Amoxiclav is a combination drug that belongs to the group of beta-lactam antibiotics. The therapeutic effects are provided by the active substances - amoxicillin - one of the best penicillin antibiotics and clavulanic acid - the most powerful known beta-lactamase inhibitor.
The combination of these substances leads to the appearance of special properties of Amoxiclav:
- irreversible blockade of β-lactamases of microorganisms, which allows amoxicillin to have an antibacterial effect even on resistant pathogens;
- high bioavailability;
- penetrates well into most tissues and body fluids, creating a high concentration that is necessary to destroy sensitive pathogenic bacteria.
The mechanism of action of amoxicillin in Amoxiclav is bactericidal activity - disruption of the synthesis of a component of the bacterial cell wall, which causes their dissolution. Clavulanic acid is a β-lactam inhibitor and exhibits equal activity against both gram-positive and gram-negative bacteria. Protects amoxicillin from destruction by enzymes - β-lactamases, thereby expanding the spectrum of action of amoxicillin.
Amoxiclav is manufactured by the pharmaceutical company Lek Pharmaceuticals dd in Slovenia. There are various dosage forms of the drug on the Ukrainian pharmaceutical market. This is an important point in choosing Amoxiclav when prescribing it to patients of different age categories and severity of the disease.
Advantages of using Amoxiclav:
- predictable effectiveness and non-toxicity of penicillins;
- wider spectrum of action, compared with amoxicillin and oral cephalosporins due to the presence of clavulanic acid;
- applicable in all age groups;
- food intake does not affect the absorption of the drug.
Among dosage forms, the ease of use of Amoxiclav suspension should be noted. The drug is equipped with a measuring syringe for dosing accuracy. The possibility of using the suspension three times in children minimizes the development of resistance and meets international requirements for rational antibiotic therapy.
Indications
Amoxiclav is intended for the treatment of bacterial infections caused by microorganisms sensitive to the drug:
- severe infections of the throat, nose, and ear (such as mastoiditis, peritonsillar infections, epiglotitis, and sinusitis with associated severe systemic signs and symptoms)
- exacerbation of chronic bronchitis (after confirmation of diagnosis)
- community-acquired pneumonia
- cystitis;
- pyelonephritis;
- infections of the skin and soft tissues, including bacterial cellulitis, animal bites, severe dentoalveolar abscesses with widespread cellulitis;
- infections of bones and joints, including osteomyelitis;
- intra-abdominal infections;
- genital infections in women.
Prevention of bacterial infections during major surgical interventions in the following areas:
- gastrointestinal tract;
- pelvic organs;
- chairman and neck;
- biliary tract.
When prescribing antibacterial drugs, one should be guided by the rules for their proper use.
Indications for use of Amoxiclav
The use of the drug is so widespread that some doctors starting their therapeutic practice prescribe it at every opportunity. In the situation with diseases of the otolaryngology organs, this is:
- otitis, including purulent;
- tonsillitis;
- sinusitis;
- pharyngolaryngitis.
When the urinary system is affected, Amoxiclav can also be prescribed. These diseases include chronic cystitis, prostatitis, and urethritis.
Diseases of the respiratory system are rarely treated without amoxicillin. For bronchitis of bacterial etiology and pneumonia, this particular drug is used. In addition, the antibiotic has shown its effectiveness against:
- infections affecting bones and connective tissue;
- soft tissue diseases caused by bacterial infection;
- cholecystitis;
- diseases of the pelvic organs.
Some types of surgery require the patient to take a course of antibiotics to prevent superinfection.
Compound
Active ingredients: amoxicillin, clavulanic acid;
1 bottle contains 1000 mg of amoxicillin in the form of sodium salt and 200 mg of clavulanic acid in the form of potassium salt.
Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotics) that inhibits one or more enzymes, often referred to as penicillin binding proteins (PBPs), in the biosynthetic metabolism of bacterial peptidoglycan, an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, resulting in cell lysis and death.
Amoxicillin is sensitive to the breakdown of beta-lactamases produced by resistant bacteria; therefore, the spectrum of activity of amoxicillin as monotherapy does not include organisms that produce these enzymes.
Clavulanic acid is a beta-lactam, structurally related to penicillins. It disables some beta-lactamase enzymes, thereby preventing the inactivation of amoxicillin. Clavulanic acid as monotherapy does not have a clinically useful antibacterial effect.
Directions for use and doses
Doses are given as amoxicillin/clavulanic acid content unless the dose of the individual component is indicated.
