Betaklav - instructions for use, dose, side effects, contraindications

Amoxicillin trihydrate 300.00 / 600.00 / 1050.00 mg, equivalent to amoxicillin 250.00 / 500.00 / 875.00 mg, potassium clavulanate 125.00 / 125.00 / 125.00 mg equivalent to clavulanic acid + cellulose Microcrystalline (1: 1) 328.125 / 328.125 / 328.125 mg

Excipients

Cellulose microcrystalline 22,85 / 90,575 / 18,00 mg, magnesium stearate 6,50 / 9,77 / 14,00 mg, silicon colloidal dioxide 6,50 / 10.50 / 10,00 mg, sodium carboxymethyl starch 13,00 / 21.00 / 29.00 mg

Shell

Dimethicone 0.10 / 0.20 / 0.20 mg, Tabcoat TS-1709 MB white 30.00 / 30.00 / 30.00 mg

Composition Tabcoat TS-1709 MB white

Hypromellose 16.50 / 16.50 / 16.50 mg, propylene glycol 1.50 / 1.50 / 1.50 mg, ethylene glycol 3.00 / 3.00 / 3.00 mg, talc 3.00 / 3.00 / 3.00 mg, titanium dioxide 6.00 / 6.00 / 6.00 mg

Description:

Tablets 250 mg + 125 mg

White, oval form tablets, film-coated with a risk on one side.

Tablets: 500 mg + 125 mg

White, oval-shaped tablets, film-coated, with a risk on one side.

Tablets 875 mg + 125 mg

White, oval-shaped tablets, film-coated, with a risk on one side.

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

ATX: & nbsp

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

Pharmacodynamics:

BetaClave® is a combination drug that includes amoxicillin (semisynthetic aminopenicillin) and clavulanic acid (a competitive irreversible beta-lactamase inhibitor).

Amoxicillin acts bactericidal, inhibiting the synthesis of the bacterial wall. Clavulanic acid has an affinity for beta-lactamases and forms a stable complex with them, as a result of which it prevents enzymatic degradation of amoxicillin and ensures its bactericidal action. Clavulanic acid inhibits beta-lactamase II-V type according to the Richmond-Sykes classification. Such enzymes can produce Gram-positive and Gram-negative, including anaerobic, microorganisms, such as Staphylococcus spp., Haemophilus influenzae, Moraxella catarrhal is, Klebsiella spp., Escherichia coli, Neisseria spp., Proteus spp., Yersinia enterocolitica, Bacteroides spp. Clavulanic acid is not active against type I beta-lactamases produced Enterobacter spp., Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Combined drug amoxicillin and clavulanic acid has bactericidal action in vivo on the following microorganisms:

Gram-positive aerobes:

Staphylococcus aureus

Streptococcus pneumoniae

Streptococcus pyogenes

Gram-negative aerobes:

Enterobacter spp.

Escherichia coli

Haemophilus influenzae

Klebsiella spp.

Moraxella catarrhalis

The combined preparation of amoxicillin and clavulanic acid has a bactericidal effect in vitro on the following microorganisms:

Gram-positive aerobes:

Bacillis antracis

Corynebacterium spp.

Enterococcus faecalis

Enterococcus faecium

Listeria monocytogenes

Nocardia asteroides

Coagulase-negative staphylococci (including Staphylococcus epidermidis) Streptococcus agalactiae

Streptococcus spp.

Streptococcus spp. groups viridans

Gram-positive anaerobes:

Clostridium spp.

Peptococcus spp.

Peptostreptpcoccus spp.

Gram-negative aerobes:

Bordetella pertussis

Brucella spp.

Gardnerella vaginalis

Helicobacter pylori

Legionella spp.

Neisseria gonorrhoeae

Neisseria meningitidis

Pasteurella multocida

Proteus mirabilis

Proteus vulgaris

Salmonella spp.

Shigella spp.

Vibrio cholerae

Yersinia enterocolitica

Gram-negative anaerobes:

Bacteroides spp. (including Bacteroides fragilis)

Fusobacterium spp.

Other:

Borrelia burgdorferi

Chlamydia spp.

