Amoxicillin + Clavulanic acid - instructions for use, dose, side effects, contraindications

Excipients: cellulose microcrystalline 80.58 mg / 118.83 mg / 110.74 mg, sodium carboxymethyl starch 6.65 mg / 10 mg / 14.35 mg, silicon dioxide colloid 6.65 mg / 10 mg / 14.35 mg, magnesium stearate 6.65 mg / 10 mg / 14.35 mg, opadrai white 06B58855 (hypromellose-5cP 14.62 mg / 21.49 mg / 30.96 mg, hypromellose-15cP 1.36 mg / 1.99 mg / 2.88 mg, macrogol-400 2.18 mg / 3.21 mg / 4.62 mg, titanium dioxide 6.12 mg (8.99 mg / 12.96 mg).

Description:

Dosage of 250 mg + 125 mg: biconvex, oval-shaped tablets coated with a white or almost white-colored film shell, engraved "A" on one side and "63" on the other side.

On the cross section: the core is light yellow, surrounded by a film shell of white or almost white color.

Dosage 500 mg + 125 mg: biconcave, oval-shaped tablets coated with a white or almost white film shell, engraved "A" on one side and "64" on the other side.

On the cross-section: the core is light yellow, surrounded by a film sheath white or almost white.

Dosage 875 mg + 125 mg: biconvex, oval-shaped tablets coated with a white or almost white film shell, engraved "A" on one side and between the engraving "6" and "5" on the other side.

On the cross section: the core is light yellow, surrounded by a film shell of white or almost white color.

Pharmacotherapeutic group:Antibiotic-penicillin semisynthetic + beta-lactamase inhibitor

ATX: & nbsp

J.01.C.R.02 Amoxicillin in combination with enzyme inhibitors

Pharmacodynamics:

Broad-spectrum antibiotic; contains semisynthetic penicillin amoxicillin and the beta-lactamase inhibitor clavulanic acid.

Amoxicillin is a semisynthetic broad-spectrum antibiotic that is active against many Gram-positive and Gram-negative microorganisms. Amoxicillin (β-lactamases, therefore, the spectrum of its antibacterial activity does not include β-lactamase-producing microorganisms.) Clavulanic acid inhibits the majority of clinically significant β-lactamases (Types 2, 3, 4 and 5 according to Richmond Sykes classification) produced Staphylococcus spp., Escherichia coli, Proteus mirabilis, Haemophilus influenzae, Moraxella catarrhal is, Bacteroides spp. It is inactive for type I β-lactamases produced Enterobacter spp., Morganella morganii, Pseudomonas aeruginosa, Serratia spp., Acinetobacter spp. The presence of clavulanic acid protects amoxicillin from the destructive effect of β-lactamases and expands the spectrum of its antibacterial activity with the inclusion of microorganisms usually resistant to other penicillins and cephalosporins. This combination provides a high bactericidal activity of the combination "amoxicillin + clavulanic acid" (including against strains of microorganisms resistant to amoxicillin). Thus, the combination "amoxicillin + clavulanic acid" acts bactericidally on a wide range of gram-positive and gram-negative bacteria (including strains that have become resistant to beta-lactam antibiotics due to production of beta-lactamases).

The combination of "amoxicillin + clavulanic acid" is active in vivo and in vitro for the following microorganisms:

Gram-positive aerobes: Staphylococcus aureus (except methicillin-resistant strains), Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus saprophyticus, Enterococcus spp. (at Tom number of, Enterococcus faecium, Enterococcus faecalis);

gram-negative aerobes: Enterobacter spp., Escherichia coli, Haemophilus influenzae, Klebsiella spp., Moraxella catarrhalis, Neisseria gonorrhoeae;

anaerobic bacteria: Bacteroides spp. (incl. Bacteroides fragilis).

The combination of amoxicillin + clavulanic acid "is active in vitro for the following microorganisms:

Gram-positive aerobes: Streptococcus spp. (including, Streptococcus groups viridans), Enterococcus faecalis, Staphylococcus saprophyticus, Streptococcus milleri, Streptococcus bovis, Streptococcus agalactiae), Staphylococcus epidermidis (except methicillin-resistant strains), Corynebacterium spp., Listeria monocytogenes, Nocardia aster about ides;

gram-negative aerobes: Bordetella pertussis, Brucella spp., Gardnerella vaginalis, Helicobacter pylori, Klebsiella spp., Legionella pneumophila, Neisseria meningitidis, Pasteurella multocida, Proteus mirabilis, Proteus vulgaris, Salmonella spp., Shigella spp., Vibrio cholerae, Yersinia enterocolitica (moderately sensitive);

anaerobic bacteria: Clostridium spp. (Besides Clostridium difficile), Peptostreptococcus spp., Fusobacterium spp.;

Other: Treponema pallidum, Leptospira icterohaemorrhagiae, Chlamydiae spp., Borrelia burgdorferi.

