FLEMOKLAV soljutab

Active material: Amoksiцillin, Clavulanic acid
When ATH: J01CR02
CCF: Antibiotics penicillin with a broad-spectrum beta-lactamase inhibitor
ICD-10 codes (testimony): A46, A54, A57, H66, J00, J01, J02, J03, J04, J15, J20, J31, J32, J35.0, J37, J42, J47, J85, J86, J90, K81.0, K81.1, K83.0, L01, L02, L03, L08.0, L30.3, M00, M86, N10, N11, N30, N34, N41, N70, N71, N72, N73.0, O08.0, O85, T79.3, Z29.2
When CSF: 06.01.02.04.02
Manufacturer: ASTELLAS PHARMA EUROPE B.V. (Netherlands)

Pharmaceutical form, composition and packaging

Dispersible tablets oblong, from white to yellow with brown spots dot, without risk, labeled “421” and company logo.

Excipients: microcrystalline cellulose, krospovydon, vanillin, apricot flavor, saxarin, magnesium stearate.

4 PC. – blisters (5) – packs cardboard.

Dispersible tablets oblong, from white to yellow with brown spots dot, without risk, labeled “422” and company logo.

Excipients: microcrystalline cellulose, krospovydon, vanillin, apricot flavor, saxarin, magnesium stearate.

4 PC. – blisters (5) – packs cardboard.

Dispersible tablets oblong, from white to yellow with brown spots dot, without risk, labeled “424” and company logo.

Excipients: microcrystalline cellulose, krospovydon, vanillin, apricot flavor, saxarin, magnesium stearate.

4 PC. – blisters (5) – packs cardboard.

Dispersible tablets oblong, white to yellow, without risk, labeled “425” and the graphic part of the logo of the company; allowed brown spot spot.

Excipients: cellulose dispersion, microcrystalline cellulose, krospovydon, vanillin, tangerine flavor, lemon flavor, saxarin, magnesium stearate.

7 PC. – blisters (2) – packs cardboard.

Pharmacological action

Broad-spectrum antibiotic; combined formulation of amoxycillin and clavulanic acid – ингибитора b-лактамаз. It is active against gram-positive and gram-negative microorganisms (including strains, продуцирующие b-лактамазы).

Amoxicillin is bactericidal, It inhibits the synthesis of bacterial cell wall peptidoglycan. Clavulanic acid inhibits β-lactamase II, III, Type IV and V – classification Richmond-Sykes). Not active against β-lactamase type I, produced by Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high affinity for penicillinases, thereby forming a stable complex with the enzyme, which prevents enzymatic degradation under the influence of amoxicillin β-lactamase, and extends the range of its actions.

Flemoklav Soljutab^® active against aerobic Gram-positive bacteria: Streptococcus spp., Staphylococcus spp. (except methicillin-resistant strains of), Enterococcus spp., Corynebacterium spp., Bacillus anthracis, Listeria monocytogenes; anaerobic gram-positive bacteria: Clostridium spp. (other than Clostridium difficile), Peptococcus spp., Peptostreptococcus spp.; Aerobic Gram-negative bacteria: Escherichia coli, Klebsiella spp., Proteus spp., Yersinia enterocolitica, Salmonella spp., Shigella spp., Haemophilus influenzae, Haemophilus ducreyi, Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Moraxella catarrhalis, Gardnerella vaginalis, Brucella spp., Pasteurella multocida, Vibrio cholerae, Helicobacter pylori; anaerobic gram-negative bacteria: Bacteroides spp., including Bacteroides fragilis, Fusobacterium spp.

Pharmacokinetics

Amoksiцillin

Absorption

After ingestion is rapidly absorbed from the gastrointestinal tract. Absorption with oral amoxicillin is 90-94%. The absolute bioavailability up 94%. Simultaneous food intake does not affect absorption.

C_max plasma levels achieved after 1-2 h after administration. After a single dose 500 mg / 125 mg (Amoxicillin / clavulanic acid) the average concentration of amoxicillin (through 8 no) is 0.3 mg / l.

