White Pills or white with a yellowish tint, round, flat-cylindrical shape with chamfer and risk.

Suction

Absorption fast, high (93%), food intake does not affect absorption, does not breaks down in the acidic environment of the stomach. When taken orally at a dose of 250 mg and 500 mg, maximum plasma concentration - 5 mcg/ml and 10 mcg/ml, respectively.

Time to reach The maximum concentration after oral administration is 1-2 hours.

Distribution

Partly (10–20%) is metabolized to form inactive metabolites.

Derivation

Period half-life (T_1/2) - 1–1.5 & nbsp; hours. Displayed 50-70% unchanged by the kidneys by tubular excretion (80%) and glomerular filtration (20%), liver - 10-20%. In a small amount excreted in breast milk. If kidney function is impaired (creatinine clearance [CC] ≤15 ml/min) T_1/2 is extended to 8.5 hours. Amoxicillin is removed by hemodialysis.

Special Groups patients

Age

Has a large volume of distribution - high concentrations are found in blood plasma, bronchial secretions (in purulent bronchial secretions, the distribution is weak), liver, lymph nodes, uterus, ovaries, paranasal sinuses, pleural and peritoneal fluid, saliva and lacrimal fluid, urine, skin contents blisters, lung tissue, intestinal mucosa, middle ear fluid, and paranasal sinuses, bones, adipose tissue, gallbladder (concentration in bile exceeds the concentration in blood plasma by 10 times - with normal patency bile ducts), fetal tissues. When the dose is doubled, the concentration also doubled. In amniotic fluid and umbilical cord vessels the concentration of amoxicillin is about 50% of the concentration in blood plasma pregnant woman. Poorly crosses the blood-brain barrier inflammation of the meninges (meningitis) concentration in the cerebrospinal fluid increases to 20% of plasma concentration. Association with plasma proteins blood - 15–25%.

Metabolism

T_1/2amoxicillin y children aged 3 months to 2 years is similar to T_1/2in older children age and adults.

Because elderly patients are more likely to reduce kidney function, dose selection is carried out with caution, it is also necessary to monitor kidney function.

Gender

On Receive inside in healthy men and women, the sex of patients does not have a significant influence on the pharmacokinetics of amoxicillin.

Renal insufficiency

General serum clearance of amoxicillin increases in proportion to the decrease kidney function. In case of impaired renal function (CC <15 ml/min) T< sub>1/2 is extended and can reach 8.5 hours with anuria.

Hepatic insufficiency

In patients with impaired liver function, dose selection is carried out with caution, as well as regular monitoring of liver function is necessary.

Amoxicillin is an aminobenzyl penicillin, a semi-synthetic antibiotic broad spectrum of activity, which has a bactericidal effect as a result of inhibition of bacterial cell wall synthesis.

Threshold minimum inhibitory concentration (MIC) values ​​for various sensitive organisms vary.

Prevalence resistant strains varies geographically and at different times, so it is desirable to be guided by local information on resistance, especially when tia treatment unwanted infections.

Borders resistance

Border MIC values ​​for amoxicillin according to the European Committee for Research Antimicrobial Susceptibility Test (EUCAST) version 5.0.

^1. Wild Enterobacteriaceae are classified as susceptible to aminopenicillin. AT some countries prefer a separate classification of wild types strains of E. coli and P. mirabilis as intermediates. In that In this case, the MIC breakpoint S ≤0.5 mg/l should be used.

^2. Most staphylococci produce amoxicillin-resistant penicillinase. Methicillin-resistant strains, with some exceptions, are resistant to beta-lactam preparations.

^3. Susceptibility to amoxicillin can be determined using the value of susceptibility to ampicillin.

^4. Susceptibility streptococci of groups A, B, C and G to penicillin can be determined using susceptibility values ​​to benzylpenicillin.

^5. Border values ​​refer to non-meningitis strains only. If strains are classified as an intermediate of ampicillin, then oral treatment should be avoided amoxicillin. Susceptibility is determined by the MIC value for ampicillin.

