Flemoklav Solyutab®

General characteristics. Structure:

Active agent: amoxicillin trihydrate (that corresponds to amoxicillin to the basis) - 145,7mg (125 mg), 291 mg (250 mg), 528,8 mg (0,5 g); potassium clavulanate (that corresponds to clavulanic acid) 37,2 mg (31,25 mg), 74,5 mg (62,5 mg), 148,9 mg (125 mg).
Excipients: microcrystallic cellulose, кросповидон, vanillin, apricot fragrance, saccharin, magnesium stearate.

Description
Tablets of oblong shape from white till yellow color with brown dot spots without risks and the having markings: "421" - at a dosage of 125 mg +31,25 mg; "422" - 250 mg of +62,5 mg; "424" - 0,5 g +125 mg and logs of firm.

Pharmacological properties:

Pharmacodynamics. An antibiotic of a broad spectrum of activity, the combined drug of amoxicillin and clavulanic acid - inhibitor beta лактамаз. Works bakteritsidno, synthesis of a bacterial wall oppresses. It is active concerning gram-positive and gram-negative microorganisms (including the strains producing beta lactamelements). The clavulanic acid which is a part of drug suppresses II, III, IV and V types beta лактамаз, is inactive concerning the beta laktamaz of the I type produced by Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid possesses a high tropnost to penicillinases thanks to what forms a stable complex with enzyme that prevents enzymatic degradation of amoxicillin under the influence of a beta laktamaz and expands a range of its action.
Flemoklav Solyutab® shows activity in the relation:
Aerobic gram-positive bacteria: Streptococcus pyogenes, Streptococcus viridans, Streptococcus pneumoniae, Staphylococcus aureus (including the strains producing beta lactamelements), Staphylococcus epidermidis (including the strains producing beta lactamelements) 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 the strains of above-mentioned bacteria producing beta lactamelements), Neisseria meningitides, 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 the strains producing beta lactamelements).

Pharmacokinetics. Amoxicillin:
Absolute bioavailability of amoxicillin reaches 94%. Absorption does not depend on meal. The maximum concentration in plasma is noted in 1-2 hours after amoxicillin reception. After reception of a single dose 500/125mg (amoxicillin/clavulanic acid) average concentration of amoxicillin (after 8 hours) makes O. Zmgl. Linkng with serum proteins makes about 17-20%. Amoxicillin gets through a placental barrier and in small amounts gets into breast milk.
Amoxicillin is metabolized in a liver (10% of the entered dose), mostly is removed through kidneys (52 ± 15% of a dose in not changed look within 7 hours) and a small amount is removed with bile. The elimination half-life at patients with normal function of kidneys makes about 1 hour (0.9-1.2 h) of blood serum, at patients with clearance of creatinine within 10-30 ml/min. makes 6 hours, and in case of an anury fluctuates in limits between 10 and 15 hours. Drug is removed at a hemodialysis.

Clavulanic acid:
Absolute bioavailability of clavulanic acid makes about 60%. Absorption does not depend on meal. The maximum concentration in blood of clavulanic acid is noted in 1-2 hours after reception. After reception of a single dose of 0,5 g / 125 mg (amoxicillin/clavulanic acid) average maximum concentration of clavulanic acid reaches 0.08 mg/l in 8 hours. Linkng with proteins of a blood plasma makes 22%. Clavulanic acid gets through a placental barrier. There are no reliable data about penetration into breast milk.
Clavulanate is metabolized in a liver (50-70%) and about 40% are removed through kidneys (18-38% in not changed look). The general clearance makes about 260 ml/min. The elimination half-life at patients with normal function of kidneys makes about 1 hour, patients with clearance of creatine have 20 - 70 ml/min. - 2.6 hours, and at an anury - within 3 - 4 hours. Drug is removed at a hemodialysis.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to drug:
- upper respiratory tracts and ENT organs (including average otitis, sinusitis, tonsillitis, pharyngitis);
- lower respiratory tracts: chronic bronchitis and its aggravations, community-acquired pneumonia;
- skin and soft tissues;
- kidneys and lower urinogenital ways.

