Pharmacological action of Augmentin

Combined preparation of amoxicillin and clavulanic acid - beta-lactamase inhibitor. Acts bactericidal, 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 that produce beta-lactamases): Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Bordetella pertussis, Yersinia enterocolitica, Gardnerella vaginalis, Neisseria meningitidon, Neisseria ducrein formerly Pasteurella), Campylobacter jejuni; anaerobic gram-negative bacteria (including strains producing beta-lactamases): Bacteroides spp., including Bacteroides fragilis.

Clavulanic acid inhibits types II, III, IV and V beta-lactamases, is inactive against type I beta-lactamases produced by Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. Clavulanic acid has a high tropism 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 rapidly absorbed in 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 μg / ml, clavulanic acid - 0.8-2.2 μg / ml, at a dose of 500/125 mg every 12 hours Cmax of amoxicillin - 5.09-7.91 μg / ml, clavulanic acid - 1.19-2.41 μg / ml, at a dose of 500/125 mg every 8 hours Cmax of amoxicillin - 4.94-9.46 μg / ml, clavulanic acid - 1.57-3.23 μg / ml, at a dose of 875/125 mg Cmax amoxicillin - 8.82-14.38 μg / ml, clavulanic acid - 1.21-3.19 μg / ml.

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

The time to reach the maximum inhibitory concentration of 1 μg / 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 taking 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 - 0.9 and 1.07 hours - for amoxicillin, 0.9 and 1.12 hours - for clavulanic acid, respectively. It is 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.

Indications of the active substances of the drug Amoxicillin + Clavulanic acid

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

Prevention of infections in surgery.

Dosing of Augmentin tablets

Inside

in / in.

Doses are given in terms of amoxicillin. The dosage regimen is set individually, depending on the severity of the course and localization of the infection, the sensitivity of the pathogen.

Children under 12 years old - in the form of a suspension, syrup or drops for oral administration.

A single dose is set depending on age: children under 3 months - 30 mg / kg / day in 2 divided doses; 3 months and older - for infections of mild severity - 25 mg / kg / day in 2 doses or 20 mg / kg / day in 3 doses, for severe infections - 45 mg / kg / day in 2 doses or 40 mg / kg / days in 3 doses.

Adults and children over 12 years old or weighing 40 kg or more: 500 mg 2 times / day or 250 mg 3 times / day. For severe infections and respiratory tract infections - 875 mg 2 times / day or 500 mg 3 times / day.

The maximum daily dose of amoxicillin for adults and children over 12 years old is 6 g, for children under 12 years old - 45 mg / kg body weight.

The maximum daily dose of clavulanic acid for adults and children over 12 years old is 600 mg, for children under 12 years old - 10 mg / kg body weight.

In case of difficulty in swallowing in adults, the use of a suspension is recommended.

When preparing a suspension, syrup and drops, water should be used as a solvent.

For intravenous administration, adults and adolescents over 12 years of age are administered 1 g (for amoxicillin) 3 times a day, if necessary - 4 times a day. The maximum daily dose is 6 g. For children 3 months – 12 years old - 25 mg / kg 3 times a day; in severe cases - 4 times a day; for children under 3 months: premature and in the perinatal period - 25 mg / kg 2 times a day, in the postperinatal period - 25 mg / kg 3 times a day.

Duration of treatment - up to 14 days, acute otitis media - up to 10 days.

For the prevention of postoperative infections during operations lasting less than 1 hour, during induction anesthesia, a dose of 1 g intravenous is administered. For longer operations - 1 g every 6 hours during the day. At a high risk of infection, the administration can be continued for several days.

In chronic renal failure, the dose and frequency of administration are adjusted depending on the CC: if CC is more than 30 ml / min, dose adjustment is not required; with CC 10-30 ml / min: inside - 250-500 mg / day every 12 hours; i / v - 1 g, then 500 mg i / v; with CC less than 10 ml / min - 1 g, then 500 mg / day intravenously or 250-500 mg / day orally in one dose. For children, the dose should be reduced in the same way.

Patients on hemodialysis - 250 mg or 500 mg orally at one time or 500 mg IV, an additional 1 dose during dialysis and 1 more dose at the end of dialysis.

Overdose

Symptoms: dysfunction of the gastrointestinal tract and water-electrolyte balance.

Treatment: symptomatic. Hemodialysis is effective.

Interaction

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

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

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

Reduces the effectiveness of oral contraceptives, drugs, during the metabolism of which PABA is formed, ethinylestradiol - the risk of bleeding "breakthrough".

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

Allopurinol increases the risk of skin rashes.

Special instructions

During the 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, the drug should be taken with meals.

The development of superinfection is possible due to the growth of microflora insensitive to it, which requires a corresponding change in antibiotic therapy.

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

After reconstitution, the suspension should be stored for no more than 7 days in the refrigerator, but not frozen.

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

Cases of the development of necrotizing colitis in newborns, in pregnant women with premature rupture of the membranes have been identified.

Since the tablets contain the same amount of clavulanic acid (125 mg), it should be borne in mind that 2 tablets of 250 mg (for amoxicillin) are not equivalent to 1 tablet of 500 mg (for amoxicillin).

Contraindications

Hypersensitivity (including to cephalosporins and other beta-lactam antibiotics), infectious mononucleosis (including the appearance of a measles-like rash), phenylketonuria, episodes of jaundice or liver dysfunction as a result of the use of amoxicillin / clavulanic acid in anamnesis ; 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 effect

From the digestive system: nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, increased activity of "hepatic" transaminases, in rare cases - cholestatic jaundice, hepatitis, liver failure (more often in the elderly, men, with prolonged therapy), pseudomembranous and hemorrhagic colitis (can also develop after therapy), enterocolitis, black "hairy" tongue, darkening of tooth enamel.

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

From the nervous system: dizziness, headache, hyperactivity, anxiety, change in behavior, seizures.

Local reactions: in some cases - phlebitis at the intravenous injection site.

Allergic reactions: urticaria, erythematous rash, rarely - exudative erythema multiforme, anaphylactic shock, angioedema, extremely rarely - exfoliative dermatitis, malignant exudative erythema (Stevens-Johnson syndrome), serous allergic vasculitis, pustular syndrome, acute exomatous disease ...

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