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

Active substance: amoxicillin trihydrate (which corresponds to amoxicillin base) - 1019.8 mg (875.0 mg); potassium clavulanate (which corresponds to clavulanic acid) - 148.9 mg (125 mg).

Excipients: Dispersed cellulose - 30.4 mg, microcrystalline cellulose - 125.9 mg, crospovidone 64.0 mg, vanillin 1.0 mg, mandarin flavoring 9.0 mg, lemon flavor 11.0 mg, saccharin 13.0 mg, magnesium stearate 6.0 mg.

Description:Tablets are dispersible oblong form from white to yellow, without risks, labeled "425" and graphic part of the company logo. Brown spots are allowed.

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 amoxicillin activity does not extend to microorganisms that produce this enzyme. Clavulanic acid, a beta-lactamase inhibitor structurally related to penicillins, has the ability to inactivate a wide spectrum of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins.

Clavulanic acid has sufficient efficacy against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against type 1 chromosomal beta lactamases that 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 agalactiae¹^,²

Streptococcus spp. (others 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

Youteraboutides spp.

Capnocytophaga spp.

Eikenella corrodens

Fusobacterium nucleatum

Fusobacterium spp.

Porphyromonas spp.

Prevotella spp.

Other:

Borrelia burgdorferi

Leptospira icterohaemorrhagiae

Treponema pallidum.

Bacteria for which the acquired resistance to a combination of amoxicillin and clavulanic acid is probable

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 burnetti

Mycoplasma spp.

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

²- strains of these bacteria do not produce β-lactamases.Sensitivity to monotherapy with amoxicillin suggests a similar sensitivity to the combination of amoxicillin and clavulanic acid.

Pharmacokinetics:Suction

Both active substances of the preparation Flemoclav Solutab®, amoxicillin and clavulanic acid, are quickly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of active substances is optimal in case of taking the drug at the beginning of food intake.

After a single administration of Flemoklava Solutab® at a dose of 875/125 mg (amoxicillin / clavulanic acid) the maximum concentration of amoxicillin in plasma blood is created after 1.5 hours (t_max), and is 12 μg / ml (C_m_Oh), clavulanic acid - after 1 hour, amounting to 3 μg / ml. PFC (the indicator "area under the pharmacokinetic curve") of amoxicillin and clavulanic acid is 33 μg / L and 6 μg / L, respectively. Absorption of amoxicillin for oral administration reaches 90%, the absolute bioavailability of clavulanic acid is on the average 60%.

Distribution

As with intravenous administration of a combination of amoxicillin and clavulanic acid,therapeutic concentrations of amoxicillin and clavulanic acid are found in various tissues and interstitial fluid (in the gall bladder, abdominal tissue, skin, fat and muscle tissues, synovial and peritoneal fluids, bile secretion). Amoxicillin and clavulanic acid have a weak degree of binding to plasma proteins. Approximately 17-20% of amoxicillin and 22% of clavulanic acid binds to blood plasma proteins.

In animal studies, no cumulation of the components of the Flemoclav Solutab® preparation in any organ was detected.

Amoxicillin, like most penicillins, penetrates into breast milk. Breast milk also found trace amounts of clavulanic acid. Except for the possibility of developing sensitization, diarrhea, or candidiasis of the oral mucosa, no other adverse effects of amoxicillin and clavulanic acid on the health of infants fed by breast milk are known. Studies of reproductive function in animals have shown that amoxicillin and clavulanic acid penetrate the placental barrier.However, there was no adverse effect on the fetus.

Metabolism

10-25% of the initial dose of amoxicillin is excreted in the urine as an inactive metabolite (penicillic acid). Clavulanic acid, undergoes intensive metabolism to 2,5-dihydro-4- (2-hydroxyethyl) -5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxybutan-2-one and is excreted by the kidneys , through the gastrointestinal tract, and also with exhaled air in the form of carbon dioxide.

Excretion

The total clearance for the two active substances is 25 l / h, half-life (t 1/2) amoxicillin 1.1 hours, clavulanic acid 0.9 hours. Approximately 60-80% amoxicillin and 30-50% clavulanic acid is excreted through the kidneys within the first 6 hours after taking the drug.

Simultaneous administration of probenecid slows the excretion of amoxicillin, but not clavulanic acid (see section "Interaction with other drugs").

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:

- Upper respiratory tract infections (including ENT diseases), for example, relapsing tonsillitis, sinusitis, otitis media, usually caused by 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^#.