When choosing a dose of a drug to treat a specific infection, you must consider:
- expected pathogens and their expected sensitivity to antibacterial substances (see section “Peculiarities of application”);
- severity and location of infection;
- the patient's age, weight, and renal function status, as described below.
If necessary, alternative forms of Amoxiclav ® can be used (for example, with higher doses of amoxicillin and/or a different ratio of amoxicillin and clavulanic acid).
These dosage forms of Amoxiclav ® can be used in a daily dose of up to 3000 mg of amoxicillin and 600 mg of clavulanic acid. If it is necessary to use a higher dose of amoxicillin, a drug with a different amoxicillin/clavulanic acid ratio should be prescribed to avoid ultra-high daily doses of clavulanic acid.
The duration of treatment is determined by the doctor individually. Some infections (such as osteomyelitis) require long-term treatment. The duration of treatment should not exceed 14 days without assessing the results of use and the clinical picture (see Section “Peculiarities of use”).
Dosage for adults and children weighing ≥ 40 kg
Standard dose is 1000 mg/200 mg every 8:00.
Prevention of complications during surgical interventions.
For operations lasting less than 1 hour, the recommended dose is from 1000 mg / 200 mg to 2000 mg / 200 mg during induction of anesthesia (a dose of 2000 mg / 200 mg can be achieved using the appropriate intravenous form of the drug).
For operations lasting more than 1 hour, the recommended dose ranges from 1000 mg / 200 mg to 2000 mg / 200 mg when injecting anesthesia, a dose of 1000 mg / 200 mg can be administered 3 times within 24 hours.
If there are clinical signs of infection during surgery, a course of treatment with intravenous or oral administration of the drug should be prescribed in the postoperative period.
Dosage for children weighing <40 kg.
Children over 3 months: 25 mg/5 mg/kg every 8:00.
Children under 3 months of age or weighing less than 4 kg: 25 mg/5 mg/kg body weight every 12:00.
Features of drug administration.
Amoxiclav ® is administered by intravenous injection (stream) or by periodic infusion (drip). The drug cannot be administered intramuscularly.
For children under 3 months of age, Amoxiclav ® is prescribed only as an intravenous infusion.
Treatment can begin with the administration of Amoxiclav ® and continue with oral forms.
Preparation of solution for intravenous injection.
500 mg / 100 mg dissolve the contents of the vial in 10 ml of water for injection (final volume - 10.5 ml)
1000 mg / 200 mg dissolve the contents of the vial in 20 ml of water for injection (final volume - 20.9 ml).
Reconstituted solutions have a yellowish (pale straw) color. Use only clear solutions. The solution should be used within 20 minutes after recovery, inject the drug slowly over 3-4 minutes directly into a vein or through a catheter, drip-wise.
Preparation of solution for intravenous infusion
Reconstituted as shown above, the solution of 500 mg / 100 mg is then added without delay to 50 ml of infusion fluid or the solution of 1000 mg / 200 mg - up to 100 ml of infusion fluid (it is better to use a mini-container or burette). The infusion should be carried out over 30-40 minutes.
The solution for infusion is chemically and physically stable for 2-3 hours at a temperature of 25°C or 8:00 at a temperature of 5°C. From a microbiological point of view, it is better to administer the prepared solution immediately.
Various solvents can be used for intravenous infusions. A satisfactory concentration of the antibiotic is maintained at 5°C and at room temperature (25°C) in the recommended volumes specified in the instructions.
Amoxiclav: instructions for adults
The main rule of taking antibiotics is to follow the prescribed course of treatment. The mistake patients make is that at the first sign of a retreat in the symptoms of the disease, many give up treatment, believing that long-term antibiotic therapy causes irreparable damage to all body systems. However, in fact, this is precisely how resistant colonies of microorganisms are formed, which over time adapt to life even under the influence of an antibiotic. For example, for cystitis, a one-time dose of the drug relieves pain and pain already on the second day of treatment. But this is only the absence of symptoms.
The bacteria that caused this damage to the urinary system have not yet died, they have only lost their ability to provoke unpleasant symptoms of the disease. Stopping treatment early will allow the surviving bacteria to evolve so that the next time taking the same drug does not prevent them from multiplying and being active.
A single and daily dose is prescribed by the attending physician, because it depends on the severity of the disease and the patient’s condition. As a rule, the maximum dosage of Amoxiclav in the amount of 875 + 125 does not exceed twice the dose of the drug per day with an interval of 12 hours. To achieve maximum effect, you need to stick to the same hour of taking the drug. The duration of the course, regardless of the single dose and the number of prescribed doses, cannot be shorter than 7 days.
