Arlet 875mg+125mg 14 pcs. film-coated tablets

pharmachologic effect

Semi-synthetic antibiotic penicillin + beta-lactamase inhibitor.

Composition and release form Arlet 875mg+125mg 14 pcs. film-coated tablets

Tablets - 1 tablet:

Active ingredients: Amoxicillin trihydrate (in terms of amoxicillin) - 875 mg; Potassium clavulanate (in terms of clavulanic acid) - 125 mg;
Excipients: Low molecular weight povidone (low molecular weight medical polyvinylpyrrolidone 12600±2700) - 30.0 mg; Talc - 33.0 mg; Pregelatinized starch (starch 1500) - 249.0 mg; Calcium stearate (calcium stearate) - 16.5 mg; Colloidal silicon dioxide (Aerosil) - 16.5 mg; Microcrystalline cellulose - 51.7 mg;
Shell composition: Hypromellose (hydroxypropyl methylcellulose) - 19.1 mg; Propylene glycol - 15.5 mg; Macrogol 4000 (polyethylene glycol 4000) - 10.0 mg; Titanium dioxide - 5.4 mg.

5, 7 or 10 tablets in a blister pack made of polyvinyl chloride film and printed varnished aluminum foil.

1, 2 or 3 blister packs with a sachet of silica gel are sealed into a bag made of a combined multilayer foil-based material. The package with instructions for use is placed in a cardboard pack.

7, 10, 14, 20 or 21 tablets in orange glass jars with screw-on plastic caps or in polymer jars. A desiccant in the form of a round tablet or a bag of silica gel is placed in each jar.

7, 10, 14, 20 or 21 tablets in orange glass jars with a screw cap with silica gel and a tamper evident seal or a tamper evident cap with a silica gel sachet.

Each jar with instructions for use is placed in a cardboard pack.

Description of the dosage form

Biconvex, oblong, film-coated tablets, white or almost white.

Characteristic

Broad-spectrum antibiotic.

Directions for use and doses

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.

To reduce possible side effects from the digestive system, it is recommended to take the drug at the beginning of meals. The tablet is swallowed whole, without chewing, with a glass of water.

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

For mild to moderate infections - 1 tablet (250 mg + 125 mg) 3 times a day.

For moderate and severe infections - 1 tablet (500 mg + 125 mg) 3 times a day.

For severe infections - 1 tablet (875 mg + 125 mg) 2 times a day.

Children from 6 to 12 years old

The daily dose is usually 20-30 mg/kg amoxicillin and 5-7.5 mg/kg clavulanic acid.

For children aged 6-12 years (with body weight less than 40 kg), the usual dose of the drug is 1 tablet (250 mg + 125 mg) 2-3 times a day or 1 tablet (500 mg + 125 mg) 2 times a day. day. For severe infections, these doses can be doubled.

Children weighing 40 kg or more should be dosed as adults.

The minimum course of treatment with the drug is 5 days. The duration of treatment is determined by the attending physician. Treatment should not continue for more than 14 days without repeated medical examination. The duration of treatment for acute uncomplicated otitis media is 5-7 days.

It must be remembered that 2 tablets (250 mg + 125 mg) are not equivalent to 1 tablet (500 mg + 125 mg), because they contain 2 times more clavulanic acid.

The maximum daily dose of amoxicillin is: for adults and children 12 years of age and older (with a body weight of 40 kg or more) - 6 g, for children under 12 years of age (with a body weight of less than 40 kg) - 45 mg / kg of body weight.

The maximum daily dose of clavulanic acid (in the form of potassium clavulanate) is: for adults and children 12 years of age and older (body weight 40 kg or more) - 600 mg, for children under 12 years of age (body weight less than 40 kg) - 10 mg /kg body weight.

Patients with impaired renal function

Adults and children 12 years of age and older or with a body weight of 40 kg or more undergo dose adjustment and frequency of administration depending on creatinine clearance (CC):

when CC is more than 30 ml/min, no dose adjustment is required;
with CC 10-30 ml/min: 1 tablet (250 mg + 125 mg) 2 times a day (for mild and moderate infections) or 1 tablet (500 mg + 125 mg) 2 times a day (for moderate and severe course of infection);
with CC less than 10 ml/min: 1 tablet (250 mg + 125 mg) once a day (for mild and moderate infections) or 1 tablet (500 mg + 125 mg) once a day (for moderate and severe infections) infections).

Tablets (875 mg + 125 mg) should be used only in patients with CC more than 30 ml/min.

For anuria, the interval between dosing should be increased to 48 hours or more.

Patients on hemodialysis

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

Adults are usually prescribed 1 tablet (500 mg + 125 mg) or 2 tablets (250 mg + 125 mg) every 24 hours (1 time per day). Children are prescribed (15 mg/kg+3.75 mg/kg) once a day.

