Amoxicillin + clavulanic acid express 875 mg + 125 mg 14 pcs. dispersible tablets

Amoxicillin + clavulanic acid express 875 mg + 125 mg 14 pcs. dispersible tablets

pharmachologic effect

Semi-synthetic antibiotic penicillin + beta-lactamase inhibitor.

Composition and release form Amoxicillin + clavulanic acid express 875 mg + 125 mg 14 pcs. dispersible tablets

Tablets - 1 tablet:

• Active ingredients: amoxicillin trihydrate in terms of amoxicillin - 1004.43 mg (875.00 mg); potassium clavulanate + microcrystalline cellulose (1:1) in terms of clavulanic acid - 297.82 mg (125.00 mg);
• Excipients: microcrystalline cellulose 302 - 1.70 mg; crospovidone - 421.51 mg; vanillin - 1.00 mg; saccharin - 16.11 mg; magnesium stearate - 7.43 mg; tangerine flavor - 9.00 mg, lemon flavor - 11.00 mg.

Dispersible tablets 875 mg+125 mg.

7 tablets each in a blister pack made of polyamide/aluminum/PVC composite material and printed varnished aluminum foil.

2 blister packs along with instructions for use are placed in a cardboard pack.

7, 8 tablets each in a blister pack made of PVC/PVDC film and printed varnished aluminum foil.

1 blister pack with a sachet of silica gel is placed in a package made of a combined material.

2 packages of combined material together with instructions for use are placed in a cardboard pack.

14 tablets of 125 mg + 31.25 mg, 250 mg + 62.5 mg in a polypropylene bottle, sealed with a high-density polyethylene cap with silica gel and tamper evident.

10 tablets of 500 mg + 125 mg in a polypropylene bottle, sealed with a high-density polyethylene cap with silica gel and tamper evident.

5 tablets 875 mg + 125 mg in a polypropylene bottle, sealed with a high-density polyethylene cap with silica gel and tamper evident.

A self-adhesive label is placed on the bottle.

1 bottle along with instructions for medical use is placed in a cardboard pack.

Description of the dosage form

Tablets are from white to light yellow, oval, biconvex, marbling and the presence of isolated brown inclusions are allowed.

Directions for use and doses

For oral administration.

The dosage regimen is set individually depending on the age, body weight, kidney function of the patient, 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 tablet is swallowed whole with a glass of water, or dissolved in half a glass of water (minimum 30 ml), stirring thoroughly before use.

The minimum course of antibacterial therapy is 5 days.

Treatment should not continue for more than 14 days without reviewing the clinical situation. If necessary, it is possible to carry out stepwise therapy (initially, parenteral administration of amoxicillin + clavulanic acid, followed by switching to oral administration).

For adults and children over 12 years of age weighing ≥ 40 kg, the drug is prescribed at 500 mg/125 mg 3 times a day or 875 mg/125 mg 2 times a day.

The maximum daily dose should not exceed 2400 mg/600 mg per day.

For children aged 1 to 12 years with a body weight of 10 to 40 kg, the dosage regimen is set individually based on the clinical situation and the severity of the infection.

The recommended daily dose ranges from 20 mg/5 mg/kg per day to 60 mg/15 mg/kg per day and is divided into 2-3 doses. There are no clinical data on the use of amoxicillin/clavulanic acid in a 4:1 ratio in doses > 40 mg/10 mg/kg per day in children under two years of age. The maximum daily dose for children is 60 mg/15 mg/kg per day.

Low doses of the drug are recommended for the treatment of skin and soft tissue infections, as well as recurrent tonsillitis; high doses of the drug are recommended for the treatment of diseases such as otitis media, sinusitis, lower respiratory tract and urinary tract infections, bone and joint infections.

There is insufficient clinical data to recommend the use of the drug at a dose of more than 40 mg/10 mg/kg/day in 3 divided doses (ratio 4:1) in children under 2 years of age. An approximate dosage regimen for pediatric patients is presented in the table below:

*there is insufficient clinical data to recommend the use of the drug at a dose of more than 40 mg/10 mg/kg/day in 3 doses (ratio 4:1) in children under 2 years of age.

