Expiration date: 12/2025

Composition and form of issue:

Dispersible tablets 1 tab.

amoxicillin (as amoxicillin trihydrate) 125 mg

clavulanic acid (in the form of potassium clavulanate) 31, 25 mg

other ingredients: microcrystalline cellulose, crospovidon, vanilla, apricot flavor, saccharin, magnesium stearate 

in blister 4 PCs. in a pack of cardboard blisters 5.

Dispersible tablets 1 tab.

amoxicillin (as amoxicillin trihydrate) 250 mg

clavulanic acid (in the form of potassium clavulanate) 62, 5 mg

other ingredients: microcrystalline cellulose, crospovidon, vanilla, apricot flavor, saccharin, magnesium stearate 

in blister 4 PCs. in a pack of cardboard blisters 5.

Dispersible tablets 1 tab.

amoxicillin (as amoxicillin trihydrate) 500 mg

clavulanic acid (in the form of potassium clavulanate) 125 mg

other ingredients: microcrystalline cellulose, crospovidon, vanilla, apricot flavor, saccharin, magnesium stearate 

in blister 4 PCs. in a pack of cardboard blisters 5.

Dispersible tablets 1 tab.

amoxicillin (as amoxicillin trihydrate) 875 mg

clavulanic acid (in the form of potassium clavulanate) 125 mg

inactive ingredients: dispersible cellulose MCC crospovidon the vanilla flavor, tangerine flavor, citric saccharin magnesium stearate 

in e blisters 7 PC. in the stack cartons 2 blister.

Description of dosage form:

Tablets oblong form from white to yellow with brown spots, without the risks, marked: "421" — at a dosage of 125 mg + 31, 25 mg "422" — 250 mg + 62, 5 mg "424" — 500 mg + 125 mg "425" — 875 mg + 125 mg and graphic part of the logo of the company.

Characteristic:

Combined preparation containing semi-synthetic penicillin and beta-lactamase inhibitor.

Pharmacokinetics:

Tablets 125 mg + 31, 25 mg 250 mg + 62, 5 mg 500 mg + 125 mg

Amoxicillin. The absolute bioavailability of amoxicillin is 94%. Absorption does not depend on the meal. Cmax in plasma is observed 1-2 h after administration of amoxicillin. After a single dose of 500 mg + 125 mg (amoxicillin + clavulanic acid) the average concentration of amoxicillin (after 8 h) is 0, 3 mg/L. the Binding to serum proteins is approximately 17-20%. Amoxicillin penetrates the placental barrier and into breast milk in small amounts.

Amoxicillin is metabolized in the liver (10% of the dose). For the most part, it is excreted through the kidneys (52±15)% of the dose (unchanged for 7 hours) and in a small amount — with bile. T1/2 of serum in patients with normal renal function is approximately 1 h (0, 9-1, 2 h), patients with Cl creatinine 10-30 ml/min is 6 h, and in the case of anuria varies between 10 and 15 h Displayed in hemodialysis.

Clavulanic acid. Absolute bioavailability of clavulanic acid is approximately 60%. Absorption does not depend on the meal. Cmax clavulanic acid in the blood is observed 1-2 h after administration. After taking amoxicillin with clavulanic acid in a single dose of 500 mg + 125 mg, the average Cmax of clavulanic acid (0, 08 mg/l) is achieved after 8 hours.Binding to plasma proteins is 22%. Clavulanic acid penetrates through the placental barrier. There are no reliable data on penetration into breast milk.

Clavulanate is metabolized in the liver (50-70%) and about 40% is excreted through the kidneys (18-38% — unchanged). Total Cl is approximately 260 ml/min. T1/2 in patients with normal renal function is approximately 1 hour in patients with Cl creatinine clearance 20-70 ml/min, 2, 6 h, when anurii — within 3-4 hours Displayed in hemodialysis.

