Amoxicillin EXPRESS, 500 mg 20 pcs

Pharmacodynamics

Amoxicillin is a semisynthetic penicillin (a beta-lactam antibiotic) that inhibits one or more enzymes (known as penicillin-binding proteins – PBPs) that play a role in peptidoglycan biosynthesis. Peptidoglycan is a structural element of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by lysis and death of the bacterial cell.

Amoxicillin is degraded by beta-lactamases that can be produced by some bacteria, making them resistant to amoxicillin. Thus, the spectrum of activity of unprotected amoxicillin does not include microorganisms producing these enzymes.

Pharmacokinetics/pharmacodynamics

The time beyond the minimum suppressive concentration (T > MPC) is considered a major determinant of amoxicillin efficacy.

Resistance mechanisms

The main mechanisms of resistance to amoxicillin are:

enzymatic inactivation by beta-lactamases;

PBS mutation, which decreases the affinity of the antibiotic for the target.

Permeability of the bacterial cell wall or active excretion of the antibiotic from the cell (efflux) can cause or contribute to bacterial resistance in Gram-negative bacteria.

The prevalence of resistance can vary by geographic location and over time for certain species. It is advisable to focus on local information about resistance, especially when treating severe infections. If necessary, qualified advice should be sought if local prevalence is such that the efficacy of the drug in treating specific types of infections is questionable.

MMP limit values

Minimum suppressive concentrations (MSCs) for amoxicillin according to European Committee on Antibiotic Susceptibility Testing (EUCAST) criteria, version 5.0:

Microorganisms Marginal MPC value (mg/L)

Sensitive ≤ Resistant >

Enterobacteriaceae 81 8

Staphylococcus spp. note2 note2

Enterococcus spp.3 4 8

Streptococcus spp. group A, B, C and G note4 note4

Streptococcus pneumoniae note5 note5

Viridans group streptococci 0.5 2

Haemophilus influenzae 26 26

Moraxella catarrhalis note7 note7

Neisseria meningitidis 0.125 1

Gram-positive anaerobes except Clostridium difficile8 4 8

Gram-negative anaerobes8 0.5 2

Helicobacter pylori 0.1259 0.1259

Pasteurella multocida 1 1

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Nonspecific borderline values10 2 8

1 Wild-type strains of Enterobacteriaceae are classified as sensitive to aminopenicillins. In some countries, E. coli and P. mirabilis wild-type isolates are classified as moderately resistant. In this case, a borderline IPC value of S≤0.5 mg/L is used.

2 Most staphylococci produce penicillinases and are resistant to amoxicillin. Methicillin-resistant strains of staphylococci, with rare exceptions, are resistant to all beta-lactam antibiotics.

3 Amoxicillin sensitivity is assessed by ampicillin.

4 The sensitivity of group A, B, C and G streptococci to penicillins is evaluated based on their sensitivity to benzylpenicillin.

5 Borderline values refer to isolates isolated in all types of infection except meningitis. If an isolate is evaluated as moderately resistant to ampicillin, oral amoxicillin should not be administered. Sensitivity is assessed by the MPC of ampicillin.

6 Borderline values are based on intravenous administration. Beta-lactamase-producing strains are classified as resistant.

7 Microorganisms that produce beta-lactamases are classified as resistant.

8 Sensitivity to amoxicillin is assessed by sensitivity to benzylpenicillin.

9 Boundary values are set at the epidemiologic cut-off point (ECOFF) value, which distinguishes wild-type isolates from those with reduced sensitivity.

10 Non-vidospecific borderline values are based on doses of 0.5 g 3 or 4 times daily (1.5 to 2 g/day).

Sensitivity of microorganisms to amoxicillin in vitro

Sensitive microorganisms usually

Gram-positive aerobes:

Enterococcus faecalis

Beta-haemolytic streptococci (groups A, B, C and G)

Listeria monocytogenes

Microorganisms that may have acquired resistance mechanisms to amoxicillin

Gram-negative aerobes:

Escherichia coli

Haemophilus injluenzae

Helicobacter pylori

Proteus mirabilis

p> Salmonella typhi

Salmonella paratyphi

Pasteurella multocida

Gram-positive aerobes

/p>

Coagulase-negative staphylococci

Staphylococcus aureus £

Streptococcus pneumoniae

The Streptococcus viridans group

Gram-positive aerobes:

Clostridium spp.

Gram-negative aerobes:

Fusobacterium spp.

Others:

Borrelia burgdorferi

Microorganisms with natural resistance ţ

Gram-positive aerobes:

Enterococcus faesiumţium

Gram-negative aerobes:

Acinetobacter spp.

