Betaclav tablets are coated. 875 mg + 125 mg 14 pcs. (Amoxicillin, Clavulanic acid)

Pharmacological action

Pharmacotherapeutic group: Semi-synthetic antibiotic-penicillin + beta-lactamase inhibitor

ATX:

J.01.CR02 Amoxicillin in combination with

enzyme inhibitors Pharmacodynamics:

Mechanism of action

Amoxicillin is a semi-synthetic broad-spectrum antibiotic with activity against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by beta-lactamases, and therefore the activity spectrum of amoxicillin does not extend to the microorganisms that produce this enzyme.

Clavulanic acid, a beta-lactamase inhibitor structurally related to penicillins, has the ability to inactivate a wide range of beta-lactamases found in penicillin and cephalosporin resistant microorganisms. Clavulanic acid is sufficiently effective against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against chromosome beta-lactamases type 1, which are not inhibited by clavulanic acid.

The presence of clavulanic acid in BetaclavВ® protects amoxicillin from destruction by enzymes - beta-lactamases, which allows to expand the antibacterial spectrum of amoxicillin.

The following is the in vitro combination activity of amoxicillin with clavulanic acid.

Bacteria commonly susceptible to the combination of amoxicillin with clavulanic acid

Gram-positive aerobes

Bacillus anthracis

Enterococcus faecalis

Listeria monocytogenes

socrdocpocptocpocptoc. Streptococcus streptococcus streptococci (other beta hemolytic streptococci) 1, 2

Staphylococcus aureus (methicillin-sensitive) 1

Staphylococcus saprophyticus (methicillin-sensitive)

Coagulase-negative staphylococci (methicillin-sensitive)

Gram-positive anaerobes

.

Peptococcus niger

Peptostreptococcus magnus

Peptostreptococcus micros

Peptostreptococcus spp.

Gram-negative aerobes

Bordetella pertussis

Haemophilus influenzae1

Helicobacter pylori

Moraxella catarrhalis1

Neisseria gonorrhoeae

Pasteurella multocida srdlrd srdlrd

Capnocytophaga spp.

Eikenella corrodens

Fusobacterium nucleatum

Fusobacterium spp.

Porphyromonas spp.

Prevotella spp. Other



Borrelia burgdorferi

Leptospira icterohaemorrhagiae

Treponema pallidum

Bacteria for which the probability acquired resistance to the combination of amoxicillin with clavulanic acid

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 pneumoniae1,2

Streptococcus group Viridans

Bacteria that are naturally resistant to the combination of amoxicillin with 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 burnetii

Mycoplasma spp.

1 - for these bacteria, the clinical efficacy of a combination of amoxncillin with clavulanic acid has been demonstrated in clinical studies.

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

Pharmacokinetics:

Absorption

Both active ingredients of BetaclavВ®, amoxicillin and clavulanic acid are rapidly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. The absorption of the active ingredients of BetaclavВ® is optimal when taking the drug at the beginning of a meal.

The following shows the pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in separate studies when healthy fasting volunteers took:

- 1 tablet containing amoxicillin and clavulanic acid, 500 mg + 125 mg (625 mg)

- 500 mg of amoxicillin srdl 125 mg clavulanic acid

- 2 tablets of the drug containing amoxicillin and clavulanic acid, 875 mg + 125 mg (1000 mg).

Basic pharmacokinetic parameters

Drugs

Dose

(mg)

Cmax

(mg / l)

Tmax

(hours)

AUC

(mhh / l) srdlrd ppm acid / 2

clkp1 / 2 500 mg + 125 mg

500

6.5

1.5

23.2

1.3

Amoxicillin / Clavulanic acid, 875 mg + 125 mg

1750

11.64 В± 2.78

1.50

( 1.0-2.5)

53.52 В± 12.31

1.19 В± 0.21

Amoxicillin, 500 mg

500

6.5

1.3

19.5

1.1

Clavulanic acid

Clavulanic acid, 125 mg

125

3.4

0.9

7.8

0.7

Amoxicillin / Clavulanic acid, 500 mg + 125 mg

125

2.8

1.3

7.3

0.8

Amoxicillin / Clavulanic acid, 875 mg + 125 mg

250

2.18 В± 0.99

1.25

(1.0-2.0)

10.16 В± 3.04

0.96 В± 0.12

Cmax - maximum concentration in blood plasma.