Features of application
Use during pregnancy or breastfeeding
Pregnancy. Reproductive studies in animals of oral and parenteral forms of Amoxiclav ® did not reveal any teratogenic effects. One study in women with premature rupture of membranes reported that prophylactic use of the drug may be associated with an increased risk of necrotizing enterocolitis in the newborn. As with the use of other medicines, the use of Amoxiclav ® should be avoided during pregnancy, especially in the first trimester, unless, in the opinion of a doctor, such use is necessary.
Breastfeeding period. Both active components of the drug are excreted into breast milk (there is no information on the effect of clavulanic acid on a breastfed infant). Accordingly, a breastfed infant may develop diarrhea and fungal infection of the mucous membranes, so breastfeeding should be stopped. The possibility of allergic reactions should be taken into account. Amoxiclav ® can be used during breastfeeding only when, in the opinion of the doctor, the benefits of use will outweigh the risks.
Children
Use for children from the first days of life.
The ability to influence the reaction rate when driving vehicles or other mechanisms
Studies on the ability of the drug to influence the reaction rate when driving vehicles or other mechanisms have not been conducted. However, undesirable effects may occur (such as allergic reactions, dizziness, convulsions), which may affect the ability to drive a car or use other machinery (see section “Adverse Reactions”).
Overdose
Symptoms. Symptoms of gastrointestinal upset and fluid and electrolyte imbalance may occur. Crystalluria associated with taking amoxicillin has been observed, which in some cases led to renal failure (see section "Peculiarities of use").
In patients with impaired renal function and in patients taking high doses of the drug, seizures may occur.
Deposition of amoxicillin in bladder catheters has been recorded, mainly after administration in high doses. The patency of catheters should be regularly checked (see Section “Peculiarities of Application”).
Treatment. Gastrointestinal disorders can be treated symptomatically with attention to fluid/electrolyte balance.
Amoxicillin/clavulanic acid can be removed from the bloodstream using hemodialysis.
Amoxiclav 400mg+57mg/5ml 17.5g 70ml powder for oral suspension
pharmachologic effect
Antibiotic - semi-synthetic penicillin + beta-lactamase inhibitor.
Composition and release form Amoxiclav 400 mg + 57 mg/5 ml 17.5 g 70 ml powder for the preparation of suspension for oral administration
Powder for the preparation of a suspension for oral administration - 5 ml of suspension:
- active ingredients: amoxicillin (in the form of trihydrate) - 400 mg; clavulanic acid (in the form of potassium salt) - 57 mg;
- excipients: citric acid (anhydrous) - 2.694 mg; sodium citrate (anhydrous) - 8.335 mg; MCC and carmellose sodium - 28.1 mg; xanthan gum - 10 mg; colloidal silicon dioxide - 16.667 mg; silicon dioxide - 0.217 g; wild cherry flavor - 4 mg; lemon flavoring - 4 mg; sodium saccharinate - 5.5 mg; mannitol - up to 1250 mg.
Powder for the preparation of suspension for oral administration, 400 mg + 57 mg/5 ml. Primary packaging - 8.75 g (35 ml of ready-made suspension), 12.50 g (50 ml of ready-made suspension), 17.50 g (70 ml of ready-made suspension) or 35.0 g (140 ml of ready-made suspension) powder in a bottle dark glass with a screw cap made of HDPE with a control ring and a gasket inside the cap. Or 17.5 g (70 ml of ready-made suspension) in a dark glass bottle with a ring mark (70 ml) with a HDPE screw cap with a control ring and a gasket inside the cap.
Secondary packaging - 1 fl. together with a graduated dosage pipette in a cardboard box.
Description of the dosage form
Powder for oral suspension: white to yellowish-white powder. The finished suspension is an almost white to yellow homogeneous suspension.
Directions for use and doses
Inside
The daily dose of suspensions is 125+31.25 mg/5 ml and 250+62.5 mg/5 ml (to facilitate correct dosing, a dosage pipette is inserted into each package of suspensions 125+31.25 mg/5 ml and 250+62.5 mg/5 ml, graduated at 5 ml, with a scale of division of 0.1 ml or a dosing spoon with a capacity of 5 ml, with ring marks in the cavity at 2.5 and 5 ml).
Newborns and children up to 3 months - 30 mg/kg/day (for amoxicillin), divided into 2 doses (every 12 hours).
