Flemoclav Solutab - instructions for use, dose, side effects, contraindications

The current substance: amoxicillin trihydrate (which corresponds to amoxicillin base) - 145.7 mg (125 mg); potassium clavulanate (corresponding to clavulanic acid) - 37.2 mg (31.25 mg).

Excipients: microcrystalline cellulose - 81.8 mg; crospovidone - 25.0 mg; vanillin - 0.25 mg; apricot flavor - 2.25 mg; saccharin - 2.25 mg; magnesium stearate - 1.25 mg.

Tablet 250 mg / 62.5 mg contains:

Active substance: amoxicillin trihydrate (which corresponds to amoxicillin base) -291.4 mg (250 mg); potassium clavulanate (which corresponds to clavulanic acid) - 74.5 mg (62.5 mg).

Excipients: microcrystalline cellulose - 163.6 mg; crospovidone - 50.0 mg; vanillin - 0.5 mg; apricot perfume - 4,5 mg; saccharin 4.5 mg; magnesium stearate - 2.5 mg.

Tablet 500 mg / 125 mg contains:

Active substance: amoxicillin trihydrate (which corresponds to amoxicillin base) - 582.8 mg (500 mg); potassium clavulanate (corresponding to clavulanic acid) - 148.9 mg (125 mg).

Excipients: microcrystalline cellulose - 327.3 mg; crospovidone - 100.0 mg; vanillin - 1.0 mg; apricot flavor - 9.0 mg; saccharin 9.0 mg; magnesium stearate 5.0 mg.

Description:The oblong form from white to yellow colored tablets with brown spot spots without risks and labeled "421" - for a dosage of 125 mg + 31.25 mg; "422" - for the dosage of 250 mg + 62.5 mg; "424" - for the dosage of 500 mg + 125 mg and the company logo.

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

ATX: & nbsp

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

Pharmacodynamics:

Mechanism of action

Amoxicillin is a semisynthetic broad-spectrum antibiotic with activity against many Gram-positive and Gram-negative microorganisms. In the same time, amoxicillin is subject to destruction by beta-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms, which produce this enzyme. Clavulanic acid - a beta-lactamase inhibitor, structurally related penicillins, has the ability to inactivate a wide range of beta-lactamase detected in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid has sufficient efficacy against plasmid beta-lactamases, which most often determine the resistance of bacteria,and is not effective against chromosomal beta-lactamases type 1, which are not inhibited by clavulanic acid.

The presence of clavulanic acid in the preparation Flemoclav Solutab® protects amoxicillin from destruction by enzymes - beta-lactamases, which allows to expand the antibacterial spectrum of amoxicillin. The activity of a combination of amoxicillin with clavulanic acid in vitro.

Bacteria, usually sensitive to a combination of amoxicillin and clavulanic acid

Gram-positive aerobes:

Bacillus anthracis

Enterococcus faecalis

Listeria monocytogenes

Nocardia asteroides

Streptococcus pyogenes^1,2

Streptococcus agalactiae^1,2

Streptococcus spp. (other beta-hemolytic streptococci)^1,2

Staphylococcus aureus (sensitive to methicillin)¹

Staphylococcus saprophyticus (sensitive to methicillin)

Coagulase-negative staphylococci, (sensitive to methicillin)

Gram-positive anaerobes:

Clostridium spp.

Peptococcus niger

Peptostreptococcus magnus

Peptostreptococcus micros

Peptostreptococcus spp.

Gram-negative aerobes:

Bordetella pertussis

Haemophilus influenzae¹

Helicobacter pylori

Moraxella catarrhalis¹

Neisseria gonorrhoeae

Pasteurella multocida

Vibrio cholerae

Gram-negative anaerobes:

Bacteroides fragilis

Bacteroides spp.

Capnocytophaga spp.

Eikenella corrodens

Fusobacterium nucleatum

Fusobacterium spp.

Porphyromonas spp.

Prevotella spp.

Other:

Borrelia burgdorferi

Leptospira icterohaemorrhagiae

Treponema pallidum

Bacteria for which it is probable acquired resistance to combination of amoxicillin with clavulanic acid

Gram-negative aerobes:

Escherichia coli¹

Klebsiella oxytoca

Klebsiella pneumoniae¹

Klebsiella spp.

Proteus mirabilis

Proteus vulgaris

Proteus spp.

Salmonella spp.

Shigella spp.

Gram-positive aerobes:

Corynebacterium spp.

