Arlet - instructions for use, dose, side effects, contraindications

Composition per one tablet Active substances:	250 mg + 125 mg	500 mg + 125 mg	875 mg + 125 mg
Amoxicillin trihydrate (in terms of amoxicillin)	250 mg	500 mg	875 mg
Potassium clavulanate (in terms of clavulanic acid) Excipients: Kernel composition:	125 mg	125 mg	125 mg
Povidone low molecular weight (polyvinylpyrrolidone low molecular weight medical 12600 ± 2700)	14.0 mg	20.0 mg	30.0 mg
Talc	12.8 mg	21.4 mg	33.0 mg
Pregelatinised starch (starch 1500)	119.4 mg	191.2 mg	249.0 mg
Calcium stearate (calcium stearic acid)	6.4 mg	10.7 mg	16.5 mg
Silica colloidal dioxide (aerosil)	6.4 mg	10.7 mg	16.5 mg
Microcrystalline cellulose	45.2 mg	90.2 mg	51.7 mg
Core mass: Shell composition:	640 mg	1067 mg	1550 mg
Hepromellosis (hydroxypropylmethylcellulose)	8.0 mg	13.0 mg	19.1 mg
Propylene glycol	6.0 mg	10.0 mg	15.5 mg
Macrogol 4000 (polyethylene glycol 4000)	3.9 mg	6.5 mg	10.0 mg
Titanium dioxide	2.1 mg	3.5 mg	5.4 mg
Film coated tablet weight	660 mg	1100 mg	1600 mg

Description:

Biconvex, oblong tablets covered with a film membrane, white or almost white.

Pharmacotherapeutic group:Antibiotic-penicillin semisynthetic + beta-lactamase inhibitor.

ATX: & nbsp

J.01.C.R.02 Amoxicillin in combination with enzyme inhibitors

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 the 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.

Arlet® contains 2 active ingredients: amoxicillin (semisynthetic penicillin with a broad spectrum of antibacterial activity) and clavulanic acid (irreversible inhibitor of β-lactamases).

Amoxicillin is a semisynthetic broad-spectrum antibiotic that is active against many Gram-positive and Gram-negative microorganisms. Amoxicillin is degraded by β-lactamases, therefore the microorganisms producing β-lactamases are not included in the spectrum of its antibacterial activity.

Clavulanic acid is a β-lactam compound with the ability to inactivate a wide spectrum 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 practically does not have its own antibacterial activity. Clavulanic acid inhibits β-lactamase II, III, IV and V types (according to the Richmond-Sykes classification), but is inactive for type I β-lactamases produced Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp.

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

The drug has a broad spectrum of bactericidal antibacterial action. 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. (at t.h. 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. (Besides Clostridium difficile), Fusobacterium spp., Peptococcus spp., Peptostreptococcus spp., Prevotella spp .;

- others 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.

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

The maximum concentration in the blood plasma is reached about 1 hour after admission. 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 amount of distribution. The therapeutic concentrations of both active substances are determined in different organs,tissues and body fluids: in the lungs, sputum, abdominal organs, pelvic organs (uterus, ovaries, prostate gland), in the middle ear, in the 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 secretion, in a purulent discharge, in the interstitial fluid.

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

Plasma protein binding moderate: 25% for the clavulanic acid and 18% for amoxycillin.

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

Amoxicillin is partially metabolized in the liver (10% of the administered dose) to inactive metabolites, clavulanic acid is subjected to intensive metabolism 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 for 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 by glomerular filtration (40-65%), partly in the form of metabolites, and also by the intestine.

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

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

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:

- infection of the ENT organs (acute and chronic sinusitis, otitis media, zaglugal abscess, tonsillitis, pharyngitis);

- infection of the lower respiratory tract (acute bronchitis with bacterial superinfection, exacerbation of chronic bronchitis, community-acquired pneumonia);

- urinary tract infection (cystitis, urethritis, pyelonephritis, pyelitis);

- infection in obstetrics and gynecology (salpingitis, salpingo-oophoritis, cervicitis, bacterial vaginitis, endometritis, pelvioperitonitis, septic abortion);

- skin and soft tissue infections (erysipelas, impetigo, secondarily infected dermatoses, phlegmon, abscess, wound infection, including after animal and human bites);

- infections of bone and connective tissues (including osteomyelitis);

- infection of the biliary tract (cholecystitis, cholangitis);

- chancroid (soft chancre);

- odontogenic infections;

- infection of the digestive system (dysentery, salmonellosis, salmonella carcinoma).