After receiving a single dose 875 mg / 125 mg (Amoxicillin / clavulanic acid) C_max amoxycillin plasma is 12 ug / ml.

Distribution

After receiving a single dose 875 mg / 125 mg (Amoxicillin / clavulanic acid) AUC of amoxicillin 33 g × h / l. Binding to serum proteins is approximately 17-20%.

Amoxicillin crosses the placental barrier and small amounts excreted in breast milk.

Metabolism

A small proportion of amoxicillin is metabolized by hydrolysis of the beta-lactam ring to inactive metabolites (main – penitsillovaya and penamaldovaya acid).

Deduction

About 60-80% amoxicillin eliminated via the kidneys during the first 6 h after dosing. T_1/2 is 0.9-1.2 no.

Pharmacokinetics in special clinical situations

If the kidney function (KK within 10-30 ml / min) T_1/2 is 6 no, and in the case of anuria varies between 10 and 15 no. Displayed in hemodialysis.

Clavulanic acid

Absorption

After ingestion is rapidly absorbed from the gastrointestinal tract. The absolute bioavailability of approximately 60%. Simultaneous food intake does not affect absorption. C_max in plasma is approximately 1-2 h after administration. After a single dose 500/125 mg (amoxicillin / clavulanic acid) the average concentration of clavulanic acid up 0.08 mg / l (through 8 no).

After receiving a single dose 875 mg / 125 mg (Amoxicillin / clavulanic acid) C_max clavulanic acid in the plasma is 3 ug / ml.

Distribution

After receiving a single dose 875 mg / 125 mg (Amoxicillin / clavulanic acid) AUC clavulanic acid is 6 g × h / l.

Binding to serum proteins is 22%. Clavulanic acid crosses the placental barrier. Reliable data on the allocation of breast milk is not.

Metabolism

Clavulanic acid is subjected to intensive metabolism by hydrolysis and subsequent decarboxylation.

Deduction

About 30-50% clavulanic acid eliminated via the kidneys during the first 6 h after dosing. T_1/2 approximately 1 no.

The total clearance of amoxicillin and clavulanic acid is 25 l /.

Pharmacokinetics in special clinical situations

If the kidney function (KK from 20 to 70 ml / min) T_1/2 is 2.6 no, and in anuria ranges 3-4 no. Displayed in hemodialysis.

Testimony

Infectious-inflammatory diseases, caused by susceptible to malaria infections:

- Infections of the upper respiratory tract and ENT (incl. otitis media, sinusitis, tonsillitis, pharyngitis);

- Infections of the lower respiratory tract (incl. exacerbation of chronic bronchitis, COPD, community-acquired pneumonia);

- Bone and joint infections, incl. osteomyelitis (Only Pill 875 mg / 125 mg);

- Infections in obstetrics and gynecology (Only Pill 875 mg / 125 mg);

- Infections of the skin and soft tissues;

- Infections of the kidneys and urinary tract (incl. cystitis, pyelonephritis).

Dosage regimen

Adults and children over 12 and children under age 12 years old with a body weight more 40 kg Flemoklav Soljutab^® dose 875 mg / 125 mg administered 2 times / day (every 12 no).

Children under 12 years old with a body weight of less than 40 kg appoint Flemoklav Soljutab^® in smaller dosages.

Adults and children weighing more than 40 kg the drug is prescribed for 500 mg / 125 mg 3 times / day. At heavy, Chronic, recurrent infections This dose may be doubled.

The dosage regimen for children is shown in Table. The daily dose is generally 20-30 mg amoxycillin and 5-7.5 mg of clavulanic acid per kg body weight.

At severe infections these doses can be double (The maximum daily dose is 60 mg amoxycillin and 15 mg of clavulanic acid per kg body weight).

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

At renal impairment elimination of amoxicillin and clavulanic acid by the kidneys slows. Depending on the severity of renal failure dose Flemoklav Soljutab^® (per amoxicillin) should not exceed shown in Table.

Flemoklav Soljutab^® dose 875 mg / 125 mg can only be used glomerular filtration rate more 30 ml / min. This dose adjustment is required.