In children aged

Special patient groups

Elderly patients

No dosage regimen adjustment is required. In elderly patients with impaired renal function, the dose should be adjusted as indicated below for adults with impaired renal function.

Patients with impaired renal function

In patients with renal failure, the excretion of clavulanic acid and amoxicillin through the kidneys is slow. Depending on the severity of renal failure, the total dose of Amoxicillin + Clavulanic acid EXPRESS (expressed as amoxicillin dose) should not exceed the amounts presented in the table.

Tablets 875 mg/125 mg should be used only in patients with creatinine clearance more than 30 ml/min, and no dosage adjustment is required.

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

Patients on hemodialysis

Correction of the dosage regimen is based on the maximum recommended dose of amoxicillin, presented in the table.

Patients with liver dysfunction

Treatment is carried out with caution, and liver function is regularly monitored.

There is insufficient data to change the recommended dosage regimen in these patients.

Pharmacodynamics

Mechanism of action

Amoxicillin is a semisynthetic broad-spectrum antibiotic that is active against many gram-positive and gram-negative microorganisms. At the same time, amoxicillin is susceptible to destruction by beta-lactamases, and therefore the spectrum of activity of amoxicillin does not extend to microorganisms that produce these enzymes.

Clavulanic acid is a beta-lactamase inhibitor, structurally related to penicillins, and has the ability to inactivate a wide range of beta-lactamases commonly found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is quite effective against plasmid beta-lactamases, which most often cause bacterial resistance.

The two main mechanisms of resistance to the combination of amoxicillin and clavulanic acid are:

1. Inactivation by bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including various amino acid sequences classified as Ambler classes B, C, and D.
2. Changes in penicillin-binding proteins that reduce the affinity of the antibacterial agent for the target. Reduced outer membrane permeability and efflux pump mechanisms may cause or contribute to resistance, especially among Gram-negative microorganisms.

The presence of clavulanic acid in the drug protects amoxicillin from destruction by enzymes - beta-lactamases, which expands the antibacterial spectrum of amoxicillin.

Pharmacodynamic effects

Below is a classification of microorganisms according to their in vitro sensitivity to the combination of amoxicillin and clavulanic acid.

Bacteria usually susceptible to the combination of amoxicillin and clavulanic acid

Gram-positive aerobes: Bacillus anthracis; Enterococcus faecalis; Listeria monocytogenes; Nocardia asteroids; Streptococcus pyogenes (1,2); Streptococcus agalactiae (1,2); Streptococcus spp. (other beta-hemolytic streptococci) (1,2); Staphylococcus aureus (methicillin sensitive) (1); Staphylococcus saprophyticus (methicillin sensitive).

Coagulase-negative staphylococci (sensitive to methicillin).

Gram-positive anaerobes: Clostridium spp.; Peptococcus niger; Peptostreptococcus magnus; Peptostreptococcus micros; Peptostreptococcus spp.

Gram-negative aerobes: Bordetella pertussis; Haemophilus influenzae(1); Helicobacter pylori; Moraxella catarrhalis(1); Neisseria gonorrhoeae; Pasteurella multocida; Vibrio cholerae.

Gram-negative anaerobes: Bacteroides fragilis; Bacteroides spp.; Capnocytophaga spp.; Eikenella corrodens; Fusobacterium nucleatum; Fusobacterium spp.; Porphyromonas spp.; Prevotella spp.

Other: Borrelia burgdorferi; Leptospira icterohaemorrhagiae; Treponema pallidum.

Bacteria for which acquired resistance to the combination of amoxicillin and clavulanic acid is likely.

Gram-negative aerobes: Escherichia coli(1); Klebsiella oxytoca; Klebsiella pneumoniae1; Klebsiella spp.; Proteus mirabilis; Proteus vulgaris; Proteus spp.; Salmonella spp.; Shigella spp.

Gram-positive aerobes: Corynebacterium spp.; Enterococcus faecium; Streptococcus pneumoniae (1,2).