Tmax - time to reach maximum plasma concentration.

AUC - area under the concentration-time curve.

T1 / 2 - elimination half-life.

Distribution of

As with the intravenous combination of amoxicillin with clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are found in various tissues and interstitial fluid (in the gallbladder, abdominal tissues, skin, adipose and muscle tissues, synovial and peritoneal fluids purulent discharge).

Amoxicillin and clavulanic acid have a weak degree of binding to plasma proteins. Studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin in blood plasma binds to blood plasma proteins.

In animal studies, no cumulation of the components of BetaclavВ® in any organ was found. Amoxicillin, like most penicillins, passes into breast milk. Traces of clavulanic acid may also be found in breast milk. With the exception of the possibility of sensitization, diarrhea, or candidiasis of the oral mucosa, no other negative effects of amoxicillin and clavulanic acid on the health of breast-fed children are known.

Animal reproductive studies have shown that amoxicillin and clavulanic acid cross the placental barrier. However, no adverse effects on the fetus were detected.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys as an inactive metabolite (penicilloic acid). Clavulanic acid is extensively metabolized to 2,5-dihydro-4- (2-hydroxyethyl) -5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and excreted by the kidneys, through the digestive tract, as well as with exhaled air in the form of carbon dioxide.

Excretion

Like other penicillins, amoxicillin is excreted mainly by the kidneys, while clavulanic acid is excreted by both the renal and extrarenal mechanisms. About 60-70% of amoxicillin and about 40-65% of clavulanic acid are excreted by the kidneys unchanged in the first 6 hours after application.

The simultaneous administration of probenecid slows the excretion of amoxicillin, but not clavulanic acid (see section Interaction with other medicines).

Indications

The combination of amoxicillin with clavulanic acid is indicated for the treatment of bacterial infections of the following locations, caused by microorganisms sensitive to the combination of amoxicillin with clavulanic acid:

infections of the upper respiratory tract (including ENT infections), for example, recurrent tonsillitis, sinusitis, otitis media, usually caused by Streptococcus pneumoniae, Haemophilus influenzae #, Moraxella catarrhalis pyptoptes and Streptococcus pyrrhocida streptococcus pyrrhocida infection lower respiratory tract, for example, exacerbation of chronic bronchitis, lobar pneumonia and bronchopneumonia, usually caused by Streptococcus pneumoniae, Haemophilusinfluenzae # and Moraxella catarrhalis #

urinary tract infections, for example, cystitis, urethritis, pi lonefrit,

infection of female genital mutilation, usually caused by types semeystvaEnterobacteriaceae1 (mainly Escherichia coli #), Staphylococcus saprophyticus, and species of the genus of Enterococcus, and gonorrhea, infections of the skin and soft tissues caused by Neisseria gonorrhoeae #

, usually caused by Staphylococcus aureus #, Streptococcus pyogenes and species of the genus Bacteroides #

infections of the bones and joints, for example, osteomyelitis, usually caused by Staphylococcus aureus **, if necessary, prolonged treatment with srd e.g. periodontitis, odontogenic maxillary sinusitis, severe dental abscesses with spreading

cellulitis, other mixed infections (e.g. septic abortion, postpartum sepsis, intra-abdominal sepsis) within the steps Ata therapy.

Some representatives of this kind of microorganism produce beta-lactamase, which makes them insensitive to amoxicillin (see also the section Pharmacological properties).

Infections, caused by microorganisms sensitive to amoxicillin, can be treated with Betaclav® because amoxicillin is one of its active ingredients.

Betaclav® is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as microorganisms producing beta-lactamase, sensitive to the combination of amoxicillin with clavulanic acid.