Leptospira icterohaemorrhagiae

Treponema pallidum

Pharmacokinetics:

Pharmacokinetic options both components are similar and at combinations they do not affect the pharmacokinetics of each other

Suction. Both components of the drug are rapidly absorbed after ingestion, simultaneous intake of food does not have a significant effect on absorption. Bioavailability with oral administration is about 90%. The time to reach the maximum concentration in the plasma is approximately 1.1-1.5 hours.The maximum concentration of amoxicillin (C_m_Oh) with oral administration in a dose of 250 mg of amoxicillin + 125 mg of clavulanic acid was about 3.7 mg / l, with a dose of 500 mg of amoxicillin + 125 mg of clavulanic acid - about 6.5 mg / l, and with a dose of 875 mg amoxicillin + 125 mg clavulanic acid - about 10.5 mg / l, respectively. FROM_m_Oh clavulanic acid when administered orally at a dose of 250 mg of amoxicillin + 125 mg of clavulanic acid was about 2.2 mg / l, when administered at a dose of 500 mg of amoxicillin + 125 mg of clavulanic acid - about 2.8 mg / l, and when taken orally in a dose of 875 mg amoxicillin + 125 mg clavulanic acid - about 2.2 mg / l, respectively.

Distribution. Both components are characterized by a good volume of distribution - high concentrations of amoxicillin and clavulanic acid are found in plasma, sputum, bronchial secretion, pleural fluid, lung tissue, middle ear, prostate gland, peritoneal fluid, uterus, ovaries, adipose tissue. With meningitis, penetration through the blood-brain barrier is observed, but amoxicillin poorly penetrates through non-inflamed meninges. Amoxicillin and clavulanic acid penetrate the placental barrier and in low concentrations are found in breast milk. Amoxicillin and clavulanic acid bind to plasma proteins, respectively, by 17-20% and 22-30%.

Metabolism, excretion. Amoxicillin partially metabolized with the formation of inactive metabolites, is excreted mainly by the kidneys: tubular secretion and glomerular filtration. Clavulanic acid is actively metabolized in the liver and is excreted by glomerular filtration, partly in the form of metabolites. Approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted unchanged for the first 6 hours. About 10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of inactive penicillic acid. Clavulanic acid in the human body 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 and through the gastrointestinal tract. The half-life is 1-1.3 hours for amoxicillin and 1-1.2 hours for clavulanic acid.

With renal failure, the clearance of amoxicillin with clavulanic acid decreases, so dose adjustment is required.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to amoxicillin:

- infections of the lower respiratory tract (bronchitis, pneumonia);

- infection of the ENT - organs (sinusitis, tonsillitis, otitis media);

- infections of the genitourinary system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, bacterial prostatitis, cervicitis, salpingitis, salpingoophoritis, endometritis, bacterial vaginitis, septic abortion, chancroid, gonorrhea);

- infections of the skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses, abscess, phlegmon, wound infection);

- infection of bones and joints (osteomyelitis).

Contraindications:

Hypersensitivity (including to cephalosporins and other beta-lactam antibiotics), infectious mononucleosis, episodes of jaundice or impaired liver function as a result of the use of amoxicillin and clavulanic acid in the anamnesis.

Children under 12 years of age or at a body weight of less than 40 kg (for this dosage form).

Chronic renal failure (creatinine clearance less than 30 ml / min) for tablets 875 mg + 125 mg.

Carefully:

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

Pregnancy and lactation:

The combined preparation of amoxicillin and clavulanic acid during pregnancy is recommended to be prescribed only in cases when the expected benefit from its administration for the mother exceeds the potential risk for the fetus. The drug can be used during breastfeeding. Except for the risk of sensitization associated with the penetration of trace amounts of the active ingredients of this preparation into breast milk, no other adverse effects were found in infants fed breastfeeding.

Dosing and Administration:

Inside. The dosage regimen is set individually depending on the age and body weight of the patient, the severity of the course and localization of the infectious process, as well as the sensitivity of the pathogen. The minimum course of antibacterial therapy is 5 days. Treatment should not be continued for more than 14 days without reviewing the clinical situation.

Adults and children over 12 years of age or over 40 kg body weight:

Mild and moderate infections - 1 tablet of 250 mg + 125 mg 3 times a day or 1 tablet of 500 mg + 125 mg 2 times a day.

Severe infections or infections of the lower respiratory tract - 1 tablet of 875 mg + 125 mg 2 times a day or 1 tablet of 500 mg + 125 mg 3 times a day. Since the tablets contain the same amount of clavulanic acid (125 mg), it should be noted that 2 tablets of 250 mg + 125 mg are not equivalent to 1 tablet of 500 mg + 125 mg.

The maximum daily dose of amoxicillin for adults and children over 12 years is 6 g, clavulanic acid is 600 mg.

In chronic renal insufficiency, dose adjustment and frequency of administration are carried out depending on the creatinine clearance (CK):

With QC more than 30 ml / min dose adjustment is not required;

With KK 10-30 ml / min: 1 tablet of 250 mg + 125 mg twice a day (for mild and moderate infections) or 1 tablet of 500 mg + 125 mg 2 times a day (for severe infections or infections of the lower respiratory tract );

When QC is less than 10 ml / min: 1 tablet of 250 mg + 125 mg once a day (for mild and moderate infections) or 1 tablet of 500 mg + 125 mg once a day (for severe infections or infections of the lower respiratory tract) ;

Patients on hemodialysis: 1 tablet of 500 mg + 125 mg or 2 tablets of 250 mg + 125 mg every 24 hours in combination with 1 dose during hemodialysis and 1 dose after hemodialysis, because the concentration of amoxicillin and clavulanic acid decreases.

