Arlette

General characteristics. Structure:

Structure on one tablet	250 mg + 125 mg	500 mg + 125 mg	875 mg + 125 mg
Active agents:
Amoxicillin trihydrate (in terms of amoxicillin)	250 mg	500 mg	875 mg
Potassium clavulanate (in terms of clavulanic acid)	125 mg	125 mg	125 mg
Excipients:
Structure of a kernel:
Povidone low-molecular (polyvinylpirrolidone low-molecular medical 12600±2700)	14,0 mg	20,0 mg	30,0 mg
Talc	12,8 mg	21,4 mg	33,0 mg
Starch prezhelatinizirovanny (starch 1500)	119,4 mg	191,2 mg	249,0 mg
Calcium stearate (calcium stearino- vokisly)	6,4 mg	10,7 mg	16,5 mg
Silicon dioxide colloid (aerosil)	6,4 mg	10,7 mg	16,5 mg
Cellulose microcrystallic	45,2 mg	90,2 mg	51,7 mg
Mass of a kernel:	640 mg	1067 mg	1550 mg
Structure of a cover:
hypromellose (oksipropilmetiltsellyuloza)	8,0 mg	13,0 mg	19,1 mg
Propylene glycol	6,0 mg	10,0 mg	15,5 mg
Macrogoal 4000 (polyethyleneglycol 4000)	3,9 mg	6,5 mg	10,0 mg
Titanium dioxide	2,1 mg	3,5 mg	5,4 mg
Mass of a tablet coated	660 mg	1100 mg	1600 mg

Pharmacological properties:

Pharmacodynamics. An antibiotic of a broad spectrum of activity from group of ingibitorozashchishchenny penicillin, steady against influence of enzymes β-лактамаз, the β-laktamny antibiotics (penicillin, cephalosporins, karbapenem) developed by many pathogenic microorganisms for protection (stability) against action. Bacterial β-lactamelements destroy (hydrolyze) an antibiotic on inactive fragments (substances). The bacteria developing β-lactamelements are steady (rezistentna) against penicillin and cephalosporins.
The drug Arlet® contains 2 active ingredients: amoxicillin (semi-synthetic пеницилли­н with a wide range of antibacterial activity) and clavulanic acid (neobratiyomy inhibitor β-лактамаз).
Amoxicillin - a semi-synthetic antibiotic of a broad spectrum of activity, active concerning many gram-positive and gram-negative microorganisms. Amoxicillin is exposed to destruction by β-lactamelements therefore the microorganisms producing β-lactamelements do not enter a range of its antibacterial activity.
Clavulanic acid - the β-laktamny connection having ability to inactivate a wide range β-лактамаз by formation of the stable inactivated complex with them that prevents enzymatic destruction of amoxicillin.
Clavulanic acid is similar on structure to β-laktamny antibiotics, but has practically no own antibacterial activity. Clavulanic acid inhibits β-lactamelements II, III, IV and V types (on classification of Richmond Sykes), but is inactive in the relation β-лактамаз type I, the produced Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp.
Presence of clavulanic acid as a part of drug protects amoxicillin from destruction by β-lactamelements and expands a range of its antibacterial activity with inclusion in it of microorganisms, usually resistant (steady) against it and to other penicillin and cephalosporins.
Drug possesses a wide range of bactericidal antibacterial action.
It is active concerning the following microorganisms:
- gram-positive aerobes: Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus agalactiae. Streptococcus bovis; Staphylococcus aureus (except Methicillinum - resistant strains), Staphylococcus epidermidis (except Methicillinum - resistant strains), Staphylococcus saprophyticus and others koagulazo-negative staphylococcus, 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 anaerobe bacterias: Actinomyces israelii, Bacteroides spp. (including Bacteroides fragilis), 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 key pharmacokinetic parameters of amoxicillin and clavulanic acid are similar. In a combination amoxicillin and clavulanic acid do not influence pharmacokinetics of each other.
Both components are quickly and completely soaked up after intake, meal almost does not influence extent of absorption, however clavulanic acid is better soaked up at reception of a tablet of drug at the beginning of food.
The maximum concentration in a blood plasma are reached approximately in 1 hour after reception. Values of the maximum concentration are made for amoxicillin (depending on a dose) by 3-12 mkg/ml, for clavulanic acid - about 2 mkg/ml.
Both components are characterized by the large volume of distribution. Therapeutic concentration of both active agents are defined in various bodies, fabrics and fluid mediums of an organism: in lungs, a phlegm, abdominal organs, bodies of a small pelvis (a uterus, ovaries, a prostate gland), on average to fish soup, in skin, a liver, palatine tonsils, paranasal sinuses, a gall bladder; in fatty, bone and muscular fabrics; in pleural, synovial and peritoneal liquids; in bile, urine, saliva, a bronchial secret, in purulent separated, in intersticial liquid.
Amoxicillin and clavulanic acid do not get through a blood-brain barrier at an uninflammed meninx.
Linkng with proteins of plasma moderate: 25% for clavulanic acid and 18% for amoxicillin.
Amoxicillin and clavulanic acid get through a placental barrier (the negative impact on a fruit is not revealed) and in trace concentration are emitted with breast milk.
Amoxicillin is partially metabolized in a liver (10% of the entered dose) to inactive metabolites, clavulanic acid is exposed to intensive metabolism in a liver (50-70% of the entered dose).
Amoxicillin is removed from an organism preferential by kidneys by canalicular secretion and glomerular filtering (52±15% of a dose in not changed look during 7 h) and a small amount - with bile. About 10-25% of an initial dose of amoxicillin are removed by kidneys in the form of inactive penitsilloyevy acid. Clavulanic acid is removed by kidneys by glomerular filtering (40-65%), partially in the form of metabolites, and also intestines.
The elimination half-life (T1/2) of amoxicillin and clavulanic acid makes 1-1,5 hours. At patients with a heavy renal failure (clearance of creatinine of 10-30 ml/min.) the elimination half-life increases till 7,5 o'clock for amoxicillin and till 4,5 o'clock for clavulanic acid. At an anury of T1/2 of both active agents fluctuates between 10 and 15 hours.
Both components are removed a hemodialysis and insignificant quantities - peritoneal dialysis.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to drug:
- infections of ENT organs (acute and chronic sinusitis, average otitis, retropharyngeal abscess, tonsillitis, pharyngitis);
- lower respiratory tract infections (an acute bronchitis with bacterial superinfection, an exacerbation of chronic bronchitis, community-acquired pneumonia);
- infections of urinary tract (cystitis, urethritis, pyelonephritis, pyelitis);
- infections in obstetrics and gynecology (a salpingitis, a salpingo-oophoritis, a cervicitis, a bacterial vaginitis, an endometritis, a pelviperitonitis, septic abortion);
- infections of skin and soft tissues (the ugly face, impetigo for the second time infected a dermatosis, phlegmon, abscess, a wound fever including after stings of animals and the person);
- infections of bone and connecting fabrics (including osteomyelitis);
- infections of bilious ways (cholecystitis, cholangitis);
- шанкроид (venereal ulcer);
- dontogenous infections;
- infections of the alimentary system (dysentery, salmonellosis, salmonellezny carriage).

Route of administration and doses:

 Inside.
The mode of dosing is set individually depending on age, body weight, function of kidneys of the patient, and also from severity of an infection.
For reduction of possible side effects from the alimentary system it is recommended to accept drug at the beginning of food. The tablet is swallowed entirely, without chewing, washing down with a glass of water.
Adults and children are more senior than 12 years or with body weight more than 40 kg: 
Slight and medium-weight infections (except lower respiratory tract infections) - on 1 tablet (250 mg +125 mg) 3 times a day or on 1 tablet (500 mg +125 mg) 2 times a day.
Heavy infections or lower respiratory tract infections - on 1 tablet (500 mg +125 mg) 3 times a day or on 1 tablet (875 mg + 125 mg) 2 times a day.
Dontogenous infections - on 1 tablet (250 mg +125 mg) 3 times a day or on 1 tablet (500 mg +125 mg) 2 times a day within 5 days.
Children from 6 to 12 years 
The daily dose makes usually 20-30 mg/kg of amoxicillin and 5-7,5 mg/kg of clavulanic acid. For children at the age of 6-12 years (with body weight less than 40 kg) a usual dose of drug - on 1 tablet (250 mg +125 mg) 2-3 times a day or on 1 tablet (500 mg +125 mg) 2 times in knocks. At heavy infections these doses can be doubled. 
Children with a body weight of 40 kg and more should appoint doses as the adult.
The minimum course of treatment drug makes 5 days. Duration of a course of treatment is defined by the attending physician. Treatment should not continue more than 14 days without repeated medical examination. Duration of treatment of acute uncomplicated average otitis makes 5-7 days. 
It is necessary to remember that 2 tablets on (250 mg +125 mg) are not equivalent to 1 tablet (500 mg +125 mg) since they contain twice more clavulanic acid.
The maximum daily dose of amoxicillin makes: for adults and children 12 years are more senior (with the body weight of 40 kg and more) - 6 g, for children are younger than 12 years (with body weight less than 40 kg) 45 mg/kg of body weight. 
The maximum daily dose of clavulanic acid (in the form of potassium clavulanate) makes: for adults and children 12 years are more senior (with the body weight of 40 kg and more) - 600 mg, for children are younger than 12 years (with body weight less than 40 kg) - 10 mg/kg of body weight. 
Patients with renal failures
 To adults and children 12 years are more senior or with body weight more than 40 kg carry out dose adjustment and frequency rate of reception depending on the clearance of creatinine (CC): 
at KK more than 30 ml/min. dose adjustment is not required;
at KK of 10-30 ml/min.: on 1 tablet (250 mg +125 mg) 2 times a day (at slight and medium-weight infections) or on 1 tablet (500 mg +125 mg) 2 times a day (at heavy infections or lower respiratory tract infections);
at KK less than 10 ml/min.: on 1 tablet (250 mg +125 mg once a day (at slight and medium-weight infections) or on 1 tablet (500 mg +125 mg) once a day (at heavy infections or lower respiratory tract infections).
At an anury - the interval between dosing should be increased till 48 o'clock and more.
The patients who are on a hemodialysis 
Corrections of doses are based on the maximum recommended amoxicillin dose. 
The adult on 1 tablet (500 mg +125 mg) or 2 tablets (250 mg +125 mg) each 24 h usually appoint (1 time a day). To children appoint (15 mg/kg +3,75 mg/kg) 1 time a day. 
IN ADDITION 1 dose during the session of dialysis and one more dose at the end of dialysis session (for compensation of decrease in serumal concentration of amoxicillin and clavulanic acid).
Patients with abnormal liver functions 
Treatment is carried out with care usual doses; regularly carry out monitoring of function of a liver.
Patients of advanced age
 Dose adjustment is not required; doses are same, as for adults. At elderly patients with renal failures the dose is adjusted as it is stated above for adults with renal failures.

Features of use:

With care use drug at patients with abnormal liver functions, during treatment regularly control function of a liver.
At course treatment it is necessary to control functions of a hemopoiesis, a liver and kidneys.
Adequate correction of the mode of dosing or increase in intervals between administrations of drug is required from patients with heavy renal failures.
For the purpose of decrease in risk of development of side reactions from a GIT it is necessary to accept drug during food.
As tablets of the combined drug of 250 mg / 125 mg and 500 mg / 125 mg contain identical amount of clavulanic acid (125 mg), 2 tab. on 250 mg / 125 to mg are not equivalent to 1 tab. of 500 mg / 125 to mg.
High concentration of amoxicillin give false positive reaction when determining glucose in urine when using a reactant of Benedict or solution of Fellinga (recommend to apply enzymatic reactions with glucosidase).
Influence on ability to driving of motor transport and to control of mechanisms
Drug in the recommended doses does not influence ability to driving of transport and control of difficult mechanisms.

