Arlet, 500 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 broad 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

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

– ENT organ infections (acute and chronic sinusitis middle otitis tonsillitis abscess tonsillitis pharyngitis);

– Lower respiratory tract infections (acute bronchitis with bacterial superinfection exacerbation of chronic bronchitis, outpatient pneumonia);

– urinary tract infections (cystitis urethritis pyelonephritis pyelitis);

– infections in obstetrics and gynecology (salpingitis salpingo-oophoritis cervicitis bacterial vaginitis endometritis penile peritonitis septic abortion);

– skin and soft tissue infections (rye impetigo secondary infected dermatosis phlegmon abscess wound infection including.

– 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 carrier).

Active ingredient

Composition

1 tablet contains:

The active ingredients:

amoxicillin trihydrate 500 mg,

clavulanic acid 125 mg;

Excipients: polyvinylpyrrolidone (povidone), talc (magnesium disilicate), starch 1500, calcium stearate (calcium stearate), aerosil (colloidal silica), microcrystalline cellulose.

The composition of the shell: hypromellose (oxypropyl methylcellulose), propylene glycol, titanium dioxide, polyethylene oxide 4000 (macrogol 4000).

How to take, the dosage

Ingestion.

The dosing regimen is individualized depending on the patient’s age, body weight, renal function, and the severity of the infection.

To reduce possible side effects on the digestive system, it is recommended that the drug be taken at the beginning of a meal. The whole tablet should be swallowed without chewing, followed by a glass of water.

Adults and children over 12 years of age or with body weight over 40 kg;

Mild to moderate infections (except lower respiratory tract infections): 1 tablet (250 mg+125 mg) 3 times daily or 1 tablet (500 mg+125 mg) 2 times daily.

Severe infections or lower respiratory tract infections – 1 tablet (500 mg+125 mg) 3 times daily or 1 tablet (875 mg+125 mg) 2 times daily.

Odontogenic infections – 1 tablet (250 mg+125 mg) 3 times daily or 1 tablet (500 mg+125 mg) 2 times daily for 5 days.

Children 6 to 12 years old

The daily dose is usually 20-30 mg/kg amoxicillin and 5-75 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. In severe infections, these doses may be doubled.

Children weighing 40 kg or more should be prescribed doses like 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. The treatment should not continue for more than 14 days without repeated medical examination. The duration of treatment of acute uncomplicated otitis media is 5-7 days.

We should remember that 2 tablets (250 mg +125 mg) are not equivalent to 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 old (with body weight of 40 kg or more) – 6 g for children under 12 years old (with body weight less than 40 kg) – 45 mg/kg of body weight.

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

Patients with impaired renal function

Adults and children over 12 years of age or with body weight over 40 kg have dose adjustment and administration frequency depending on creatinine clearance (CK): at CK over 30 ml/min no dose adjustment is required;

In CK 10-3 0 ml/min: 1 tablet (250 mg+125 mg) 2 times daily (for mild to moderate infections) or 1 tablet (500 mg+125 mg) 2 times daily (for severe infections or lower respiratory tract infections);

for CK less than 10 ml/min: 1 tablet (250 mg+125 mg once daily (for mild to moderate infections) or 1 tablet (500 mg+125 mg) once daily (for severe infections or lower respiratory tract infections).

In case of 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+375 mg/kg) once daily. ADD 1 dose during a dialysis session and another dose at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

Patients with hepatic dysfunction

Treatment is with caution with usual doses; regular monitoring of liver function is performed.

Elderly patents

Dose adjustment is not required; doses are the same as in adults. In elderly patients with impaired renal function, the dose is adjusted as above for adults with impaired renal function.

Interaction

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

Concomitant administration with allopurinol increases the frequency of exanthema.

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

It increases the effectiveness of indirect anticoagulants (by suppressing the intestinal microflora it reduces the synthesis of vitamin K and the prothrombin index). When concomitant use of anticoagulants, it is necessary to monitor blood clotting parameters.

Decreases the effectiveness of oral contraceptives drugs in the metabolism of which para-aminobenzoic acid ethinyl estradiol is formed – 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).

Concomitant use with methotrexate – increases the toxicity of methotrexate.

Special Instructions

Before starting treatment, a detailed history of prior hypersensitivity reactions to penicillin or cephalosporin antibiotics or other allergens must be taken.