Enterococcus faecium

Streptococcus pneumoniae^1,2

streptococci groups Viridans²

Bacteria that have natural resistance to a combination of amoxicillin and clavulanic acid

Gram-negative aerobes:

Acinetobacter spp.

Citrobacter freundii

Enterobacter spp.

Hafnia alvei

Legionella pneumophila

Morganella morganii

Providencia spp.

Pseudomonas spp.

Serratia spp.

Stenotrophomonas maltophilia

Yersinia enterocolitica

Other:

Chlamydia pneumoniae

Chlamydia psittaci

Chlamydia spp.

Coxiella burnetii

Mycoplasma spp.

¹for these types of microorganisms, the clinical efficacy of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.

²strains of these bacterial species do not produce β-lactamases.

Sensitivity to monotherapy with amoxicillin suggests a similar sensitivity to the combination of amoxicillin and clavulanic acid.

Pharmacokinetics:

Suction

Amoxicillin and clavulanic acid completely dissociate in aqueous solution at physiological pH values. Both active components of the drug, amoxicillin and clavulanic acid, are quickly and well absorbed from the digestive tract (gastrointestinal tract) after oral administration. Absorption of the active substances is optimal at the beginning of the meal. Bioavailability Amoxicillin and clavulanic acid when ingested high.After a single administration of Flemoklava Solutab® at a dose of 500 mg of amoxicillin / 125 mg of clavulanic acid, the maximum concentration of amoxicillin in the blood plasma is created after 1.5 hours (1.0-2.5 hours), and is 7.19 ± 2.26 μg / ml (Cmax), clavulanic acid - after 1.5 hours (1.0-2.0 hours), amounting to 2.4 ± 0.83 μg / ml. PFK (indicator "area under pharmacokinetic curve ") amoxicillin and clavulanic acid is 53.5 ± 8.87 μg * h / l and 15.72 ± 3.86 μg * h / l, respectively.

Plasma concentrations of amoxicillin and clavulanic acid, obtained with the use of amoxicillin / clavulanate, are similar to those for oral administration of equivalent doses of amoxicillin and clavulanic acid alone.

Distribution

Approximately 18% of amoxicillin and 25% of clavulanic acid bind to plasma proteins. The apparent volume of distribution is 0.3-0.4 l / kg for amoxicillin and about 0.2 l / kg for clavulanic acid. Amoxicillin poorly distributed into the cerebrospinal fluid.

In animal studies, no cumulation of the drug components in the body tissues was detected.

Like most penicillins, amoxicillin penetrates into breast milk.Clavulanic acid also is found in breast milk in trace concentrations. Amoxicillin and clavulanic acid penetrate the placental barrier.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of inactive metabolite (penicillic acid). Clavulanic acid, is subject to intensive metabolism and is excreted by the kidneys, intestines, and also with exhaled air in the form of carbon dioxide.

Excretion

After a single dose of Flemoklava Solutab® at a dose of 500 mg / 125 mg, the half-life of amoxicillin is 1.15 ± 0.20 h, clavulanic acid 0.98 ± 0.12 h, and the total clearance is about 25 l / h. Approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted by the kidneys unchanged for the first 6 hours after taking 1 tablet of the drug 250/125 mg or 500/125 mg. The greatest amount of clavulanic acid is excreted within the first 2 hours after administration. In various studies, it was shown that up to 50-85% of amoxicillin and up to 27-60% of clavulanic acid are excreted through the kidneys within 24 hours. Simultaneous administration of probenecid delayed the excretion of amoxicillin, but does not affect the excretion of clavulanic acid by the kidneys (see "Interaction with other medicinal products ").

Pharmacokinetics in special cases

Age features

Amoxicillin half-life in children 3 months - 2 years old does not differ from that in older children and adults. Children of the first week of life (including premature) should not be prescribed more than 2 times a day because of the immaturity of the renal elimination pathway. Because of the possible reduction in kidney function, the dose should be selected carefully for elderly patients with caution. You may need to monitor kidney function.

Sexual features

When taken orally amoxicillin / clavulanic acid healthy men and women have no significant effect on the patient's sex on the pharmacokinetics of the active components of the drug.

Impaired renal function

Total Clearance amoxicillin / clavulanic acid decreases in proportion to the decrease in renal function. Especially noticeably, the clearance of amoxicillin is disturbed, since the greater part of it is excreted by the kidneys. Thus, if the kidney function is impaired, the dose of the drug should be adjusted to avoid excessive concentration of amoxicillin and to maintain the required level of clavulanic acid.