Enterobacter spp.

Klebsiella spp.

Pseudomonas spp.

Gram-negative aerobes:

Bacteroides spp. (many strains of Bacteroides fragilis are resistant)

Others:

Chlamydia spp

Mycoplasma spp.

Legionella spp.

ţ Natural intermediate sensitivity in the absence of acquired resistance mechanisms.

£ Almost all strains of S. aureus are resistant to amoxicillin due to production of penicillinases. Methicillin-resistant strains of Staphylococcus aureus (MRSA) are also resistant to amoxicillin.

Pharmacokinetics

Amoxicillin completely dissociates in aqueous solution at physiological pH. Amoxicillin is quickly and well absorbed after oral administration. When oral administration the bioavailability of amoxicillin is about 70% and the time to reach maximum plasma concentration (Tmax) is 1 -2 hours.

The following are the results of pharmacokinetic studies obtained when amoxicillin 250 mg 3 times daily is taken by groups of healthy volunteers on an empty stomach:

C max Tmaõ* AUC(0-24 h) T 1/2

(µg/mL) (h) (µg x h/mL) (h)

3.3±1.12 1.5 (1.0-2.0) 26.7±4.56 1.36±0.56

*Median (range) value

In the 250-3000 mg dose range, bioavailability varies linearly with dose (measured by C max and AUC). Simultaneous intake of food has no effect on the absorption of amoxicillin.

Hemodialysis may be used to eliminate amoxicillin from the circulation.

Distribution

About 18% of the total amount of amoxicillin in plasma is bound to plasma proteins. The apparent volume of distribution is approximately 0.3-0.4 L/kg. After intravenous administration, amoxicillin is detected in the gallbladder, abdominal tissues, skin, adipose tissue, muscle, synovial and peritoneal fluids, bile and pus. Amoxicillin poorly penetrates into the cerebrospinal fluid.

Amoxicillin, like most penicillins, can be detected in breast milk. Amoxicillin passes through the placental barrier.

Biotransformation

Amoxicillin is partially excreted in the urine as inactive penicillic acid in amounts equivalent to 10-25% of the dose taken.

Elimination

Amoxicillin is mainly excreted through the kidneys.

The elimination half-life is on average 1 h, and the average total clearance is approximately 25 l/h in healthy subjects who participated in the study. Approximately 60-70% of amoxicillin is excreted unchanged in the urine within the first 6 h after a single dose of 250 mg or 500 mg. In many studies the period of excretion of 50-85% of amoxicillin with urine was 24 hours.

The concomitant administration of probenecid slows the excretion of amoxicillin.

Age

The half-life of amoxicillin is about the same in children aged 3 months to 2 years, in older children and in adults. Very young children (including premature infants) are not administered amoxicillin more than twice daily during the first week of life, taking into account the immaturity of the renal excretion route. Since decreased renal function may occur in the elderly, the dose should be adjusted with caution and renal function should be periodically monitored for this category of patients.

Gender

After oral administration of amoxicillin in male and female patients who participated in the studies, no significant effect of gender on the pharmacokinetics of amoxicillin was found.

Renal dysfunction

The total plasma clearance of amoxicillin decreases in proportion to the deterioration of renal function.

Hepatic impairment

Caution should be exercised in patients with hepatic impairment, and periodic monitoring of liver function should be performed.

Indications

Infections caused by microorganisms sensitive to the drug, including:

– acute bacterial sinusitis;

– acute otitis media;

– acute streptococcal tonsillitis and pharyngitis;

– exacerbation of chronic bronchitis;

– community-acquired pneumonia;

– acute cystitis;

– asymptomatic bacteriuria during pregnancy;

– acute pyelonephritis;

– typhoid and paratyphoid;

– dental abscess with subcutaneous tissue inflammation;

– prosthetic joint infections;

– Lyme disease;

– prevention of bacterial endocarditis in oral and upper respiratory surgical procedures.

In combination with other drugs, according to the eradication regimen, it is used to treat diseases of the digestive tract associated with Helicobacter pylori.

The official clinical guidelines for antibiotic therapy should be considered when choosing an antibiotic.

Active ingredient

Composition

How to take, the dosage

The drug Amoxicillin EXPRESS is administered orally regardless of meals.

The tablet should be dissolved in water (at least 50 ml) and mixed thoroughly immediately before use. The resulting mixture, which has a mild fruity taste, should be taken immediately after preparation.