Dosing of the drug Amoxiclav® with a dosing pipette - calculation of single doses for the treatment of infections in newborns and children up to 3 months (Table 3).
Table 3
| Body weight, kg | 2 | 2,2 | 2,4 | 2,6 | 2,8 | 3 | 3,2 | 3,4 | 3,6 | 3,8 | 4 | 4,2 | 4,4 | 4,6 | 4.8 |
| Suspension 156.25, ml (2 times a day) | 1,2 | 1,3 | 1,4 | 1,6 | 1,7 | 1,8 | 1,9 | 2 | 2,2 | 2,3 | 2,4 | 2,5 | 2,6 | 2,8 | 2,9 |
| Suspension 312.5, ml (2 times a day) | 0,6 | 0,7 | 0,7 | 0,8 | 0,8 | 0,9 | 1 | 1 | 1,1 | 1,1 | 1,2 | 1,3 | 1,3 | 1,4 | 1,4 |
Children over 3 months - from 20 mg/kg for mild and moderate infections to 40 mg/kg for severe infections and lower respiratory tract infections, otitis media, sinusitis (amoxicillin) per day, divided into 3 doses (every 8 h).
Dosing of the drug Amoxiclav® with a dosing pipette - calculation of single doses for the treatment of mild and moderate infections in children over 3 months (at the rate of 20 mg/kg/day (for amoxicillin) (Table 4).
Table 4
| Body weight, kg | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 |
| Suspension 156.25, ml (3 times a day) | 1,3 | 1,6 | 1,9 | 2,1 | 2,4 | 2,7 | 2,9 | 3,2 | 3,5 | 3,7 | 4 | 4,3 | 4,5 | 4,8 | 5,1 | 5,3 | 5,6 | 5,9 |
| Suspension 312.5, ml (3 times a day) | 0,7 | 0,8 | 0,9 | 1,1 | 1,2 | 1,3 | 1,5 | 1,6 | 1,7 | 1,9 | 2 | 2,1 | 2,3 | 2,4 | 2,5 | 2,7 | 2,8 | 2,9 |
| Body weight, kg | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 | 33 | 34 | 35 | 36 | 37 | 38 | 39 | |
| Suspension 156.25, ml (3 times a day) | 6,1 | 6,4 | 6,7 | 6,9 | 7,2 | 7,5 | 7,7 | 8 | 8,3 | 8,5 | 8,8 | 9,1 | 9,3 | 9,6 | 9,9 | 10,1 | 10,4 | |
| Suspension 312.5, ml (3 times a day) | 3,1 | 3,2 | 3,3 | 3,5 | 3,6 | 3,7 | 3,9 | 4 | 4,1 | 4,3 | 4,4 | 4,5 | 4,7 | 4,8 | 4,9 | 5,1 | 5,2 |
Dosing of the drug Amoxiclav® with a dosing pipette - calculation of single doses for the treatment of severe infections in children over 3 months (at the rate of 40 mg/kg/day (for amoxicillin) (Table 5).
Table 5
| Body weight, kg | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 |
| Suspension 156.25, ml (3 times a day) | 2,7 | 3,2 | 3,7 | 4,3 | 4,8 | 5,3 | 5,9 | 6,4 | 6,9 | 7,5 | 8 | 8,5 | 9,1 | 9,6 | 10,1 | 10,7 | 11,2 | 11,7 |
| Suspension 312.5, ml (3 times a day) | 1,3 | 1,6 | 1,9 | 2,1 | 2,4 | 2,7 | 2,9 | 3,2 | 3,5 | 3,7 | 4 | 4,3 | 4,5 | 4,8 | 5,1 | 5,3 | 5,6 | 5,9 |
| Body weight, kg | 23 | 24 | 25 | 26 | 27 | 28 | 29 | 30 | 31 | 32 | 33 | 34 | 35 | 36 | 37 | 38 | 39 | |
| Suspension 156.25, ml (3 times a day) | 12,3 | 12,8 | 13,3 | 13,9 | 14,4 | 14,9 | 15,5 | 16 | 16,5 | 17,1 | 17,6 | 18,1 | 18,7 | 19,2 | 19,7 | 20,3 | 20,8 | |
| Suspension 312.5, ml (3 times a day) | 6,1 | 6,4 | 6,7 | 6,9 | 7,2 | 7,5 | 7,7 | 8 | 8,3 | 8,5 | 8,8 | 9,1 | 9,3 | 9,6 | 9,9 | 10,1 | 10,4 |
Dosing of the drug Amoxiclav® with a dosing spoon (in the absence of a dosing pipette) - recommended doses of suspensions depending on the child’s body weight and the severity of the infection (Table 6).
