Augmentin SR - instructions for use, dose, side effects, contraindications

Name of components	Amount, mg
*Immediate Release Layer (HB):*
Active substances
Amoxicillin trihydrate, equivalent	654,1
amoxicillin	(562,5)
Potassium clavulanate equivalent to clavulanate	76,2
acid	(62,5)
Excipients
Microcrystalline cellulose	136,4
Sodium carboxymethyl starch	18,0
Silica dioxide colloidal anhydrous	6,3
Magnesium stearate	9,0
Total (HB-layer)	900,0
*The layer providing gradual release (PV):*
Active substances
Amoxicillin sodium, equivalent	480,8
amoxicillin	(437,5)
Excipients
Microcrystalline cellulose		111,7
Xanthan gum		14,0
Lemon acid		78,0
Silica dioxide colloidal anhydrous		1,5
Magnesium stearate		14,0
Total (PV layer)		700,0
Total mass of the core of the tablet		1600,0
*Components of aqueous film shell:*
Hypromellose (6 cp)		11,6
Hypromellose (15 cps)		3,9
Titanium dioxide		15,1
Macrogol 3350		2,3
Macrogol 8000		2,3
*The total weight of the film-coated tablet*		*1635,2*

Description:

The tablets, covered with a film shell, are white, capsular-shaped, on one side there is engraved "AS 1000 / 62.5", on the other - a separation groove.

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

ATX: & nbsp

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

Pharmacodynamics:Mechanism of action

Amoxicillin is a semisynthetic broad-spectrum antibiotic with activity against many Gram-positive and Gram-negative microorganisms. In the same time amoxicillin is subject to destruction by beta-lactamases, and therefore the spectrum of amoxicillin activity does not extend to microorganisms that produce this enzyme.

Clavulanic acid, a beta-lactamase inhibitor structurally related to penicillins, has the ability to inactivate a wide spectrum of beta-lactamases found in microorganisms resistant to penicillins and cephalosporins. Clavulanic acid has sufficient efficacy against plasmid beta-lactamases, which most often cause bacterial resistance, and is not effective against type 1 chromosomal beta-lactamases,which are not inhibited by clavulanic acid.

The presence of clavulanic acid in the preparation of Augmentin ® protects amoxicillin from destruction by enzymes - beta-lactamases, which allows to expand the antibacterial spectrum of amoxicillin.

The activity of a combination of amoxicillin with clavulanic acid in vitro is given below.

Bacteria, usually sensitive to a combination of amoxicillin and clavulanic acid

Gram-positive aerobes

Bacillus anthracis

Enterococcus faecalis

Listeria monocytogenes

Nocardia asteroides

Streptococcus pyogenes^1,2

Streptococcus agalactiae^1,2

Streptococcus spp. (other beta-hemolytic streptococci)^1,2

Staphylococcus aureus (sensitive to methicillin)¹

Staphylococcus saprophyticus (sensitive to methicillin)

Coagulase-negative staphylococci (sensitive to methicillin)

Gram-positive anaerobes

Clostridium spp.

Peptococcus niger

Peptostreptococcus magnus

Peptostreptococcus micros

Peptostreptococcus spp.

Gram-negative aerobes

Bordetella pertussis

Haemophilus influenzae¹

Helicobacter pylori

Moraxella catarrhalis¹

Neisseria gonorrhoeae

Pasteurella multocida

Vibrio cholerae

Gram-negative anaerobes

Bacteroides fragilis

Bacteroides spp.

Capnocytophaga spp.

Eikenella corrodens

Fusobacterium nucleatum

Fusobacterium spp.

Porphyromonas spp.

Prevotella spp.

Other

Borrelia burgdorferi

Leptospira icterohaemorrhagiae

Treponema pallidum

Bacteria for which the acquired resistance to a combination of amoxicillin and clavulanic acid is probable

Gram-negative aerobes

Escherichia coli1

Klebsiella oxytoca

Klebsiella pneumoniae¹

Klebsiella spp.

Proteus mirabilis

Proteus vulgaris

Proteus spp.

