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

Introduction

Acute bacterial rhinosinusitis (ABRS) and tonsillopharyngitis (TP) are the most common infectious diseases of the upper respiratory tract (URT) requiring antibiotic therapy (ABT) encountered by primary care physicians.
ABRS is the fifth most common infectious disease requiring antibiotic therapy. In the United States, about $3.5 billion per year is spent on the treatment of all registered cases of ABRS. About 1.1% of all patient visits to the clinic are associated with TF [1]. The majority of upper respiratory tract infections (URTI) are of viral etiology. Acute viral rhinosinusitis (RS) occurs 200 times more often than bacterial [2], and streptococcal TF accounts for only 5–15% of all cases of this disease in adults [3].

In the etiological structure of MS and TF of bacterial etiology, the most common pathogens are streptococci, Haemophilus influenzae, and less often other bacteria.

Among adults, Streptococcus pneumoniae occurs in 20–43% of ABRS cases, Haemophilus influenzae – in 22–35%, Moraxella catarrhalis – in 2–10% [3].

Streptococcal tonsillitis/TF is tonsillitis or pharyngitis caused by group A β-hemolytic streptococcus (Streptococcus pyogenes). Other causative agents of bacterial pharyngitis are less common, these include β-hemolytic streptococci of groups C and G, Corynebacterium diphtheriae, Arcanobacterium haemolyticum. In some cases, TF may be caused by Neisseriagonorrhoeae, Francisellatularensis, and Yersinia enterocolitica. Less common are Mycoplasma pneumoniae and Chlamydophila pneumoniae. Also in rare cases, a mixed infection with the release of anaerobic pathogens occurs [3].

To select the optimal therapeutic tactics and reduce the risk of unjustified use of antibacterial drugs (ABP), it is necessary to clearly differentiate the viral and bacterial nature of MS and TF.

From 1985 to 1992, ABRS accounted for 7% to 12% of all antibiotic prescriptions [4], and according to the US National Ambulatory Care Survey, by 2002 this figure among adult patients increased to 21% [5].

The resistance of URI pathogens to commonly used antibiotics is increasing at an increasing rate, and the task of modern antibiotics is to overcome this resistance.

Mechanisms of antibiotic resistance and ways to overcome them

Since the discovery of the bactericidal effect of penicillin in 1929, many antibiotics have been developed to overcome the increasing microbial resistance to antibiotics among respiratory pathogens.

A penicillin-resistant strain of S. pneumoniae (minimum inhibitory concentration [MIC] - 0.25 μg/ml) was first isolated in the USA in 1974. Since 1990, there has been an increase in resistance among isolated S. pneumoniae strains [5]. According to one recent study, in the United States, 37% were sensitive to penicillin (MIC < 0.12 μg/ml), 12% had intermediate sensitivity (MIC 0.12–1 μg/ml), and 25% were resistant (MIC ≥ 2 μg/ml) [6].

Resistance to β-lactams is determined by two mechanisms: the production of β-lactamases and modification of penicillin-binding proteins (PBPs) [7].

Resistance of H. influenzae and M. catarrhalis to β-lactams is mainly associated with the production of β-lactamases [8]. There has been a steady increase in the number of H. influenzae strains producing β-lactamases: in 1990, 16.5% of such strains were reported, in 1995 – 36.4%. In recent years, this growth has slowed down somewhat: currently their frequency is about 30% [14].

β-lactamases produced by bacteria destroy β-lactam antibiotics even before they reach the surface of the bacterial cell and cause a bactericidal effect. This mechanism can be overcome by administering a combination of a β-lactam with a β-lactamase inhibitor, which allows the drug to reach the cell surface and exert a bactericidal effect.

In 1984, the first β-lactamase inhibitor, clavulanic acid, in combination with amoxicillin, was introduced into clinical practice in the United States [9]. Inactivation of β-lactamases with clavulanic acid leads to the fact that up to 98% of H. influenzae strains become sensitive to the action of the antibiotic [6].

Unlike H. influenzae and M. catarrhalis, whose mechanisms of resistance to β-lactams are associated with the production of β-lactamases, the resistance of S. pneumoniae depends on the modification of PBPs [10], membrane-bound proteins that catalyze the transfer of peptide chains associated with peptidoglycan, through the bacterial cell wall. Beta-lactams, interacting with PBP, block the cross-linking of peptide chains that maintain the structure of peptidoglycan. As a result of this interaction, the cell wall cannot maintain osmotic resistance, and the cell undergoes lysis. When the structure of the active transpeptidase center of PBP changes, the affinity of the antibiotic for it decreases, which requires a higher concentration of the antibiotic. This resistance mechanism can be overcome when the clinically achieved concentration of ABP exceeds the concentration required to inhibit the growth of the corresponding strain of bacteria for a long time. This can be achieved by administering the antibiotic parenterally at an adequate dose or by increasing the dose of the oral antibiotic [11].