Table 6
| Body weight, kg | Age (approx.) | Mild/moderate course | Severe course | ||
| 125+31.25 mg/5 ml | 250+62.5 mg/5 ml | 125+31.25 mg/5 ml | 250+62.5 mg/5 ml | ||
| 5–10 | 3–12 months | 3 × 2.5 ml (½ spoon) | 3 × 1.25 ml | 3 × 3.75 ml | 3 × 2 ml |
| 10–12 | 1–2 years | 3 × 3.75 ml | 3 × 2 ml | 3 × 6.25 ml | 3 × 3 ml |
| 12–15 | 2–4 years | 3 × 5 ml (1 spoon) | 3 × 2.5 ml (½ spoon) | 3 × 7.5 ml (1½ spoons) | 3 × 3.75 ml |
| 15–20 | 4–6 years | 3 × 6.25 ml | 3 × 3 ml | 3 × 9.5 ml | 3 × 5 ml (1 spoon) |
| 20–30 | 6–10 years | 3 × 8.75 ml | 3 × 4.5 ml | — | 3 × 7 ml |
| 30–40 | 10–12 years | — | 3 × 6.5 ml | — | 3 × 9.5 ml |
| ≥40 | ≥12 years | Amoxiclav® tablets | |||
Daily dose of suspension 400 mg+57 mg/5 ml
The dose is calculated per kg of body weight depending on the severity of the infection. From 25 mg/kg - for mild and moderate infections to 45 mg/kg - for severe infections and lower respiratory tract infections, otitis media, sinusitis (in terms of amoxicillin) per day, divided into 2 doses.
To facilitate correct dosing, a dosage pipette is inserted into each package of the 400 mg + 57 mg/5 ml suspension, graduated simultaneously into 1, 2, 3, 4, 5 ml and into 4 equal parts.
Suspension 400 mg+57 mg/5 ml is used in children over 3 months.
Table 7
Recommended dose of suspension depending on the child’s body weight and severity of infection
| Body weight, kg | Age (approx.) | Recommended dose, ml | |
| Severe course | Moderate course | ||
| 5–10 | 3–12 months | 2×2,5 | 2×1,25 |
| 10–15 | 1–2 years | 2×3,75 | 2×2,5 |
| 15–20 | 2–4 years | 2×5 | 2×3,75 |
| 20–30 | 4 years - 6 years | 2×7,5 | 2×5 |
| 30–40 | 6–10 years | 2×10 | 2×6,5 |
Exact daily doses are calculated based on the child's body weight, not his age.
The maximum daily dose of amoxicillin is 6 g for adults and 45 mg/kg for children.
The maximum daily dose of clavulanic acid (in the form of potassium salt) is 600 mg for adults and 10 mg/kg for children.
In patients with impaired renal function, the dose should be adjusted based on the maximum recommended dose of amoxicillin.
Patients with creatinine Cl >30 ml/min do not require any dose adjustment.
Adults and children weighing more than 40 kg (the indicated dosage regimen is used for moderate and severe infections)
For patients with creatinine Cl 10-30 ml/min - 500/125 mg 2 times a day.
With Cl creatinine
For patients on hemodialysis, the recommended dose is 500/125 mg every 24 hours, plus 500/125 mg during dialysis and another dose at the end of dialysis (since serum concentrations of amoxicillin and clavulanic acid are reduced).
Children weighing less than 40 kg
With creatinine Cl 10–30 ml/min, the recommended dose is 15/3.75 mg/kg 2 times a day (maximum 500/125 mg 2 times a day).
With Cl creatinine
For hemodialysis, the recommended dose is 15/3.75 mg/kg once a day. Before hemodialysis - 15/3.75 mg/kg. To restore appropriate concentrations of the drug in the blood, it is necessary to take another dose of 15/3.75 mg/kg after hemodialysis.
The course of treatment is 5–14 days. The duration of treatment is determined by the attending physician. Treatment should not continue for more than 14 days without repeated medical examination.
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 this enzyme.
Clavulanic acid is a beta-lactamase inhibitor, structurally related to penicillins, and has the ability to inactivate a wide range of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid is sufficiently effective against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against type I chromosomal beta-lactamases, which are not inhibited by clavulanic acid.
The presence of clavulanic acid in the drug protects amoxicillin from destruction by enzymes - beta-lactamases, which expands the antibacterial spectrum of amoxicillin.
