Betaclave, 875 mg+125 mg, film-coated tablets, 14 pcs.

Pharmacological properties of the drug Betaclave

Betaclave is a combination drug that contains amoxicillin (a broad-spectrum penicillin antibiotic) and clavulanic acid (a powerful irreversible β-lactamase inhibitor). Amoxicillin inhibits the last stage of bacterial cell wall construction by inhibiting the activity of transpeptidases, enzymes involved in the synthesis of peptidoglycan, which is an important component of the outer membrane of bacteria. Inadequate synthesis of peptidoglycan causes the formation of a deformed, osmotically unstable outer membrane, which leads to destruction and death of the bacterial cell. Penicillins can also damage the bacterial cell wall by inhibiting the activity of an inhibitor of murein hydrolase, an enzyme involved in cell division. Clavulanic acid has little antibacterial activity, but it acts as a potent irreversible inhibitor of β-lactamases. It forms stable inactive complexes with enzymes and, as a result, prevents the breakdown of amoxicillin. Betaclave has a bactericidal effect on gram-positive and some gram-negative bacteria, including bacteria producing β-lactamases and microorganisms resistant to amoxicillin: gram-positive aerobic bacteria - Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Streptococcus agalactiae, Staphylococcus aureus, Staphylococcus epidermidis, List eria monocytogenes, Enterococcus faecalis, Enterococcus faecium, Corynebacterium spp., Bacillus anthracis, Nocadia asteroides; gram-negative aerobic bacteria - Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Proteus spp., Klebsiella spp., Neisseria gonorrhoeae, Neisseria meningitidis, Bordetella pertussis, Brucella spp., Pasteurella multocida, Salmonella spp., Shigella spp., Vibrio cholerae, Yerisinia enterocolitica ; anaerobic bacteria - Peptococcus spp., Peptostreptococcus spp., Clostridium spp., Bacteroides spp., Fusobacterium spp. 5 minutes after intravenous administration of 1.2 g of Betaclava, the concentration of amoxicillin in the blood serum is 99 mcg/ml, and the concentration of clavulanic acid is 27 mcg/ml. When taken orally, the absorption of amoxicillin in the gastrointestinal tract is 90%, clavulanic acid - 60%. After absorption, 30% of clavulanic acid and 20% of amoxicillin are bound to blood proteins. Amoxicillin and clavulanic acid readily penetrate body tissues and fluids, with the exception of the brain and CSF. The degree of their accumulation is dose-dependent. Amoxicillin and clavulanic acid easily penetrate the placental barrier and are excreted in small amounts in breast milk. An infant may experience sensitization to the components of the drug. The half-life of amoxicillin and clavulanic acid is about 1 hour. Clavulanic acid is intensively metabolized in the liver, excreted primarily by the kidneys, and partially excreted in feces and exhaled air. The renal elimination of amoxicillin from the body is carried out mainly by tubular secretion, and clavulanic acid - mainly by glomerular filtration, therefore probenecid does not affect the excretion of clavulanic acid. In the first 6 hours, 60–80% of amoxicillin in active form is excreted in the urine. For clavulanic acid, this amount is 30–50%. A decrease in creatinine clearance to a level of ≤10 ml/min leads to the accumulation of clavulanic acid in the body.

Betaclave, 875 mg+125 mg, film-coated tablets, 14 pcs.

The pharmacokinetic parameters of both components are similar and in combination they do not affect each other’s pharmacokinetics

Suction. Both components of the drug are rapidly absorbed after oral administration; simultaneous food intake does not have a significant effect on absorption. Bioavailability when taken orally is about 90%. The time to reach maximum plasma concentration is approximately 1.1-1.5 hours. The maximum concentration of amoxicillin (Cmax) when taken orally at a dose of 250 mg amoxicillin + 125 mg clavulanic acid was about 3.7 mg/l, when taken at a dose of 500 mg amoxicillin + 125 mg clavulanic acid - about 6.5 mg/l, and when taken at a dose of 875 mg of amoxicillin + 125 mg of clavulanic acid - about 10.5 mg/l, respectively. Cmax of clavulanic acid when taken orally at a dose of 250 mg amoxicillin + 125 mg clavulanic acid was about 2.2 mg/l, when taken orally at a dose of 500 mg amoxicillin + 125 mg clavulanic acid - about 2.8 mg/l, and when taken orally orally at 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 secretions, pleural fluid, lung tissue, middle ear, prostate gland, peritoneal fluid, uterus, ovaries, adipose tissue. In meningitis, penetration of the blood-brain barrier is observed, but amoxicillin penetrates poorly through non-inflamed meninges. Amoxicillin and clavulanic acid cross the placental barrier and are found in low concentrations in breast milk. Amoxicillin and clavulanic acid bind to plasma proteins by 17 - 20% and 22 - 30%, respectively.