At hepatic dysfunction the drug should be administered with caution. It is necessary to monitor liver function.

To avoid side effects from the digestive system is recommended to take the drug at the beginning of the meal. Swallow whole tablets, with a glass of water, or dissolve it in half a glass of water (minimum 30 ml), stirring thoroughly before use.

Side effect

The incidence of adverse events was classified as follows:: often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10 000, <1/1000), rarely (<1/10 000).

From the hematopoietic system: rarely – thrombocytosis, gemoliticheskaya anemia; rarely – leukopenia, granulocytopenia, thrombocytopenia, pancytopenia, anemia. These adverse reactions are reversible and disappear after cessation of therapy.

On the part of the coagulation system: rarely – increased prothrombin time and bleeding time. These adverse reactions are reversible and disappear after cessation of therapy.

From the nervous system: rarely – dizziness, headache, convulsions (in the case of renal impairment, or drug overdose); rarely – hyperactivity, anxiety, alarm, insomnia, disturbance of consciousness, violent behavior.

Cardio-vascular system: rarely – vasculitis.

From the digestive system: often – abdominal pain, nausea (often in overdose), vomiting, flatulence, diarrhea (primarily, reactions from the digestive system are transient in nature and rarely expressed; their intensity can be reduced, taking the drug at the beginning of a meal); psevdomembranoznыy colitis (in the case of severe and persistent diarrhea in patients receiving the drug or for 5 weeks after completion of therapy), in most cases it is caused by Clostridium difficile; rarely – intestinal candidiasis, gemorragicheskiy colitis, diskoloratsiya surface layer of the tooth enamel.

Liver: often – slight increase in liver enzymes; rarely – hepatitis and cholestatic jaundice. Symptoms of liver function abnormalities occur during treatment or after discontinuation of therapy, but in some cases they may occur several weeks after stopping treatment; more common in men and older patients 60 years; in children are very rare (< 1/10 000). Risk of adverse reactions increases when using the drug more 14 days. Abnormal liver function, usually, reversible, However, sometimes there are severe and in very rare cases (< 1/10 000) (only in patients with serious underlying medical conditions or while receiving potentially hepatotoxic drugs) may be fatal.

With the genitourinary system: infrequently – itch, burning and vaginal discharge; rarely – interstitial nephritis.

Allergic reactions: often – skin rash and itching; morbilliform rash, poyavlyayushtayasya of 5-11 day after start of therapy. The appearance of hives immediately after receiving the drug with a high degree of probability is a manifestation of an allergic reaction and require discontinuation of the drug. Rarely – bullous or exfoliative dermatitis (erythema multiforme exudative, Stevens-Johnson syndrome, toxic epidermal necrolysis), anaphylactic shock, drug fever, eozinofilija, angioedema (angioedema), laryngeal edema, serum sickness, gemoliticheskaya anemia, sensitization vasculitis, interstitial nephritis.

Other: infrequently – bacterial or fungal superinfection (long-term therapy or repeated courses of therapy).

Contraindications

- Abnormal liver function (incl. jaundice) upon receipt of amoxicillin / clavulanic acid history;

- Infectious mononucleosis;

- Lymphocytic leukemia;

- Renal failure (glomerular filtration ≤ 30 ml / min) – dispersible tablet 875 mg / 125 mg;

- Children under the age of 12 years old with a body weight of less than 40 kg (dispersible tablet 875 mg / 125 mg);

- Hypersensitivity to amoxicillin, clavulanic acid and other ingredients;

- Hypersensitivity to other beta-lactam antibiotics (penicillins and cephalosporins).

FROM caution It should be prescribed in severe hepatic insufficiency, chronic renal failure, diseases of the digestive tract (incl. a history of colitis, associated with the use of penicillins).

Pregnancy and lactation

When using Flemoklav Soljutab^® Pregnancy was not observed its negative effects on the fetus or newborn. Use of the drug in the II and III trimester of pregnancy is possible after a medical assessment of the risk / benefit. In the I trimester of pregnancy use Flemoklav Soljutab^® should be avoided.