Of all the currently existing oral β-lactams and macrolides, amoxicillin/clavulanic acid (clavulanate) is the only oral antibiotic that inhibits more than 90% of strains of the three main types of respiratory pathogens [12].

Multidrug resistance (i.e., resistance to 3 or more classes of antibacterial drugs) in pneumococci is of great clinical importance, since it significantly limits clinicians in choosing the optimal antibacterial drug. Penicillin-resistant strains of S. pneumoniae are often resistant to macrolides, cephalosporins, sulfonamides, and tetracyclines. Penicillin-resistant pneumococci are multidrug-resistant more often than penicillin-sensitive pneumococci [13]. It is especially important to take this fact into account in patients with failed previous antibacterial therapy or who have allergic reactions to some antibacterial drugs.

Currently, there is a large selection of antibiotics for the treatment of ABRS and TF: β-lactams, macrolides, tetracyclines, trimethoprim/sulfamethoxazole, fluoroquinolones, etc., but the widespread use of certain classes of antibiotics has led to an increase in resistance among URI pathogens [5]. Since the proportion of pathogens resistant to antibacterial drugs is growing, in his daily clinical practice the doctor must have clear criteria for choosing one or another antibacterial drug. There are many clinical guidelines to help the clinician make a choice in favor of the optimal ABP for the treatment of ABRS or TF.

Arlet tablets capt/vol 500mg+125mg jar N14x1 Synthesis AKO

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 over 12 years of age or weighing more than 40 kg: Mild and moderate infections (except lower respiratory tract infections) - 1 tablet (250 mg + 125 mg) 3 times a day or 1 tablet (500 mg + 125 mg) ) 2 times a day. Severe infections or lower respiratory tract infections - 1 tablet (500 mg + 125 mg) 3 times a day or 1 tablet (875 mg + 125 mg) 2 times a day. Odontogenic infections - 1 tablet (250 mg + 125 mg) 3 times a day or 1 tablet (500 mg + 125 mg) 2 times a day for 5 days. 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. knocks. 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. The maximum daily dose of amoxicillin is: for adults and children over 12 years of age (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 over 12 years of age (weighing 40 kg or more) - 600 mg, for children under 12 years of age (weighing less than 40 kg) - 10 mg/ kg body weight. Patients with impaired renal function. Adults and children over 12 years of age or with a body weight of more than 40 kg undergo dose adjustment and frequency of administration depending on creatinine clearance (CC): with creatinine clearance (CC) 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 severe infections or lower respiratory tract infections); 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 severe infections or infections of the lower respiratory tract). For anuria, the dosing interval 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 (once daily). Children are prescribed (15 mg/kg + 3.75 mg/kg) once daily. ADDITIONALLY 1 dose during the dialysis session and another dose at the end of the session dialysis (to compensate for decreased serum concentrations of amoxicillin and clavulanic acid).Patients with impaired liver function.Treat with caution at usual doses; regularly monitor liver function.Elderly patients.No dose adjustment required;dosages are the same as for adults.In In elderly patients with impaired renal function, the dose is adjusted as above for adults with impaired renal function.

Bacterial rhinosinusitis and their treatment

ABRS is an acute bacterial infection accompanied by inflammation of the mucous membrane of the cavity and paranasal sinuses. In most cases, ABRS is a complication of a previous viral URTI.

Based on the duration of bacterial MS, we distinguish between ABRS, relapsing ABRS, chronic MS, and exacerbation of chronic MS.

More than 50% of all cases of ABRS are caused by S. pneumoniae and H. influenzae. About 10% of cases of ABRS in adults can be represented by a mixed infection, including anaerobic flora (Bacteroidesspp., Prevotellaspp., Porphyromonasspp., Fusobacterium spp. Peptostreptococcus spp.). Staphylococcus aureus, S. pyogenes, and other streptococci can also act as etiological agents of ABRS. Less than 5% of ABRS are caused by aerobic gram-negative bacteria – Pseudomonas aeruginosa, Klebsiella spp. and Escherichia coli. The role of Mycoplasma pneumoniae and Chlamydophila pneumoniae remains controversial [1].