Viridans group streptococci

Bacteria that are naturally resistant to the combination of amoxicillin and 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 effectiveness of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.

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

Pharmacokinetics

Suction

Both active ingredients of the drug, amoxicillin and clavulanic acid, are quickly and well absorbed when taken orally. Absorption of active substances is optimal if the drug is taken at the beginning of a meal.

The following are data on the pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in different studies when healthy volunteers took it on an empty stomach:

• 1 tablet of the drug amoxicillin + [clavulanic acid] 250 mg + 125 mg (375 mg);
• 2 tablets of the drug amoxicillin + [clavulanic acid] 250 mg + 125 mg (375 mg);
• 1 tablet of the drug amoxicillin + [clavulanic acid] 500 mg + 125 mg (625 mg);
• 2 tablets of the drug amoxicillin + [clavulanic acid] 875 mg + 125 mg (1000 mg);
• 500 mg amoxicillin;
• 125 mg clavulanic acid.

Main pharmacokinetic parameters:

Cmax is the maximum concentration in blood plasma.

Tmax is the time to reach the maximum concentration in the blood plasma. AUC is the area under the “cone-haired” tongue curve.

Disorders of the liver and biliary tract: uncommon - moderate increase in the activity of aspartate aminotransferase and/or alanine aminotransferase (AST and/or ALT). This reaction has been observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown; unknown - hepatitis and cholestatic jaundice. These reactions are observed in patients receiving therapy with penicillin antibiotics and cephalosporins.

Adverse reactions from the liver were 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 completion 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, and deaths have been reported in extremely rare cases. In almost all cases, these were individuals with serious comorbidities or patients receiving concurrent potentially hepatotoxic drugs.

Disorders of the skin and subcutaneous tissues: infrequently - rash, itching, urticaria; rarely - erythema multiforme; unknown - Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis (AGEP), drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

If allergic skin reactions occur, treatment with Amoxicillin + Clavulanic Acid EXPRESS should be discontinued.

Renal and urinary tract disorders: unknown - interstitial nephritis, crystalluria.

Drug interactions

The simultaneous use of Amoxicillin + Clavulanic acid EXPRESS and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore the simultaneous use of the drug Amoxicillin + Clavulanic acid EXPRESS and probenecid may lead to an increase and persistence in the blood concentration of amoxicillin, but not clavulanic acid.

Concomitant use of allopurinol and amoxicillin may increase the risk of allergic skin 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 down the elimination of methotrexate from the body by inhibiting its tubular secretion, therefore, the simultaneous use of Amoxicillin + Clavulanic acid EXPRESS and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, the drug Amoxicillin + Clavulanic acid EXPRESS can affect the intestinal microflora, leading to a decrease in the absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives.

The literature describes rare cases of an increase in the international normalized ratio (INR) in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe the drug Amoxicillin + Clavulanic acid EXPRESS with anticoagulants, the prothrombin time or INR should be carefully monitored when prescribing or discontinuing the drug Amoxicillin + Clavulanic acid EXPRESS; dose adjustment of anticoagulants for oral administration may be required.

In patients receiving mycophenolate mofetil, after starting the combination of amoxicillin and clavulanic acid, there was a decrease in the concentration of the active metabolite, mycophenolic acid, before taking the next dose of the drug by approximately 50%. Changes in this concentration may not accurately reflect overall changes in mycophenolic acid exposure.

Clavulanic acid

Stylab / Catalog / Antibacterial drugs / Clavulanic acid

Clavulanic acid was first discovered in 1974-1975 in the UK. It is produced by the bacteria Streptomyces clavuligerus. Chemically, it is a bicyclic beta-lactam containing neither a penicillin nor a cephalosporin core. Clavulanic acid is active against some bacteria, including legionella , chlamydia, neisseria, streptococci, staphylococci . However, it is not used as a stand-alone antibiotic. The most important property of clavulanic acid is its ability to inhibit beta-lactamases. These are enzymes that protect bacteria from the action of beta-lactam antibiotics . They destroy beta-lactams before they can damage the bacterial cell wall. It is beta-lactamases that provide bacterial resistance to penicillins and cephalosporins. They are produced by both gram-positive and gram-negative bacteria.

