminotransferase and/or aspartate aminotransferase; very rarely - increased concentrations of bilirubin and alkaline phosphatase, impaired liver function; with simultaneous use of other penicillins and cephalosporins - cholestatic jaundice, hepatitis;
• other: discoloration of teeth (yellow, gray or brown discoloration); often – candidiasis of the mucous membranes.

* Liver side effects are usually reversible and occur during or shortly after treatment. Occurs mainly in older people and men. May be associated with long-term use of the drug. Liver dysfunction may be varying degrees severity, from mild to life threatening(mainly in patients with severe pre-existing diseases and people receiving potentially hepatotoxic drugs) medicines).

Overdose

In most cases, overdose causes gastrointestinal disorders (diarrhea, abdominal pain, vomiting) and disturbances in water and electrolyte balance. Anxiety, dizziness, insomnia, and in isolated cases (in patients receiving the drug in high doses and patients with impaired renal function) – seizures are also possible. The development of amoxicillin crystalluria, in some cases leading to renal failure, has been described.

Treatment of overdose is symptomatic. Special attention pay attention to the normalization of water and electrolyte balance. If necessary, hemodialysis is performed.

special instructions

Before the beginning antibacterial therapy The physician should obtain a detailed personal history from the patient regarding previous sensitivity reactions to penicillins, cephalosporins, or other allergens.

There have been reports of serious hypersensitivity reactions to penicillins, including fatal. The risk of such reactions is especially high in patients with a history of hypersensitivity reactions to penicillins. If allergic reactions develop, the drug Amoxicillin + Clavulanic acid is immediately discontinued and alternative therapy is prescribed. In case of serious anaphylactic reactions Urgent implementation of appropriate measures (administration of epinephrine) is necessary. Intravenous administration of glucocorticosteroids, oxygen therapy, and airway management (if necessary, intubation) may be required.

During therapy, it is necessary to remember about the possible development of superinfection (it is usually caused by Candida fungi and Pseudomonas bacteria). In this case, discontinue the drug and/or prescribe appropriate therapy.

If infectious mononucleosis is suspected, the use of Amoxicillin + Clavulanic acid is not recommended, since there is a high risk of measles-like skin rash, which makes diagnosing the disease difficult.

During long-term therapy, the growth of insensitive microorganisms is possible.

Amoxicillin + Clavulanic acid, like other antibacterial drugs, can cause pseudomembranous colitis from mild degree severity to life-threatening. In this regard, in case of diarrhea that occurs during treatment or after its completion, it is necessary to assume the likelihood of pseudomembranous colitis. If diarrhea is severe or occurs for a long time, the drug is discontinued and the patient is examined. You should not take medications that inhibit intestinal motility.

In rare cases, patients with reduced diuresis may develop crystalluria, mainly during parenteral therapy. When administering amoxicillin in high doses, drinking plenty of fluids and maintaining adequate diuresis is recommended to reduce the risk of amoxicillin crystal formation.

Due to clavulanic acid in the composition, the antibiotic may cause a false-positive Coombs test result.

Amoxicillin + Clavulanic acid in oral dosage forms leads to high levels of amoxicillin in the urine, which distorts the results when determining glucose in the urine (for example, Fehling's test or Benedict's test). If this diagnostic test is necessary, the glucose oxidant method should be used.

When prescribing anticoagulants simultaneously, prothrombin time or INR (international normalized ratio) should be carefully monitored. If necessary, their dose should be adjusted.

Amoxicillin + Clavulanic acid in oral dosage forms may cause discoloration of the surface layer of tooth enamel. To prevent this, you should ensure adequate oral care (brushing your teeth regularly and thoroughly).

Impact on the ability to drive vehicles and complex mechanisms

The drug Amoxicillin + Clavulanic acid can cause side effects from the central nervous system, so caution should be used when performing any work that requires speed of reactions and/or attention.

Use during pregnancy and lactation

In studies of reproductive function in animals with oral and parenteral use of the combination of amoxicillin + clavulanic acid, no teratogenic effect was detected. In a single study in women with premature rupture membranes It has been established that prophylactic use of amoxicillin in combination with clavulanic acid may increase the risk of developing necrotizing enterocolitis in newborns. During pregnancy, the drug is prescribed only if the expected benefits of therapy for the woman outweigh the potential risks to the fetus.

Amoxicillin + Clavulanic acid can be used during lactation. No adverse effects in children receiving breast-feeding, were not observed, with the exception of the risk of developing hypersensitivity reactions, candidiasis of the oral mucosa or diarrhea, which is due to the penetration of trace amounts of the active substances of the drug into breast milk. If these reactions occur in a child, breastfeeding should be stopped during treatment.

Use in childhood

Amoxicillin + Clavulanic acid in tablet form is not used to treat children under 12 years of age.

For impaired renal function

In chronic renal failure, the drug should be used with caution.

For liver dysfunction

The drug Amoxicillin + Clavulanic acid is contraindicated in cases of impaired liver function and cholestatic jaundice associated with the use of a combination of amoxicillin and clavulanic acid or penicillin in the anamnesis.

In severe liver failure, the drug should be used with caution. Treatment must be carried out under regular monitoring of liver function.

Drug interactions

Bacteriostatic agents (sulfonamides, macrolides, tetracyclines, lincosamides, chloramphenicol) have an antagonistic effect.

With the simultaneous use of bactericidal antibiotics (including cephalosporins, aminoglycosides, rifampicin, vancomycin, cycloserine), a synergistic effect is observed.

The drug Amoxicillin + Clavulanic acid enhances the effect of indirect anticoagulants (suppresses intestinal microflora, reduces the prothrombin index and vitamin K synthesis). If it is necessary to use such a combination, blood clotting indicators should be monitored.

Diuretics, non-steroidal anti-inflammatory drugs, phenylbutazone, allopurinol and drugs that block tubular secretion, when used simultaneously, increase the concentration of amoxicillin.

The drug Amoxicillin + Clavulanic acid increases the toxicity of methotrexate and reduces the effect of oral contraceptives. When combined with ethinyl estradiol or with drugs whose metabolism produces para-aminobenzoic acid, there is a risk of breakthrough bleeding.

Allopurinol increases the likelihood of developing skin allergic reactions.

The drug solution is pharmaceutically incompatible with solutions containing bicarbonate, glucose, dextran, lipids, proteins, and blood. Incompatible with aminoglycosides. The solution must not be mixed with any other medicines in one syringe/infusion bottle.

The absorption of amoxicillin and clavulanic acid is increased by ascorbic acid, and reduced by laxatives, glucosamine, aminoglycosides, and antacids.

The suspension prepared from the powder can be stored for no more than 7 days in the refrigerator (at a temperature of + 6 ° C). Do not freeze.