Amoxicillin+Clavulanic acid, 1 g+0.2 g

A combined preparation of amoxicillin and clavulanic acid – beta-lactamase inhibitor. It acts bactericidally, inhibits the synthesis of the bacterial wall.

Active against aerobic gram-positive bacteria (including strains producing beta-lactamases): Staphylococcus aureus; aerobic gram-negative bacteria: Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis. The following pathogens are sensitive only in vitro: Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp, Listeria monocytogenes; anaerobic Clostridium spp., Peptococcus spp., Peptostreptococcus spp.; and aerobic Gram-negative bacteria (including beta-lactamase-producing strains): Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp, Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus ducreyi, Yersinia multocida (formerly Pasteurella), Campylobacter jejuni; anaerobic Gram-negative bacteria (including beta-lactamase-producing strains): Bacteroides spp. including Bacteroides fragilis.

Clavulanic acid inhibits types II, III, IV and V beta-lactamases, it is not active against type I beta-lactamases produced by Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high tropism to penicillinases, due to which it forms a stable complex with the enzyme, which prevents enzymatic degradation of amoxicillin under the influence of beta-lactamases.

Pharmacokinetics

After oral administration, both components are rapidly absorbed in the gastrointestinal tract. Simultaneous intake of food has no effect on absorption. TCmax is 45 min. After an oral dose of 250/125 mg every 8 hours the Cmax of amoxicillin is 2.18-4.5 µg/ml, clavulanic acid – 0.8-2.2 µg/ml, in a dose of 500/125 mg every 12 hours the Cmax of amoxicillin is 5.09-7.91 µg/ml, clavulanic acid – 1.19-2.41 mcg/mL, at a dose of 500/125 mg every 8 h Cmax of amoxicillin was 4.94-9.46 mcg/mL, clavulanic acid was 1.57-3.23 mcg/mL, at a dose of 875/125 mg Cmax of amoxicillin was 8.82-14.38 mcg/mL, clavulanic acid was 1.21-3.19 mcg/mL.

After intravenous administration at doses of 1000/200 and 500/100 mg, the Cmax of amoxicillin was 105.4 and 32.2 µg/mL, respectively, and of clavulanic acid was 28.5 and 10.5 µg/mL.

The time to reach the maximum inhibitory concentration of 1 µg/mL for amoxicillin is similar when administered in 12 h and 8 h in both adults and children.

Plasma protein binding: amoxicillin – 17-20%, clavulanic acid – 22-30%.

Both components are metabolized in the liver: amoxicillin – by 10% of the administered dose, clavulanic acid – by 50%.

T1/2 after 375 and 625 mg doses is 1 and 1.3 h for amoxicillin, 1.2 and 0.8 h for clavulanic acid, respectively. T1/2 after intravenous administration in doses of 1200 and 600 mg – 0.9 and 1.07 hours for amoxicillin, 0.9 and 1.12 hours for clavulanic acid, respectively. Excreted mainly by the kidneys (glomerular filtration and tubular secretion): 50-78 and 25-40% of the administered dose of amoxicillin and clavulanic acid are excreted unchanged within the first 6 h after administration, respectively.

Indications

Treatment of infectious and inflammatory diseases caused by sensitive pathogens: lower respiratory tract infections (bronchitis, pneumonia, pleural empyema, lung abscess); infections of the ENT organs (sinusitis, tonsillitis, otitis media); infections of the genitourinary system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, cervicitis, salpingitis, salpingoophoritis, tubo-ovarian abscess, endometritis, bacterial vaginitis, septic abortion, postpartum sepsis, pelvioperitonitis, chancroid, gonorrhea); infections of the skin and soft tissues (erysipelas, impetigo, secondary infected dermatoses, abscess, cellulitis, wound infection); osteomyelitis; postoperative infections.

Prevention of infections in surgery.

Pharmacological effect

A combined drug of amoxicillin and clavulanic acid, a beta-lactamase inhibitor. It has a bactericidal effect and inhibits the synthesis of the bacterial wall.

Active against aerobic gram-positive bacteria (including strains producing beta-lactamases): Staphylococcus aureus; aerobic gram-negative bacteria: Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis. The following pathogens are sensitive only in vitro: Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus anthracis, Streptococcus pneumoniae, Streptococcus viridans, Enterococcus faecalis, Corynebacterium spp., Listeria monocytogenes; anaerobic Clostridium spp., Peptococcus spp., Peptostreptococcus spp.; as well as aerobic gram-negative bacteria (including strains producing beta-lactamases): Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus ducreyi, Yersinia multocida (formerly Pasteurella), Campylobacter jejuni; anaerobic gram-negative bacteria (including beta-lactamase producing strains): Bacteroides spp., including Bacteroides fragilis.