Salmonella spp.

Shigella spp.

Gram-positive aerobes

Coiynebacterium spp.

Enterococcus faecium

Streptococcus pneumoniae^1,2

Streptococcus group Viridans

Bacteria that have natural resistance to a combination of amoxicillin and clavulanic acid

Gram-negative aerobes

Acinetobacter spp.

Citrobacterfreundii

Enterobacter spp.

Hafnia alvei

Legionella pneumophila

Morganella morganii

Providencia spp.

Pseudomonas spp.

Serratia spp.

Stenotrophomonas maltophilia

Yersinia enterocolitica

Other

Chlamydia pneumoniae

Chlamydia psittaci Chlamydia spp. Coxiella burnetii

Mycoplasma spp.

¹ - for these bacteria, the clinical efficacy of a combination of amoxicillin with clavulanic acid has been demonstrated in clinical studies.

² - strains of these bacteria do not produce beta-lactamases.

Sensitivity to monotherapy with amoxicillin suggests a similar sensitivity to the combination of amoxicillin and clavulanic acid.

Pharmacokinetics:

Suction

Both active substances of the drug Augmentin® SR, amoxicillin and clavulanic acid, readily dissolve in aqueous solutions with a physiological pH value, are rapidly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of active substances is optimal in case of taking the drug at the beginning of food intake.

Below are the pharmacokinetic parameters of amoxicillin and clavulanic acid after taking two tablets of the drug Augmentin SR in healthyvolunteers at the beginning of food intake.

Mean value of pharmacokinetic parameters

A drug	Dose (mg)	T> MPK'h (%)	FROMmOh (mg / L)	Tmax (H)	AUC (ICGH h / ml)	T1 / 2 (H)
Amoxicillin
Augmentin® SR 1000 mg + 62.5 mg x 2	2000	5,9 (49,4)	17,00	1.50	71,60	1,27
Clavulanic acid
Augmetin ®SR 1000 mg + 62.5 mg x 2	125	ND	2.05	1.03	5,29	1,03

T> MPC h (%) is the time (as a percentage of the time interval between doses), during which the concentration of the drug in the blood is above the minimum inhibitory concentration for a particular pathogen.

FROMmah - the maximum concentration in the blood plasma.

Tmah - time to reach the maximum concentration in the blood plasma.

AUC is the area under the concentration-time curve.

T1 / 2 - half-life.

ND - undefined.

1 - for bacteria with a minimum inhibitory concentration (MIC) of 4 mg / l.

The drug Augmentin® SR has a unique pharmacological profile, the T> MIC characteristic of this drug is not achieved when taking tablets with immediate release of active substances containing a combination of amoxicillin and clavulanic acid.

Distribution

As with intravenous administration of a combination of amoxicillin and clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid are produced in various tissues and interstitial fluid(in the gall bladder, abdominal cavity tissues, skin, fat and muscle tissues, 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 bind to plasma proteins.

In animal studies, no cumulation of the components of the Augmentin® SR preparation in any organ was detected.

Amoxicillin, like most penicillins, penetrates into breast milk. Breast milk also found trace amounts of clavulanic acid. With the exception of the possibility of developing sensitization, diarrhea and candidiasis of the oral mucosa, no other adverse effects of amoxicillin and clavulanic acid on the health of infants fed by breast milk are known. Studies of reproductive function in animals with the use of the drug Augmentin ® SR showed that amoxicillin and clavulanic acid penetrate the placental barrier. However, there was no adverse effect on the fetus.

Metabolism

10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic acid). Clavulanic acid undergoes intensive metabolism to 2,5-dihydro-4- (2-hydroxyethyl) -5-oxo-III-pyrrole-3-carboxylic acid and 1-amino-4-hydroxybutan-2-one and is excreted by the kidneys, Through the gastrointestinal tract, as well as with exhaled air in the form of carbon dioxide.

Excretion

Like other penicillins, amoxicillin is excreted mainly by the kidneys, whereas clavulanic acid is excreted through both renal and extrarenal mechanisms.