^6. Border values ​​refer to intravenous use. Strains positive for beta-lactamase should be considered resistant.

^7. Strains, synthesizing beta-lactamases should be considered as resistant.

^8. Susceptibility to amoxicillin can be determined using the value of susceptibility to benzylpenicillin.

^9. Border values ​​relative approach the epidemiological cut-off points that distinguish between wild types of strains and strains with reduced susceptibility.

^10. Border values ​​without a specific type of bacteria refer to a dosage of at least 0.5 g 3-4 times a day (from 1.5 to 2 g / day).

Sensitivity microorganisms to amoxicillin in the laboratory

Usually susceptible pathogens

Aerobic Gram-positive organisms:

Enterococcus faecalis

Beta Hemolytic streptococci (groups A, B, C and G)

Listeria monocytogenes

Types of bacteria that which acquired resistance is possible

Aerobic Gram-negative microorganisms:

Escherichia coli

Haemophilus influenzae

Helicobacter pylori

Proteus mirabilis

Salmonella typhi

Salmonella paratyphi

Shigella spp.

Pasteurella multocida

Vibrio cholerae

Aerobic Gram-positive organisms:

Coagulase-negative staphylococci

Staphylococcus aureus?

Streptococcus pneumoniae

Streptococcus groups viridans

Fusobacterium spp.

Anaerobic Gram-positive organisms:

Clostridium spp.

Anaerobic Gram-negative microorganisms:

Fusobacterium spp.

Other microorganisms:

Borrelia burgdorferi

Of course resistant organisms ₣

Aerobic Gram-positive organisms:

Enterococcus faecium ₣

Aerobic Gram-negative microorganisms:

Acinetobacter spp.

Enterobacter spp.

Klebsiella spp.

Pseudomonas spp.

Anaerobic Gram-negative microorganisms:

Bacteroides spp. (some Bacteroides fragilis strains are resistant)

Other microorganisms:

Chlamydia spp.

Mycoplasma spp.

Legionella spp.

₣ — Natural medium sensitivity in the absence of acquired residence mechanisms.

? - Nearly all S strains. aureus are resistant to amoxicillin, as they produce penicillinase.

Bacteria can have resistance to amoxicillin as a result of the production of beta-lactamase, hydrolyzing aminopenicillins (which may be inhibited by clavulanic acid), changes in penicillin-binding proteins, impaired permeability to drug or efflux pump mechanism. In one microorganism several mechanisms of resistance are present at the same time, which explains existence of variable and unpredictable cross-resistance to other beta-lactams and antibacterials from other groups.

Infectious-inflammatory diseases caused by microorganisms sensitive to amoxicillin:

-        infections upper respiratory tract (tonsillopharyngitis, sinusitis, acute otitis media);

-        infections lower respiratory tract (acute bacterial bronchitis, exacerbation of chronic bronchitis, community-acquired pneumonia);

-        infections genitourinary system (pyelonephritis, pyelitis, cystitis, urethritis, endometritis, cervicitis, gonorrhea);

-        abdominal infections (cholangitis, cholecystitis);

-        eradication Helicobacter pylori in patients with duodenal ulcer intestines or stomach (always in combination with other drugs);

-        infections skin and soft tissues (erysipelas, impetigo, secondarily infected dermatoses);

-        leptospirosis, listeriosis;

-        disease Lyme;

-        infections gastrointestinal tract (enterocolitis, typhoid fever, dysentery, salmonellosis (caused by Salmonella typhi sensitive to ampicillin), salmonella carrying;

-        prevention bacterial endocarditis during surgical procedures in the oral cavity and upper respiratory tract.

-        Increased sensitivity to amoxicillin, beta-lactam antibiotics (other penicillins, cephalosporins, monobactams, carbapenems) or other components of the drug;

-        infectious mononucleosis, lymphocytic leukemia;

-        children's age up to 3 years (for this dosage form).