ADDITIONALLY 1 dose during the dialysis session and another dose at the end of the dialysis session (to compensate for decreased serum concentrations of amoxicillin and clavulanic acid).

Patients with liver dysfunction

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

Elderly patients

No dose adjustment is required; doses are the same as for adults. In elderly patients with impaired renal function, the dose is adjusted as above for adults with impaired renal function.

Pharmacodynamics

A broad-spectrum antibiotic from the group of inhibitor-protected penicillins, resistant to the effects of β-lactamase enzymes produced by many pathogenic microorganisms for protection (resistance) from the action of β-lactam antibiotics (penicillins, cephalosporins, carbapenems). Bacterial β-lactamases destroy (hydrolyze) the antibiotic into inactive fragments (substances). Bacteria that produce β-lactamases are resistant (resistant) to penicillins and cephalosporins.

The drug Arlet® contains 2 active ingredients: amoxicillin (semi-synthetic penicillin with a wide spectrum of antibacterial activity) and clavulanic acid (irreversible β-lactamase inhibitor).

Amoxicillin is a semisynthetic broad-spectrum antibiotic that is active against many gram-positive and gram-negative microorganisms. Amoxicillin is destroyed by β-lactamases, so the spectrum of its antibacterial activity does not include microorganisms that produce β-lactamases.

Clavulanic acid is a β-lactam compound that has the ability to inactivate a wide range of β-lactamases by forming a stable inactivated complex with them, which prevents the enzymatic destruction of amoxicillin.

Clavulanic acid is similar in structure to β-lactam antibiotics, but has virtually no antibacterial activity of its own. Clavulanic acid inhibits β-lactamases types II, III, IV and V (according to the Richmond-Sykes classification), but is inactive against type I β-lactamases produced by Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp.

The presence of clavulanic acid in the composition of the drug protects amoxicillin from destruction by β-lactamases and expands the spectrum of its antibacterial activity to include microorganisms that are usually resistant (resistant) to it and to other penicillins and cephalosporins.

The drug has a wide spectrum of bactericidal antibacterial action.

Active against the following microorganisms:

gram-positive aerobes: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus agalactiae. Streptococcus bovis; Staphylococcus aureus (except methicillin-resistant strains), Staphylococcus epidermidis (except methicillin-resistant strains), Staphylococcus saprophyticus and other coagulase-negative staphylococci, Enteroccocus spp. (including Enterococcus faecalis), Bacillis anthracis, Corynebacterium spp., Listeria monocytogenes, Nocardia asteroides;
gram-negative aerobes: Escherichia coli, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis, Bordetella petrussis, Brucella spp., Campylobacter jejuni, Eikenella corrodens, Enterobacter spp., Gardnerella vaginalis, Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, Pasteurella multocida, Pro teus spp ., Salmonella spp., Shigella spp., Vibrio cholerae, Yersinia enterocolitica;
gram-positive and gram-negative anaerobes: Actinomyces israelii, Bacteroides spp. (including Bacteroides fragihs), Clostridium spp. (except Clostridium difficile), Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp., Prevotella spp.;
other microorganisms: Borrelia burgdorferi, Chlamydia spp., Helicobacter pylori, Leptospira icterohaemorrhagiae, Treponema pallidum.

Pharmacokinetics

The main pharmacokinetic parameters of amoxicillin and clavulanic acid are similar. In combination, amoxicillin and clavulanic acid do not affect each other's pharmacokinetics.

Both components are quickly and completely absorbed after oral administration; food intake has almost no effect on the degree of absorption, however, clavulanic acid is better absorbed when taking a tablet of the drug at the beginning of a meal.

Maximum plasma concentrations are reached approximately 1 hour after administration. The maximum concentration values for amoxicillin (depending on the dose) are 3-12 μg/ml, for clavulanic acid - about 2 μg/ml.

Both components are characterized by a large volume of distribution. Therapeutic concentrations of both active substances are determined in various organs, tissues and fluids of the body: in the lungs, sputum, abdominal organs, pelvic organs (uterus, ovaries, prostate), middle ear, skin, liver, palatine tonsils, paranasal sinuses, gall bladder; in adipose, bone and muscle tissues; in pleural, synovial and peritoneal fluids; in bile, urine, saliva, bronchial secretions, in purulent discharge, in interstitial fluid.

Amoxicillin and clavulanic acid do not penetrate the blood-brain barrier when the meninges are not inflamed.

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

Amoxicillin and clavulanic acid penetrate the placental barrier (no negative effects on the fetus have been identified) and are excreted in trace concentrations in breast milk.

Amoxicillin is partially metabolized in the liver (10% of the administered dose) to inactive metabolites, clavulanic acid undergoes intensive metabolism in the liver (50-70% of the administered dose).