Pharmacokinetics:

Suction

Both active ingredients amoxicillin and clavulanic acid are rapidly and completely absorbed from the gastrointestinal tract (GIT) after ingestion. The maximum concentration of the drug in the blood plasma (C_m_Oh) is achieved 1 hour after taking the drug. Absorption of the active ingredients of the combination "amoxicillin + clavulanic acid" is optimal in case of admission at the beginning of the meal.

Distribution

Amoxicillin and clavulanic acid have a moderate degree of binding to blood plasma proteins. Studies have shown that 25% of the total amount of clavulanic acid and 18% of amoxicillin bind to plasma proteins.High concentrations are found in the body fluids and tissues (lung, pleural, peritoneal, synovial fluids, tonsils, bronchial secretions, prostate, peritoneal abscess, muscle tissue, adipose tissue, secretions sinuses, middle ear). Amoxicillin, as and most penicillins penetrate into breast milk. Breast milk also found trace amounts of clavulanic acid. In experimental studies it was established that amoxicillin and clavulanic acid penetrate the placental barrier.

Excretion

Like other penicillins, amoxicillin It is eliminated in the kidneys, whereas clavulanic acid through both the renal and extrarenal mechanisms. Approximately 60-70% amoxycillin and about 40-65% of clavulanic acid excreted by the kidneys in unchanged form in the first 6 hours after application of 1 tablet 250 mg / 125 mg or 500 mg / 125 mg. About 10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of inactive penicillic acid. Clavulanic acid in the human body is exposed to an intensive metabolism 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 and intestines.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to the combination "amoxicillin + clavulanic acid":

- Infections of ENT organs, for example, relapsing tonsillitis, sinusitis, otitis media, usually caused Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pyogenes.

- Infections of the lower respiratory tract, for example exacerbations of chronic bronchitis, lobar pneumonia and bronchopneumonia, usually caused Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.

- Urinary tract infections, such as cystitis, urethritis, pyelonephritis, infections of female genitalia, usually caused by species of the family Enterobacteriaceae (mainly Escherichia coli), Staphylococcus saprophyticus and species Enterococcus, as well as gonorrhea caused by Neisseria gonorrhoeae.

- Infections of the skin and soft tissues, usually caused Staphylococcus aureus, Streptococcus pyogenes and species Bacteroides.

- Infections of bones and joints, for example, osteomyelitis, usually caused by Staphylococcus aureus, if necessary, prolonged therapy.

- Other mixed infections, for example, post-abortive sepsis, postpartum sepsis, intra-abdominal infections (as part of stepwise therapy).

Contraindications:

- Pincreased sensitivity to penicillins, cephalosporins, other beta-lactam antibiotics and other components of the drug;

- Cholestatic jaundice and impaired liver function associated with the administration of a combination of "amoxicillin + clavulanic acid" or penicillin in history;

- infectious mononucleosis (including when there is a measles-like rash);

- creatinine clearance (CK) less than 30 ml / min (for tablets 875 mg / 125 mg)

- children under 12 years (for this dosage form).

Carefully:

Pregnancy, lactation, impaired liver function, gastrointestinal diseases (including colitis in history, associated with the use of penicillins), impaired renal function.

Pregnancy and lactation:

There were no teratogenic effects of the drug. In the presence of indications, the combination "amoxicillin + clavulanic acid" is permissible to prescribe during pregnancy, if the benefit to the mother exceeds the potential risk to the fetus. In a single study in women with premature rupture of membranes, it was found that preventive therapy with the combination "amoxicillin + clavulanic acid" may be associated with an increased risk of developing necrotizing enterocolitis in newborns.

It is possible to use the combination "amoxicillin + clavulanic acid" during lactation, but it should be taken into account that trace concentrations of amoxicillin are found in breast milk.Except for the risk of sensitization, no other adverse effects of amoxicillin and clavulanic acid on the health of infants fed by breast milk are known.

Dosing and Administration:

The dosage regimen is set individually depending on the age, body weight, kidney function, and also on the severity of the infection.

For optimal absorption and reduce possible side effects from the digestive system, the drug is recommended to be taken at the beginning of the meal.

If necessary, it is possible to perform stepwise therapy (first intravenous administration of the drug with a subsequent transition to oral administration).

Adults and children over 12 years of age or weighing more than 40 kg

For infections of mild to moderate severity: 500 mg / 125 mg every 12 hours or 250 mg / 125 mg every 8 hours.