Route of administration and doses:

To prevent dispepsichesky symptoms, Flemoklav Solyutab appoint at the beginning of meal. The tablet is swallowed entirely, washing down with a glass of water, or dissolve it in half of glass of water (at least 30 ml), carefully stirring before the use.

Duration of treatment depends on weight of an infection and should not without special need exceed 14 days.

To adults and children with body weight more than 40 kg drug appoint on 0,5 g / 125 mg 3 times/days. At heavy, recurrent and persistent infections these doses can be doubled.

For children aged from 3 months up to 2 years (with the body weight about 5-12 kg) the daily dose makes 20-30 mg of amoxicillin and 5-7.5 mg of clavulanic acid on body weight kg. Usually it makes a dose of 125/31.25 mg 2 times/days.

For children aged from 2 up to 12 years (with the body weight about 13-37 kg) the daily dose makes 20-30 mg of amoxicillin and 5-7.5 mg of clavulanic acid on body weight kg. Usually it makes a dose of 125/31.25 mg 3 times/days for children aged from 2 up to 7 years (body weight about 13-25 kg) and 250/62.5 mg are 3 times/days old for children aged from 7-12 years (body weight about 25-37 kg). At heavy infections these doses can be doubled (the maximum daily dose makes 60 mg of amoxicillin and 15 mg of clavulanic acid on body weight kg).

Patients with an impaired renal function
Patients with a renal failure have a removal of clavulanic acid and amoxicillin through kidneys in a slowed-up way. Depending on weight of a renal failure the general dose Flemoklava Solyutab® (expressed in an amoxicillin dose) should not exceed the quantities presented in the table:

Glomerular filtration rate              Adult                              Children
10-30                                        ml/min. 0,5 g of 2 times/days                       of 15 mg/kg of 2 times/days
<10                                         ml/min. 0,5 g in day                             of 15 mg/kg a day
Hemodialysis                                           of 0,5 g a day and 0,5                  g 15 mg/kg a day and 15 mg/kg 
                                                            in time and after dialysis        of 15 mg/kg a day and 15 mg/kg
                                                                                                            in time and after dialysis

Patients with an abnormal liver function
The combination of amoxicillin/clavulanic acid has to be appointed with care to patients with damages of a liver. Function of a liver has to be under constant control.

Features of use:

At treatment by penicillin patients with hypersensitivity to them can have anaphylactic reactions. Treatment of Flemoklav Solyutabom® in such cases has to be immediately stopped and replaced with other suitable therapy. For treatment of an acute anaphylaxis urgent administration of adrenaline, corticosteroids and elimination of respiratory insufficiency can be required.

There is a possibility of cross stability and hypersensitivity with other penicillin or cephalosporins. As well as in case of use of other penicillin of a broad spectrum of activity there can be superinfections of fungal or bacterial genesis (in particular - candidiasis), especially at patients with chronic diseases and/or dysfunctions of immune system. In case of superinfection administration of drug is cancelled and/or select suitable therapy.

At patients with renal failures the dose needs to be selected, proceeding from weight of a state.

To patients with abnormal liver functions a combination amoxicillin/clavulanic acid has to be appointed with care and under constant medical control. Flemoklav Solyutab® should not be applied more than 14 days without assessment of function of a liver.

Increase in a prothrombin time is seldom noted. Amoxicillin/clavulanic acid have to be appointed with care to the patients receiving anti-coagulative therapy.
Not fermental methods of definition of sugar of urine, and also the urobilinigen test can yield false positive results.

Side effects:

Allergic skin reactions: urticaria, erythematic rashes, it is rare - a multiformny exudative erythema, is extremely rare - exfoliative dermatitis, a malignant exudative erythema (Stephens-Johnson's syndrome), in certain cases develops so-called "rash of the fifth day" (a korevidny dieback). Reactions depend on a dose of drug and a condition of the patient.
Reactions from the alimentary system: nausea, vomiting, diarrhea, an abnormal liver function, increase in activity of "hepatic" transaminases, in isolated cases - cholestatic jaundice, hepatitis, pseudomembranous colitis. Increase in activity of transaminases (ACT and ALT), bilirubin and an alkaline phosphatase is usually noted at males and at elderly patients, 65 years are especially more senior. For prevention of the undesirable phenomena drug is recommended to be accepted at the beginning of meal. The risk of similar changes increases at administration of drug more than 14 days. The specified phenomena very seldom are noted at children. Above-mentioned changes usually appear during treatment or right after. Can sometimes appear in several weeks after drug withdrawal. Generally reactions from the alimentary system have passing and insignificant character, but sometimes happen expressed.
Others: candidiasis, development of superinfection, reversible increase in a prothrombin time.