With caution

-        allergic reactions (including bronchial asthma, hay fever, hypersensitivity to acetylsalicylic acid) in history;

-        diseases history of gastrointestinal tract (especially colitis associated with the use of antibiotics);

-        renal insufficiency;

-        pregnancy and the period of breastfeeding.

Results Animal studies do not indicate a direct or indirect effect on reproductive toxicity. Limited data on the use of amoxicillin in time of pregnancy in a person does not indicate an increased risk of congenital malformations. The drug can be used during pregnancy only when the expected benefit to the mother outweighs the potential risk to the fetus.

Amoxicillin excreted in breast milk in small amounts, if necessary, it is possible the use of the drug during breastfeeding. In a child who is breastfeeding, diarrhea, sensitization and fungal infections may develop mucosal infections, so it may be necessary to stop breastfeeding feeding. Amoxicillin should be used during breastfeeding only after evaluation by the attending physician of the benefit/risk ratio.

Inside, before or after eating. The dose of the drug depends on the sensitivity of the pathogen infection, the severity of the disease and the localization of the infectious process.

To provide the following dosing regimen for children under 12 years of age, preferably taking amoxicillin in dosage form - powder for the preparation of a suspension for ingestion.

Adults and children over 13 years old and/or weighing more than 40 kg

Usually assigned 250 mg-500 mg 3 times a day or 500 mg-1000 mg 2 times a day day. For sinusitis, community-acquired pneumonia and other severe infections it is recommended to prescribe 500 mg-1000 mg 3 times a day. The maximum daily dose is 6 g.

Children 3 to 5 years and / or body weight from 15 kg to 19 kg

Usually assigned 250-500 mg 3 times a day or 500-1000 mg 2 times a day. In cases when there is a high risk of infection with resistant Streptococcus pneumoniae, higher doses are recommended - 500 mg 2-3 times a day. day.

Children 5 to 13 years and / or body weight from 19 kg to 40 kg

Usually recommend 250 mg 3 times a day. In cases where there is a high probability resistant Streptococcus pneumoniae infections are recommended higher doses - 500-1000 mg 3 times a day.

Maximum daily dose for children - 100 mg / kg / day.

Lyme Disease (borreliosis) - early stage

Adults and children over 13 years old and/or weighing more than 40 kg

500 mg–1000 mg 3 times a day to a maximum daily dose of 4 g divided by several doses, within 14 days (10-21 days).

Children 3 to 5 years and / or body weight from 15 kg to 19 kg

250 mg 3 times a day.

Children 5 to 13 years and / or body weight from 19 kg to 40 kg

500mg 2-3 times a day (at the rate of 50 mg / kg / day, divided into 3 doses).

Eradication Helicobacter pylori patients with duodenal ulcer or stomach (always in combination with other drugs)

For adults 1000 mg twice daily in combination with a proton pump inhibitor (eg, omeprazole, lansoprazole) and another antibiotic (eg, clarithromycin, metronidazole) for 7 days.

Children over 13 years and / or weighing more than 40 kg - 1000 mg 2 times in the composition combination therapy.

Children 3 to 5 years and / or body weight from 15 kg to 19 kg

250-500 mg 2 times a day.

Children 5 to 13 years and / or body weight from 19 kg to 40 kg

500–1000 mg 2 times a day (based on 50 mg / kg / day, divided into 2 doses).

Prevention bacterial endocarditis

For adults and children over 13 years old and/or weighing over 40 kg: recommended 2 g 30–60 minutes before surgery.

Children recommended:

- from 3 to 5 years and/or 15-19 kg body weight: 750-1000 mg (based on 50 mg/kg/day) before the procedure;

- 5–12 years and / or body weight 20-40 kg: 1000-2000 mg (based on 50 mg/kg/day) before the procedure.