Below is the activity of the combination of amoxicillin and clavulanic acid in vitro.
Grampore-positive aerobes: Bacillus Anthracis, Enterococcus Faecalis, Listeria MonocyTogenes, NoCardia Asteroides, Streptococcus Pyogenes1,2, Streptococcus Agalactiae1,2, other beta-heemolytic statococci1, 2, Staphylococcus aureus (sensitive to methicillin) 1, Staphylococcus saprophyticus (sensitive to methicillin), coagulase-negative staphylococci (sensitive to methicillin).
Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae1, Helicobacter pylori, Moraxella catarrhalis1, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.
Other: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.
Gram-positive anaerobes: species of the genus Clostridium, Peptococcus niger, Peptostrepiococcus magnus, Peptostreptococcus micros, species of the genus Pepto streptococcus.
Gram-negative anaerobes: Bcicteroides fragilis, species of the genus Bacteroides, species of the genus Capnocytophaga, Eikenella corrodens, Fusobacterium nucleatum, species of the genus Fusobacterium, species of the genus Porphyromonas, species of the genus Prevotella.
Bacteria for which acquired resistance to the combination of amoxicillin and clavulanic acid is likely
Gram-negative aerobes: Escherichia coli1, Klebsiella oxytoca, Klebsiella pneumoniae, species of the genus Klebsiella, Proteus mirabilis, Proteus vulgaris, species of the genus Proteus, species of the genus Salmonella, species of the genus Shigella. Streptococcus pneumoniae1,2, streptococci of the Viridans group.
Gram-positive aerobes: species of the genus Corynebacterium, Enterococcus faecium.
Bacteria that are naturally resistant to the combination of amoxicillin and clavulanic acid
Gram-negative aerobes: species of the genus Acinetobacter, Citrobacter freundii, species of the genus Enterobacter, Hafhia alvei, Legionella pneumophila, Morganella morganii, species of the genus Providencia, species of the genus Pseudomonas, species of the genus Serratia, Stenotrophomonas maltophilia, Yersinia enterocolitica.
Other: Chlamydia pneumoniae, Chlamydia psittaci, species of the genus Chlamydia, Coxiella burnetii, species of the genus Mycoplasma.
1For these bacteria, the clinical effectiveness of the combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.
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
The active ingredients of the drug are quickly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of active ingredients is optimal when the drug is used with food.
The following are the pharmacokinetic parameters of amoxicillin and clavulanic acid after administration at a dose of 45 mg/6.4 mg/kg, divided into two doses, by patients under 12 years of age.
Average value of pharmacokinetic parameters
| Cmax (mg/ml) | T max (h) | AUC (mg in h/l) | T1/2 (h) | |
| Amoxicillin | 11,99±3,28 | 1,0 (1,0-2,0) | 35,2±5,0 | 1,22±0,28 |
| Clavulanic acid | 5,49±2,71 | 1,0 (1,0-2,0) | 13,26±5,88 | 0,99±0,14 |
- Cmax - maximum concentration in blood plasma;
- Tmax is the time to reach the maximum concentration in the blood plasma;
- AUC—area under the concentration-time curve;
- T1/2 - half-life.
Metabolism
About 10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic acid). Clavulanic acid in the human body undergoes intensive metabolism with the formation of 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and is excreted by the kidneys, through the gastrointestinal tract, and also with exhaled air in the form of carbon dioxide.
Distribution
As with intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are found in various tissues and interstitial fluid (gallbladder, abdominal tissue, skin, adipose and muscle tissue, synovial and peritoneal fluids, bile, purulent discharge) .
Amoxicillin and clavulanic acid have a weak degree of binding to plasma proteins. Studies have shown that about 25% of the total amount of clavulanic acid and 18% of amoxicillin in the blood plasma is bound to plasma proteins.
The volume of distribution is approximately 0.3-0.4 L/kg for amoxicillin and approximately 0.2 L/kg for clavulanic acid. Amoxicillin and clavulanic acid do not penetrate the blood-brain barrier when the meninges are not inflamed. Amoxicillin (like most penicillins) is excreted in breast milk.
Trace amounts of clavulanic acid may also be found in breast milk. With the exception of the possibility of sensitization, diarrhea and candidiasis of the oral mucosa, there are no other known negative effects of amoxicillin and clavulanic acid on the health of breastfed infants.
Animal reproductive studies have shown that amoxicillin and clavulanic acid cross the placental barrier. However, no negative effects on the fetus were detected.