Contraindications:

- hypersensitivity to amoxicillin, clavulanic acid and other components of the drug;

- hypersensitivity to other beta-lactam antibiotics (penicillins and cephalosporins);

- violations of the liver (including jaundice) with amoxicillin + clavulanic acid in history;

- infectious mononucleosis or lymphocytic leukemia (risk of occurrence of exanthema);

- children under 6 years of age (for this dosage form);

- Children under 12 years old with chronic renal failure (for this dosage form);

- chronic renal failure (creatinine clearance less than 30 ml / min) for tablets only with a dosage of 875 mg + 125 mg;

Before using the drug, be sure to consult a doctor!

Carefully:

Pregnancy, the period of breastfeeding, severe hepatic insufficiency, diseases of the gastrointestinal tract (including colitis in the anamnesis associated with the use of penicillins), chronic renal failure.

If you have one of the listed diseases - before using the drug, always consult a doctor!

Pregnancy and lactation:

The drug may be administered during pregnancy only in those cases where the intended benefit to the mother exceeds 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 active ingredients into the breast milk in trace amounts, no other adverse effects in infants fed breastfeeding can be noted. If the child develops sensitization, diarrhea, or mucosal candidiasis, breast-feeding should be discontinued.

Dosing and Administration:

Inside.

The dosage regimen is set individually depending on the age, body weight, function of the patient's kidneys, and also on 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 the meal. 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 for 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 infections of the lower respiratory tract - 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 a body weight of 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 in knocking. In severe infections, these doses can be doubled.

Children weighing 40 kg or more should be given doses as adults.

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

It should be remembered that 2 tablets (250 mg + 125 mg) are not equivalent 1 tablet (500 mg + 125 mg), because they contain twice as much clavulanic acid.

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

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

Patents with impaired renal function

Adults and children over 12 years of age or with a body weight of more than 40 kg do dose adjustment and frequency of reception depending on the clearance of creatinine (CC): with QC more than 30 ml / min dose adjustment is not required;

with KK 10-3 0 ml / min: 1 tablet (250 mg + 125 mg) twice a day (for mild and moderate infections) or 1 tablet (500 mg + 125 mg) 2 times a day (for severe infections or infections of the lower respiratory tract);

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).

When anuria - the interval between dosing should be increased to 48 hours or more.

Patents on hemodialysis

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

Adults usually appoint 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 one more dose at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

Patents with impaired liver function

Treat with caution in usual doses; regularly monitor liver function.

Patents of the elderly

Correction of the dose is not required; Doses are the same as for adults. In elderly patients with impaired renal function, the dose is adjusted as indicated above for adults with impaired renal function.

Side effects:

Classification by frequency of development: often - from 1 to 10%, infrequently from 0,1 to 1%, edfrom 0.01 to 0.1%, very rarely - less than 0.01%

Allergic reactions: infrequently - hives, erythematous eruptions; rarely - multi-form exudative erythema; 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, there is a so-called "rash of the fifth day" (cortex exanthema).

From the digestive system: often - nausea, vomiting, diarrhea, abdominal pain, liver failure (more often in the elderly, men, with prolonged therapy), increased activity of hepatic transaminases; rarely - hepatitis, cholestatic jaundice; Very rarely glossitis, gastritis, stomatitis, hemorrhagic colitis (also can develop after therapy), pseudomembranous colitis, enterocolitis, black hairy tongue, darkening of tooth enamel. An increase in the 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 with taking the drug for more than 14 days. These phenomena are very rare in children. The above changes usually appear during treatment or immediately after. Sometimes they may appear several weeks after the drug is discontinued. In general, the reactions from the digestive system are transient and insignificant, but sometimes are severe.

On the part of the hematopoiesis system: rarely - reversible leukopenia (including neutropenia), thrombocytopenia, reversible agranulocytosis and hemolytic anemia; very rarely - lengthening bleeding time, anemia, eosinophilia, thrombocytosis.

From the central nervous system: often - dizziness, headache, reversible hyperactivity and convulsions (seizures may occur if the kidney function is impaired or in patients receiving high doses of the drug), very rarely - insomnia, agitation, anxiety, behavior change.