The list below shows possible side effects in the decreasing order:
Often
Digestive tract: nausea, vomiting, diarrhea, abdominal pain
Immune responses: small tortoiseshell
Skin and soft tissues: dieback
Seldom
Blood and lymphatic system: changes in composition of blood (leukopenia, thrombocytopenia, hemolitic anemia)
Gepato-biliarnaya system: cholestatic jaundice, hepatitis
Immune system: Quincke's disease, vasculitis
System of a blood coagulation: lengthening of a prothrombin time
Urinary system: intersticial nephrite

Isolated cases
Acute anaphylaxis, Quincke's disease, pseudomembranous colitis, multiformny erythema, exfoliative dermatitis.

Interaction with other medicines:

Antacids, glycosamine, laxative medicines, aminoglycosides slow down and reduce absorption; ascorbic acid increases absorption.
Bactericidal antibiotics (including aminoglycosides, cephalosporins, Cycloserinum, Vancomycinum, rifampicin) have synergistic action; bacteriostatic medicines (macroleads, chloramphenicol, linkozamida, tetracyclines, streptocides) - antagonistic.
Increases efficiency of indirect anticoagulants (suppressing intestinal microflora, reduces synthesis of vitamin K and a prothrombin ratio). At a concomitant use of anticoagulants it is necessary to watch indicators of coagulability of blood.
Reduces efficiency of oral contraceptives, medicines in the course of which metabolism paraaminobenzoic acid, ethinylestradiol - risk of development of bleedings of "break" is formed.
Diuretics, Allopyrinolum, phenylbutazone, the non-steroidal anti-inflammatory drugs and other medicines blocking canalicular secretion increase concentration of amoxicillin (clavulanic acid is removed generally by glomerular filtering).
Allopyrinolum increases risk of development of skin rash.
Amoxicillin should not be appointed with Disulfiramum.
Simultaneous use of amoxicillin and digoxin can lead to increase in concentration of digoxin in a blood plasma.

Contraindications:

Hypersensitivity to amoxicillin, clavulanic acid or other components. Hypersensitivity to others beta лактамным to antibiotics, such as penicillin and cephalosporins. Jaundice or dysfunction of a liver at reception of amoxicillin/clavulanate in the anamnesis. At patients with an infectious mononucleosis or a lymphoid leukosis the risk of a dieback therefore amoxicillin/clavulanic acid should not be appointed in the presence of these diseases increases.

With care: a heavy liver failure, digestive tract diseases (including the colitis in the anamnesis connected using penicillin), a chronic renal failure.

Pregnancy and lactation
The adverse effect of amoxicillin/clavulanate on a fruit and newborns when using by his pregnant women was not noted. Use in II and III trimesters of pregnancy is considered safe. During the I trimester drug has to be appointed with care.

Amoxicillin is emitted with breast milk. There are no data on release of clavulanic acid with breast milk. Harmful effects on the child when feeding by a breast against the background of reception of a combination of amoxicillin and clavulanic acid were not noted.

Overdose:

The overdose can lead to such gastrointestinal symptoms as nausea, vomiting and diarrhea with possible disturbance of water and electrolytic balance.

Treatment. Appoint absorbent carbon. It is necessary to support water and electrolytic balances. At spasms appoint diazepam. Other symptoms are treated symptomatic. In case of a heavy renal failure the hemodialysis has to be carried out.

Storage conditions:

List B. To store at a temperature not above 25 °C, in the place, unavailable to children. Period of validity: 3 years. Not to use after the termination of the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

The tablets dispersed on 125 mg +31,25 mg either 250 mg +62,5 mg, or 500 mg +125 mg. On 4 tablets (one dosage) in the blister manufactured of polyamide and polyvinyl chloride films which are laminated from two parties by aluminum foil and polyurethane adhesive. On 5 blisters together with the application instruction place in a cardboard pack.