Removal
Amoxicillin is eliminated primarily by the kidneys, while clavulanic acid is eliminated through both renal and extrarenal mechanisms. After a single oral dose of 875 mg/125 mg or 500 mg/125 mg, approximately 60-70% of amoxicillin and 40-65% of clavulanic acid are excreted unchanged by the kidneys during the first 6 hours. The average half-life (T1/2) of amoxicillin/clavulanic acid is approximately 1 hour, and the average total clearance is approximately 25 L/h in healthy patients. In various studies, it was found that amoxicillin excretion by the kidneys within 24 hours is approximately 50-85%, clavulanic acid - 27-60%. The largest amount of clavulanic acid is excreted during the first 2 hours after administration.
The pharmacokinetics of amoxicillin/clavulanic acid does not depend on the gender of the patient.
Patients with impaired renal function
The total clearance of amoxicillin/clavulanic acid decreases in proportion to the decrease in renal function. The decrease in clearance is more pronounced for amoxicillin than for clavulanic acid, because Most amoxicillin is excreted by the kidneys. Doses of the drug for renal failure should be selected taking into account the undesirability of amoxicillin accumulation while maintaining normal levels of clavulanic acid.
Patients with liver dysfunction
In patients with impaired liver function, the drug is used with caution. It is necessary to constantly monitor liver function.
Both components are removed by hemodialysis and minor amounts by peritoneal dialysis.
Indications for use Amoxiclav 400mg+57mg/5ml 17.5g 70ml powder for the preparation of suspension for oral administration
Infections caused by sensitive strains of microorganisms:
- upper respiratory tract and ENT organs (including acute and chronic sinusitis, acute and chronic otitis media, retropharyngeal abscess, tonsillitis, pharyngitis);
- lower respiratory tract (including acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia);
- urinary tract (eg cystitis, urethritis, pyelonephritis);
- in gynecology;
- skin and soft tissues, including human and animal bites;
- bone and connective tissue;
- biliary tract (cholecystitis, cholangitis);
- odontogenic.
Contraindications
- hypersensitivity to the components of the drug;
- history of hypersensitivity to penicillins, cephalosporins and other beta-lactam antibiotics;
- history of cholestatic jaundice and/or other liver dysfunction caused by taking amoxicillin/clavulanic acid;
- infectious mononucleosis and lymphocytic leukemia;
With caution: history of pseudomembranous colitis, gastrointestinal diseases, liver failure, severe renal impairment, pregnancy, lactation, simultaneous use with anticoagulants.
Application Amoxiclav 400mg+57mg/5ml 17.5g 70ml powder for the preparation of suspension for oral administration during pregnancy and breastfeeding
During pregnancy and lactation, Amoxiclav® is used only if the expected benefit to the mother outweighs the potential risk to the fetus and child.
Amoxicillin and clavulanic acid pass into breast milk in small quantities.
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 patients with severe renal impairment, adequate dose adjustment or increased intervals between doses is required.
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.
In patients who are hypersensitive to penicillins, cross-allergic reactions with cephalosporin antibiotics are possible.
In women with premature rupture of membranes, it was found that prophylactic therapy with amoxicillin + clavulanic acid may be associated with an increased risk of developing necrotizing colitis in the newborn.
Crystalluria very rarely occurs in patients with reduced diuresis. During the use of large doses of amoxicillin, it is recommended to take sufficient fluids and maintain adequate diuresis to reduce the likelihood of amoxicillin crystal formation.
Lab tests. High concentrations of amoxicillin give a false-positive reaction to urine glucose when using Benedict's reagent or Fehling's solution. It is recommended to use enzymatic reactions with glucosidase.
Impact on the ability to drive a car or perform work that requires increased speed of physical and mental reactions. Due to the possibility of developing side effects from the central nervous system, such as dizziness, headache, convulsions, during treatment, care should be taken when driving and other activities that require concentration and speed of psychomotor reactions.
Overdose
There are no reports of death or life-threatening side effects due to drug overdose.
Symptoms: in most cases - gastrointestinal disorders (abdominal pain, diarrhea, vomiting), anxiety, insomnia, dizziness are also possible, and in isolated cases - seizures.
Treatment: in case of overdose, the patient should be under medical supervision, treatment should be symptomatic.
In case of recent use (less than 4 hours) of the drug, it is necessary to perform gastric lavage and prescribe activated charcoal to reduce absorption. Amoxicillin/potassium clavulanate is removed by hemodialysis.