Studies have shown that, on average, approximately 60-70% of amoxicillin and about 40-65% of clavulanic acid is excreted by the kidneys unchanged. Simultaneous administration of probenecid slows the excretion of amoxicillin, but does not slow the excretion of clavulanic acid (see section "Interaction with other drugs").

Indications:

The drug Augmentin SR is indicated for the treatment of bacterial infections of the following localizations caused by microorganisms sensitive to the combination of amoxicillin and clavulanic acid.

- Respiratory tract infections, for example community-acquired pneumonia,exacerbation of chronic bronchitis, acute bacterial sinusitis, commonly caused by Streptococcus pneumoniae (including penicillin-resistant strains), Haemophilus influenzae *, Moraxella catarrhalis * and Streptococcus pyogenes.

- Prevention of local infections after surgery in dentistry.

* - some strains of these bacteria produce beta-lactamases, which makes them insensitive to monotherapy with amoxicillin (see section "Pharmacological properties"). Infections caused by microorganisms sensitive to amoxicillin can be treated with the Augmentin® SR preparation, since amoxicillin is one of its active substances. The drug Augmentin® SR is also indicated for the treatment of mixed infections caused by microorganisms that are sensitive to amoxicillin, as well as by microorganisms producing beta-lactamase that are sensitive to a combination of amoxicillin and clavulanic acid. The sensitivity of bacteria to the combination of amoxicillin and clavulanic acid varies depending on the region and over time. Wherever possible, local sensitivity data should be taken into account. If necessary, the collection of microbiological samples and analysis for bacteriological sensitivity should be carried out.

Contraindications:

- Hypersensitivity to amoxicillin, clavulanic acid, other components of the drug, beta-lactam antibiotics (for example, penicillins, cephalosporins) in the anamnesis;

- previous episodes of jaundice or impaired liver function with a combination of amoxicillin and clavulanic acid in history;

- Children's age till 16 years;

- impaired renal function (creatinine clearance less than 30 ml / min);

- hemodialysis.

Carefully:

The drug Augmentin® SR should be used with caution in patients with impaired hepatic function.

Pregnancy and lactation:

Pregnancy

In studies of reproductive function in animals, oral and parenteral administration of a combination of amoxicillin and clavulanic acid did not produce teratogenic effects. In a single study in women with premature rupture of membranes, it was found that preventive therapy with the drug may be associated with an increased risk of developing necrotizing enterocolitis in newborns. Like all medicines, Augmentin® SR is not recommended for use during pregnancy, unless the expected benefit to the mother exceeds the potential risk to the fetus.

Breastfeeding period

The drug Augmentin ® SR can be used during breastfeeding. Except for the possibility of developing sensitization, diarrhea, or candidiasis of the oral mucosa associated with the penetration of trace amounts of the active ingredients of this preparation into breast milk, no other adverse effects were observed in infants fed breastfeeding. In case of adverse effects in children who are breastfeeding, it is necessary to stop it.

Dosing and Administration:

For oral administration.

To optimize absorption, the drug should be taken at the beginning of the meal.

Treatment should not last more than 14 days without reviewing the clinical situation. The tablets of the Augmentin® SR preparation have a separation groove that allows them to be broken in half for ease of ingestion, but not to reduce the dose: both halves must be taken simultaneously. The recommended dose of the drug is 2 tablets 2 times a day.

Adults (16 years and over)

Respiratory tract infections: 2 tablets 2 times a day for 7-10 days, including:

Community-acquired pneumonia	2 tablets 2 times a day for 7-10 days
Exacerbation of chronic bronchitis	2 tablets 2 times a day for 7 days
Acute sinusitis of bacterial etiology	2 tablets 2 times a day for 10 days

Prevention of local infections after surgical dental interventions: 2 tablets 2 times a day for 5 days starting 3 hours after the intervention.

Special patient groups

Children under 16 years old

Not applicable.

Elderly patients

No dosage adjustment is required.

