Arlet, 875 mg+125 mg 14 pcs

Pharmacotherapeutic group

Penicillin semisynthetic antibiotic + beta-lactamase inhibitor

ATX code: J01CR02

Pharmacodynamics:

A broad spectrum antibiotic from the group of penicillin inhibitor-resistant β-lactamase enzymes produced by many pathogenic microorganisms to protect (resist) 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 two active substances: amoxicillin (semi-synthetic penicillin with a broad spectrum of antibacterial activity) and clavulanic acid (irreversible inhibitor of β-lactamases).

Amoxicillin is a broad spectrum semi-synthetic antibiotic active against many Gram-positive and Gram-negative microorganisms. Amoxicillin is degraded by β-lactamases; therefore the spectrum of its antibacterial activity does not include microorganisms producing β-lactamases.

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

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

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

The drug has a wide spectrum of bactericidal antibacterial activity. It is 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 Ente- roccocus 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 corro- dens Enterobacter spp. Gardnerella vaginalis Haemophilus ducreyi Neisseria gonorrhoeae Neisseria meningitidis Pasteurella multocida Proteus 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 the pharmacokinetics of each other.

The two components are quickly and completely absorbed after oral intake Food intake has little effect on the degree of absorption; however, clavulanic acid is better absorbed when a tablet of the drug is taken at the beginning of a meal.

The maximum plasma concentrations are reached about 1 hour after ingestion. Values of maximum concentration for amoxicillin (depending on the dose) are 3-12 mcg/ml for clavulanic acid – about 2 mcg/ml.

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

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

The binding to plasma proteins is moderate: 25% for clavulanic acid and 18% for amoxicillin.

Amoxicillin and clavulanic acid penetrate the placental barrier (no adverse effect on the fetus was found) and in trace concentrations are excreted with the breast milk.

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

Amoxicillin is excreted from the body mainly by the kidneys through tubular secretion and glomerular filtration (52±15% of the dose in unchanged form within 7 hours) and a small amount – in the bile. About 10-25% of the initial dose of amoxicillin is excreted by the kidneys as inactive penicillic acid. Clavulanic acid is excreted by the kidneys through glomerular filtration (40-65%) partially as metabolites and by the intestine.

The half-life (T1/2) of amoxicillin and clavulanic acid is 1-15 hours. In patients with severe renal impairment (creatinine clearance 10-30 ml/min) the half-life increases to 75 hours for amoxicillin and 45 hours for clavulanic acid. In anuria, the T1/2 of both active substances varies between 10 and 15 hours.

The two components are eliminated by hemodialysis and minor amounts by peritoneal dialysis.

Indications

Infections caused by sensitive strains of microorganisms:
– infections of the upper respiratory tract and ENT organs (acute and chronic sinusitis, acute and chronic otitis media, retropharyngeal abscess, tonsillitis, pharyngitis);
– infections of the lower respiratory tract (acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia);
– urinary tract infections;
– infections in gynecology;
– infections of the skin and soft tissues;
– infections of bone and connective tissue;
– biliary tract infections (cholecystitis, cholangitis);
– odontogenic infections.

Pharmacological effect

Pharmacotherapeutic group

Semi-synthetic antibiotic penicillin + beta-lactamase inhibitor

ATX code: J01CR02

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 active against many gram-positive and gram-negative microorganisms. Amocicillin is destroyed by β-lactamases; therefore, 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 type II III IV and V β-lactamases (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 usually 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 Proteus 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 gland) in the middle ear, in the skin of the liver, palatine tonsils, paranasal sinuses, gallbladder; in adipose bone and muscle tissue; 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 were detected) 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 through 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 1-15 hours. In patients with severe renal impairment (creatinine clearance 10-30 ml/min), the half-life increases to 75 hours for amoxicillin and to 45 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.

Special instructions

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.

In order to reduce the risk of side effects from the gastrointestinal tract, the drug should be taken with meals.

Active ingredient

Amoxicillin, Clavulanic acid

Composition

1 tablet contains

amoxicillin trihydrate 825 mg,

clavulanic acid 125 mg;

excipients:

polyvinylpyrrolidone (povidone),

talc (magnesium hydrosilicate),

starch 1500,

calcium stearate (calcium stearate),

Aerosil (silicon dioxide colloidal),

microcrystalline cellulose.

shell composition:

hypromellose (hydroxypropyl methylcellulose), propylene glycol, titanium dioxide, polyethylene oxide 4000 (macrogol 4000).

Pregnancy

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

Amoxicillin and clavulanic acid pass into breast milk in small quantities, so if it is necessary to use the drug during lactation, the issue of stopping breastfeeding should be decided.

Contraindications

Hypersensitivity (including to cephalosporins and other beta-lactam antibiotics), infectious mononucleosis (including with the appearance of a measles-like rash), children under 3 years of age (for this dosage form).

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

Side Effects

From the digestive system: loss of appetite, nausea, vomiting, diarrhea; rarely – impaired liver function, increased activity of alanine aminotransferase (ALT) or aspartic aminotransferase (AST); in isolated cases – cholestatic jaundice, hepatitis, pseudomembranous colitis.

Allergic reactions: itching, urticaria, erythematous rashes; rarely – exudative erythema multiforme, angioedema, anaphylactic shock; in isolated cases – exfoliative dermatitis, Stevens-Johnson syndrome.

From the hematopoietic system: reversible increase in prothrombin time, leukopenia, reversible agranulocytosis and hemolytic anemia.

From the central nervous system: dizziness, headache, reversible hyperactivity and convulsions.

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

Other: candidiasis and other types of superinfection.

Interaction

Concomitant use with methotrexate increases the toxicity of methotrexate. Prescription together with allopurinol increases the incidence of exanthema. Antacids, glucosamine, laxatives, aminoglycosides – slow down and reduce absorption; ascorbic acid increases absorption. Bactericidal antibiotics (including aminoglycosides, cephalosporins, cycloserine, vancomycin, rifampicin) have a synergistic effect; bacteriostatic drugs (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) – 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 and other drugs that block tubular secretion increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).

Overdose

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

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 by hemodialysis.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 °C

Shelf life

2 years

Manufacturer

Sintez, Russia