Tablets 875 mg + 125 mg

After a single administration of the Bottle solyutab dose 875 mg + 125 mg (amoxicillin + clavulanic acid) Cmax amoxicillin in the blood plasma is created through 1, 5 h and is 12 mg/ ml, clavulanic acid-1 h, 3 µg / ml. AUC amoxicillin and clavulanic acid-33 µg·h / l and 6 µg·h / l, respectively. Absorption of amoxicillin in oral administration reaches 90%, the absolute bioavailability of clavulanic acid is an average of 60%.

Approximately 17-20% of the amoxicillin and 22% of clavulanic acid is associated with blood plasma proteins. Total Cl for the two active substances is 25 l/h, T1/2 of amoxicillin — 1, 1 h, clavulanic acid — 0, 9 h. Approximately 60-80% of the amoxicillin and 30-50% of the clavulanic acid are excreted via the kidneys during the first 6 h after administration of the drug. The amoxicillin is excreted mainly unchanged, a small portion is metabolized by hydrolysis of the beta-laktamnogo ring to the active metabolites (the main — penicillata and benamaldena acid). Clavulanic acid is subjected to intense metabolism by hydrolysis and subsequent decarboxylation.

Description of the pharmacological action:

Acts bactericidal, inhibits the synthesis of bacterial walls. Active against gram-positive and gram-negative microorganisms (including strains producing beta-lactamases). Included in the preparation clavulanic acid suppresses II, III, IV and V types of beta-lactamases, inactive against beta-lactamase type I, produced Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high tropism to penicillinases, thereby forming a stable complex with the enzyme, which prevents the enzymatic degradation of amoxicillin under the influence of beta-lactamases and expands the spectrum of its action.

Flemo?lav shows activity against:

• aerobic gram-positive bacteria Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae, Staphylococcus aureus (including strains producing beta-lactamase), Staphylococcus epidermidis (including strains, producing beta-lactamases) Enterococcus faecalis, Corynebacterium spp., Bacillus anthracis, Listeria monocytogenes
  
• anaerobic gram-positive bacteria Clostridium spp., Peptococcus spp., Peptostreptococcus spp.
  
• aerobic gram-negative bacteria Escherichia coli, Klebsiella spp., Proteus mirabilis, Proteus vulgaris, Yersinia enterocolitica, Salmonella spp., Shigella spp., Haemophilus influenzae, Haemophilus ducreyi, Neisseria gonorrhoeae (including strains of the above bacteria producing beta-lactamases), Neisseria meningitidis, Bordetella pertussis, Gardnerella vaginalis, Brucella spp., Branhamella catarrhalis, Pasteurella multocida, Campylobacter jejuni, Vibrio cholerae, Moraxella catarrhalis, Helicobacter pylori
  
• anaerobic gram-negative bacteria Bacteroides spp., including Bacteroides fragilis (including strains producing beta-lactamases).
  

Indications:

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

• diseases of the upper respiratory tract and ENT-organs (including otitis media, sinusitis, tonsillitis, pharyngitis)
  
• lower respiratory tract (including exacerbation of chronic bronchitis, COPD, community-acquired pneumonia)
  
• skin and soft tissue infections
  
• urinary system (including cystitis, pyelonephritis).
  

Additionally for tablets 875 mg + 125 mg:

• bone and joint infections (including osteomyelitis)
  
• obstetrics and gynecology.
  

Contraindications:

• hypersensitivity to amoxicillin, clavulanic acid and other components of the drug
  
• hypersensitivity to other beta-lactam antibiotics (penicillins and cephalosporins)
  
• the presence of jaundice or liver dysfunction when taking amoxicillin + clavulanic acid in the anamnesis
  
• infectious mononucleosis
  
• lymphocytic leukaemia.
  

Additionally for tablets 875 mg + 125 mg:

• renal failure with glomerular filtration &le 30 ml/min
  
• children up to 12 years with body weight <40 kg.
  

With caution:

• severe hepatic insufficiency
  
• diseases of the gastrointestinal tract (including history of colitis associated with the use of penicillins)
  
• chronic renal failure.
  