Renal insufficiency

Patients, on hemodialysis

Patients, on peritoneal dialysis

Maximum dose of amoxicillin 500 mg/day

Most common Adverse drug reactions (ADRs) include diarrhea, nausea, and skin rash. Classification of adverse reactions by organs and systems, indicating the frequency their occurrence: very often (≥1/10), often (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), including isolated reports, frequency unknown (frequency cannot be estimated based on available data).

Infectious and parasitic diseases

Very rare: candidiasis of the skin and mucous membranes.

Opis Violations hand blood and lymphatic system

Very rare: reversible leukopenia (including neutropenia or agranulocytosis), reversible thrombocytopenia, hemolytic anemia. Increased bleeding time and prothrombin time.

Opis Violations aspects of the immune system

Very rare: heavy allergic reactions, including angioedema, anaphylaxis, serum sickness and allergic vasculitis.

Frequency unknown: Jarisch-Herxheimer reaction, allergic acute coronary syndrome (syndrome Kounis).

Opis Violations side of the nervous system

Very rare: hyperkinesia, dizziness and convulsions.

Frequency unknown: aseptic meningitis.

Opis Violations sides of the gastrointestinal tract

* Often: diarrhea, nausea.

* Uncommon: vomiting.

Very rare: antibiotic-associated colitis (including pseudomembranous and hemorrhagic colitis), black "hairy" tongue.

Opis Violations sides of the liver and biliary tract

Very rare: hepatitis and cholestatic jaundice. Increased activity of aspartate aminotransferase (ACT) and/or moderate alanine aminotransferase (ALT) in blood plasma.

Opis Violations sides of the skin, subcutaneous tissue

*Often: skin rash.

*Uncommon: hives and pruritus.

Very rare: skin reactions, such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative dermatitis, acute generalized exanthematous pustulosis (EGEP) and drug rash with eosinophilia and systemic symptoms (DRESS syndrome).

Opis Violations sides of the kidneys and urinary system

Very rare: interstitial nephritis, crystalluria.

* Frequency the frequency of occurrence of ADR data was obtained from the results of clinical studies involving, in total, about 6000 adult patients and children treated amoxicillin.

Probenecid: application amoxicillin and probenecid are not recommended, because probenecid reduces renal tubular secretion of amoxicillin, thereby increasing its plasma concentration and lengthening the time of its stay in the blood serum.

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

Bactericidal antibiotics (including aminoglycosides, cephalosporins, cycloserine, vancomycin, rifampicin, quinolones) have a synergistic effect;

bacteriostatic preparations (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) — antagonistic (decreases the effectiveness of amoxicillin).

Increases effectiveness of indirect anticoagulants (suppressing intestinal microflora, reduces the synthesis of vitamin K and prothrombin index); reduces the effectiveness of estrogen-containing oral contraceptives, drugs, in the process of mmetabolism which para-aminobenzoic acid is formed, ethinylestradiol - risk breakthrough bleeding. However, there are cases in the literature of increased international normalized ratio (INR) in patients receiving maintenance therapy with acenocoumarol or warfarin, which is prescribed a course treatment with amoxicillin. If necessary, the simultaneous use of drugs INR should be carefully monitored when amoxicillin is added or removed. In addition, it may be necessary to adjust the dose of anticoagulants for ingestion.

Diuretics, allopurinol, oxyphenbutazone, phenylbutazone, non-steroidal anti-inflammatory drugs and drugs that block tubular secretion, reducing tubular secretion, increase the concentration of amoxicillin in the blood.

When simultaneous use with allopurinol increases the risk of developing a skin rash. Reduces clearance and increases toxicity of methotrexate.

Enhances absorption of digoxin.

During Healing amoxicillin are possible: false-positive samples of the Coombs test and for the determination glucose in the urine.

Symptoms

Nausea, vomiting, diarrhea, crystalluria, disturbance of water and electrolyte balance (as a consequence vomiting and diarrhea), convulsions, agitation, confusion.

