Amoxicillin, 250 mg capsules 16 pcs

Amoxicillin is an antibacterial bactericidal acid-resistant broad-spectrum agent of the group of semisynthetic penicillins.

Inhibits transpeptidase, disrupts the synthesis of peptidoglycan (a supporting protein of the cell wall) during division and growth, causes lysis of bacteria.

The drug is active against both Gram-positive and Gram-negative microorganisms due to its wide spectrum of action.

The clinically relevant gram-negative microorganisms sensitive to amoxicillin include Escherichia coli, Proteus mirabilis, Salmonella, Shigella, Campilobacter, Haemophilus influenzae, Bordetella pertussis, Leptospira, Chlamydia.

In addition, amoxicillin is active against all microorganisms sensitive to penicillin G, such as Streptococcus group A,B,C,G,H,I,M, Streptococcus pneumoniae, staphylococci and Neisseria spp, not

Penicillinase-producing, Erysipelothrix rhysiopathiae, Corynebacterium, Bacillus anthracis, Actinomycetes, Streptobacilli, Spirillium minus, Pastereulla multocida, Listeria, Spirochaeta (Leptospira, Treponema, Borrelia) and others.

as well as various anaerobic microorganisms (including peptococci, peptostreptococci, clostridia and fusobacteria).

Pharmacokinetics

Absorption is fast, high (93%), food intake has no effect on absorption, it is not destroyed in the acidic environment of the stomach.

In oral doses of 125 and 250 mg, the maximum concentration is 1.5-3 mcg/ml and 3.5-5 mcg/ml, respectively.

The action develops 15-30 min after administration and lasts 8 h. Time of reaching maximum concentration after oral administration is 1-2 hours.

It has a large volume of distribution – high concentrations are found in plasma, sputum, bronchial secretion (poor distribution in purulent bronchial secretion), pleural and peritoneal fluid, urine,

content of skin blisters, lung tissue, intestinal mucosa, female reproductive organs, prostate, middle ear fluid, bone, adipose tissue, gallbladder (with normal liver function), fetal tissues.

If the dose is increased by a factor of 2, the concentration also increases by a factor of 2. The concentration in bile exceeds the concentration in plasma by 2-4 times.

In the amniotic fluid and umbilical cord vessels, the concentration of amoxicillin is 25-30% of the level in the plasma of the pregnant woman.

Poorly penetrates the blood-brain barrier; in inflammation of the cerebral membranes (meningitis), the concentration in the cerebrospinal fluid is about 20%. Binding with plasma proteins is 17%.

Partially metabolized to form inactive metabolites. Elimination half-life is 1-1.5 hours.

It is eliminated 50-70% unchanged by kidneys through tubular (80%) and glomerular filtration (20%), liver – 10-20%.

In a small amount is excreted with breast milk. In patients with impaired renal function (creatinine clearance less than or equal to 15 ml/min) the half-life is prolonged up to 8.5 hours.

Amoxicillin is eliminated by hemodialysis.

Indications

Infectious and inflammatory diseases caused by microorganisms sensitive to amoxicillin:

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

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

– Infections of the urogenital system (pyelonephritis, pyelitis, cystitis, urethritis, endometritis, cervicitis, gonorrhea);

– abdominal infections (cholangitis, cholecystitis);

– eradication of Helicobacter pylori in patients with duodenal or gastric ulcer disease (always in combination with other drugs);

– skin and soft tissue infections (rye, impetigo, secondary infected dermatoses);

– leptospirosis, listeriosis;

– Lyme disease;

– gastrointestinal tract infections (enterocolitis, typhoid, dysentery, salmonellosis (caused by Salmonella typhi, sensitive to ampicillin), salmonellosis carrier;

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

Active ingredient

Composition

Composition per tablet

Active ingredient:

Amoxicillin trihydrate (in terms of amoxicillin) – 250.0 mg.

Excipients

Potato starch – 112.6 mg, talcum powder – 3.7 mg, magnesium stearate – 3.7 mg.

How to take, the dosage

Orally, before or after meals.

Adults and children over 10 years of age (with body weight over 40 kg) are prescribed 500 mg 3 times daily; in severe course of infection 750 mg – 1 g 3 times daily.