Amoxicillin is excreted from the body primarily by the kidneys by tubular secretion and glomerular filtration (52±15% of the dose unchanged within 7 hours) and a small amount - with bile. About 10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of inactive penicillic acid.

Clavulanic acid is excreted by the kidneys through glomerular filtration (40-65%), partly in the form of metabolites, and also by the intestines.

The half-life (T1/2) of amoxicillin and clavulanic acid is 1-1.5 hours. In patients with severe renal impairment (creatinine clearance 10-30 ml/min), the half-life increases to 7.5 hours for amoxicillin and to 4.5 hours for clavulanic acid. With anuria, T1/2 of both active substances ranges between 10 and 15 hours.

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

Indications for use Arlet 875mg+125mg 14 pcs. film-coated tablets

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

infections of the ENT organs (acute and chronic sinusitis, otitis media, retropharyngeal abscess, tonsillitis, pharyngitis);
lower respiratory tract infections (acute bronchitis with bacterial superinfection, exacerbation of chronic bronchitis, community-acquired pneumonia);
urinary tract infections (cystitis, urethritis, pyelonephritis, pyelitis);
infections in obstetrics and gynecology (salpingitis, salpingoophoritis, cervicitis, bacterial vaginitis, endometritis, pelvioperitonitis, septic abortion);
infections of the skin and soft tissues (erysipelas, impetigo, secondary infected dermatoses, cellulitis, abscess, wound infection, including after animal and human bites);
infections of bone and connective tissue (including osteomyelitis);
biliary tract infections (cholecystitis, cholangitis);
chancroid (soft chancroid);
odontogenic infections;
infections of the digestive system (dysentery, salmonellosis, salmonellosis carriage).

Contraindications

Hypersensitivity to amoxicillin, clavulanic acid and other components of the drug;
hypersensitivity to other beta-lactam antibiotics (penicillins and cephalosporins);
liver dysfunction (including jaundice) when taking amoxicillin + clavulanic acid in the anamnesis;
infectious mononucleosis or lymphocytic leukemia (risk of exanthema);
children under 6 years of age (for this dosage form);
children under 12 years of age with chronic renal failure (for this dosage form);
chronic renal failure (creatinine clearance less than 30 ml/min) only for tablets with a dosage of 875 mg + 125 mg.

Before using the drug, be sure to consult your doctor.

With caution: pregnancy, breastfeeding, severe liver failure, diseases of the gastrointestinal tract (including a history of colitis associated with the use of penicillins), chronic renal failure.

If you have one of the listed diseases, be sure to consult your doctor before using the drug.

Application Arlet 875mg+125mg 14 pcs. film-coated tablets during pregnancy and breastfeeding

The drug can be prescribed during pregnancy only in cases where the expected benefit to the mother outweighs the potential risk to the fetus.

The drug can be taken during breastfeeding. With the exception of the risk of sensitization associated with the release of trace amounts of the active substances of the drug into breast milk, no other adverse effects can be observed in breastfed infants. If a child develops sensitization, diarrhea or candidiasis of the mucous membranes, breastfeeding should be stopped.

special instructions

Before starting treatment, it is necessary to obtain a detailed history regarding previous hypersensitivity reactions to penicillin or cephalosporin antibiotics or other allergens.

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 antibiotics of this group. If an allergic reaction occurs, discontinue treatment with the drug and initiate alternative therapy. In case of severe hypersensitivity reactions, adrenaline (epinephrine) should be administered immediately. Oxygen therapy, intravenous corticosteroids, and airway management, including intubation, may also be required.

Cases of the development of necrotizing colitis were identified in newborns and in pregnant women with premature rupture of membranes who received prophylactic therapy with amoxicillin/clavulanic acid.

When treating mild diarrhea (caused by Clostridium difficile) during a course of treatment, antidiarrheal drugs that reduce intestinal motility should be avoided; Kaolin- or attapulgite-containing antidiarrheal drugs can be used. If diarrhea is severe, consult a doctor.

Treatment must continue for another 48-72 hours after the disappearance of clinical signs of the disease.

When using estrogen-containing oral contraceptives and amoxicillin simultaneously, other or additional methods of contraception should be used.

Amoxicillin and clavulanic acid can provoke nonspecific binding of immunoglobulins and albumins to the erythrocyte membrane, which can cause a false positive reaction with the Coombs test.

Use the drug with caution in patients with impaired liver function.

The severity of side effects from the digestive system can be reduced by taking the drug at the beginning of meals.

In patients receiving the drug, an increase in prothrombin time may rarely be observed, therefore, when taking the drug simultaneously with anticoagulants, appropriate monitoring should be carried out.

Crystalluria may very rarely occur in patients with reduced diuresis. When taking amoxicillin in high doses, it is recommended to take enough fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.

During a course of treatment, it is necessary to monitor the state of the function of the hematopoietic organs, liver, and kidneys.

In patients with severe renal impairment, adequate dose adjustment or increased dosing intervals is required.