Side effects Amoxiclav 400mg+57mg/5ml 17.5g 70ml powder for suspension for oral administration
From the digestive system: loss of appetite, nausea, vomiting, diarrhea, abdominal pain, gastritis, stomatitis, glossitis, black “hairy” tongue, darkening of tooth enamel, hemorrhagic colitis (can also develop after therapy), enterocolitis, pseudomembranous colitis, disorder liver function, increased activity of ALT, AST, alkaline phosphatase and/or bilirubin levels in the blood plasma, liver failure (more often in the elderly, men, with long-term therapy), cholestatic jaundice, hepatitis.
Allergic reactions: itching, urticaria, erythematous rashes, erythema multiforme exudative, angioedema, anaphylactic shock, allergic vasculitis, exfoliative dermatitis, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, a syndrome similar to serum sickness, toxic epidermal necrolysis.
From the hematopoietic system and lymphatic system: reversible leukopenia (including neutropenia), thrombocytopenia, hemolytic anemia, reversible increase in PT (when used together with anticoagulants), reversible increase in bleeding time, eosinophilia, pancytopenia, thrombocytosis, agranulocytosis.
From the central nervous system: dizziness, headache, convulsions (may occur in patients with impaired renal function when taking high doses of the drug).
From the urinary system: interstitial nephritis, crystalluria, hematuria.
Other: candidiasis and other types of superinfection.
From the side of the central nervous system: hyperactivity. Feelings of anxiety, insomnia, behavior changes, agitation.
Drug interactions
Antacids, glucosamine, laxatives, aminoglycosides slow down absorption, ascorbic acid increases absorption.
Diuretics, allopurinol, phenylbutazone, NSAIDs and other drugs that block tubular secretion (probenecid) increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).
The simultaneous use of Amoxiclav® and methotrexate increases the toxicity of methotrexate.
Prescription together with allopurinol increases the incidence of exanthema. Concomitant use with disulfiram should be avoided.
Reduces the effectiveness of drugs, during the metabolism of which PABA is formed; ethinyl estradiol - risk of breakthrough bleeding.
The literature describes rare cases of increased INR in patients with the combined use of acenocoumarol or warfarin and amoxicillin. If simultaneous use with anticoagulants is necessary, PT or INR should be carefully monitored when prescribing or discontinuing the drug.
The combination with rifampicin is antagonistic (mutual weakening of the antibacterial effect). The drug Amoxiclav® should not be used simultaneously in combination with bacteriostatic antibiotics (macrolides, tetracyclines), sulfonamides due to a possible decrease in the effectiveness of the drug Amoxiclav®.
The drug Amoxiclav® reduces the effectiveness of oral contraceptives.
The drug Amoxiclav® and aminoglycoside antibiotics are chemically incompatible.
Amoxiclav® should not be mixed in a syringe or infusion bottle with other drugs.
Avoid mixing with solutions of dextrose, dextran, sodium bicarbonate, as well as with solutions containing blood, proteins, lipids.
Interaction with other drugs and other types of interactions
Anticoagulants for oral use. Oral anticoagulants and penicillin antibiotics are widely used in practice without reports of interactions. However, cases of an increase in the international normalization coefficient have been described in patients taking acenocoumarol or warfarin and who were prescribed a course of treatment with amoxicillin. If concomitant use of drugs is necessary, the prothrombin index or international normalization ratio (INR) should be carefully monitored when amoxicillin is added or discontinued. In addition, it may be necessary to adjust the dose of anticoagulants for oral use (see Sections “Peculiarities of use” and “Adverse reactions”).
Methotrexate. Penicillins may reduce the elimination of methotrexate, causing a potential increase in toxicity.
Probenecid. Concomitant use of probenecid is not recommended. Probenecid reduces the renal tubular secretion of amoxicillin. Concomitant use of probenecid may lead to an increase in the level and duration of amoxicillin (but not clavulanic acid) presence in the blood.
Mycophenolate mofetil. In patients treated with mycophenolate mofetil, predose concentrations of the active metabolite MPA may decrease by approximately 50% after initiation of oral amoxicillin with clavulanic acid. This change in predose level may not be entirely consistent with the change in total MPA exposure. Therefore, a change in mycophenolate mofetil dosage is usually not required unless there is clinical evidence of graft dysfunction. However, close monitoring is necessary during coadministration and for some time after antibiotic therapy.
Note!
Description of the drug Amoxiclav por. d/r-ra d/in. 1000mg/200mg vial. No. 5 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