The main goal of therapy for ABRS and exacerbation of chronic MS is eradication of the pathogen and restoration of sinus sterility, which is necessary both to resolve the disease itself and to prevent complications and chronicity of the process. Therefore, antibiotics occupy the main place in therapy.

Since isolation of the pathogen from the sinuses is not used in routine clinical practice, ABT of patients with ABRS is usually empirical in nature [5], based on data on the structure and antibiotic resistance of pathogens in the region.

In relapsing and chronic MS, for successful treatment it is necessary that the choice of ABP be based on the results of a study of the sensitivity of microflora isolated from the sinuses.

When choosing an antibiotic for the treatment of ABRS, the clinician should be guided by the severity of the disease, the dynamics of the patient’s condition, and information about previously prescribed antibiotics [2]. According to available data, in Russia, S. pneumoniae and H. influenzae isolated from various infections remain highly sensitive to amoxicillin, amoxicillin/clavulanate, amoxicillin/sulbactam and second generation cephalosporins. However, a high frequency of resistance to co-trimoxazole and tetracyclines was noted (in 32.4 and 27.1% of pneumococcal strains and in 15.7 and 6.2% of Haemophilus influenzae strains, respectively) [1].

According to the severity of the course, it is advisable to distinguish 2 groups of patients: 1st - patients with a mild course who have not received antibiotics in the previous 4-6 weeks, and 2nd - patients who have received antibiotics in the previous 4-6 weeks, or patients with a moderate course regardless from taking antibiotics. The severity of the disease does not indicate the risk of isolating a resistant pathogen, however, patients with a more severe course of the process are less likely to spontaneously resolve ABRS [1].

Recent antibiotic therapy (within the previous 4–6 weeks) is a risk factor for infection with a resistant pathogen [5].

In case of mild disease in patients who have not received antibiotics in the previous 4–6 weeks, in regions with a low incidence of antibiotic resistance in pathogens, the ABP of choice is amoxicillin (at a dose of 1.5–4 g/day), amoxicillin/clavulanate (1.75–4 /0.250 g/day), amoxicillin/sulbactam and cefuroxime. If you are allergic to β-lactam antibiotics, macrolides (azithromycin, clarithromycin) or clindamycin are used. The use of co-trimoxazole and doxycycline is not recommended due to the high frequency of resistance of pathogens to them, as well as the risk of developing dangerous toxic-allergic reactions [1, 5].

For patients with mild ABRS who have received antibiotics in the previous 4–6 weeks, amoxicillin/clavulanate, amoxicillin/sulbactam, levofloxacin, gemifloxacin, or moxifloxacin are recommended in areas with a high incidence of penicillin resistance in pneumococci and/or β-lactamase production in H. influenzae; combinations of drugs: amoxicillin or clindamycin with cefixime [1, 5].

However, it is recommended to limit the widespread use of fluoroquinolones, since frequent use of these drugs in patients with moderately severe disease can lead to the development of resistance [14].

The likelihood of clinical effectiveness of first-line oral therapy is greater than 90% for high-dose amoxicillin/clavulanate 4/0.25 g, amoxicillin/clavulanate 1.75/0.25 g, and respiratory fluoroquinolones (gatifloxacin, levofloxacin, and moxifloxacin) and ranges from 83 to 88% for high doses of amoxicillin at doses of 4.0 and 1.5 g/day, respectively [2]. Second generation cephalosporins have low activity against penicillin-resistant strains of S. pneumoniae [6], and therefore cannot be recommended as a treatment for patients at risk of infection with such a pathogen [5].

In severe cases of the disease, drugs are prescribed parenterally (intravenously or intramuscularly). It is recommended to use cephalosporin II (cefuroxime), III (cefotaxime, ceftriaxone) or IV generations (cefepime), inhibitor-protected penicillins (amoxicillin/clavulanate, amoxicillin/sulbactam, ampicillin/sulbactam), carbapenems, flutoquinolones (ciprofloxacin, ofloxacin, levofloxacin). Stepped therapy is indicated, in which ABT begins with intravenous or intramuscular administration of antimicrobial drugs for 3–4 days, and then switches to oral administration of the same or a similar spectrum of ABP activity [1, 2].

A systematic analysis of randomized clinical trials of ABT RS did not reveal any advantages in clinical outcomes in patients with ABRS treated with amoxicillin compared with cephalosporins or macrolides [15]. New fluoroquinolones also had no advantages over β-lactam antibiotics, and, accordingly, cannot be recommended as first-line therapy [20].