Application for pregnancy and breastfeeding:

There was no adverse effect of amoxicillin/clavulanate on the fetus and newborns when used by pregnant women. Use in the II and III trimesters of pregnancy is possible after a medical assessment of the risk/benefit of treatment. In the first trimester of the drug should be avoided.

Both components of the drug penetrate the blood-placental barrier and are excreted in breast milk. It is possible to use the drug during breastfeeding.

In the case of the development of the child's sensitization and the occurrence of diarrhea or candidiasis of the mucous membranes of breast-feeding should be discontinued.

Side effect:

Tablets 125 mg + 31, 25 mg 250 mg + 62, 5 mg 500 mg + 125 mg

Allergic skin reactions: hives, rash, erythematous rash, rarely — erythema multiforme exudative, extremely rare — exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), erythema multiforme. The reactions depend on the dose and the patient's condition.

From the digestive tract: nausea, vomiting, diarrhea, abdominal pain, impaired liver function, increased activity of hepatic transaminases, in isolated cases — pseudomembranous colitis.

Increased activity of transaminases (AST and ALT), bilirubin and schf is usually observed in males and elderly patients, especially older than 65 years. These phenomena are very rare in children. The above changes usually appear during treatment or immediately after. Sometimes may appear a few weeks after discontinuation of the drug. Basically the reaction from the digestive system are transient and minor in nature, but sometimes pronounced. To prevent undesirable phenomena, the drug is recommended to take at the beginning of a meal. The risk of such changes increases when taking the drug for more than 14 days.

On the part of the blood and lymphatic system: rarely — changes in the composition of the blood (leukopenia, thrombocytopenia, hemolytic anemia) lengthening prothrombin time (reversible).

From the hepatobiliary system: rarely-cholestatic jaundice, hepatitis.

From the immune system: rarely — angioedema, vasculitis.

From the urinary system: interstitial nephritis.

Other: candidiasis, the development of superinfection. In isolated cases-anaphylactic shock.

Tablets 875 mg + 125 mg

Infections: infrequently (&ge1/1000, <1/100) — bacterial or fungal superinfections (with prolonged therapy or repeated courses of therapy).

From the blood and hematopoietic system: rarely (&ge1 / 10000, <1/1000) — thrombocytosis, hemolytic anemia is very rare (<1/10000) — leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, anemia, increased PV and bleeding time. These adverse reactions are reversible and disappear after discontinuation of therapy.

Allergic reactions: often (&ge1/100, < 1/10) — skin rashes and itching morbilliform rash appearing on 5-11 days after starting therapy. The appearance of urticaria immediately after starting the drug with a high degree of probability is a manifestation of an allergic reaction and requires the abolition of the drug rarely (&ge1 / 10000, <1/1000) - bullous or exfoliative dermatitis (multiform exudative erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis), anaphylactic shock other allergic reactions-drug fever, eosinophilia, angioedema (edema), angioedema), serum sickness, hemolytic anemia, allergic vasculitis, interstitial nephritis.

From the nervous system: rarely (&ge1/10000, <1/1000) — dizziness, headache, convulsions (in the case of impaired renal function or overdose of the drug) very rare (<1/10000) — hyperactivity, anxiety (anxiety), insomnia, disturbance of consciousness, aggressive behavior.

Cardiovascular system: rarely (&ge1/10000, <1/1000) — vasculitis.

Reactions from the digestive system: often (&ge1/100, <1/10) — abdominal pain, nausea (more often with an overdose), vomiting, flatulence, diarrhea (mainly reactions from the digestive system are transient and rarely pronounced intensity can be reduced, taking the drug at the beginning of a meal) pseudomembranous colitis (in the case of severe and persistent diarrhea during administration of the drug or within 5 weeks after the end of therapy) in most Clostridium difficult rarely (&ge 1/10000, <1/1000) — intestinal candidiasis, hemorrhagic colitis, discoloration of the surface layer of tooth enamel.