The sensitivity of bacteria to the combination of amoxicillin with clavulanic acid varies by region and over time. Where possible, local sensitivity data should be taken into account. If necessary, microbiological samples should be collected and analyzed for bacteriological sensitivity.

Contraindications

Hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (e.g. penicillins, cephalosporins) in the anamnesis.

Previous episodes of jaundice or impaired liver function with a history of amoxicillin and clavulanic acid.

Children under 12 years old or body weight less than 40 kg.

Severe renal impairment (creatinine clearance <30 ml / min) (for a dosage of 875 mg + 125 mg).

Caution: Betaclav® should be used with caution in patients with impaired liver function.

Use in pregnancy and lactation

Pregnancy

In studies of reproductive function in animals, oral and parenteral administration of the combination of amoxicillin + clavulanic acid did not cause teratogenic effects.

In a single study in women with premature rupture of membranes, prophylactic therapy was found to be associated with an increased risk of necrotizing enterocolitis in newborns.

Like all medicines, Betaclav® is not recommended for use during pregnancy, unless the expected benefit to the mother outweighs the potential risk to the fetus.

Breastfeeding period

Betaclav® can be used during breastfeeding. Except for the possibility of sensitization, diarrhea, or candidiasis of the oral mucous membranes associated with the penetration of trace amounts of the active ingredients of this drug into breast milk, no other adverse effects were observed in breast-fed infants. In case of adverse effects in breast-fed infants, breast-feeding should be discontinued.

Special instructions

Before starting treatment with BetaclavВ®, a detailed history should be collected regarding previous hypersensitivity reactions to penicillins, cephalosporins or other substances that cause an allergic reaction in the patient.

Serious and sometimes fatal hypersensitivity reactions (including anaphylactoid and severe skin adverse reactions) to penicillins are described. The risk of such reactions is highest in patients having a history of hypersensitivity reactions to penicillins. In case of an allergic reaction, it is necessary to discontinue treatment with BetaclavВ® and begin appropriate alternative therapy. In case of severe anaphylactic reactions, epinephrine should be administered to the patient immediately. Oxygen therapy, intravenous administration of glucocorticosteroids, and airway management, including intubation, may also be required.

In case of skin allergic reactions, treatment with BetaclavВ® should be discontinued.

In the case of suspected infectious mononucleosis, BetaclavВ® should not be used, since in patients with this disease, amoxicillin can cause a measles-like skin rash, which makes it difficult to diagnose the disease.

Long-term treatment with BetaclavВ® may lead to excessive proliferation of insensitive microorganisms.

Cases of the occurrence of pseudomembranous colitis when taking antibiotics are described, the severity of which can vary from mild to life-threatening. Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after the use of antibiotics. If diarrhea is prolonged or severe, or the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be examined.

In general, BetaclavВ® is well tolerated and has a low toxicity characteristic of all penicillins. During long-term therapy with BetaclavВ®, it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis.

In patients receiving a combination of amoxicillin with clavulanic acid simultaneously with indirect (for oral administration) anticoagulants, in rare cases, an increase in prothrombin time (increased INR) was reported. With the simultaneous use of indirect (for oral administration) anticoagulants with a combination of amoxicillin with clavulanic acid, monitoring of the relevant indicators is necessary. To maintain the desired effect of anticoagulants for oral administration, dosage adjustment may be required.

In patients with impaired renal function, the dose of BetaclavВ® should be reduced accordingly to the degree of impairment (see section Dosage and Administration, subsection Patients with impaired renal function).

Crystalluria is very rare in patients with reduced diuresis, mainly with parenteral therapy. During the administration of high doses of amoxicillin, it is recommended to take a sufficient amount of liquid and maintain adequate diuresis to reduce the likelihood of the formation of amoxicillin crystals (see section Overdose).

Ingestion of BetaclavВ® 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, a Benedict test, a Feling test). In this case, it is recommended to use the glucose oxidase method for determining the concentration of glucose in the urine.

Clavulanic acid can cause nonspecific binding of immunoglobulin G and albumin to red blood cell membranes, which leads to false positive Coombs test results.