Healing

Symptomatic - gastric lavage, activated charcoal, saline laxatives, medicinal means to maintain water and electrolyte balance, hemodialysis.

Side Effects of Amoxicillin (Amoxil, Trimox)

Before start treatment with amoxicillin, the patient should be asked in detail regarding previous hypersensitivity reactions to penicillins, cephalosporins and other beta-lactams.

In patients who having hypersensitivity to penicillins, cross-over allergic reactions with cephalosporin antibiotics.

Serious and sometimes fatal hypersensitivity reactions (including anaphylactoid and severe skin adverse reactions) were reported in patients treated with penicillin. Data development reactions are more likely in individuals with a history of hypersensitivity to penicillin, and in individuals with atopy. If an allergic reaction occurs, discontinue amoxicillin therapy and initiate appropriate alternative therapy.

Have been checked out rare cases of hypersensitivity reactions of the type of allergic acute coronary syndrome (Kounis syndrome), if it develops during treatment amoxicillin, appropriate treatment is used.

When healing it is necessary to monitor the state of the function of the hematopoietic organs, liver and kidneys. An increase in the activity of "liver" enzymes and a change in the number of blood cells.

For long use may develop cases of superinfection, candidiasis (especially vulvovaginal candidiasis).

When receiving almost of all antibacterial drugs, the development of antibiotic- associated colitis up to a life-threatening condition. It follows take into account when diarrhea occurs and during or after antibiotic therapy. In case of development of antibiotic-associated colitis, drug therapy stop immediately and consult your doctor for prescribing appropriate treatment. The use of drugs that inhibit intestinal peristalsis, contraindicated.

Occurrence generalized erythema with fever accompanied by pustules, at the onset treatment may be a symptom of acute generalized exanthematous pustulosis (OGEP). This ADR requires discontinuation of amoxicillin treatment and is a contraindication for its further use in any situation.

Should be avoided use of amoxicillin if a patient is suspected of developing an infectious mononucleosis, since the appearance of a measles-like rash has been associated with the use of amoxicillin in the treatment of infectious mononucleosis. Reaction Jarisch-Herxheimer was observed after the use of amoxicillin in patients with Lyme disease. Its immediate cause is bactericidal activity amoxicillin against the bacteria that cause Lyme disease, spirochete Borrelia burgdorferi. Patients should be assured that this reaction is common and usually self-limiting a consequence of the use of antibiotics in patients with Lyme disease. Treatment necessarily continues for 48-72 hours after the disappearance of clinical signs of disease.

Seizures can occur in patients with impaired renal function or in patients receiving high doses of the drug, or those with predisposing factors (eg, history of seizures, treatment for epilepsy, or meningitis). With renal insufficiency, it is necessary to adjust the dosing regimen depending on degree of renal failure.

In patients with reduced diuresis, crystalluria was very rarely observed, mainly with parenteral therapy. When using high doses of amoxicillin, it is recommended maintain adequate fluid intake and diuresis to reduce the possibility of developing crystalluria associated with the use of amoxicillin. At patients with a catheterized bladder should be checked regularly catheter patency.

Exists the likelihood of being affected by elevated serum amoxicillin concentrations and urine on the results of some laboratory tests. When using chemical methods, a high concentration of amoxicillin in the urine may be the cause false positive test results.

For definition the presence of glucose in the urine during treatment with amoxicillin is recommended use enzymatic glucose oxidase methods. The use of amoxicillin may distort the results of the quantitative determination of estriol in pregnant women women.

Influence on ability to drive vehicles, mechanisms

No data on the effect of amoxicillin on the ability to drive a car or other mechanical means.

Research about the effect of amoxicillin on the ability to drive vehicles, mechanisms were not carried out. Patients should be warned about the possibility development of allergic reactions, dizziness and the appearance of convulsions, which may affect the ability to drive vehicles, mechanisms. If the described adverse events occur, you should refrain from performing the specified activities.