Clavulanic acid is used in combination with beta-lactams. With their help, meningitis, endocarditis, sepsis, bronchitis and pneumonia, peritonitis, bacterial diseases of the kidneys, urinary tract and reproductive system, and skin infections are treated. In addition, combined agents are also used for the prevention of diseases, for example, before surgery. Of these, the most famous is “Amoxiclav” (“Panklav”, “Augmentin”, “Verklav”, “Amovikombe”), containing amoxicillin. In veterinary medicine, Amoxiclav is used to treat infections in dogs and cats, as well as pigs, sheep, cows and poultry. It should not be used on rabbits, hamsters, guinea pigs and laying hens, whose eggs are intended for food.

In addition to reducing the activity of beta-lactamases, clavulanic acid enhances the immune response to infection, which increases the effectiveness of combination drugs. Thus, in studies of penicillin-resistant Staphylococcus aureus, amoxicillin reduced the degree of its phagocytosis - the absorption and digestion of bacteria by cells of the immune system. The addition of clavulanic acid, on the contrary, stimulated this process. However, this is only true for bacteria resistant to beta-lactams: studies on strains that do not produce beta-lactamase have not revealed significant differences in the intensity of phagocytosis under the influence of amoxicillin alone and its combination with clavulanic acid.

When taken orally, clavulanic acid is absorbed in the digestive tract and then quickly excreted in the urine. It is also removed from tissues quickly, including after injections. Clavulanic acid is excreted in small amounts in milk.

Clavulanic acid is used in combination with other drugs. Therefore, side effects are usually considered for the drug as a whole, rather than for individual substances. Combination therapy with beta-lactams and clavulanic acid is associated with an increased risk of cholestasis and drug-induced hepatitis occurring during or shortly after treatment. These conditions are usually not life-threatening. There are known cases of allergic reactions caused by clavulanic acid.

The LD50 of clavulanic acid for rats and mice exceeds 2000 mg/kg body weight, which means it is slightly toxic to mammals. Poisoning with this substance causes nausea, diarrhea and abdominal pain. In rare cases, in addition to these symptoms, rash, hyperactivity, or drowsiness were noted. Clavulanic acid does not exhibit genotoxic or carcinogenic properties. However, experiments on rats and mice showed its reproductive toxicity.

In the European Union, the maximum permissible levels of clavulanic acid in food products of animal origin are limited by law. Thus, pork, beef and the fat of these animals should not contain more than 100 mcg/kg of this substance. The content of clavulanic acid in pork and beef liver should not exceed 200 mcg/kg, in kidneys - 400 mcg/kg, in cow's milk - 200 mcg/kg. In the Russian Federation and the EAEU countries, maximum permissible levels of clavulanic acid in food products have not been established.

Literature

1. Amoxicillin + Clavulanic acid. Register of medicines of the Russian Federation.
2. Clavulanic acid. PubChem.
3. Clavulanic Acid. Summary Report (2). Committee For Veterinary Medical Products. EMEA/MRL/776/01-FINAL. February 2001
4. Finlay J, Miller L, Poupard JA. A review of the antimicrobial activity of clavulanate. J Antimicrob Chemother. 2003 Jul;52(1):18-23. Epub 2003 May 29.
5. Dufour V, Millon L, Faucher JF, Bard E, Robinet E, Piarroux R, Vuitton DA, Meillet D. Effects of a short-course of amoxicillin/clavulanic acid on systemic and mucosal immunity in healthy adult humans. Int Immunopharmacol. 2005 May;5(5):917-28.
6. Tortajada Girbés M, Ferrer Franco A, Gracia Antequera M, Clement Paredes A, García Muñoz E, Tallón Guerola M (2008). Hypersensitivity to clavulanic acid in children. Allergol Immunopathol (Madr). 36 (5): 308–10.

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