In severe infections and infections of the respiratory system: 1 tablet 875 mg / 125 mg 2 times a day or 1 tablet 500 mg / 125 mg 3 times a day.

The maximum daily dose of amoxicillin for adults and children over 12 years is 6 g. The maximum daily dose of clavulanic acid for adults and children over 12 years is 600 mg.

The minimum course of antibiotic therapy is 5 days.After 2 weeks after the start of treatment, it is recommended to evaluate the clinical situation for making a decision on the continuation of the course of antibiotic therapy. The duration of treatment of acute uncomplicated otitis media is 5-7 days.

It should be remembered that 2 tablets of the drug at 250 mg / 125 mg are not equivalent to one tablet of the drug 500 mg / 125 mg.

Application for renal dysfunction

Correction of doses is based on the maximum recommended dose of amoxicillin and is performed taking into account the values of CC.

QC Dosing regimen

>30 ml / min Correction of dose is not required

10-30 ml / min 1 tablet 500 mg / 125 mg 2 times / day or 1 tablet 250 mg (with lung and medium-heavy infection) 2 times / day

<10 ml / min 1 tablet 500 mg / 125 mg 1 time / day or 1 tablet 250 mg / 125 mg (with light and medium-heavy infection) 1 time / day

Tablets 875 mg / 125 mg should be used only in patients with CK> 30 ml / min.

Patients on hemodialysis

Adults are assigned 1 tablet (500 mg / 125 mg) or 2 tab (250 mg / 125 mg) every 24 hours. Additionally, 1 dose is given during the dialysis session and 1 dose at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulan acid).

Application for violations of liver function

The combination "amoxicillin + clavulanic acid" should be used with caution in this category of patients, as well as a regular monitoring of liver function. There is insufficient data for correcting the dosing regimen in this category of patients.

Elderly patients

Correction of the dose is not required.

In elderly patients with impaired renal function, the dose should be adjusted as described above for adults with impaired renal function.

Side effects:

From the hematopoietic system: anemia, reversible leukopenia (including neutropenia), thrombocytopenia, thrombocytopenic purpura, eosinophilia, thrombocytosis, reversible agranulocytosis and hemolytic anemia, increased bleeding time and prothrombin time.

From the skin and subcutaneous tissues: angioedema, anaphylactic reactions, whey-like syndrome, allergic vasculitis, anaphylactic shock, skin rash, itching, urticaria, erythema multiforme, erythema rash, erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustules.

From the central nervous system: dizziness, headache, reversible hyperactivity and convulsions, behavioral changes, confusion, insomnia, agitation, anxiety. Seizures may occur in patients with impaired renal function and in patients receiving high doses of the drug.

From the gastrointestinal tract: diarrhea, nausea, vomiting, dyspeptic phenomena, gastritis, stomatitis, glossitis, enterocolitis, black "hairy" tongue.

Dyspepsia, antibiotic-associated colitis (pseudomembranous and hemorrhagic) was also noted.

From the side liver: moderate increase in activity aspartate aminotransferase (ACT) and / or alanine aminotransferase (ALT). In addition, hepatitis, cholestatic jaundice, impaired liver function were noted. There is also an increase in the concentration of bilirubin, alkaline phosphatase.

Side effects from the liver are reversible, occur during or shortly after the end of treatment. Occur mainly in men and elderly patients and may be associated with long-term therapy. Dysfunction of the liver can be of varying severity, up to life-threatening (mainly in patients with severe previous illnesses or in patients who received potentially hepatotoxic drugs).

From the side of the kidneys and urinary tract: interstitial nephritis, crystalluria, hematuria.

Other: Candidiasis of the mucous membranes, change in staining of the teeth (brown, yellow or gray staining).

Overdose:

Symptoms: predominantly gastrointestinal disorders (abdominal pain, vomiting, diarrhea) and disturbances of the water-electrolyte balance. In addition, a small number of patients had rash, hyperactivity, or drowsiness. Amoxicillin crystalluria is described, in some cases leading to the development of renal failure.

Treatment: carrying out symptomatic therapy, correction of water-electrolyte balance. Amoxicillin + clavulanic acid is removed from the blood by hemodialysis.

Interaction:

Antacids, glucosamine, laxative drugs, aminoglycosides slow down and reduce the absorption of the combination "amoxicillin + clavulanic acid"; ascorbic acid increases absorption.

Probenecid reduces tubular secretion of amoxicillin,and therefore simultaneous use with probenecid can lead to an increase in the concentration of amoxicillin, but not clavulanic acid. The combination "amoxicillin + clavulanic acid" is not recommended to be used simultaneously with probenecid. Bacteriostatic medicinal products (macrolides, chloramphenicol, lincosamides, tetracyclines, sulfonamides) have an antagonistic effect.