The following factors should be considered when choosing a dose of Amoxicillin EXPRESS to treat certain infections:

The duration of treatment depends on the type of infection and the patient’s clinical response and should be as short as possible. Some infections are subject to longer treatment duration.

Adults and children ≥40 kg

Indication for use *

Dose*

Acute bacterial sinusitis

250 mg-500 mg every 8 hours or 750 mg -1 g every 12 hours

Asymptomatic bacteriuria during pregnancy

Acute pyelonephritis

In severe infections 750 mg-1 g every 8 hours

Dental abscess with subcutaneous tissue inflammation

10-30

Maximum 500 mg twice daily

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15 mg/kg twice daily (maximum 500 mg twice daily)

Less than 10

Maximum 500 mg per day

/td>

15 mg/kg once daily (maximum 500 mg daily)

*Parenteral treatment is preferred in most cases.

Patients receiving hemodialysis

Amoxicillin may be eliminated from the bloodstream during hemodialysis.

Hemodialysis

Adults and children >40 kg

15 mg/kg/day once

One additional dose of 15 mg/kg is required before hemodialysis.

To restore circulating levels of the drug after hemodialysis, an additional dose of 15 mg/kg should be given.

Patients receiving peritoneal dialysis

The maximum dose of amoxicillin is 500 mg daily.

Patients with impaired liver function

Care should be taken and liver function should be monitored regularly.

Interaction

Probenecid

The simultaneous use of amoxicillin and probenecid is not recommended. Probenecid reduces the secretion of amoxicillin in the renal tubules. Concomitant use of probenecid may lead to increased concentration of amoxicillin in the blood.

Allopurinol

The concomitant use of allopurinol during treatment with amoxicillin increases the likelihood of allergic skin reactions.

Tetracyclines

Tetracyclines and other bacteriostatic antibiotics may affect the bactericidal effect of amoxicillin.

Peroral anticoagulants

Peroral anticoagulants and penicillin-based antibiotics are often used together in practice, with no reports of interaction. However, the literature describes cases of increased international normalized ratio in patients treated with acenocoumarol or warfarin against the background of a prescribed course of amoxicillin. If concomitant administration of drugs is necessary, prothrombin time or international normalized ratio should be carefully monitored at the beginning of treatment and after discontinuation of amoxicillin treatment. In addition, it may be necessary to adjust the dose of oral anticoagulants.

Methotrexate

Penicillin antibiotics may decrease methotrexate excretion, which may be accompanied by increased toxicity.

Special Instructions

Hypersensitivity reactions

Before starting treatment with amoxicillin, attention should be paid to the presence of hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics in the history.

Serious and sometimes fatal hypersensitivity reactions (including anaphylactic reactions and severe skin reactions) have been reported in patients treated with penicillin. The development of these reactions is more likely in people with a history of hypersensitivity to penicillins and in individuals with atopy. In case of allergic reactions the treatment with amoxicillin should be discontinued and an appropriate alternative treatment should be prescribed.

Acute coronary syndrome associated with hypersensitivity (Coneys syndrome)

Intensitive microorganisms

In some types of infections before prescribing amoxicillin it is necessary to first establish the causative agent and its sensitivity to the drug, or to make sure that the pathogen is likely to be treatable with amoxicillin. This includes patients with urinary tract infections and severe ear, nose, and throat infections.

Convulsions

Convulsions may occur in patients with renal failure, in patients receiving high doses of the drug, as well as in patients with predisposing factors – the presence of seizures in the history, treatment of epilepsy or meningitis, etc.

Renal failure

In patients with renal failure, the dose should be adjusted according to the degree of renal failure.

Skin reactions

The occurrence of generalized erythema with fever accompanied by pustules in the initial phase of treatment may be a symptom of OSEP (see section “Side effects”). In this case, amoxicillin administration should be discontinued, and its subsequent use will be contraindicated in all situations.

The use of amoxicillin by patients with suspected infectious mononucleosis should be avoided, since a rash (exanthema) associated with the use of amoxicillin in this disease may occur.

Jarisch-Herxheimer reaction

Jarisch-Herxheimer reaction has been observed after using amoxicillin in patients with Lyme disease. This reaction is associated with the bactericidal effect of amoxicillin on Lyme disease pathogens, Borrelia burgdorferi spirochaetes. Patients should be explained that this reaction is a common side effect of Lyme disease treatment with antibiotics and usually goes away on its own.

The overgrowth of insensitive microorganisms

Prolonged use of the drug can sometimes lead to an overgrowth of amoxicillin-insensitive microorganisms (superinfection).