Metabolism, excretion. Amoxicillin is partially metabolized to form inactive metabolites and is excreted mainly by the kidneys: tubular secretion and glomerular filtration. Clavulanic acid is actively metabolized in the liver and 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 by the kidneys during 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-hydroxy-butan-2-one and 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.

In case of renal failure, the clearance of amoxicillin with clavulanic acid is reduced, so dose adjustment is required.

Indications for use of the drug Betaclave

Infections caused by gram-positive and gram-negative bacteria sensitive to the drug: ENT organs and respiratory tract - acute sinusitis, otitis media, recurrent tonsillitis, acute bronchitis, chronic bronchitis in the acute phase, pneumonia, empyema, lung abscess; skin and soft tissues - boils and abscesses, phlegmon, infected wounds, including after animal bites; genitourinary system - cystitis, urethritis, pyelonephritis, septic abortion, pelvic infections, chancroid, gonorrhea; other infections - osteomyelitis, sepsis, diverticulitis, liver abscess, biliary tract infections and periodontal infections; prevention of infections during surgical interventions on the gastrointestinal tract, pelvic organs, head and neck, heart, kidneys, biliary tract, as well as joint replacement.

Use of the drug Betaclave

Powder for the preparation of injection solution The drug is administered by intravenous infusion over 3–4 minutes. The dose depends on the severity of the infectious disease, the age and body weight of the patient, as well as renal function. Adults and children over the age of 12 years are usually prescribed 1.2 g every 8 hours, and for severe infections - every 6 hours. Children aged 3 months to 12 years with body weight ≤40 kg are prescribed 30*–55* * mg/kg body weight every 8 hours, and for severe infections - every 6 hours. Newborns (under 1 month), including premature ones, are prescribed 30*–55** mg/kg every 12 hours, and severe infections - every 8 hours. Infants (1–3 months) are prescribed 30*–55** mg/kg every 8 hours. To prevent postoperative infections, 1.2 g of the drug is administered intravenously before anesthesia. If the surgical intervention lasts 1 hour, the patient can be given 3 more injections every 8 hours. The duration of use of the drug in adults and children should not exceed 14 days, provided that the clinical need for further use of the drug has not been re-evaluated. If the patient's condition allows, it is recommended to switch to taking the drug for oral administration.

Dosing of the drug for renal failure

Notes: *30 mg corresponds to 25 mg amoxicillin and 5 mg clavulanic acid; **55 mg corresponds to 45 mg amoxicillin and 10 mg clavulanic acid; ***600 mg corresponds to 500 mg amoxicillin and 100 mg clavulanic acid.

The solution for injection must be prepared immediately before administration. When dissolved, a transparent pink solution is formed, which later becomes yellow or slightly opalescent. The contents of the bottle should be dissolved in at least 20 ml of water for injection or 0.9% sodium chloride solution for injection and administered intravenously slowly (over 3–4 minutes). Tablets Take orally without chewing, with a glass of water, immediately before meals. Adults, adolescents and children weighing 40 kg are prescribed 1 Betaclava tablet every 12 hours (2 times a day). The duration of taking the drug should not exceed 14 days without repeated medical examination. The dose of the drug for patients with impaired renal function should be reduced. In case of moderately severe renal failure (creatinine clearance 0.5 ml/s or 30 ml/min), no dose adjustment is required. In case of renal failure with a creatinine clearance of 0.16–0.5 ml/s or 10–30 ml/min, 1 Betaclava tablet (625 mg) is prescribed every 12 hours (2 times a day).

Side effects of the drug Betaclave

The most common symptoms are diarrhea, nausea and vomiting. During treatment, superinfection caused by resistant microorganisms may develop. It is possible to develop candidal stomatitis and vaginitis or pseudomembranous colitis with severe and persistent diarrhea. In this case, the drug should be discontinued and adequate treatment prescribed. Hypersensitivity reactions are possible, such as pruritus, maculopapular rash, urticaria, exfoliative dermatitis, toxic epidermal necrolysis and vasculitis, arthralgia, myalgia, angioedema, bronchospasm, anaphylactic shock, erythema multiforme, and in isolated cases, Stevens-Johnson syndrome. In some cases, an increase in the activity of liver enzymes was noted, in isolated cases - cholestatic jaundice, hepatitis, liver failure, interstitial nephritis and hematuria, liver failure. The latter most often develops in men, elderly people (over 65 years old) and with a treatment duration of 14 days. Possible development of leukopenia, thrombocytopenia, eosinophilia, anemia, including hemolytic anemia. Side effects from the central nervous system occur extremely rarely. Dizziness, headache, confusion, hallucinations and seizures may occur. These effects may occur mainly in patients with renal failure or when the drug is administered in very high doses. Possible pain, swelling and thrombophlebitis at the injection site.