Increases the effectiveness of indirect anticoagulants (suppressing the intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). With the simultaneous use of anticoagulants, it is necessary to monitor the coagulability of blood. Reduces the effectiveness of oral contraceptives (this should be informed to patients), drugs, in the process of metabolism which produces para-aminobenzoic acid (PABA), ethinyl estradiol - the risk of bleeding "breakthrough".

Diuretics, allopurinol, phenylbutazone, non-steroidal anti-inflammatory drugs (NSAIDs) and other drugs that block tubular secretion, increase the concentration of amoxicillin (clavulanic acid is excreted mainly by glomerular filtration).

Allopurinol increases the risk of skin rash.

Special instructions:

Before starting treatment, you must collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Serious and sometimes fatal hypersensitivity reactions (anaphylactic reactions) to penicillins are described. The risk of occurrence of such reactions is highest in patients who have a history of hypersensitivity reactions to antibiotics of this group.

In case of an allergic reaction, it is necessary to stop treatment with the drug and start alternative therapy. In severe reactions of hypersensitivity, adrenaline should be administered immediately (epinephrine). Oxygen therapy, intravenous glucocorticosteroids, and airway patency, including intubation, may also be required.

In course treatment it is necessary to monitor the status of the functions of the organs of hematopoiesis, liver and kidneys.

It is necessary to refrain from using the combination "amoxicillin + clavulanic acid" in case of suspected infectious mononucleosis, since in patients with this disease amoxicillin can cause skin rashes, which makes it difficult to diagnose the disease.

The severity of gastrointestinal side effects can be reduced by taking the combination "amoxicillin + clavulanic acid" at the beginning of the meal.

High concentrations of the drug give a false positive reaction to glucose in the urine when using a Benedict reagent or Fehling solution (it is recommended to use enzymatic reactions with glucose oxidase).

In patients taking antibacterial drugs, including amoxicillin, should take into account the risk of developing pseudomembranous colitis of varying severity.

About cases of diarrhea associated with Clostridium difficile, was reported in connection with the use of almost all antibacterial drugs, including a combination of "amoxicillin + clavulanic acid." The severity of diarrhea can range from mild forms to heavy. Treatment with antibacterial drugs disrupts the normal intestinal microflora, which leads to excessive growth Clostridium difficile. Clostridium difficile produces toxins A and B, which lead to the development of diarrhea associated with Clostridium difficile. Excessive amount of toxins produced by strains Clostridium difficile, can cause an increase in mortality among patients, since such infections can be resistant to antimicrobial therapy, and may require a columnectomy.

The possibility of developing diarrhea associated with Clostridium difficile, should be considered in all patients with diarrhea that followed the use of antibiotics. Careful medical supervision for 2 months is necessary for patients who have had diarrhea associated with Clostridium difficile after using antibacterial drugs.

In case of suspicion of the possibility of developing diarrhea associated with Clostridium difficile or confirmed diagnosis, it is necessary to cancel the antibiotic. It should be appropriate control of water-electrolyte balance, antibiotic therapy C. difficile, and examination for the need for surgical intervention.

In women with premature rupture of membranes, it was found that preventive therapy with the combination "amoxicillin + clavulanic acid" may increase the risk of necrotizing enterocolitis in newborns.

Long-term treatment with the combination of "amoxicillin + clavulanic acid" can be accompanied by excessive growth of insensitive microorganisms.

To reduce the formation of crystals of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain adequate diuresis.

In most cases, the dyeing of the teeth was removed with the usual brushing of teeth.

Effect on the ability to drive transp. cf. and fur:Since the combination "amoxicillin + clavulanic acid" can cause dizziness, care should be taken when driving or other mechanisms.

Form release / dosage:

Tablets, film-coated 250 mg + 125 mg, 500 mg + 125 mg, 875 mg + 125 mg.

Packaging:

For 7 tablets in a blister of three-layer PA / Aluminum / PVC film and aluminum foil.

2 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

In a dry place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001372

Date of registration:20.12.2011 / 28.08.2013

Expiration Date:20.12.2016

The owner of the registration certificate: Pfizer Inc. Pfizer Inc. USA

Manufacturer: & nbsp

AUROBINDO PHARMA, Ltd. India

Representation: & nbspAurobindo Pharma, ZAOAurobindo Pharma, ZAO

Information update date: & nbsp19.08.2017

Illustrated instructions

Instructions

Amoxicillin + Clavulanic acid (Amoxicillin + Clavulanic acid)