Impaired liver function

In patients with impaired liver function, the drug should be administered with caution. It is necessary to regularly monitor liver function.

Indications:

The combination of amoxicillin with clavulanic acid is indicated for the treatment of bacterial infections of the following localizations caused by microorganisms sensitive to a combination of amoxicillin and clavulanic acid:

- infections of the upper respiratory tract (including ENT diseases), for example, recurrent tonsillitis, sinusitis, otitis media, usually caused Streptococcus pneumoniae, Haemophilus influenzae^#, Moraxella catarrhalis^# and Streptococcus pyogenes.

- Infections of the lower respiratory tract, for example, exacerbation of chronic bronchitis, lobar pneumonia and bronchopneumonia, usually caused Streptococcus pneumoniae, Haemophilus influenzae^# and Moraxella catarrhalis^#.

- urinary tract infections, for example, cystitis, urethritis, pyelonephritis, infections of female genitalia, usually caused by species of the family Enterobacteriaceae¹(mainly Escherichia coli^#), Staphylococcus saprophyticus and species Enterococcus, as well as gonorrhea caused by Neisseria gonorrhoeae^#.

- skin and soft tissue infections, usually caused by Staphylococcus aureus^#, Streptococcus pyogenes and species Bacteroides^#.

- infections of bones and joints, for example, osteomyelitis, usually caused by Staphylococcus aureus^#, if necessary, long-term therapy is possible.

- odontogenic infections, for example, periodontitis, odontogenic maxillary sinusitis, severe dental abscesses with spreading cellulitis.

- other mixed infections (eg, septic abortion, postpartum sepsis, intra-abdominal sepsis) within the framework of stepwise therapy.

# Individual representatives of this kind of microorganisms produce beta-lactamase, which makes them insensitive to amoxicillin (see also the section "Pharmacological properties"). Infections caused by microorganisms sensitive to amoxicillin can be treated with Flemoclav Solutab®, because amoxicillin is one of its active ingredients. Flemoclav Solutab® is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as by microorganisms producing beta-lactamase that are sensitive to a combination of amoxicillin and clavulanic acid.

The sensitivity of bacteria to the combination of amoxicillin and clavulanic acid varies depending on the region and over time.Wherever possible, local sensitivity data should be taken into account. If necessary, the collection of microbiological samples and analysis for bacteriological sensitivity should be carried out.

Contraindications:

- Hypersensitivity to amoxicillin, clavulanic acid and other components of the drug, as well as to other beta-lactam antibiotics (penicillins and cephalosporins) in the anamnesis;

- Presence of a history of jaundice or liver failure due to amoxicillin / clavulanic acid;

- Children age up to 1 year or body weight up to 10 kg (because of the impossibility of dispensing the dosage form in this category of patients).

Carefully:Severe hepatic insufficiency, diseases of the gastrointestinal tract (including colitis in history, associated with the use of penicillins), chronic renal failure.

Pregnancy and lactation:

Pregnancy

In studies of reproductive function in animals, oral and parenteral administration of the drug amoxicillin + clavulanic acid did not cause teratogenic effects.

In a single study in women with premature rupture of membranes, it was found that preventive therapy with the drug may be associated with an increased risk of developing necrotizing enterocolitis in newborns. Like all medications, Flemoclav Solutab® is not recommended for use during pregnancy, unless the expected benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding period

The preparation Flemoclave Solutab ® can be used during breastfeeding. Except for the possibility of developing sensitization, diarrhea, or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active ingredients of this preparation into breast milk, no other adverse effects were observed in infants fed breastfeeding. In case of adverse effects in children who are breastfeeding, it is necessary to stop breastfeeding.

Dosing and Administration:

For oral administration.

Dosing mode is set individually depending on the age, body weight, kidney function of the patient, and also on the severity of the infection. To reduce potential abnormalities from the gastrointestinal tract and to optimize absorption, the drug should be taken at the beginning of the meal. The tablet is swallowed whole, with a glass of water, or dissolve it in half a glass of water (at least 30 ml), stirring thoroughly before use. The minimum course of antibiotic therapy is 5 days.

Treatment should not last more than 14 days without reviewing the clinical situation. If necessary, stepwise therapy is possible (at first parenteral administration amoxicillin + clavulanic acid with the subsequent transition to oral administration).

Adults and children over 12 years of age with a body weight ≥ 40 kg the drug is prescribed at 500 mg / 125 mg 3 times / day.