In acute uncomplicated gonorrhea 3 g is prescribed once; when treating women the repeated use of the indicated dose is recommended.

In acute infectious diseases of the gastrointestinal tract (paratyphoid, typhoid) and biliary tract, in gynecological infectious diseases in adults 1.5-2 g 3 times a day or 1-1.5 g 4 times a day.

In leptospirosis in adults – 0.5-0.75 g 4 times a day for 6-12 days.

In case of salmonella carriage in adults – 1.5-2 g 3 times a day for 2-4 weeks.

In prophylaxis of endocarditis during minor surgical interventions in adults – 3 to 4 g 1 hour before the procedure. If necessary the second dose is administered after 8-9 hours.
In children the dose is reduced twice.

In patients with kidney dysfunction and creatinine clearance 15-40 ml/min, the interval between doses is increased up to 12 hours; in creatinine clearance less than 10 ml/min the dose is reduced by 15-50 %; in anuria – maximum dose 2 g/day.

Interaction

Probenecid: the use of amoxicillin and probenecid is not recommended because probenecid reduces renal tubular secretion of amoxicillin, thereby increasing its plasma concentration and prolonging its time in the blood serum.

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

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

The bacteriostatic drugs (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) are antagonistic (reduces the effectiveness of amoxicillin).

Increases the effectiveness of indirect anticoagulants (by suppressing intestinal microflora, reduces the synthesis of vitamin K and prothrombin index); reduces the effectiveness of estrogen-containing oral contraceptives, drugs, in the metabolism of which paraaminobenzoic acid is formed, ethinylestradiol – risk of bleeding “breakthrough”. However, in the literature there have been described cases of increased international normalized ratio (INR) in patients receiving maintenance therapy with acenocoumarol or warfarin who are prescribed treatment with amoxicillin. If there is a need for concomitant use of drugs, INR should be carefully monitored when adding or withdrawing amoxicillin. In addition, it may be necessary to adjust the dose of anticoagulants for oral administration.

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

Concomitant use with allopurinol increases the risk of skin rash. Reduces clearance and increases toxicity of methotrexate.

Accelerates absorption of digoxin.

During treatment with amoxicillin, false-positive tests for Coombs test and urine glucose determination are possible.

Special Instructions

Before starting therapy with amoxicillin, the patient should be questioned in detail about previous hypersensitivity reactions to penicillins, cephalosporins and other beta-lactams.

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

Serious and sometimes fatal hypersensitivity reactions (including anaphylactoid and severe skin adverse reactions) have been reported in patients treated with penicillin. The development of these reactions is more likely in persons with a history of hypersensitivity to penicillin and in those with atopy. In case of allergic reactions it is necessary to discontinue therapy with amoxicillin and prescribe an appropriate alternative therapy.

There have been rare cases of hypersensitivity reactions of the type of allergic acute coronary syndrome (Coneys syndrome), in case of its development during treatment with amoxicillin appropriate treatment is used.

When treating it it is necessary to monitor the hematopoietic, hepatic and renal function. Increased activity of “liver” enzymes and changes in the number of blood cells have been reported.

Long-term use may lead to cases of superinfection, candidiasis (especially vulvovaginal candidiasis).

With almost all antibiotic drugs the development of antibiotic-associated colitis up to life-threatening condition is possible. This should be considered when diarrhea occurs and during the period of antibiotic therapy or after it ends. If antibiotic-associated colitis develops, therapy with the drug should be stopped immediately and the attending physician should be consulted for appropriate treatment. The use of drugs inhibiting intestinal peristalsis is contraindicated.

The occurrence of generalized erythema with fever accompanied by pustules at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis (AEP). This GER requires discontinuation of amoxicillin treatment and is a contraindication to its future use in all situations.