From the hepatobiliary system: often (&ge 1/100, <1/10) — a slight increase in the activity of liver enzymes rarely (&ge1/10000, <1/1000) — hepatitis and cholestatic jaundice. Symptoms of liver dysfunction occur during treatment or immediately after discontinuation of therapy, but in some cases they may appear a few weeks after discontinuation of the drug are more common in men and patients over 60 years of age in children — very rare (<1/10000). The risk of adverse reactions increases when the drug is used for more than 14 days. Liver disorders, usually reversible, sometimes severe and in very rare cases (<1/10000) and only in patients with severe comorbidities or while taking potentially hepatotoxic drugs can lead to death.

Urogenital system: infrequently (&ge 1/1000, <1/100) — itching, burning and vaginal discharge rarely (>1/10000, <1/1000) — interstitial nephritis.

Drug interaction:

Tablets 125 mg + 31, 25 mg 250 mg + 62, 5 mg 500 mg + 125 mg

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

Bactericidal antibiotics (including aminoglycosides, cephalosporins, cycloserine, vancomycin, rifampicin) have a synergistic effect bacteriostatic antimicrobials (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) — antagonistic.

Increases the effectiveness of indirect anticoagulants (suppresses intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). The simultaneous administration of anticoagulants is necessary to monitor the indicators of blood coagulation.

Reduces effectiveness of oral contraceptives, drugs, in the process of metabolism which produce PABA, ethinyl estradiol (the risk of breakthrough bleeding).

Diuretics, allopurinol, phenylbutazone, NSAIDs and other drugs that block tubular secretion, increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration). Allopurinol increases the risk of skin rashes.

Amoxicillin should not be prescribed with disulfiram.

Simultaneous use of amoxicillin and digoxin can lead to an increase in the concentration of digoxin in blood plasma.

Tablets 875 mg + 125 mg

Other antimicrobial drugs. When combined with some bacteriostatic drugs (eg chloramphenicol, sulfonamides, etc.), antagonism with amoxicillin/clavulanic acid in vitro was noted.

Disulfiram. Amoxicillin / clavulanic acid should not be used in conjunction with disulfiram.

Drugs that inhibit renal excretion of amoxicillin. Simultaneous administration of probenecid, phenylbutazone, oxyphenbutazone and, to a lesser extent, acetylsalicylic acid, indomethacin and sulfinpyrazone increases concentration and longer amoxicillin in blood plasma and bile. Excretion of clavulanic acid is not violated.

Antacids, glucosamine, laxatives, aminoglycosides slow down and reduce the absorption of ascorbic acid increases the absorption of amoxicillin.

Allopurinol. The appointment of allopurinol and amoxicillin can increase the risk of skin rashes.

Sulfasalazine. Aminopenicillins can decrease the concentration of sulfasalazine in serum.

Methotrexate. Amoxicillin reduces the renal clearance of methotrexate, which can lead to an increase in the risk of its toxic effects. While taking with amoxicillin is necessary to monitor the concentration of methotrexate in the blood serum.

Digoxin. Against the background of amoxicillin / clavulanic acid may increase the absorption of digoxin.

Anticoagulants. While taking indirect anticoagulants may increase the risk of bleeding.

Hormonal contraceptive. In rare cases, against the background of amoxicillin, there was a decrease in the effectiveness of oral contraceptives, so patients should recommend the use of non-hormonal methods of contraception.

Method of application and doses:

Inside, at the beginning of the meal (to prevent dyspeptic symptoms), without chewing, drinking a glass of water or dissolving the tablet in half a glass of water (at least 30 ml), thoroughly stirred before use.

The duration of treatment depends on the severity of the infection and should not exceed 14 days without special need.

Adults and children over 12 years, as well as children under 12 years weighing more than 40 kg the drug is prescribed for 500 mg + 125 mg 3 times a day or 875 mg + 125 mg 2 times a day. A single dose is taken at the same time intervals. In severe, recurrent and chronic infections, these doses can be doubled.

Children under 12 years of age with a body weight up to 40 kg appoint Flemo?lav Solutab with smaller doses: 125 mg + 31, 25 mg, 250 mg + 62, 5 mg, 500 mg + 125 mg.