ABT for relapsing MS and exacerbations of chronic MS is not fundamentally different from therapy for ABRS. Its duration for ABRS and relapsing acute MS is 10–14 days, and for exacerbation of chronic MS – up to 4–6 weeks. In chronic MS, ABT is less important than complex treatment, and sometimes surgical intervention. Taking into account the role of anaerobic bacteria in the etiology of chronic MS, it is recommended to prescribe inhibitor-protected penicillins (amoxicillin/clavulanate, amoxicillin/sulbactam) for treatment for 4–6 weeks [5].

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.

Tonsillopharyngitis and its treatment

Pharyngitis/TF is one of the most common infectious diseases encountered by both general practitioners and specialists in hospital settings. The most common is streptococcal pharyngitis, for which ABT is indicated in 100% of cases. Unlike Neisseria gonorrhoeae and C. diphtheriae, the isolation of which is also an absolute indication for ABT, group A β-hemolytic streptococcus (GABHS) is much more common in everyday practice.

Culture examination of an oropharyngeal smear is one of the main methods for confirming the diagnosis of pharyngitis caused by GABHS. For a more accurate diagnosis, a smear should be taken from both the tonsils and the back wall of the pharynx. The sensitivity of the method is 97, and the specificity is 99%. However, study results are usually available no earlier than 48 hours later [1].

When choosing an antibacterial therapy for GABHS-pharyngitis, it is necessary to pay attention to the effectiveness, safety, spectrum of activity of the drug, dosage regimen and cost of treatment. When treating GABHS pharyngitis, it is possible to use a variety of drugs, including natural penicillin and its derivatives (amoxicillin, ampicillin), cephalosporins, macrolides and clindamycin.

GABHS are highly sensitive to β-lactams, which remain the only class of antimicrobials to which GABHS has not developed resistance [16]. Benzylpenicillin and phenoxymethylpenicillin remain the drugs of choice due to their effectiveness and safety in this disease [1].

Tetracyclines, sulfonamides and co-trimoxazole do not eradicate GABHS, so they should not be used as a treatment for acute streptococcal TF caused even by strains susceptible to them in vitro.

I generation cephalosporins can be used in patients allergic to penicillins, provided there are no immediate allergic reactions to β-lactam antibiotics.

GABHS resistance to macrolides in Russia is 13–17%, so they are only alternative drugs for patients with allergies to penicillins [1, 20].

When isolating GABHS that is resistant to erythromycin and in the presence of an allergy to β-lactams, clindamycin can be used [1].

If the patient has received antibiotics in the previous month, amoxicillin/clavulanate or amoxicillin/sulbactam is used [1].

The duration of therapy with most antibacterial drugs to achieve eradication of the pathogen should be 10 days. However, in recent years, studies have appeared that prove the effectiveness of short courses of ABT. Thus, a recent study compared the effectiveness of treatment for acute GABHS-TF with clarithromycin at a dose of 15 and 30 mg/kg/day, amoxicillin/clavulanate at a dose of 43.8/62 mg/kg/day for 5 days and phenoxymethylpenicillin at a dose of 30 mg /kg/day for 10 days. Clinical efficacy was similar when using all antibiotics. Long-term eradication of S. pyogenes was observed in 83% of cases in the amoxicillin/clavulanate group and 77% in the phenoxymethipenicillin group. In 26% of cases, a clarithromycin-resistant strain of S. pyogenes was isolated. The bacteriological effectiveness of amoxicillin/clavulanate and phenoxymethylpenicillin was higher than that of clarithromycin [18].

Of course, when treating streptococcal pharyngitis, the oral route of administration of ABP is optimal. Indications for parenteral administration are low patient compliance or severe disease (in this case, benzylpenicillin is administered intramuscularly for 2–3 days, followed by switching to phenoxymethylpenicillin for 10 days). An alternative is a single injection of benzathine benzylpenicillin at a dose of 2.4 million units intramuscularly.

In case of recurrent TF, cultural confirmation of infection with GABHS or another pathogen is necessary. In the treatment of chronic forms of the disease, an integrated approach comes first, including local therapy, physiotherapeutic procedures, and immunocorrective therapy aimed at preventing recurrent exacerbations. If these measures are ineffective, the question of surgical intervention is raised—tonsillectomy [1].

A rational approach to the choice of ABT for recurrent TF and exacerbation of chronic tonsillitis is extremely important. It should be taken into account that such patients, as a rule, have already taken ABP several times - often on their own, without following the dosage regimen.

