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

Names of components	Amount, mg
*Active substances:*
Amoxicillin trihydrate equivalent to amoxicillin	500,00
Potassium clavulanate equivalent to clavulanic acid	125,00
*Excipients:*
Magnesium stearate	7,27
Sodium carboxymethyl starch	21,00
Silica colloidal dioxide	10,50
Microcrystalline cellulose	up to 1050,00
*Shell components:*
Titanium dioxide	11,60
Hypromellose (5 cps)	8,91
Hypromellose (15 cps)	2,97
Macrogol 4000	1,76
Macrogol 6000	1,76
Dimethicone 500 (Silicone oil)	0,013
Weight of a tablet	1077,00

Description:

Oval-shaped tablets are white to almost white in color, covered with a film shell, with an embossed "AS" inscription and a risk on one side.

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 that 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 (methicillin-sensitive) 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 likely:

Gram-negative aerobes:

Escherichia coli1

Klebsiella oxytoca

Klebsiella pneumoniae

Klebsiella spp.

Proteus mirabilis

Proteus vulgaris

Proteus spp.

Salmonella spp.

Shigella spp.

Gram-positive aerobes:

Corynebacterium spp.

Enterococcus faecium

Streptococcus pneumoniae

Streptococcus group Viridans

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

Gram-negative aerobes:

Acinetobacter spp.

Citrobacter freundii

Enterobacter spp.

Plafiiia 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 clavulan acid has been demonstrated in clinical studies.

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

Sensitivity to monotherapy with amoxicillin suggests a similar sensitivity tocombination of amoxicillin with clavulanic acid.

Pharmacokinetics:

Suction

Both active substances of the drug Augmentin®, amoxicillin and clavulanic acid, are quickly and completely absorbed from the gastrointestinal tract (GIT) after oral administration. Absorption of active substances of the drug Augmentin® is optimal in case of taking the drug at the beginning of food intake.

The pharmacokinetic parameters of amoxicillin and clavulanic acid obtained in different studies are shown below when healthy volunteers on an empty stomach took:

1 tablet of the drug Augmentin 250 mg + 125 mg (375 mg);

2 tablets of the drug Augmentin, 250 mg + 125 mg (375 mg);

1 tablet of the drug Augmentin®, 500 mg + 125 mg (625 mg);

500 mg of amoxicillin;

125 mg of clavulanic acid.

Basic pharmacokinetic parameters

Preparations	Dose (mg)	FROM max (mg / L)	t ^mOh (hours) s)	AUC (mgx h / l)	T1 /₂ (clock)
Amoxicillin
Augmentin®, 250 mg + 125 mg	250	3,7	1,1	10,9	1,0
Augmentin®, 250 mg + 125 mg, 2 tablets	500	5,8	1,5	20,9	1,3
Augmentin®, 500 mg + 125 mg	500	6,5	1,5	23,2	1,3
Amoxicillin, 500 mg	500	6,5	1,3	19,5	1,1
Clavulanic acid
Augmentin®, 250 mg + 125 mg	125	2,2	1,2	6,2	1,2
Augmentin®, 250 mg + 125 mg, 2 tablets	250	4,1	1,3	11,8	1,0
Clavulanic acid, 125 mg	125	3,4	0,9	7,8	0,7
Augmentin®, 500 mg + 125 mg	125	2,8	1,3	7,3	0,8

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.

When using the drug Augmentin, concentrations of amoxicillin in plasma are similar to those when administered orally equivalent doses of amoxicillin.

Distribution

As with the intravenous administration of a combination of amoxicillin with clavulanic acid, therapeutic concentrations of amoxicillin and clavulanic acid is found in various tissues and interstitial fluid (in the gallbladder tissues of abdominal, skin, fat and muscle tissues, synovial and peritoneal fluids, bile, purulent) .

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 components of the Augmentin® preparation in any organ.

Amoxicillin, like most penicillins, penetrates into breast milk.Traces of clavulanic acid can also be detected in breast milk. Except for the possibility of developing sensitization, diarrhea, or 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 have shown 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-1 H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxybutan-2-one and is excreted by the kidneys , through the gastrointestinal tract, and also with exhaled air in the form of carbon dioxide.

Excretion

Like other penicillins, amoxicillin is excreted mainly by the kidneys, whereas clavulanic acid - through both renal and extrarenal mechanisms. Approximately 60-70% amoxicillin and about 40-65% clavulanic acid is excreted by the kidneys unchanged in the first 6 hours after the appointment of 1 tablet of the drug Augmentin®,coated with a film coating, 250 mg + 125 mg or 500 mg + 125 mg. Simultaneous administration of probenecid slows the excretion of amoxicillin, but not clavulanic acid (see section "Interaction with other drugs").