Side effects:

From the digestive system: nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, cholestatic jaundice, hepatitis, liver failure (more common in the elderly, women, long-term therapy), colitis (including pseudomembranous), black "hairy" tongue, darkening of the tooth enamel, increased activity of " hepatic "transaminases, an increase in bilirubin and alkaline phosphatase activity.

On the part of the organs of hematopoiesis: reversible increase in prothrombin time and bleeding time, thrombocytopenia, thrombocytosis, eosinophilia, leukopenia, agranulocytosis, hemolytic anemia.

From the central nervous system: dizziness, headache, hyperactivity, anxiety, behavior change, convulsions.

Allergic reactions: urticaria, erythematous rashes, multiforme exudative erythema, anaphylactic shock, angioedema, exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), allergic vasculitis syndrome similar to serum sickness, acute generalized exanthematous pustulosis.

From the side of the kidneys and urinary tract: interstitial nephritis, crystalluria, hematuria.

Other: Candidiasis, development of superinfection.

Overdose:

Symptoms: a violation of the function of the gastrointestinal tract and water electrolyte balance.

Treatment: symptomatic. Hemodialysis is effective.

Interaction:

It is not recommended to use a combined preparation of amoxicillin and clavulanic acid simultaneously with probenecid. Probenecid reduces the tubular secretion of amoxicillin, so their simultaneous application can lead to an increase and persistence of amoxicillin concentration in the serum, while the serum concentration of clavulanic acid does not change.

Antacids, glucosamine, laxatives slow down and reduce the absorption of amoxicillin; ascorbic acid - Increases.

Allopurinol increases the risk of skin rashes.

Diuretics, allopurinol, phenylbutazone and non-steroidal anti-inflammatory drugs, other drugs that block tubular secretion, increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).

Like other broad-spectrum antibiotics,the combined preparation of amoxicillin and clavulanic acid may reduce the effectiveness of oral contraceptives, and patients should be informed about this.

In the literature, rare cases of an increase in the international normalized relationship are described (MHABOUT) in patients with the joint use of acenocoumarol or warfarin and amoxicillin. If simultaneous application of combined amoxicillin and clavulanic acid with indirect anticoagulants is necessary, prothrombin time or INR should be carefully monitored when the drug is prescribed or withdrawn.

Special instructions:

Severity of gastrointestinal symptoms decreases with admission drug at the beginning of the meal.

At course treatment it is necessary to monitor the status of the functions of the organs of hematopoiesis, liver and kidneys.

It is possible to develop superinfection by selecting the resistant forms of the pathogen.

There may be false-positive results in determining glucose in the urine. In this case, it is recommended to use a glucose oxidase method to determine the concentration of glucose in the urine.

In patients who are hypersensitive to penicillins, there may be cross-allergic reactions with cephalosporin antibiotics.

In the case of suspected infectious mononucleosis, the drug should not be used because patients with this disease amoxicillin can cause a skinlike skin rash, which makes it difficult to diagnose the disease.

Effect on the ability to drive transp. cf. and fur:

Given the likelihood of side effects from the central nervous system, care should be taken when driving vehicles and working with mechanisms.

Form release / dosage:Film coated tablets 250 + 125 mg, 500 + 125 mg, 875 + 125 mg.

Packaging:

Film coated tablets 250 + 125 mg:

10 tablets per strip aluminum. On 2 strips together with the instruction on application place a pack of cardboard.

Film coated tablets 500 + 125 mg:

For 6, 7 or 10 tablets in an aluminum strip. On 1 or 2 strips (6, 7 or 10 tablets) together with the instruction for use are placed in a cardboard pack.

Film-coated tablets 875 + 125 mg:

For 4, 7 or 10 tablets in an aluminum strip.For 2 or 3 strips with instructions for use put in a pack of cardboard.

Storage conditions:

In dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children!

Shelf life:

Film coated tablets 250 + 125 mg

2 years.

Film coated tablets 500 + 125 mg; 875 + 125 mg

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008707/10

Date of registration:25.08.2010 / 03.06.2015

Expiration Date:Unlimited

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

MICRO LABS, Limited India

Representation: & nbspKRKA KRKA Slovenia

Information update date: & nbsp24.01.2017

Illustrated instructions

Instructions

BetaClave® (Betaklav®)