Side effects:

From the alimentary system: appetite loss, nausea, vomiting, diarrhea; seldom - abnormal liver functions, increase in activity of ALT and nuclear heating plant; in isolated cases - cholestatic jaundice, hepatitis, pseudomembranous colitis.

From TsNS: dizziness, headache, reversible hyperactivity and spasms.

From system of a hemopoiesis: reversible increase in a prothrombin time, leukopenia, reversible agranulocytosis and hemolitic anemia.

From an urinary system: intersticial nephrite, crystalluria.

Allergic reactions: itch, urticaria, erythematic rash; seldom - a mnogoformny exudative erythema, a Quincke's disease, an acute anaphylaxis; in isolated cases - exfoliative dermatitis, Stephens-Johnson's syndrome.

Others: development of superinfection (including candidiasis).

Interaction with other medicines:

At simultaneous use of Arlet® increases toxicity of a methotrexate.

At simultaneous use Arlette with Allopyrinolum raises risk of development of a dieback.

At simultaneous use Arlette with antacids, a glycosamine, purgatives, aminoglycosides absorption is slowed down, with ascorbic acid - increases.

At simultaneous use Arlette with bactericidal antibiotics (including aminoglycosides, cephalosporins, Cycloserinum, Vancomycinum, rifampicin) is shown an action synergism; with antibiotics with the bacteriostatic mechanism of action (including macroleads, chloramphenicol, linkozamida, tetracyclines, streptocides) - antagonism.

At simultaneous use of Arlet® increases efficiency of effect of indirect anticoagulants due to suppression of intestinal microflora, decrease in synthesis of vitamin K and decrease in a prothrombin ratio. At purpose of this combination it is necessary to carry out dynamic control of blood tests.

At simultaneous use of Arlet® reduces efficiency of oral contraceptives.

At co-administration Arlette with drugs in the course of which metabolism para-aminobenzoic acid is formed, ethinylestradiol raises risk of development of breakthrough bleedings.

Diuretics, Allopyrinolum, phenylbutazone, NPVS and other medicines blocking canalicular secretion increase concentration of amoxicillin (clavulanic acid is removed generally by glomerular filtering).

Contraindications:

Hypersensitivity to amoxicillin, clavulanic acid and other components of drug;
- hypersensitivity to others beta лактамным to antibiotics (penicillin and cephalosporins);
- abnormal liver functions (including jaundice) at amoxicillin reception + clavulanic acid in the anamnesis;
- infectious mononucleosis or lymphoid leukosis (danger of emergence of a dieback);
- children's age up to 6 years (for this dosage form);
- children's age up to 12 years with a chronic renal failure (for this dosage form);
- a chronic renal failure (clearance of creatinine less than 30 ml/min.) only for tablets a dosage of 875 mg +125 mg;
Before drug use surely consult with the doctor! 
Use at pregnancy Drug can be appointed during pregnancy only when the estimated advantage for mother exceeds potential risk for a fruit. Drug can be accepted during breastfeeding. Except for the risk of a sensitization connected with allocation in breast milk of active agents of drug in trace quantities, it cannot be noted any other adverse effects at the babies who are on breastfeeding. In case of development in the child of a sensitization, diarrhea or candidiasis of mucous membranes feeding by a breast should be stopped.

Overdose:

Symptoms: abdominal pain, diarrhea, vomiting; also alarming excitement, sleeplessness, dizziness is possible; in some cases - convulsive attacks.

Treatment: in case of recent administration of drug (less than 4 h) it is necessary to carry out a gastric lavage and to appoint absorbent carbon for drug absorption reduction; the patient has to be under medical control, if necessary carry out symptomatic therapy. The hemodialysis is effective.

Storage conditions:

In the dry, protected from light place, at a temperature not above 25 °C. To store in the places unavailable to children. Period of validity 2 years. Not to use after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets, film cover, 250 mg +125 mg

Tablets, film cover, 500 mg +125 mg

Tablets, film cover, 875 mg +125 mg