For children aged 2 to 12 years (weighing about 13-37 kg) daily dose is 20-30 mg/kg amoxicillin and 5-7, 5 mg/kg clavulanic acid. Usually it is: for children 2-7 years (body weight about 13-25 kg) — 125 mg + 31, 25 mg 3 times a day for children 7-12 years (body weight 25-37 kg) — 250 mg + 62, 5 mg 3 times a day. In severe infections, these doses can be doubled (maximum daily dose — 60 mg/kg amoxicillin and 15 mg/kg clavulanic acid).

In patients with renal insufficiency, the excretion of clavulanic acid and amoxicillin through the kidneys is slowed. Flemo?lav Solutab dose 875 mg + 125 mg can be used only when glomerular filtration rate >30 ml/min the dose correction is not required.

Depending on the severity of renal failure, the total dose of solyutab (125 mg + 31, 25 mg, 250 mg + 62, 5 mg, 500 mg + 125 mg), expressed in the dose of amoxicillin Should not exceed the doses presented in the table:

Table

Glomerular filtration rate, ml/ min	Adults	Children
10–30	500 mg 2 times a day	15 mg / kg 2 times a day
<10	500 mg per day	15 mg / kg per day
Hemodialysis	500 mg per day and 500 mg during and after dialysis	15 mg / kg per day and 15 mg / kg during and after dialysis

Patients with liver lesions amoxicillin with clavulanic acid should be prescribed with caution. Liver function should be under constant control.

Overdose:

Symptoms: nausea, vomiting and diarrhea with possible violation of water and electrolyte balance.

Treatment: the appointment of activated carbon. Maintenance of water and electrolyte balance. Symptomatic therapy. Under convulsions is nominated by diazepam. In the case of severe renal failure — kidney dialysis.

Special instruction:

With the development of anaphylactic reactions, treatment should be immediately discontinued and replaced with other suitable therapy.

For withdrawal from the state of anaphylactic shock may require urgent introduction of adrenaline, GCS and elimination of respiratory failure.

There is a possibility of cross-resistance and hypersensitivity to other penicillins or cephalosporins. As with the use of other broad — spectrum penicillins, superinfections of fungal or bacterial origin (in particular-candidiasis) may occur, especially in patients with chronic diseases and/or disorders of the immune system. In case of superinfection, the drug is canceled and / or selected suitable therapy.

Patients with severe gastrointestinal disorders accompanied by vomiting and/or diarrhoea, purpose of Flemo?lav Solutab impractical until then, until you resolve the above mentioned symptoms, because the violation of absorption of the drug from the gastrointestinal tract.

The appearance of severe and persistent diarrhea may be associated with the development of pseudomembranous colitis, in this case, the drug is canceled and prescribed the necessary treatment. In the case of hemorrhagic colitis also requires immediate withdrawal of the drug and corrective therapy. The use of drugs that weaken intestinal motility in these cases is contraindicated.

In a single study, the prophylactic administration of amoxicillin / clavulanate in women with premature rupture of membranes increased the risk of necrotizing enterocolitis in newborns.

Flemo?lav Solutab dose 875 mg + 125 mg can be prescribed only when glomerular filtration rate >30 ml/min.

Due to the high concentration of amoxicillin in the urine, it can precipitate on the walls of the urinary catheter, so these patients need periodic change of catheters. Forced diuresis accelerates the elimination of amoxicillin and reduces its concentration in plasma.

In the event of seizures during therapy drug canceled. In one dispersible tablet Flemo?lav Solutab 875 mg + 125 mg contains 25 mg of potassium.

In patients with impaired renal function dose should be selected based on the severity of the condition.

Patients with impaired liver function combination amoxicillin / clavulanic acid should be administered with caution and under constant medical supervision. Flemo?lav Solutab should not be applied more than 14 days without an assessment of liver function.

Amoxicillin / clavulanic acid should be used with caution in patients receiving anticoagulant therapy.

Non-enzyme methods for determination of urine sugar, as well as a test for urobilinogen can give false positive results.

In the course of treatment, it is necessary to monitor the state of the function of the hematopoietic organs, liver and kidneys.