Indications:

The combination of amoxicillin with clavulanic acid is indicated for the treatment of bacterial infections of the following localizations caused by microorganisms sensitive to a combination of amoxicillin and clavulanic acid:

- Upper respiratory tract infections (including ENT diseases), for example, relapsing tonsillitis, sinusitis, otitis media, usually caused by Streptococcus pneumoniae, Haemophilus influenzae*, Moraxella catarrhalis* and Streptococcus pyogenes.

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

- Urinary tract infections, for example, cystitis, urethritis, pyelonephritis, infections of female genitalia, usually caused by species of the family Enterobacteriaceae¹(mainly Escherichia colt), 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, long-term therapy is possible.

- Odontogenic infections, for example, periodontitis, odontogenic maxillary sinusitis, severe dental abscesses with spreading cellulitis.

- Other mixed infections (eg, septic abortion, postpartum sepsis, intra-abdominal sepsis) in the framework of stepwise therapy.

* Individual representatives of this kind of microorganisms produce beta-lactamase, which makes them insensitive to amoxicillin (see also section "Pharmacological properties").

Infections caused by microorganisms sensitive to amoxicillin can be treated with the Augmentin® drug, since amoxicillin is one of its active ingredients. Augmentin® is also indicated for the treatment of mixed infections caused by microorganisms sensitive to amoxicillin, as well as by microorganisms producing beta-lactamase, 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 (eg, penicillins, cephalosporins) in history;

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

- children under 12 years of age or body weight less than 40 kg.

Carefully:

The drug Augmentin® 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 the Augmentin® drug 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® 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 ® 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 breastfeeding.

Dosing and Administration:

For oral administration.

The dosage regimen is set individually depending on the age, body weight, function of the patient's kidneys, and also on the severity of the infection. To reduce potential abnormalities from the gastrointestinal tract and to optimize absorption, the drug should be taken at the beginning of the meal.The minimum course of antibiotic therapy is 5 days.

Treatment should not last more than 14 days without reviewing the clinical situation.

If necessary, stepwise therapy is possible (first intravenous injection of the drug Augmentin in the form of a powder for the preparation of a solution for intravenous administration, followed by the transition to the drug Augmentin in oral dosage forms).

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

Adults and children 12 years of age or older or with a body weight of 40 kg or more

For 1 tablet 500 mg + 125 mg 3 times a day.

Special patient groups

Children under 12 years of age or weighing less than 40 kg

It is recommended to use other dosage forms of the drug Augmentin.

Elderly patients

No dosage adjustment is required. In elderly patients with impaired renal function, the dose should be adjusted as described below for adults with impaired renal function.

Patients with impaired renal function

Correction of the dosing regimen is based on the maximum recommended dose of amoxicillin and the value of creatinine clearance

Creatinine clearance	Dosing regimen of the drug Augmentin®
> 30 ml / min	Correction of the dosing regimen is not required
10-30l / min	1 tablet 500 mg + 125 mg (with medium and heavy the course of the infection) 2 times per day
<10 ml / min	1 tablet 500 mg + 125 mg (with medium and heavy current infection) once a day

In most cases, parenteral therapy should be preferred where possible.

Patients on hemodialysis

Correction of the dosing regimen is based on the maximum recommended dose of amoxicillin.

1 tablet 500 mg + 125 mg in a single dose every 24 hours.

During the dialysis session, 1 additional dose (one tablet) and one more tablet at the end of the dialysis session (to compensate for the decrease in serum concentrations of amoxicillin and clavulanic acid).

Patients with impaired hepatic function

Treat with caution; regularly monitor liver function. There is insufficient data to change the recommendation of the dosing regimen in such 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: candidiasis of skin and mucous membranes.

Violations of the blood and lymphatic system

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

Immune system disorders

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

Disturbances from the nervous system

Infrequent: dizziness, headache. Very rarely: reversible hyperactivity, convulsions. Seizures can occur in patients with impaired renal function, as well as in those who receive high doses of the drug. Insomnia, agitation, anxiety, behavior change.

Disorders from the gastrointestinal tract

Adults

Very often: diarrhea. Often: nausea, vomiting.

Children

Often: diarrhea, nausea, vomiting.

The entire population

Nausea was most often associated with the use of high doses of the drug. If after the beginning of taking the drug there are undesirable reactions from the digestive tract, they can be eliminated if you take Augmentin® at the beginning of the meal.