From the urinary system: very rarely - hematuria.

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

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

In most cases, overdose symptoms include disorders of the gastrointestinal tract (abdominal pain, diarrhea, vomiting), anxiety can also occur, insomnia, dizziness, and convulsions in single cases.

In case of an overdose, the patient should be under the supervision of a physician, treatment - symptomatic.

In the case of a recent intake (less than 4 hours), it is necessary to wash the stomach and appoint Activated carbon to reduce suction.

Amoxicillin + potassium clavulanate is removed during hemodialysis.

Interaction:

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

Simultaneous reception with allopurinol increases the frequency of development of exanthema.

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

Increases the effectiveness of indirect anticoagulants (suppressing the intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). With the simultaneous reception of anticoagulants, it is necessary to monitor blood coagulability.

Reduces the effectiveness of oral contraceptives, drugs, in the process of metabolism which produces paraaminobenzoic acid, ethinyl estradiol - the risk of bleeding "breakthrough".

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).

Simultaneous reception with methotrexate - increases the toxicity of methotrexate.

Special instructions:

Before starting treatment, you must collect a detailed history of previous reactions of hypersensitivity to penicillin or cephalosporin antibiotics or other allergens.

Serious and sometimes fatal hypersensitivity reactions (anaphylactic reactions) to penicillins are described.The risk of occurrence of such reactions is highest in patients who have a history of hypersensitivity reactions to antibiotics of this group. In case of an allergic reaction, it is necessary to stop treatment with the drug and start alternative therapy. In severe reactions of hypersensitivity, adrenaline should be administered immediately (epinephrine). Oxygen therapy, intravenous glucocorticosteroids, and airway patency, including intubation, may also be required.

Cases of development of necrotizing colitis in newborns, in pregnant women with premature rupture of membranes, which were used for preventive therapy with amoxicillin / clavulanic acid, were revealed.

In the treatment of mild diarrhea (caused by Clostridium difficile) against the background of course treatment should avoid antidiarrhoeal drugs that reduce peristalsis of the intestine; it is possible to use kaolin- or attapulgite-containing antidiarrhoeal drugs. With severe diarrhea, you should see a doctor.

Treatment necessarily continues for another 48-72 hours after the disappearance of clinical signs of the disease.

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

Amoxicillin and clavulanic acid can provoke non-specific binding of immunoglobulins and albumins to the erythrocyte membrane, which can be the cause of a false positive reaction in the Coombs sample.

Use with caution in patients with impaired hepatic function.

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

Patients receiving the drug may rarely experience an increase in prothrombin time, so simultaneous administration of the drug with anticoagulants should be monitored accordingly.

In patients with reduced diuresis, crystalluria can rarely occur. When taking amoxicillin in high doses, it is recommended to take a sufficient amount of fluid and maintain an adequate diuresis to reduce the likelihood of the formation of amoxicillin crystals.

In course treatment it is necessary to monitor the status of the function of the organs of hematopoiesis, liver, kidneys.

Patients with severe renal dysfunction require adequate dose adjustment or an increase in the intervals between dosing.

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

In patients with hypersensitivity to penicillins, there may be cross-allergic reactions with cephalosporin antibiotics.

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

Laboratory indicators:

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

Effect on the ability to drive transp. cf. and fur:

During the taking of the drug, care should be taken when driving vehicles, mechanisms and other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

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

Packaging:

For 5, 7 or 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

1, 2 or 3 contour mesh packages with a bag of silica gel are brewed into a bag of composite multilayered material based on foil. The package with instructions for use is placed in a pack of cardboard.

By 7, 10, 14, 20 or 21 tablets in cans of orange glass with screwed plastic caps or in polymer cans. A desiccant in the form of a round tablet or a bag of silica gel is put in each jar.

By 7, 10, 14, 20 or 21 tablets in cans of orange glass with a screw cap on silica gel and tamper control or a tamper-proof cover and a bag of silica gel.

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

Storage conditions:

In a dry, the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-002677

Date of registration:26.09.2011

The owner of the registration certificate:POLLO, LLC POLLO, LLC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspPOLLO LLC POLLO LLC Russia

Information update date: & nbsp26.09.2011

Illustrated instructions

Instructions

Arlet® (Arlet®)