Abuse and drug dependence

No drug dependence, addiction and euphoria reactions associated with the use of BetaclavВ®.

Impact on the ability to drive transp. Wed and fur.: Since the use of BetaclavВ® may cause dizziness, it is necessary to warn patients about precautions when driving or working with moving machinery.

Composition of

For 1 film-coated tablet 500 mg + 125 mg / 875 mg +125 mg: Core

Active ingredients: Amoxicillin trihydrate 573.892 mg / 1004.310 mg, equivalent to amoxicillin 500,000 mg / 875,000 mg Potassium clavulanate + Microcrystalline cellulose (1: 1) 303.834 mg / 303.834 mg, equivalent to potassium clavulanate 151.915 mg / 151.915 mg, equivalent to clavulanic acid 125,000 mg / 125,000 mg

Excipients: microcrystalline cellulose, magnesium stearate, sodium carbamdioxide Cling shell ay: Opadry white Y-1-7000 *

* Opadry white Y-1-7000: hypromellose 5 cP (E464), titanium dioxide (E171), macrogol-400

Dosage and administration

For oral administration.

The dosage regimen is set individually depending on the age, body weight, patient's kidney function, as well as the severity of the infection.

To reduce potential gastrointestinal disturbances and to optimize absorption, the drug should be taken at the beginning of a meal.

The minimum course of antibiotic therapy is 5 days.

Treatment should not be continued for more than 14 days without a review of the clinical situation. If necessary, it is possible to carry out step-by-step therapy (first, intravenous administration of a drug containing amoxicillin and clavulanic acid, in powder form, to prepare a solution for intravenous administration, followed by switching to a preparation containing amoxicillin and clavulanic acid, in oral dosage forms).

Adults and children 12 years of age or older or weighing 40 kg or more

1 tablet 500 mg + 125 mg 3 times a day.

1 tablet 875 mg + 125 mg 2 times a day.

Special patient groups

Children under 12 years of age or weighing less than 40 kg

Other dosage forms of the drug containing amoxicillin and clavulanic acid are recommended.

Elderly patients

Dosage adjustment not 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

Dosage adjustment is based on the maximum recommended dose of amoxicillin and creatinine clearance (QC).

Creatinine clearance

Dosage regimen BetaclavВ®

> 30 ml / min

Dosage adjustment not required

10-30 ml / min

1 tablet 500 mg + 125 mg (for moderate and severe infections) 2 times a day

< 10 ml / min

1 tablet 500 mg + 1 25 mg (for moderate and severe infections) 1 time per day

Patients, hemodialysis

Dosage adjustment based on maximum recommended dose of amoxicillin.

1 tablet 500 mg + 125 mg in one dose every 24 hours.

During the dialysis session, an additional 1 dose (1 tablet) and another 1 tablet at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

875 mg + 125 mg tablets should be used only in patients with CC> 30 ml / min, and no dosage adjustment is necessary.

In most cases, parenteral therapy should be preferred if possible.

Patients with impaired liver function

Treatment is carried out with caution, liver function monitoring is carried out regularly.

There is not enough data to change the recommendation of the dosing regimen in such patients.

Side effects

The adverse reactions presented below are listed in accordance with the damage to organs and organ systems and the frequency of occurrence.

Frequency of occurrence is defined as follows: very often (? 1/10), often (? 1/100 and <1/10), infrequently (? 1/1000 and <1/100), rarely (? 1/10000 and < 1/1000), very rarely (<1/10000, including isolated cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration observation.

Frequency of occurrence of adverse reactions

Infectious and parasitic diseases: often: candidiasis of the skin and mucous membranes.

Disorders of the blood and lymphatic system: rare: reversible leukopenia (including neutropenia), reversible thrombocytopenia

very rare: reversible agranulocytosis and reversible hemolytic anemia, prolonged bleeding time and prothrombin time, anemia, eosinophilia, thrombocytosis.

Immune system disorders: very rare: angioedema, anaphylactic reactions, a syndrome similar to serum sickness, allergic vasculitis.