Special instructions for the use of the drug Betaclave

The drug should be used with extreme caution in patients with hypersensitivity to cephalosporins and other β-lactam antibiotics due to possible cross-hypersensitivity. The drug should be prescribed with caution to patients with liver failure (including patients with a history of liver failure). Betaclave can increase the activity of transaminases (AlAT and AST), alkaline phosphatase and bilirubin levels in the blood serum. With prolonged use of the drug, it is recommended to monitor hematological parameters, as well as the functional state of the kidneys and liver. In patients with moderate to severe renal failure, it is recommended to increase the interval between drug administration. During the treatment period, superinfection caused by drug-resistant microorganisms ( Clostridium difficile, Candida spp. ) may develop. In case of severe and persistent diarrhea, which may indicate the development of pseudomembranous and hemorrhagic colitis, it is necessary to stop using the drug and prescribe appropriate treatment. The drug is not recommended for use in patients with lymphocytic leukemia or infectious mononucleosis, since such patients are more likely to develop allergic skin reactions when treated with amoxicillin. During treatment, patients should take sufficient fluids as the risk of crystalluria and renal failure may increase. When high concentrations of amoxicillin are created at room temperature, the urine may precipitate on the walls of the catheter installed in the bladder, so the patency of the catheter should be checked regularly. Betaclava, a powder for the preparation of an injection solution, contains 63 mg (2.74 mmol) sodium and 39.2 mg (1 mmol) potassium, which is important to consider in patients following a diet low in sodium and potassium. After parenteral administration, pain or inflammation may be observed at the injection site of the drug, which is due to the presence of potassium in its composition. Although there are no reports of a negative effect of Betaclava on the fetus or on the newborn when taking the drug during pregnancy, Betaclave can be prescribed during pregnancy only if the expected therapeutic effect for the mother exceeds the potential risk to the fetus. Both active components of Betaclava penetrate the placental barrier and are excreted into breast milk. Breastfeeding during treatment with Betaclava may contribute to the development of hypersensitivity to the components of the drug in an infant. Taking Betaclava does not affect the ability to drive vehicles or operate machinery. During treatment with the drug, a high concentration of amoxicillin in the urine may give a false-positive result for determining glucose in the urine using non-enzymatic methods. During treatment with Betaclava, a false positive result from the Coombs test is also possible.

Betaclave powder for oral suspension, 70 ml

Before using the drug, it is necessary to accurately determine the presence of a history of hypersensitivity reactions to penicillins, cephalosporins or other allergens (see Sections “Contraindications” and “Adverse Reactions”).

Serious and sometimes fatal cases of hypersensitivity (anaphylactoid reactions) have been observed in patients during penicillin therapy. Such reactions are more likely to occur in patients with a history of hypersensitivity to penicillins and in people with allergic reactions. If an allergic reaction occurs, therapy with amoxicillin/clavulanic acid should be discontinued and appropriate treatment should be instituted.

If it is proven that the infection is caused by microorganisms sensitive to amoxicillin, it is necessary to consider the possibility of switching from the amoxicillin/clavulanic acid combination to amoxicillin according to official recommendations.

This dosage form of the drug should not be used in cases where there is a high risk of possible β-lactam-resistant pathogens not mediated by clavulanic acid-sensitive β-lactamase inhibition. Not used for the treatment of pneumonia caused by penicillin-resistant strains of S. pneumoniae.

Convulsions may occur in patients with impaired renal function and if they take high doses of the drug (see Section “Adverse Reactions”).

Concomitant use of allopurinol during amoxicillin therapy increases the likelihood of allergic skin reactions.

Long-term use of the drug may cause overgrowth of non-susceptible organisms.

The development of erythema multiforme associated with pustules at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis (AGEP) (see section "Adverse reactions"). In this case, it is necessary to stop treatment; further use of amoxicillin is contraindicated.

The amoxicillin/clavulanic acid combination should be administered with caution to patients with impaired liver function.

Adverse reactions from the liver occurred mainly in men and elderly patients and were associated with long-term treatment. Such events have been reported very rarely in children. In all patient groups, signs and symptoms usually occurred during or immediately after treatment, but in some cases they appeared several months after stopping treatment. In general, these phenomena were reversible. Liver side effects can be severe and very rarely fatal. They always occurred in patients with severe concomitant diseases or with the simultaneous use of drugs known to have potential negative effects on the liver (see Section "Adverse Reactions").