Infrequent digestion. Very rarely: antibiotic-associated colitis (including pseudomembranous colitis and hemorrhagic colitis) (see section "Special instructions"), black hairy tongue, gastritis, stomatitis.

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. These reactions are observed in patients receiving therapy with other antibiotics of the penicillin series and cephalosporins. Increased bilirubin concentration and alkaline phosphatase.

Undesirable reactions from the liver have been observed mainly in men and elderly patients and can be associated with long-term therapy. These undesirable reactions are very rare in children. 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 were reports of deaths. 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: erythema multiforme. Very rarely: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis. In case of skin allergic reactions treatment with the drug Augmentin ® should be discontinued.

Disorders from the kidneys and urinary tract

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

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 failure (see section "Special instructions and precautions"). Cramps can occur in patients with impaired renal function, as well as in those who receive high doses of the drug.

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.

The results of a prospective study, which was conducted with the participation of 51 children in a toxicological center, showed that the administration of amoxicillin at a dose of less than 250 mg / kg did not lead to significant clinical symptoms and did not require gastric lavage.

Interaction:

Simultaneous use of the drug Augmentin® and probenecid is not recommended.Probenecid reduces tubular secretion of amoxicillin, and therefore simultaneous use of the drug Augmentin and probenecid can lead to an increase and persistence in the blood of the level 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 at the expense of inhibiting its tubular secretion, so the simultaneous use of the drug Augmentin and methotrexate may increase the toxicity of methotrexate.

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

In the literature, rare cases of an increase in the international normalized ratio (INR) in patients with joint use of acenocoumarol or warfarin and amoxicillin are described.If it is necessary to simultaneously prescribe the Augmentin® drug with anticoagulants, prothrombin time or INR should be closely monitored with the appointment or discontinuation of the Augmentin® drug, 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, you need to collect a detailed history of previous hypersensitivity reactions to penicillins, cephalosporins, or other substances that cause an allergic reaction in the patient. Described serious, and sometimes lethal, reactions hypersensitivity (anaphylactic reactions) to penicillins. The risk of occurrence of such reactions is highest in patients who have a history of hypersensitivity reactions to penicillins.In case of an allergic reaction, it is necessary to stop treatment with the drug Augmentin® 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 suspected infectious mononucleosis, the drug Augmentin® should not be used, since in patients with this disease amoxicillin can cause a skinlike skin rash, which makes it difficult to diagnose the disease. Long-term treatment with Augmentin® can lead to excessive reproduction insensitive microorganisms.

In general, the drug Augmentin® is well tolerated and has a characteristic of all penicillins of low toxicity. During prolonged therapy with the drug Augmentin, it is recommended to periodically evaluate the function of the kidneys, liver and hematopoiesis.

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.

In patients who received a combination of amoxicillin with clavulanic acid in conjunction with indirect (oral) anticoagulants, in rare cases, increased prothrombin time (increased INR) was reported. With the joint appointment of indirect (oral) anticoagulants with a combination of amoxicillin and clavulanic acid, you need to monitor the relevant indicators. To maintain the necessary effect of oral anticoagulants, their dose may need to be adjusted.

In patients with impaired renal function, the dose of the Augmentin® drug should be reduced, respectively, by the degree of impairment (see "Method of administration and dose" - Patients with impaired function of the nights).

In patients with reduced diuresis, crystalluria is very rare, mainly with parenteral therapy.During the administration of 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 the "Overdose" section)

Taking the drug Augmentin® Inside leads to a high content of amoxicillin in the urine, which can lead to false-positive results in the determination of 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 non-specific binding of immunoglobulin G and albumin to erythrocyte membranes, which leads to false positive results of Coombs' test.

It is necessary to use the drug Augmentin ® within 30 days from the moment of opening the package from laminated aluminum foil.

Abuse and drug dependence

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

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

Since 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, film-coated 500 mg + 125 mg.

Packaging:For 7 or 10 tablets in Al/ PVC / PVDH blister, 1 blister with a bag of silica gel in a package of laminated aluminum foil. 2 packages of laminated aluminum foil together with instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

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

Terms of leave from pharmacies:On prescription

Registration number:П N011997 / 01

Date of registration:21.06.2010 / 16.08.2013

Expiration Date:Unlimited

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

Manufacturer: & nbsp

SmithKline Beecham Pharmaceuticals United Kingdom

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

Information update date: & nbsp04.10.2017

Illustrated instructions

Instructions

Augmentin® (Augmentin®)