Disorders of the nervous system: infrequently: dizziness, headache

very rarely: reversible hyperactivity, convulsions (convulsions can occur in patients with impaired renal function, as well as in those who receive high doses of the drug), insomnia, agitation, anxiety, and behavior change.

Disorders of the gastrointestinal tract: Adults

very often: diarrhea often: nausea, vomiting.

Children

often: diarrhea, nausea, vomiting.

The entire population of

Nausea was most often associated with the use of high doses of the drug. If after the start of taking the drug there are undesirable reactions from the gastrointestinal tract, they can be eliminated if you take Betaclav® at the beginning of the meal.

Infrequent: digestive disorders

very rare: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis) (see Special instructions), black hairy tongue, gastritis, stomatitis.

Disorders of the liver and biliary tract: infrequently: moderate increase in the activity of aspartate aminotransferase and / or alanine aminotransferase (ACT and / or ALT). This reaction is observed in patients receiving beta-lactam antibiotic therapy, but

is rarely known for its clinical significance: hepatitis and cholestatic jaundice (these reactions are observed in patients receiving other penicillin antibiotics and cephalosporins), an increase in the concentration of bilirubin and alkaline phosphatase.

Adverse reactions from the liver have been observed mainly in men and elderly patients and may be associated with long-term therapy. These adverse reactions are very rarely observed in children.

The listed signs and symptoms usually occur during or immediately after the end of therapy, but in some cases they may not appear for several weeks after completion of therapy. Adverse reactions are usually reversible. Adverse reactions from the liver can be severe, in extremely rare cases there have been reports of fatal outcomes. In almost all cases, these were patients with serious concomitant pathology or patients receiving potentially hepatotoxic drugs.

Disorders of the skin and subcutaneous tissue: infrequently: skin rash, pruritus, urticaria

rare: erythema multiforme

very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous dermatitis: drug rash with eosinophilia and systemic manifestations (DRESS syndrome).

Disorders from the kidneys and urinary tract: very rare: interstitial nephritis, crystalluria (see section Overdose), hematuria.

Drug Interactions

The simultaneous use of Betaclav® and probenecid is not recommended.

Probenecid reduces the tubular secretion of amoxicillin, and therefore, the simultaneous use of Betaclav® and probenecid can increase the concentration and persistence in the blood 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 elimination of methotrexate from the body by inhibiting its tubular secretion, therefore, the simultaneous use of Betaclav® and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, Betaclav® can affect the intestinal microflora, leading to a decrease in the absorption of estrogen from the gastrointestinal tract and the effectiveness of combined contraceptives for oral administration.

The literature describes rare cases of increasing international normalized ratio (INR) in patients with the simultaneous use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously administer Betaclav with anticoagulants, prothrombin time or INR should be carefully monitored when prescribing or canceling Betaclav®, dose adjustment of anticoagulants for oral administration may be required.

In patients receiving mycophenolate mofetil, after the start of the use of the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite, mycophenolic acid, was observed before the next dose of the drug by about 50%. Changes in this concentration may not accurately reflect the general changes in the exposure of mycophenolic acid.

Overdose of

Symptoms of

Gastrointestinal symptoms and disturbances in water-electrolyte balance may be observed. Amoxicillin crystalluria is described. in some cases leading to the development of renal failure (see section Special instructions).

Seizures may occur in patients with impaired renal function, as well as in those who receive high doses of the drug.

Treatment

Gastrointestinal symptoms are symptomatic therapy, with particular attention to normalizing the water-electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

A prospective study of 51 children at a poison center showed that 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.

Storage conditions

At a temperature not exceeding 25 ° C (in the strip).

At a temperature not exceeding 25 ° C, in the original packaging (in a blister pack).

Keep out of the reach of children.

The Expiration of

is 3 years (in strip).

2 years (in blister).

Do not use after the expiry date.

Deystvuyuschee substances

Amoxicillin, clavulanic acid



pharmacy terms for prescription

Form of Treatment

tablets

Appointment

Adult prescription, Children prescribing

Indications

respiratory tract infections, Urinary tract infections, Skin infections



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