The maximum daily dose should not exceed 2400 mg / 600 mg per day.

Children aged from 1 year to 12 years with a body weight of 10 to 40 kg dosage regimen is established individually based on the clinical situation and severity of infection.

The recommended daily dose is from 20 mg / 5 mg / kg per day to 60 mg / 15 mg / kg per day and is divided into 2 to 3 doses.

Clinical data on the use of amoxicillin / clavulanic acid in a ratio of 4: 1 in doses> 40 mg / 10 mg / kg per day in children under the age of two there. The maximum daily dose for children is 60 mg / 15 mg / kg per day.

Low doses of the drug are recommended for the treatment of infections of the skin and soft tissues, as well as relapsing tonsillitis; high doses of the drug are recommended for the treatment of diseases such as otitis media, sinusitis, lower respiratory tract infections and urinary tract infections, infections of bones and joints. There is insufficient clinical data to recommend the use of the drug at a dose of more than 40 mg / 10 mg / kg / day in 3 divided doses (4: 1 ratio) in children younger than 2 years. An approximate scheme of dosing of the drug in patients of childhood is presented in the table below:

Weight of child, kg	Age (approximately)	Use of low doses of the drug	The use of high doses of the drug
10-12	1-2 years	2 times a day for 1 tablet 125 mg / 31.25 mg	3 times a day for 1 tablet 125 mg / 31.25 mg *
12-15	2-4 years	2 times a day for 1 tablet 125 mg / 31.25 mg	3 times a day for 1 tablet 250 mg / 62.5 mg
15-20	4-6 years old	3 times a day for 1 tablet 250 mg / 62.5 mg	3 times a day for 1 tablet 250 mg / 62.5 mg or 2 times a day for 500 mg / 152 mg
20-30	6-10 years	3 times a day for 1 tablet 250 mg / 62.5 mg	2 times a day for 1 tablet of 500 mg / 125 mg
30-40	10-12 years old	2 times a day for 1 tablet of 500 mg / 125 mg	3 times a day for 1 tablet of 500 mg / 125 mg
≥40	≥12 years	3 times a day for 1 tablet of 500 mg / 125 mg	3 times a day for 1 tablet of 500 mg / 125 mg

* There are not enough clinical data to recommend the use of the drug at a dose of more than 40 mg / 10 mg / kg / day in 3 divided doses (4: 1 ratio) in children younger than 2 years.

In children ≤ 6 years of age, it is preferable to use the drug in a dissolved form.

Special patient groups

Elderly patients

No dosage adjustment is required. In elderly patients with impaired renal function, the dose should be adjusted as described below for adults with impaired renal function.

Patients with impaired renal function

In patients with renal insufficiency, excretion of clavulanic acid and amoxicillin through the kidneys is slow. Depending on the severity of renal failure, the total dose of Flemoclav Solutab® (expressed in a dose of amoxicillin) should not exceed the quantities shown in the table.

Clearance creatinine	Adults and children over 12 years with a body weight ≥ 40 kg	Children aged 1 to 12 years with a body weight of 10 kg to 40 kg
>30 ml / min	Correction of the dosing regimen is not required	Correction regime dosing is not required
10-30 ml / min	500 mg / 125 mg twice daily	15 mg / 3.75 mg / kg twice daily (maximum 500 mg / 125 mg twice daily)
<10 ml / min	500 mg / 125 mg once daily	15 mg / 3.75 mg / kg once daily (maximum 500 mg / 125 mg once a day)
Hemodialysis	500 mg / 125 mg per day, plus additionally 500 mg / 125 mg during and after dialysis	15 mg / 3.75 mg / kg once daily, plus an additional 15 mg / 3.75 mg / kg before and after dialysis

In most cases, where possible, preference should be given to parenteral therapy.

Patients on hemodialysis

Correction of the dosing regimen is based on the maximum recommended dose of amoxicillin, presented in the table. Patients with impaired hepatic function Treatment is carried out with caution; regularly monitor liver function.

There is insufficient data to change the recommendation of the dosing regimen in such patients.

Side effects:

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: Often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000), rarely (<1/10 000). Frequency categories were formed on the basis of clinical studies of the drug and post-registrationobservation.

Frequency of occurrence of undesirable reactions

Infectious and parasitic diseases

Often: candidiasis of skin and mucous membranes.

Violations of the blood and lymphatic system

Rarely: reversible leukopenia (including neutropenia), reversible thrombocytopenia.