Antibiotic-associated colitis, which can range from mild to life-threatening, has been reported with almost all antibacterial drugs (see Adverse Reactions section), so it is important to consider this if patients experience diarrhea during or after antibiotic use. If antibiotic-associated colitis occurs, therapy with Betaclave® should be stopped immediately, consult a doctor and begin appropriate treatment.

The use of agents that inhibit peristalsis is contraindicated in this situation.

It is advisable to periodically monitor the functions of all body systems, including the kidneys, liver and hematopoietic system during long-term therapy.

Rarely, patients taking a combination of amoxicillin/clavulanic acid and oral anticoagulants may experience an increase in prothrombin time. When taking anticoagulants simultaneously, appropriate monitoring is necessary. It may be necessary to adjust the dose of oral anticoagulants to maintain the required level of coagulation (see the section “Interaction with other drugs and other types of interactions” and “Adverse reactions”).

In patients with impaired renal function, the dose should be adjusted according to the degree of renal impairment.

In patients with reduced urine excretion, crystalluria can very rarely be observed, mainly with parenteral administration of the drug. Therefore, to reduce the risk of occurrence during treatment with high doses, it is recommended to ensure a water balance between the liquid drunk and urine excreted (see section “Overdose”).

In patients with bladder catheterization, the patency of catheters should be regularly checked (see section "Overdose").

When treating with amoxicillin, enzymatic reactions with glucose oxidase should be used to determine the level of glucose in urine, since other methods may give false-positive results.

The presence of clavulanic acid in the drug can cause nonspecific binding of IgG and albumin on red blood cell membranes, resulting in a false positive result when performing the Coombs test.

False-positive results from the Bio-Rad Laboratories Platelis Aspergillus EIA test for Aspergillus (cross-reactions with other polysaccharides and polyfuranosates) have been reported in patients treated with amoxicillin/clavulanic acid, and such positive results in patients treated with amoxicillin/clavulanic acid should be interpreted with caution. caution and confirm with other diagnostic methods.

Drug interactions Betaclave

Caution must be exercised when treating patients who are taking oral anticoagulants, since their simultaneous use with Betaclave may enhance the effect of these drugs and cause bleeding. When amoxicillin is used concomitantly with allopurinol, a skin rash may develop. The simultaneous use of Betaclava and probenecid increases the concentration of amoxicillin in the blood serum, while the concentration of clavulanic acid does not change. With the simultaneous use of Betaclava and methotrexate, the concentration of methotrexate in the blood serum increases, as well as its toxicity. The drug reduces the effectiveness of oral hormonal contraceptives.

Betaclave tablets 875 mg+125 mg 14 pcs. in Moscow

Before starting treatment with Betaclave®, it is necessary to collect a detailed history 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 have been reported. The risk of such reactions is highest in patients with a history of hypersensitivity reactions to penicillins. If an allergic reaction occurs, treatment with Betaclave should be discontinued and appropriate alternative therapy should be initiated. In case of serious anaphylactic reactions, the patient should be given epinephrine immediately. Oxygen therapy, intravenous glucocorticosteroids, and airway management including intubation may also be required.

If allergic skin reactions occur, treatment with Betaclave should be discontinued.

If infectious mononucleosis is suspected, Betaclave® should not be used since amoxicillin can cause a measles-like skin rash in patients with this disease, which makes diagnosing the disease difficult.

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

Cases of pseudomembranous colitis have been described when taking antibiotics, 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 antibiotic use. 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, Betaclave® is well tolerated and has the low toxicity characteristic of all penicillins. During long-term therapy with Betaclave®, it is recommended to periodically evaluate renal function, liver and hematopoiesis.

In patients receiving a combination of amoxicillin and clavulanic acid simultaneously with indirect (oral) anticoagulants, an increase in prothrombin time (increase in INR) has been reported in rare cases. When using indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, monitoring of appropriate indicators is necessary. Dosage adjustments of oral anticoagulants may be necessary to maintain the desired effect.

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

In patients with reduced diuresis, crystalluria very rarely occurs, mainly during parenteral therapy. During administration of high doses of amoxicillin, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation (see section "Overdose").

Taking Betaclave® orally leads to a high level of amoxicillin in the urine, which can lead to false-positive results when determining glucose in the urine (for example, Benedict's test, Fehling's test). In this case, it is recommended to use the glucose oxidase method for determining the concentration of glucose in the urine.

Clavulanic acid may cause nonspecific binding of immunoglobulin G and albumin to red blood cell membranes, leading to false-positive Coombs test results.

Drug abuse and dependence

There was no drug dependence of addiction and euphoric reactions associated with the use of the drug Betaclave®.

Impact on the ability to drive vehicles. Wed and fur.:

Since the use of Betaclave® may cause dizziness, it is necessary to warn patients about precautions when driving a vehicle or working with moving mechanisms.