The use of amoxicillin should be avoided if a patient is suspected of developing infectious mononucleosis, because the occurrence of a rash of crust-like symptoms has been associated with the use of amoxicillin in the treatment of infectious mononucleosis. A Jarisch-Herxheimer reaction has been observed after the use of amoxicillin in patients with Lyme disease. Its proximate cause is the bactericidal activity of amoxicillin against the bacteria that are the causative agents of Lyme disease, Borrelia burgdorferi spirochaetes. Patients should be reassured that this reaction is a common and usually self-limited consequence of antibiotic use in patients with Lyme disease. Treatment is sure to continue for 48-72 hours after clinical signs of the disease have disappeared.

Convulsions may occur in patients with impaired renal function or in patients receiving high doses of the drug or who have predisposing factors (e.g., a history of seizures, treatment for epilepsy or meningitis). In patients with renal insufficiency, the dosing regimen should be adjusted according to the degree of renal insufficiency.

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

There is a possibility that elevated concentrations of amoxicillin in serum and urine may affect the results of some laboratory tests. When using chemical methods, high concentrations of amoxicillin in the urine may be the cause of false-positive test results.

To determine the presence of glucose in the urine during treatment with amoxicillin it is recommended to use enzymatic glucose oxidase methods. The use of amoxicillin can distort the results of quantitative determination of estriol in pregnant women.

Impact on the ability to drive vehicles, mechanisms

There are no data on the effect of amoxicillin on the ability to drive a car or other mechanical devices.

There have been no studies on the effect of amoxicillin on the ability to drive vehicles, mechanisms. Patients should be warned about the possibility of allergic reactions, dizziness and convulsions that may affect the ability to drive vehicles, mechanisms. In case of the occurrence of the described adverse events, one should refrain from performing the specified activities.

Contraindications

– infectious mononucleosis, lympholeukosis;

– childhood under 3 years (for this dosage form).

With caution

– Allergic reactions (including Bronchial asthma, pollinosis, hypersensitivity to acetylsalicylic acid) in history;

– A history of gastrointestinal disease (especially colitis associated with the use of antibiotics);

– renal failure;

– pregnancy and breastfeeding.

Side effects

The most common adverse drug reactions (ADRs) are diarrhea, nausea, and skin rash. Classification of adverse reactions by organs and systems by frequency of occurrence: very common (≥1/10), common (≥1/100, < 1/10), infrequent (≥1/1000, < 1/100), rare (≥1/10000, < 1/1000), very rare (< 1/10000), including individual reports, frequency unknown (frequency cannot be estimated based on available data).

Infectious and parasitic diseases

Very rare: candidiasis of the skin and mucous membranes.

Blood and lymphatic system disorders

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

Immune system disorders

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

Prevalence unknown: Jarisch-Herxheimer reaction, allergic acute coronary syndrome (Coneys syndrome).

Nervous system disorders

Very rare: hyperkinesia, dizziness and seizures.

Prevalence unknown: aseptic meningitis.

Gastrointestinal disorders

* Often: diarrhea, nausea.

* Infrequent: vomiting.

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

Hepatic and biliary tract disorders

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

Skin, subcutaneous tissue disorders

*Frequently: skin rash.

*Infrequent: urticaria and skin itching.

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

Renal and urinary system disorders

Very rare: interstitial nephritis, crystalluria.

* The incidence of these NLDs was derived from clinical studies involving, in total, about 6,000 adult patients and children treated with amoxicillin.

Overdose

Symptoms

Nausea, vomiting, diarrhea, crystalluria, water-electrolyte imbalance (as a consequence of vomiting and diarrhea), seizures, agitation, confusion.

Treatment

Symptomatic – gastric lavage, activated charcoal, saline laxatives, drugs to maintain water-electrolyte balance, hemodialysis.

Pregnancy use

The results of animal studies indicate no direct or indirect effects on reproductive toxicity. Limited data on the use of amoxicillin in humans during pregnancy do not indicate an increased risk of congenital malformations. The drug may be used during pregnancy only when the expected benefit to the mother outweighs the potential risk to the fetus.

Amoxicillin is excreted into breast milk in small amounts, if necessary, the drug can be used during breastfeeding. A child who is being breastfed may develop diarrhea, sensitization and fungal infections of the mucous membranes, therefore it may be required to stop breastfeeding. Amoxicillin should be used during breastfeeding only after evaluation by the treating physician of the benefit/risk ratio.

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