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

There have been cases of necrotizing colitis in newborns in pregnant women with premature rupture of fetal membranes who received prophylactic therapy with amoxicillin/clavulanic acid.

In treatment of mild diarrhea (caused by Clostridium difficile), anti-diarrheal medications that reduce intestinal peristalsis should be avoided; kaolin- or attapulgit-containing anti-diarrheal medications may be used during course treatment. If the diarrhea is severe, a doctor should be consulted.

The treatment necessarily continues for another 48-72 h after the clinical signs of the disease have disappeared.

In case of concomitant use of estrogen-containing oral contraceptives and amoxicillin, other or additional contraceptive methods should be used if possible.

Amoxicillin and clavulanic acid may cause non-specific binding of immunoglobulins and albumin to the erythrocyte membrane, which may cause a false positive Coombs test.

With caution use the drug in patients with liver dysfunction.

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

In patients receiving this drug prolongation of prothrombin time may rarely be observed; therefore, appropriate monitoring should be performed when concomitant use of the drug with anticoagulants.

In patients with decreased diuresis very rarely crystalluria may occur. When taking amoxicillin at high doses, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.

When taking a course of treatment it is necessary to monitor the hematopoietic function of the liver and kidneys.

In patients with severe renal dysfunction, adequate dose adjustment or increased dosing intervals are required.

The development of superinfection due to growth of microflora insensitive to it is possible, which requires appropriate modification of antibiotic therapy.

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

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

Laboratory Indicators:

High concentrations of amoxicillin give a false-positive reaction for urine glucose when using Benedict’s reagent or Fehling’s solution. Enzymatic reactions with glucosidase are recommended.

When taking the drug, caution should be exercised when driving vehicles and performing other potentially hazardous activities that require increased concentration and rapid psychomotor reactions.

Contraindications

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

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

– liver function disorders (including jaundice) when taking amoxicillin + clavulanic acid in history;

– infectious mononucleosis or lympholeukemia (risk of exanthema);

– childhood under 6 years (for this dosage form);

–

Chronic renal failure in children under 12 years of age (for this form);

Chronic renal failure (creatinine clearance

Side effects

Classification by frequency of development: frequent – 1 to 10% infrequent – 01 to 1% rare – 001 to 01% very rare – less than 001%

Allergic reactions: infrequent – urticaria erythematous rash itching; rare – erythema multiforme exudative; very rare – exfoliative dermatitis malignant exudative erythema (Stevens-Johnson syndrome) anaphylactic shock angioneurotic edema syndrome similar to serum sickness acute generalized exanthema pustulosis. In some cases, the so-called “fifth day rash” (coriaceous exanthema) appears.

Digestive system disorders: frequent – nausea vomiting diarrhea abdominal pain liver failure (more common in elderly men with long-term therapy) increased liver transaminase activity; rare – hepatitis cholestatic jaundice; very rare – glossitis gastritis stomatitis hemorrhagic colitis (can also develop after therapy) pseudomembranous colitis enterocolitis black “hairy” tongue darkening of dental enamel. Increased activity of transaminases (aspartate aminotransferase and alanine aminotransferase) bilirubin and alkaline phosphatase is usually noted in male patients and elderly patients especially over 65 years old.

The risk of these changes increases when taking the drug for more than 14 days. These phenomena are very rare in children. The above-mentioned changes usually appear during treatment or immediately afterwards. Sometimes they may appear a few weeks after discontinuation of the drug. Mostly the digestive system reactions are transient and minor, but sometimes they are pronounced.

With the hematopoietic system: rare – reversible leukopenia (including neutropenia) thrombocytopenia reversible agranulocytosis and hemolytic anemia; very rare – prolongation of bleeding time anemia eosinophilia thrombocytosis.

The central nervous system: frequently – dizziness headache reversible hyperactivity and seizures (seizures can occur with impaired renal function or in patients receiving high doses of the drug) very rarely – insomnia agitation anxiety behavior change.

Urinary system disorders: very rare – hematuria.

Others: often – 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 instructions worsen, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose

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

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

In case of recent ingestion (less than 4 hours) gastric lavage should be performed and activated charcoal prescribed to reduce absorption.

Amoxicillin+clavulanate potassium is eliminated by hemodialysis.

Pregnancy use

The drug may be administered during pregnancy only when the expected benefits to the mother exceed the potential risk to the fetus.

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

Similarities