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); ENT organ infections (sinusitis, tonsillitis, otitis media); Infections of the urogenital system and pelvic organs (pyelonephritis, pyelitis, cystitis, urethritis, prostatitis, cervicitis, salpingitis, salpingoophoritis, tuboovarian abscess, endometritis, bacterial vaginitis, septic abortion, postpartum sepsis, pelviperitonitis, soft chancre, gonorrhea); skin and soft tissue infections (rye, impetigo, secondary infected dermatoses, abscess, phlegmon, wound infection); osteomyelitis; postoperative infections.

The prevention of infections in surgery.

Active ingredient

How to take, the dosage

Intravenously, intravenously.

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

In children under 12 years of age – in the form of suspension, syrup or drops for oral administration. The single dose is established depending on age: children under 3 months – 30 mg/kg/day in 2 doses; 3 months and older – in mild infections 25 mg/kg/day in 2 doses or 20 mg/kg/day in 3 doses, in severe infections – 45 mg/kg/day in 2 doses or 40 mg/kg/day in 3 doses.

Adults and children over 12 years of age or with a body weight of 40 kg or more: 500 mg 2 times/day or 250 mg 3 times/day. In 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 it is 45 mg/kg of body weight.

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

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

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

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

The duration of treatment – up to 14 days, acute otitis media – up to 10 days.

For prevention of postoperative infections during surgeries lasting less than 1 hour during introductory anesthesia it is administered in a dose of 1 g v/v. For longer operations, 1 g every 6 hours during the day. If there is a high risk of infection, administration may be continued for several days.

In chronic renal failure dosage and administration frequency should be adjusted depending on IQ: in IQ over 30 ml/min no dose adjustment is required; in IQ 10-30 ml/min: orally – 250-500 mg/day every 12 hours; by IV – 1 g, then 500 mg by IV; in IQ less than 10 ml/min – 1 g, then 500 mg/day by IV or 250-500 mg/day by IV in one course. For children, doses should be reduced in the same manner.

Patients on hemodialysis – 250 mg or 500 mg orally in a single dose or 500 mg IV, 1 additional dose during dialysis and 1 additional dose at the end of a dialysis session.

Interaction

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

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

It increases the effectiveness of indirect anticoagulants (by suppressing intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). When concomitant use of anticoagulants, it is necessary to monitor blood clotting parameters.

Limits the effectiveness of oral contraceptives, drugs that metabolize PABA, ethinyl estradiol – the risk of bleeding “breakthrough”.

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

Allopurinol increases the risk of skin rash.

Special Instructions

During the course of treatment it is necessary to monitor the hematopoietic, hepatic and renal function.

In order to reduce the risk of gastrointestinal side effects, the drug should be taken with food.

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

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

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

Contraindications

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

With caution

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

Side effects

Digestive system disorders: Nausea, vomiting, diarrhea, gastritis, stomatitis, glossitis, increased activity of liver transaminases, in single cases – cholestatic jaundice, hepatitis, liver failure (more often in elderly, men, with long-term therapy), pseudomembranous and hemorrhagic colitis (can also develop after therapy), enterocolitis, black “hairy” tongue, darkening of tooth enamel.

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

Nervous system disorders: dizziness, headache, hyperactivity, anxiety, behavioral changes, seizures.

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

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

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

Similarities