Very rarely: reversible agranulocytosis and reversible hemolytic anemia, prolongation of bleeding time and prothrombin time, anemia, eosinophilia, thrombocytosis.

Immune system disorders

Very rarely: angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.

Disturbances from the nervous system

Infrequent: dizziness, headache.

Very rarely: reversible hyperactivity, convulsions (in the case of kidney dysfunction or drug overdose). Seizures can occur in patients with impaired renal function, as well as in those who receive high doses of the drug (see sections "Dosing and Administration", "Overdosage", "Special instructions"). Insomnia, agitation, anxiety, behavior change.

Disorders from the gastrointestinal tract

Adults:

Very often: diarrhea.

Often: nausea, vomiting.

Children:

Often: diarrhea, nausea, vomiting.

Total population:

Nausea was most often associated with the use of high doses of the drug. If after the beginning of taking the drug there are undesirable reactions from the gastrointestinal tract, they can be eliminated if you take Flemoclav Solutab® at the beginning of the meal.

Infrequently: indigestion

Very rarely: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis) (see section "Special instructions"), black "hairy" tongue, gastritis, stomatitis.

Disturbances from the liver and bile ducts

Infrequent: moderate increase in activity of aspartate aminotransferase and / or alanine aminotransferase (ACT and / or ALT). This reaction is observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown.

Very rarely: hepatitis and cholestatic jaundice. These reactions are observed in patients receiving penicillin antibiotics and cephalosporins. Increased concentrations of bilirubin and alkaline phosphatase.

Undesirable reactions from the liver were observed, mainly,in men and elderly patients and may be associated with long-term therapy. These undesirable reactions are very rare in children.

These signs and symptoms usually occur in the process or immediately after the end of therapy, but in some cases may not appear for several weeks after the completion of therapy. Undesirable reactions are usually reversible. Undesirable reactions from the liver can be severe, in extremely rare cases there have been reports of lethal outcomes. In almost all cases, it was a person with serious concomitant pathology or patients receiving potentially hepatotoxic drugs at the same time.

Disturbances from the skin and subcutaneous tissues

Infrequent: rash, itching, hives.

Rarely: erythema multiforme.

Very rarely: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

In case of skin allergic reactions, treatment with Flemoclav Solutab® should be stopped.

Disorders from the kidneys and urinary tract

Very rarely: interstitial nephritis, crystalluria (see Fig.section "Overdose"), hematuria.

Overdose:

Symptoms

Symptoms on the part of the gastrointestinal tract and violations of the water-electrolyte balance can be observed. Amoxicillin crystalluria is described, in some cases leading to the development of renal failure (see section "Special instructions and precautions").

Cramps can occur in patients with impaired renal function, as well as in those who receive high doses of the drug (see the sections "Method of administration and dose", "Side effects", "Special instructions").

Treatment

Symptoms from the gastrointestinal tract are symptomatic therapy, paying special attention to the normalization of the water-electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

The results of a prospective study, which was conducted with the participation of 51 children in a toxicological center, showed that the administration of amoxicillin at a dose of less than 250 mg / kg did not lead to significant clinical symptoms and did not require gastric lavage.

Interaction:Simultaneous use of the preparation Flemoclav Solutab® and probenecid is not recommended.Probenecid reduces the tubular secretion of amoxicillin, and therefore simultaneous use of the preparation Flemoclav Solutab® and probenecid can lead to an increase and persistence in the blood concentration of amoxicillin, but not clavulanic acid. The simultaneous use of allopurinol and amoxicillin may increase the risk of skin allergic reactions. Currently, there is no data in the literature on the simultaneous use of a combination of amoxicillin with clavulanic acid and allopurinol.

Penicillins can slow the excretion of methotrexate from the body by inhibiting its tubular secretion, so the simultaneous use of Flemoclav Solutab® and methotrexate can increase the toxicity of methotrexate.

Like other antibacterial drugs, the preparation Flemoclav Solutab® can have an effect on the intestinal microflora, leading to a decrease in absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives.

In the literature, rare cases of an increase in the international normalized ratio (INR) in patients with joint use of acenocoumarol or warfarin and amoxicillin are described.If it is necessary to simultaneously prescribe the preparation Flemoclav Solutab® with anticoagulants, prothrombin time or INR should be carefully monitored when the preparation Flemoclav Solutab® is prescribed or withdrawn, correction of the dose of anticoagulants for oral administration may be required.