- Infections of the skin and soft tissues, usually caused 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) in the framework of stepwise therapy.

^#Individual representatives of this kind of microorganisms produce beta-lactamase, which makes them insensitive to amoxicillin.also see "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, other components of the drug, beta-lactam antibiotics (eg, penicillins, cephalosporins) in history;

- previous episodes of jaundice or impaired liver function with a combination of amoxicillin and clavulanic acid in history;

- children under 12 years of age or body weight less than 40 kg;

- impaired renal function (creatinine clearance ≤ 30 ml / min).

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

Flemoclav Solutab ® can be used during breastfeeding. With the exception of the possibility of developing sensitization, diarrhea, or candidiasis of the oral mucosa,associated with the penetration of the breast milk trace amounts of the active substances of this drug, no other adverse effects in children who are breastfed, was observed. In case of adverse effects in children who are breastfeeding, it is necessary to stop breastfeeding.

Dosing and Administration:To prevent dyspeptic symptoms, Flemoclav Solutab® is prescribed 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.

For oral administration.

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.

Treatment should not last more than 14 days without reviewing the clinical situation.

If necessary, it is possible to perform stepwise therapy (first parenteral administration of the drug followed by a transition to oral administration).

Adults and children 12 years of age or older or with a body weight of 40 kg or more

For 1 tablet 875 mg / 125 mg 2 times a day.

Special patient groups

Children under 12 years of age with a body weight of less than 40 kg

It is recommended to use other doses of the preparation Flemoclav Solutab®.

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

Tablets 875 mg / 125 mg should be used only in patients with creatinine clearance greater than 30 ml / min, while adjusting the dosing regimen is not required.

In most cases, parenteral therapy should be preferred where possible. In patients with impaired renal function, convulsions may occur (see "Side effects", "Overdose").

Patients with impaired hepatic function

Treat 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-registration surveillance.

Frequency of occurrence of undesirable reactions

Infectious and parasitic diseases

Often: candidiasis of skin and mucous membranes.

Violations from 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. Seizures can occur in patients with impaired renal function, as well as in those who receive high doses of the drug (see section "Method of administration and dose" Patients with impaired renal function, "Overdose"). 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.

Infrequent digestion.

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 have been observed mainly in men and elderly patients and can 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.

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 section "Method of administration and dose" Patients with impaired renal function, "Side effects").

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 history of previous hypersensitivity reactions to penicillins, cephalosporins or other substances that cause an allergic reaction in the patient should be collected. Serious, and sometimes lethal, 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 penicillins.In case of an allergic reaction, it is necessary to stop the treatment with Flemoclav Solutab® and start the appropriate alternative therapy. In case of serious hypersensitivity reactions, the patient should be promptly administered 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 can cause a skinlike skin rash, which makes it difficult to diagnose the disease.

Prolonged treatment with Flemoclav Solutab® can lead to excessive reproduction of insensitive microorganisms.

There are cases of pseudomembranous colitis occurring when taking 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.

In general, the preparation Flemoclav Solutab ® is well tolerated and has a characteristic of all penicillins of low toxicity. During prolonged therapy with Flemoclav Solutab® it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis.

In patients who received a combination of amoxicillin with clavulanic acid in conjunction with indirect (oral) anticoagulants, in rare cases, increased prothrombin time (increased INR) was reported. When co-administration of indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, monitoring of the relevant indicators is necessary. To maintain the necessary effect of oral anticoagulants, their dose may need to be adjusted.

In patients with reduced diuresis, crystalluria is very rare, mainly with parenteral therapy. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain an adequate diuresis to reduce the likelihoodformation of crystals of amoxicillin (see section "Overdose"). The administration of the preparation Flemoclav 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 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 nonspecific binding of immunoglobulin G and albumin with erythrocyte membranes, which leads to false positive results of the Coombs test.

In one dispersible tablet, Fleymoclav Solutab® 875/125 mg contains 0.64 mmol (25 mg) of potassium. 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.

Abuse and drug dependence

There was no drug dependence, addiction and euphoria reactions associated with the use of the Flemoclav Solutab® drug.

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.Since the drug can cause side effects (eg, allergic reactions, convulsions dizziness) (see "Side effects"), patients should be warned about precautions when driving a vehicle or working with moving machinery.

Form release / dosage:Tablets are dispersible 875 mg + 125 mg

Packaging:

For 7 tablets in a blister, 2 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:2 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-000392/09

Date of registration:26.01.2009 / 14.01.2014

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®)