Patients with impaired renal function

No dosage adjustment is required for creatinine clearance greater than or equal to 30 ml / min.

It is not recommended to administer the drug to patients with creatinine clearance below 30 ml / min.

Patients on hemodialysis

Not recommended.

Impaired liver function

Treat with caution; regularly monitor liver function.

There is not enough data to recommend a dosing regimen for this group of patients.

Side effects:

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence.Frequency of occurrence is defined as follows: very often (≥1 / 10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1,000 and <1/100), rarely (≥1 / 10,000 and <1/1 000), very rarely (<1/10 000, including individual cases). Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.

Frequency of occurrence of undesirable reactions:

Infectious and parasitic diseases

Often: genital moniliasis, skin-mucous candidiasis.

Violations of the blood and lymphatic system

Rarely: reversible leukopenia (including neutropenia) and thrombocytopenia. Very rarely: reversible agranulocytosis and hemolytic anemia, prolongation of bleeding time and prothrombin time.

Immune system disorders

Very rarely: angioedema, anaphylactic reactions, a syndrome similar to serum illness, allergic vasculitis.

Disturbances from the nervous system

Infrequent: dizziness, headache, weakness. Very rarely: reversible hyperactivity, convulsions.

Disorders from the gastrointestinal tract

Very often: diarrhea. Often: nausea, abdominal pain.Infrequent: vomiting, indigestion. Very rarely: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis - see the "Special instructions" section), a black "hairy" tongue.

Disturbances from the liver and bile ducts

Infrequent: moderate increase in activity of aspartate aminotransferase and / or alanine aminotransferase (ACT and / or ALT). This reaction is observed in patients receiving beta-lactam antibiotic therapy, but its clinical significance is unknown. Very rarely: hepatitis and cholestatic jaundice. This reaction is observed in patients receiving penicillin antibiotics and cephalosporins.

Undesirable reactions from the liver have been observed mainly in men and elderly patients and can be associated with long-term therapy.

These signs and symptoms usually occur in the process or immediately after the end of therapy, but in some cases may not appear for several weeks after the completion of therapy. Undesirable reactions are usually reversible. Undesirable reactions from the liver can be severe, in extremely rare cases there have been reports of lethal outcomes.In almost all cases, these were patients with severe concomitant pathologies or patients who received potentially hepatotoxic drugs at the same time.

Disturbances from the skin and subcutaneous tissues

Infrequent: rash, itching, hives. Rarely: multimorphic erythema. Very rarely: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

Disorders from the kidneys and urinary tract

Very rarely: interstitial nephritis, crystalluria (see section "Overdose").

Overdose:

Symptoms

Symptoms on the part of the gastrointestinal tract and violations of the water-electrolyte balance can be observed. Amoxicillin crystalluria is described, in some cases leading to the development of renal insufficiency (see section "Special instructions"), in patients with impaired renal function, as well as in those who receive high doses of the drug, convulsions may occur.

Treatment

Symptoms from the gastrointestinal tract are symptomatic therapy, paying special attention to the normalization of the water-electrolyte balance. Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.

Interaction:

Simultaneous use of the drug Augmentin SR and probenecid is not recommended. Probenecid reduces the tubular secretion of amoxicillin, and therefore simultaneous use of the drug Augmentin® SR and probenecid can lead to an increase and persistence in the blood concentration of amoxicillin, but not clavulanic acid.

The simultaneous use of allopurinol and amoxicillin may increase the risk of skin allergic reactions. Currently, there is no data in the literature on the simultaneous use of a combination of amoxicillin with clavulanic acid and allopurinol. Penicillins can slow the excretion of methotrexate from the body by inhibiting its tubular secretion, so the simultaneous use of the drug Augmentin SR and methotrexate may increase the toxicity of methotrexate.

Like other antibacterial drugs, the drug Augmentin ® SR can affect the intestinal microflora, leading to a decrease in absorption of estrogens from the gastrointestinal tract and a decrease in the effectiveness of combined oral contraceptives.