Until the early 1970s. the rate of unsuccessful antibacterial therapy for GABHS-TF ranged from 2 to 10%. Since the late 1970s. the rate of failure of penicillin therapy reached 20%. Factors explaining the recurrent course of TF are low compliance of patients, re-infection from family members or carriers, concomitant colonization with S. aureus, H. influenzae, M. catarrhalis, anaerobes producing β-lactamases that inactivate penicillin; suppression of the normal immune response with unreasonably prescribed ABT, resistance of GABHS to penicillin; eradication of normal pharyngeal flora involved in the local immune defense system, and the formation of the carrier state itself [19].

According to the results of a study [20], the microflora from the deep parts of the tonsils of patients with chronic tonsillitis revealed mono-infections in 50% of cases and mixed infections in 74% of cases. The predominant pathogens were Streptoccocus viridians (30.4%), S. aureus (30.5%), Staphylococcus epidermidis (15.3%), and S. pyogenes in 11% of cases. According to the results of determining sensitivity to ABT, these microorganisms were insensitive or slightly sensitive to unprotected penicillins, first generation macrolides, and fluoroquinolones. At the same time, 100% sensitivity of these pathogens was noted to amoxicillin/clavulanate.

If the bacteriological effectiveness of therapy is insufficient, symptoms may recur after some time. Several antibiotics have shown better efficacy compared to penicillin in eradicating GABHS, and the possibility of less frequent use of these drugs allows increasing patient compliance. For GABHS infection, for patients who had not previously received ABT, cephalosporins were 5–22% more effective. For patients receiving penicillin therapy, the effectiveness was even higher. Amoxicillin/clavulanate, clarithromycin and azithromycin have better indicators of bacteriological effectiveness compared to penicillin [19].

Thus, during exacerbation of chronic tonsillitis, it is advisable to prescribe inhibitor-protected penicillins. As alternative drugs, it is possible to use macrolides, fluoroquinolones, and a combination of antibacterial drugs.

Arlet

Inside, intravenously.

Doses are given in terms of amoxicillin. The dosage regimen is set individually depending on the severity and location of the infection and the sensitivity of the pathogen.

Children under 12 years of age - in the form of a suspension, syrup or drops for oral administration. A single dose is set depending on age: children under 3 months - 30 mg/kg/day in 2 doses; 3 months and older - for mild infections - 25 mg/kg/day in 2 divided doses or 20 mg/kg/day in 3 divided doses, for severe infections - 45 mg/kg/day in 2 divided doses or 40 mg/kg/day a day in 3 doses.

Adults and children over 12 years of age or weighing 40 kg or more: 500 mg 2 times / day or 250 mg 3 times / day. For severe infections and respiratory tract infections - 875 mg 2 times / day or 500 mg 3 times / day.

The maximum daily dose of amoxicillin for adults and children over 12 years of age is 6 g, for children under 12 years of age - 45 mg/kg body weight.

The maximum daily dose of clavulanic acid for adults and children over 12 years of age is 600 mg, for children under 12 years of age - 10 mg/kg body weight.

If swallowing is difficult in adults, the use of a suspension is recommended.

When preparing suspension, syrup and drops, water should be used as a solvent.

When administered intravenously, adults and adolescents over 12 years of age are administered 1 g (amoxicillin) 3 times a day, if necessary - 4 times a day. The maximum daily dose is 6 g. For children 3 months to 12 years old - 25 mg/kg 3 times a day; in severe cases - 4 times a day; for children under 3 months: premature and in the perinatal period - 25 mg/kg 2 times a day, in the postperinatal period - 25 mg/kg 3 times a day.

Duration of treatment - up to 14 days, acute otitis media - up to 10 days.

To prevent postoperative infections during operations lasting less than 1 hour, a dose of 1 g is administered intravenously during induction of anesthesia. For longer operations - 1 g every 6 hours during the day. If the risk of infection is high, administration may be continued for several days.

In case of chronic renal failure, the dose and frequency of administration are adjusted depending on the CC: with CC more than 30 ml/min, no dose adjustment is required; with CC 10-30 ml/min: orally - 250-500 mg/day every 12 hours; IV - 1 g, then 500 mg IV; with CC less than 10 ml/min - 1 g, then 500 mg/day IV or 250-500 mg/day orally in one dose. For children, doses should be reduced in the same way.

Patients on hemodialysis - 250 mg or 500 mg orally in one dose or 500 mg intravenously, 1 additional dose during dialysis and 1 additional dose at the end of the dialysis session.