It is possible that superinfection may develop due to the growth of microflora that is insensitive to it, which requires a corresponding change in antibacterial therapy.

In patients with hypersensitivity to penicillins, cross-allergic reactions with cephalosporin antibiotics are possible.

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

Laboratory indicators:

High concentrations of amoxicillin give a false-positive reaction to urine glucose when using Benedict's reagent or Fehling's solution. It is recommended to use enzymatic reactions with glucosidase.

Impact on the ability to drive vehicles and operate machinery

While taking the drug, care should be taken when driving vehicles, machinery and when performing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions.

Overdose

In most cases, symptoms of overdose include disorders of the gastrointestinal tract (abdominal pain, diarrhea, vomiting); anxiety, insomnia, dizziness, and, in isolated cases, convulsions are also possible.

In case of overdose, the patient should be under medical supervision and treatment should be symptomatic.

In case of recent use (less than 4 hours), it is necessary to perform gastric lavage and prescribe activated charcoal to reduce absorption.

Amoxicillin + potassium clavulanate is removed during hemodialysis.

Side effects Arlet 875mg+125mg 14 pcs. film-coated tablets

Classification by frequency of development: often - from 1 to 10%, infrequently from 0.1 to 1%, rarely - from 0.01 to 0.1%, very rarely - less than 0.01%

Allergic reactions: infrequently urticaria, erythematous rash, itching; rarely - exudative erythema multiforme; very rarely - exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), anaphylactic shock, angioedema, a syndrome similar to serum sickness, acute generalized exanthematous pustulosis. In some cases, a so-called “fifth day rash” (measles exanthema) appears.

From the digestive system: often - nausea, vomiting, diarrhea, abdominal pain, liver failure (more often in the elderly, men, with long-term therapy), increased activity of liver transaminases; rarely - hepatitis, cholestatic jaundice; very rarely - glossitis, gastritis, stomatitis, hemorrhagic colitis (can also develop after therapy), pseudomembranous colitis, enterocolitis, black “hairy” tongue, darkening of tooth enamel. Increased activity of transaminases (aspartate aminotransferase and alanine aminotransferase), bilirubin and alkaline phosphatase is usually observed in males and in elderly patients, especially over 65 years of age. The risk of such changes increases when taking the drug for more than 14 days. These phenomena are very rarely observed in children. The above changes usually appear during treatment or immediately after. Sometimes they may appear several weeks after stopping the drug. Basically, reactions from the digestive system are transient and minor, but sometimes they are pronounced.

From the hematopoietic system: rarely - reversible leukopenia (including neutropenia), thrombocytopenia, reversible agranulocytosis and hemolytic anemia; very rarely - prolongation of bleeding time, anemia, eosinophilia, thrombocytosis.

From the central nervous system: often - dizziness, headache, reversible hyperactivity and convulsions (convulsions can occur in cases of impaired renal function or in patients receiving high doses of the drug), very rarely - insomnia, agitation, anxiety, changes in behavior.

From the urinary system: very rarely - hematuria.

Other: often - development of superinfection (including candidiasis), exanthema; rarely - reversible increase in prothrombin time, crystalluria, interstitial nephritis, vasculitis.

If any of the side effects indicated in the instructions get worse, or you notice any other side effects not listed in the instructions, tell your doctor.

Drug interactions

Antacids, glucosamine, laxatives, aminoglycosides - slow down and reduce absorption; ascorbic acid increases absorption.

Concomitant use with allopurinol increases the incidence of exanthema.

Bactericidal antibiotics (including aminoglycosides, cephalosporins, vancomycin, rifampicin, cycloserine) - when used simultaneously, have a synergistic effect; bacteriostatic (macrolides, chloramphenicol, lincosamides, tetracyclines) - antagonistic.

Increases the effectiveness of indirect anticoagulants (suppressing intestinal microflora, reduces the synthesis of vitamin K and the prothrombin index). When taking anticoagulants simultaneously, it is necessary to monitor blood clotting indicators.

Reduces the effectiveness of oral contraceptives, drugs, during the metabolism of which para-aminobenzoic acid is formed, ethinyl estradiol - the risk of developing “breakthrough” bleeding.

Diuretics, allopurinol, phenylbutazone, non-steroidal anti-inflammatory drugs that block tubular secretion increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).

Concomitant use with methotrexate increases the toxicity of methotrexate.

Arlet®

Before starting treatment, it is necessary to obtain a detailed history regarding previous hypersensitivity reactions to penicillin or cephalosporin antibiotics or other allergens.

For the treatment of mild diarrhea (caused by Clostridium difficile

) during a course of treatment, antidiarrheal drugs that reduce intestinal motility should be avoided; Kaolin- or attapulgite-containing antidiarrheal drugs can be used. If diarrhea is severe, consult a doctor.