In the literature, rare cases of an increase in the international normalized relationship (INR)in patients with the joint use of acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously prescribe the drug Augmentin SR with anticoagulants, prothrombin time or INR should be carefully monitored with the appointment or discontinuation of the drug Augmentin SR, a correction of the dose of anticoagulants for oral administration may be required.

In patients who received mycophenolate mofetil, after the start of the combination of amoxicillin with clavulanic acid, a decrease in the concentration of the active metabolite, mycophenolic acid, was observed, before taking the next dose of the drug by approximately 50%. Changes in this concentration can not accurately reflect the overall changes in the exposure of mycophenolic acid.

Special instructions:

Before starting treatment with Augmentin ® SR, a detailed history of previous hypersensitivity reactions to penicillins and cephalosporins should be collected. Serious and sometimes lethal 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 penicillins.In the event of an allergic reaction, it is necessary to stop treatment with the drug Augmentin SR and begin the appropriate alternative therapy. Serious anaphylactic reactions should be promptly administered to the patient epinephrine. Oxygen therapy, intravenous glucocorticosteroids, and airway patency, including intubation, may also be required. In case of any allergic reactions treatment with the drug Augmentin ® SR should be discontinued.

In case of suspected infectious mononucleosis, the drug Augmentin® SR should not be used because patients with this disease amoxicillin can cause a skinlike skin rash, which makes it difficult to diagnose the disease. Long-term treatment with the drug Augmentin® SR sometimes leads to excessive reproduction of insensitive microorganisms.

Patients who received a combination of amoxicillin with clavulanic acid together with indirect (oral) anticoagulants rarely reported increase prothrombin time (increase INR).When co-administration of indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, monitoring of the relevant indicators is necessary. To maintain the necessary effect of oral anticoagulants, their dose may need to be adjusted.

It is not necessary to adjust the dose of the drug Augmentin ® CP for patients with creatinine clearance> 30 ml / min. Contraindicated the appointment of the drug to patients with creatinine clearance below 30 ml / min.

In patients with reduced diuresis, in very rare cases, the development of crystalluria was reported, mainly with the parenteral administration of the drug. When taking high doses of amoxicillin, it is recommended to take a sufficient amount of fluid and maintain an adequate diuresis to reduce the likelihood of amoxicillin crystals (see also the section "Overdose"),

There are cases of pseudomembranous colitis occurring when taking antibiotics, the severity of which can range from mild to life-threatening. Therefore, it is important to consider the possibility of developing pseudomembranous colitis in patients with diarrhea during or after antibiotic use.If diarrhea is prolonged or severe, or the patient experiences abdominal cramps, treatment should be stopped immediately and the patient should be examined.

During prolonged therapy with the drug Augmentin ® CP it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis.

Taking the drug Augmentin8 SR inside leads to a high content of amoxicillin in the urine, which can lead to false-positive results in determining glucose in the urine (for example, the Benedict test, Feeling's test). In this case, it is recommended to use a glucose oxidant method for determining the concentration of glucose in the urine.

Clavulanic acid can cause a non-specific binding of class G and albumin immunoglobulin to erythrocyte membranes, which leads to false positive results of Coombs test.

Abuse and drug dependence

There was no drug dependence, addiction and reactions of euphoria associated with the use of the drug Augmentin® CP.

Effect on the ability to drive transp. cf. and fur:

Because the drug may cause dizziness,It is necessary to warn patients about precautions when driving a vehicle or working with moving machinery.

Form release / dosage:

Tablets with modified release, film-coated, 1000 mg + 62.5 mg.

Packaging:2 tablets in a blister of PVC or polyethylene / aluminum foil. 2 blisters in a combined package with a dividing line between them. For 4, 7 or 10 combined packages together with instructions for use in a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-001522/08

Date of registration:14.03.2008

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

GLAXO WELLCOME PRODUCTION France

Representation: & nbspGlaxoSmithKline group of companies GlaxoSmithKline group of companies Unknown

Information update date: & nbsp20.11.2013

Illustrated instructions

Instructions

Augmentin® SR (Augmentin® SR)