With almost all antibiotic drugs, it is possible to develop colitis associated with taking antibiotics. Its severity can range from mild to severe (life-threatening). Therefore, it is important to consider the possibility of this diagnosis in patients who develop diarrhea during or after the use of antibiotics. If diarrhea develops, the patient should immediately stop taking amoxicillin, consult a physician and begin appropriate treatment. Drugs that inhibit peristalsis are contraindicated in this situation.

Long-term treatment

In long-term therapy, periodic monitoring of hematopoiesis, renal and hepatic function should be performed. Increased activity of “hepatic” enzymes and changes in the number of blood cells have been reported.

Anticoagulants

Crystalluria

Crystalluria has very rarely been observed in patients with decreased diuresis, mostly during parenteral therapy. When using high doses of amoxicillin, it is recommended to maintain adequate fluid intake and diuresis to reduce the likelihood of crystalluria associated with the use of amoxicillin. In patients with catheterized bladder, the patency of the catheter should be regularly checked.

Impact on diagnostic studies

Elevated levels of amoxicillin in serum and urine may affect some laboratory studies. Because of high concentrations of amoxicillin in the urine, chemical methods often give false-positive results.

When determining glucose in the urine during treatment with amoxicillin, enzymatic glucose oxidase tests are recommended.

The use of amoxicillin may affect the results of quantitative determination of estradiol in the urine in pregnant women.

There have been no studies of the effect of amoxicillin on the ability to drive motor vehicles or operate other mechanisms. However, side effects may occur (e.g., allergic reactions, dizziness, seizures) that affect the ability to drive vehicles or operate other mechanisms.

Contraindications

Hypersensitivity to amoxicillin, other penicillins or any other component of the drug.

A history of severe immediate-type hypersensitivity reactions (e.g., anaphylaxis) to another beta-lactam antibiotic (e.g., cephalosporin, carbapenem or monobactam).

Allergic reactions (including bronchial asthma, polliposis, hypersensitivity to acetylsalicylic acid) in the history, gastrointestinal diseases in the history (especially colitis associated with antibiotic use), renal failure, infectious mononucleosis, lympholeukosis, pregnancy, breastfeeding period, prematurity, advanced age.

Side effects

The most common side effects are diarrhea, nausea, and skin rash.

The frequency of side effects is defined as follows: very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), rare (≥1/10000, < 1/ 1000), very rare (< 1/10000), unknown (cannot be estimated based on available data).

Infectious and parasitic diseases

very rare candidiasis of the skin and mucous membranes

Disorders of the blood and lymphatic system

very rare reversible leukopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia, hemolytic anemia; prolongation of bleeding time and prothrombin time

Immune system disorders

very rare severe allergic reactions such as angioneurotic edema, anaphylaxis, serum sickness and allergic vasculitis

unknown Jarisch-Herxheimer reaction, acute coronary syndrome associated with hypersensitivity (Coneys syndrome)

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Nervous system disorders

very rarely hyperkinesia, dizziness, seizures

unknown aseptic meningitis

Gastrointestinal disorders

Data from clinical studies

*frequent diarrhea and nausea

*frequent vomiting

Post-registration data

Very rare colitis associated with antibiotic administration (including pseudomembranous colitis and hemorrhagic colitis), black “hairy” tongue;

superficial discoloration of teeth**

Hepatic and biliary tract disorders

very rarely hepatitis, cholestatic jaundice, moderate increase in plasma aspartate aminotransferase and/or alanine aminotransferase activity

/p>

Skin and subcutaneous tissue disorders

Data from clinical studies

p> *often skin rash

*frequently urticaria, pruritus

Post-registration data

Very rarely, skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalized exanthematous pustulosis (OGEP), drug rash with eosinophilia and systemic symptomatology (DRESS syndrome).

Renal and urinary system disorders

very rare Interstitial nephritis, crystalluria

* The incidence of these adverse reactions was obtained on the basis of clinical studies, which in total included about 6000 adults and children who took amoxicillin.

** superficial discoloration of teeth has been reported in children. Good oral hygiene helps prevent tooth discoloration, which is addressed by brushing.

Overdose

Symptoms: gastrointestinal dysfunction – nausea, vomiting, diarrhea; consequence of vomiting and diarrhea can be a violation of water-electrolyte balance.

Amoxicillin-associated crystalluria has been observed, which in some cases may lead to renal failure. Seizures may occur in patients with impaired renal function or in patients receiving high doses of the drug.

Treatment: induce vomiting or gastric lavage followed by oral administration of activated charcoal and osmotic laxatives (sodium sulfate); measures to restore water-electrolyte balance, hemodialysis are used.

Pregnancy use

Similarities