In patients who received mycophenolate mofetil, after the start of the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite, mycophenolic acid, was observed before taking the next dose of the drug by approximately 50%. Changes in this concentration can not accurately reflect the overall changes in the exposure of mycophenolic acid.

Special instructions:Before starting treatment with Flemoclav Solutab®, a detailed anamnesis concerning previous reactions hypersensitivity to penicillins, cephalosporins or other substances that cause an allergic reaction in the patient.

Serious, and sometimes lethal, hypersensitivity reactions are described (anaphylactic reactions) to penicillins. The risk of occurrence of such reactions is highest in patients, with a history of hypersensitivity reactions to penicillins.In case of an allergic reaction, it is necessary to stop the treatment with Flemoclav Solutab® and start the appropriate alternative therapy. In severe hypersensitivity reactions, Immediately introduce the patient epinephrine. Oxygen therapy, intravenous glucocorticosteroids, and airway patency, including intubation, may also be required.

In case of skin allergic reactions, treatment with Flemoclav Solutab® should be stopped.

In case of suspected infectious mononucleosis, Flemoclav Solutab® should not be used because patients with this disease amoxicillin may cause korepodobnuyu skin rash, which makes it difficult to diagnose the disease. Long-term treatment with Flemoclav Solutab® can lead to excessive reproduction of insensitive microorganisms.

In general, the preparation Flemoclav Solutab® is well tolerated and has characteristic of all penicillins low toxicity. During prolonged therapy with Flemoclav Solutab® it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis. Cases of occurrence pseudomembranous colitis with antibiotics, the severity of which can range from mild to life-threatening. Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after antibiotic use. If the diarrhea is long or severe and the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be examined.

Patients who received a combination of amoxicillin with clavulanic acid together with indirect (oral) anticoagulants rarely reported an increase prothrombin time (increase INR). In the joint appointment of indirect (oral) anticoagulants with a combination of amoxicillin with clavulanic acid requires monitoring of relevant indicators. To maintain the necessary effect of oral anticoagulants, they need to adjust their dose.

In patients with impaired renal function, the dose of Flemoclav Solutab®should be reduced, respectively, the degree of impairment (see section "Method of administration and dose" - Patients with impaired renal function).

In patients with impaired renal function, as well as taking high doses of the drug, convulsions may occur (see sections "Dosing and Administration", "Side effects", "Overdose").

In patients with reduced diuresis, very rarely crystalluria occurs, mainly with parenteral therapy. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain adequate diuresis to reduce the likelihood of crystals of amoxicillin (see section "Overdose").

Taking the preparation Flemoclave Solutab® inside leads to a high content of amoxicillin in the urine, which can lead to false positive results in the determination of glucose in the urine (for example, the Benedict test, Feeling's test). In this case, it is recommended to use a glucose oxidant method for determining the concentration of glucose in the urine.

Clavulanic acid can cause non-specific binding of immunoglobulin G and albumin to erythrocyte membranes, which leads to false positive results of Coombs' test.

In one dispersible tablet, Flemoclav Solutab® 125 mg / 31.25 mg contains 0.16 mmol (6.13 mg) of potassium, in 250 mg / 62.5 mg - 0.32 mmol (12.3 mg), in 500 mg / 125 mg to 0.64 mmol (24.53 mg).The intake of potassium more than 1 mmol per day requires special attention in patients with reduced renal function and in those on a controlled potassium diet.

Effect on the ability to drive transp. cf. and fur:Studies on the impact on the ability to drive vehicles and work with mechanisms have not been conducted. Because the drug can cause side effects (eg, allergic reactions, dizziness, convulsions) (see "Side effects"), patients should be warned about precautions when driving a vehicle or working with moving machinery.

Form release / dosage:Tablets are dispersible at 125 mg + 31.25 mg, or 250 mg + 62.5 mg, or 500 mg + 125 mg.

Packaging:4 tablets (one dosage) in a blister pack. For 5 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016067 / 01

Date of registration:17.11.2009 / 13.01.2014

Expiration Date:Unlimited

The owner of the registration certificate:Astellas Farma Europe BVAstellas Farma Europe BV Netherlands

Manufacturer: & nbsp

ASTELLAS PHARMA EUROPE, B.V. Netherlands

Representation: & nbspASTELLAS PHARMA YUROP BV ASTELLAS PHARMA YUROP BV Netherlands

Information update date: & nbsp31.03.2017

Illustrated instructions

Instructions

Fleymoclav Solutab® (Flemoclav Solutab®)