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

Amoxicillin and clavulanic acid penetrate the blood-placental barrier and is excreted in breast milk. Perhaps the use of the drug during breastfeeding.

In the case of a child sensitization, diarrhea or candidiasis mucous membranes of breast-feeding should be discontinued.

Cautions

When receiving Flemoklav Soljutab^® there is a possibility of cross-resistance and increased sensitivity to other penicillins and cephalosporins.

In the case of anaphylactic reactions the drug should be discontinued immediately and appropriate therapy hold: for the treatment of anaphylactic shock may require urgent administration of epinephrine (adrenaline), GCS and elimination of respiratory failure.

Perhaps the development of superinfection (in particular – candidiasis), especially in patients with chronic diseases and / or disorders of the immune system. In case of superinfection taking the drug overturned and / or appropriately modify antibiotic therapy.

Patients with severe gastrointestinal disorders, accompanied by vomiting and / or diarrhea, appointment Flemoklav Soljutab^® impractical until, They are not eliminated the above symptoms, tk. may impair the absorption of the drug from the gastrointestinal tract.

The emergence of severe and persistent diarrhea may be associated with the development of pseudomembranous colitis, in this case, the drug overturned and prescribe the necessary treatment. In the case of hemorrhagic colitis and require immediate removal of the drug and corrective therapy. Use of drugs, attenuating peristalsis contraindicated in these cases.

If abnormal liver function the drug should be used with caution and under constant medical supervision. Do not use the drug more 14 days without assessment of liver function.

Against the background of the drug may experience an increase in prothrombin time. Therefore Flemoklav Soljutab^® should be used with caution in patients, receiving anticoagulant therapy (you need to follow the performance of blood clotting).

Due to the high concentrations of amoxicillin in the urine, it may be deposited on the walls of the urinary catheter, therefore, these patients require periodic change catheters. Forced diuresis accelerates excretion of amoxicillin and reduces its concentration in plasma.

During the period of Flemoklav Soljutab^® non-enzymatic methods for the determination of glucose in urine, and urobilinogen test can give false positive results.

In exchange treatment is necessary to control the functions of blood, liver and kidneys.

In the case of seizures during therapy with drug overturned.

It should be taken into account, what in 1 dispersible tablet 875 mg / 125 mg contains 25 mg of potassium.

Overdose

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

Treatment: activated charcoal and osmodiuretiki, necessary to maintain water and electrolyte balance, symptomatic therapy. In convulsions prescribe diazepam. In renal failure, severe hemodialysis.

Drug Interactions

In an application with some bacteriostatic drugs (eg, chloramphenicol, sulfonamides) antagonism was observed with amoxicillin / clavulanic acid in vitro.

Amoxicillin / clavulanic acid should not be administered concurrently with disulfiram.

Simultaneous administration of drugs, inhibiting renal excretion of amoxicillin (probenecid, phenylbutazone, oxyphenbutazone and, at least, acetylsalicylic acid, indomethacin and sulfinpyrazone), promotes concentration and longer finding amoxycillin plasma and bile. The excretion of clavulanic acid is not broken.

In an application with Flemoklav Soljutab^® antacids, Glucosamine, laxatives, aminoglycosides slow down and reduce absorption of amoxicillin, ascorbic acid increases absorption of amoxicillin.

Concomitant use Flemoklav Soljutab^® with allopurinol may increase the risk of skin rashes.

Aminopenicillins sulfasalazine can reduce the concentration of serum.

Amoxicillin decreases the renal clearance of methotrexate, that may increase the risk of its toxic effects. At simultaneous reception with amoxicillin requires monitoring methotrexate concentration in serum.

The simultaneous use of amoxicillin / clavulanic acid and digoxin may lead to increased absorption of digoxin.

In an application Flemoklav Soljutab^® and anticoagulants may increase the risk of bleeding.

In rare cases in patients receiving amoxicillin, a decrease the effectiveness of oral contraceptives, Therefore, patients should be advised to use non-hormonal methods of contraception.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year. Shelf life dispersible tablets 875 mg / 125 mg – 2 year.