Clavulanic acid inhibits types II, III, IV and V beta-lactamases; it is not active against type I beta-lactamases produced by Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high affinity for penicillinases, due to which it forms a stable complex with the enzyme, which prevents the enzymatic degradation of amoxicillin under the influence of beta-lactamases.

Pharmacokinetics

After oral administration, both components are quickly absorbed into the gastrointestinal tract. Concomitant food intake does not affect absorption. TCmax – 45 min. After oral administration at a dose of 250/125 mg every 8 hours, Cmax of amoxicillin – 2.18-4.5 mcg/ml, clavulanic acid – 0.8-2.2 mcg/ml, at a dose of 500/125 mg every 12 hours, Cmax of amoxicillin – 5.09-7.91 mcg/ml, clavulanic acid – 1.19-2.41 mcg/ml, at a dose of 500/125 mg every 8 hours Cmax of amoxicillin – 4.94-9.46 mcg/ml, clavulanic acid – 1.57-3.23 mcg/ml, at a dose of 875/125 mg Cmax of amoxicillin – 8.82-14.38 mcg/ml, clavulanic acid – 1.21-3.19 µg/ml.

After intravenous administration in doses of 1000/200 and 500/100 mg, the Cmax of amoxicillin was 105.4 and 32.2 μg/ml, respectively, and clavulanic acid was 28.5 and 10.5 μg/ml.

The time to reach a maximum inhibitory concentration of 1 mcg/ml for amoxicillin is similar when used after 12 hours and 8 hours in both adults and children.

Plasma protein binding: amoxicillin – 17-20%, clavulanic acid – 22-30%.

Both components are metabolized in the liver: amoxicillin – by 10% of the administered dose, clavulanic acid – by 50%.

T1/2 after administration at a dose of 375 and 625 mg – 1 and 1.3 hours for amoxicillin, 1.2 and 0.8 hours for clavulanic acid, respectively. T1/2 after intravenous administration at a dose of 1200 and 600 mg is 0.9 and 1.07 hours for amoxicillin, 0.9 and 1.12 hours for clavulanic acid, respectively. Excreted mainly by the kidneys (glomerular filtration and tubular secretion): 50-78 and 25-40% of the administered dose of amoxicillin and clavulanic acid are excreted, respectively, unchanged during the first 6 hours after administration.

Special instructions

During a course of treatment, it is necessary to monitor the state of the function of the hematopoietic organs, liver and kidneys.

In order to reduce the risk of side effects from the gastrointestinal tract, you should take the drug with meals.

It is possible that superinfection may develop due to the growth of microflora that is insensitive to it, which requires a corresponding change in antibacterial therapy.

May give false positive results when determining glucose in urine. In this case, it is recommended to use the glucose oxidant method for determining the concentration of glucose in the urine.

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

Active ingredient

Amoxicillin, Clavulanic acid

Composition

Powder for preparing a solution for intravenous administration 1 vial:

Contraindications

Hypersensitivity to the components of the drug (including cephalosporins and other beta-lactam antibiotics); infectious mononucleosis (including with the appearance of a measles-like rash); phenylketonuria; a history of episodes of jaundice or impaired liver function as a result of the use of amoxicillin/clavulanic acid; CC less than 30 ml/min (for tablets 875 mg/125 mg).

With caution

Pregnancy, lactation, severe liver failure, gastrointestinal diseases (including a history of colitis associated with the use of penicillins), chronic renal failure.

Side Effects

From the digestive system: nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, increased activity of liver transaminases, in isolated cases – cholestatic jaundice, hepatitis, liver failure (more often in the elderly, men, with long-term therapy), pseudomembranous and hemorrhagic colitis (can also develop after therapy), enterocolitis, black “hairy” tongue, darkening of the teeth enamels.

From the hematopoietic organs: reversible increase in prothrombin time and bleeding time, thrombocytopenia, thrombocytosis, eosinophilia, leukopenia, agranulocytosis, hemolytic anemia.

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

Local reactions: in some cases – phlebitis at the site of intravenous administration.

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

Other: candidiasis, development of superinfection, interstitial nephritis, crystalluria, hematuria.

Interaction

Antacids, glucosamine, laxatives, aminoglycosides slow down and reduce absorption; ascorbic acid increases absorption.

Bacteriostatic antibiotics (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) have an antagonistic effect.

Increases the effectiveness of indirect anticoagulants (suppressing intestinal microflora, reduces the synthesis of vitamin K and the prothrombin index). When taking anticoagulants simultaneously, it is necessary to monitor blood clotting indicators.

Reduces the effectiveness of oral contraceptives, drugs, during the metabolism of which PABA is formed, ethinyl estradiol – the risk of breakthrough bleeding.

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

Allopurinol increases the risk of developing skin rashes.

Manufacturer

Kraspharma PJSC, Russia