AUGMENTIN (Powder for oral solution)

Active material: Amoksiцillin, Clavulanic acid
When ATH: J01CR02
CCF: Antibiotics penicillin with a broad-spectrum beta-lactamase inhibitor
ICD-10 codes (testimony): A46, A54, A57, H66, J00, J01, J02, J03, J04, J15, J20, J31, J32, J35.0, J37, J42, J47, J85, J86, J90, K65.0, K81.0, K81.1, K83.0, L01, L02, L03, L08.0, L30.3, M00, M86, N10, N11, N30, N34, N41, N70, N71, N72, N73.0, O08.0, O85, T79.3, Z29.2
When CSF: 06.01.02.04.02
Manufacturer: SmithKline Beecham Pharmaceuticals (Great Britain)

Pharmaceutical form, composition and packaging

Pills, coated from white to almost white, Oval, with sunken inscription “AUGMENTIN” on one side; of presentations – from almost white to yellowish-white.

Excipients: magnesium stearate, sodium starch glycolate (Type A), silica colloidal anhydrous, microcrystalline cellulose.

The composition of the shell: Titanium dioxide, hydroxypropyl (5 cps), hydroxypropyl (15 cps), polyethylene glycol 4000, polyethylene glycol 6000, Dimethicone (Silicone oils).

10 PC. – blisters in packets of aluminum foil (2) – packs cardboard.

Pills, Film-coated from white to almost white, Oval, embossed with the inscription “AS” and Valium on one party.

Excipients: magnesium stearate, sodium carboxymethyl starch, silica colloidal anhydrous, microcrystalline cellulose.

The composition of the shell: Titanium dioxide, gipromelloza (5 cps), gipromelloza (15 cps), macrogol 4000, macrogol 6000, Dimethicone 500 (Silicone oils).

7 PC. – blisters in packets of aluminum foil (2) – packs cardboard.
10 PC. – blisters in packets of aluminum foil (2) – packs cardboard.

Pills, coated from white to almost white, Oval, Typewriter “A” and “FROM” on both sides of the tablet, and a break line on one side; of presentations – from almost white to yellowish-white.

Excipients: magnesium stearate, sodium starch glycolate (Type A), silica colloidal anhydrous, microcrystalline cellulose.

The composition of the shell: Titanium dioxide, hydroxypropyl (5 cps), hydroxypropyl (15 cps), polyethylene glycol 4000, polyethylene glycol 6000, Dimethicone (Silicone oils).

7 PC. – blisters in packets of aluminum foil (2) – packs cardboard.

Powder for oral suspension white or nearly white, with a characteristic odor; at a dilution of a suspension of white or nearly white; on standing slowly precipitate formed white or nearly white.

Excipients: Xanthan Gum, Aspartame, succinic acid, silica colloidal, hydroxypropyl, silicon dioxide, dry orange flavor 610271E (Taste Maker) and 9/027108 (Dragoco), dry raspberry flavor NN07943 (Quest), dry flavor “Light flow” 52927/AP (Firmenich).

7.7 grams – glass bottles capacity 70 ml (1) complete with a measured cap – packs cardboard.

Powder for oral suspension white or nearly white, with a characteristic odor; at a dilution of a suspension of white or nearly white; on standing slowly precipitate formed white or nearly white.

Excipients: Xanthan Gum, Aspartame, succinic acid, silica colloidal, hydroxypropyl, silicon dioxide, dry orange flavor 610271E (Taste Maker) and 9/027108 (Dragoco), dry raspberry flavor NN07943 (Quest), dry flavor “Light flow” 52927/AP (Firmenich).

12.6 grams – glass bottles capacity 70 ml (1) complete with a measured cap – packs cardboard.

Pharmacological action

Combined broad spectrum antibiotic, resistant to β-lactamases, soderzhashtiy amoksitsillin and klavulanovuyu kislotu.

Amoksiцillin – semi-synthetic broad-spectrum antibiotic, active against many Gram-positive and Gram-negative microorganisms. Amoxicillin is exposed to β-lactamases destruction, therefore in the spectrum of its antimicrobial activity of the microorganisms are not included, продуцирующие b-лактамазы.

Clavulanic acid – b-лактамное соединение, It has the ability to inactivate a wide range of β-lactamase, enzymes, that normally produce microorganisms, resistant to penicillins and cephalosporins.

The presence of clavulanic acid in the Augmentin^® It protects amoxicillin from the destructive action of β-lactamase, and extends the range of its antibacterial activity with the inclusion of microorganisms, generally resistant to other cephalosporins and penicillins.

AUGMENTIN^® active against gram-positive aerobic microorganisms: Bacillis anthracis^*, Corynebacterium spp., Enterococcus faecalis^*, Enterococcus faecium^*, Listeria monocytogenes, Nocardia asteroids, Staphylococcus aureus^*, coagulase-negative staphylococci (including Staphylococcus epidermidis), Streptococcus spp. (including Streptococcus agalactiae, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans); against gram-positive anaerobes: Clostridium spp., Peptococcus spp., Peptostreptococcus spp.; against gram-negative aerobic microorganisms: Bordetella pertussis, Brucella spp., Escherichia coli^*, Gardnerella vaginalis, Haemophilus influenzae^*, Helicobacter pylori, Klebsiella spp.^*, Legionella spp., Moraxella catarrhalis^* (Branhamella catarrhalis), Neisseria gonorrhoeae^*, Neisseria meningitidis^*, Pasteurella multocida, Proteus is wonderful^*, Proteus vulgaris^*, Salmonella spp.^*, Shigella spp.^*, Vibrio cholerae, Yersinia enterocolitica^*; against gram-negative anaerobes: Bacteroides spp^*. (including Bacteroides fragilis), Fusobacterium spp.^*; against other microorganisms: Borrelia burgdorferi, Chlamydia, Leptospira icterohemorrhagia, Treponema pale.

*- Some strains of these bacteria produce β-lactamases, causing resistance to amoxicillin alone.

Augmentin tablets^®, containing 500 mg amoxycillin and 125 mg clavulanic acid, is a dosage form a sustained release, which is different from conventional tablets other pharmacokinetic parameters. This provides sensitivity to the preparation of those strains of Streptococcus pneumoniae, in which the resistance to amoxicillin mediated penicillin-binding protein (penicillin-resistant strains of Streptococcus pneumoniae).

Pharmacokinetics

Farmakokineticheskie options amoksitsillina and klavulanovoy kislotы poluchenы in raznыh issledovaniyah in zdorovыh dobrovolytsev then taken natoshtak: 1 Augmentin tablets^® (250 mg / 125 mg), or 2 Augmentin tablets^® (250 mg / 125 mg), or 1 Augmentin tablets^® (500 mg / 125 mg), or amoksitsillina (500 mg), or clavulanic acid (125 mg) separately.

The main pharmacokinetic parameters are presented in Table.

In the application of Augmentin^® amoxicillin plasma concentrations similar to those after oral administration of equivalent doses of amoxicillin.

Absorption

Amoxicillin and Clavulanic acid is readily soluble in aqueous solution at physiological pH value and after taking Augmentin^® inside quickly and completely absorbed from the gastrointestinal tract. Absorption of active substances Augmentin^® optimal in the case of reception at the beginning of a meal.

Distribution

Therapeutic concentrations of both active substances are determined in various organs, tissues and body fluids (incl. lung, abdominal; adipose, bone and muscle tissue; plevralynoy, synovial and peritoneal fluids; in the skin, bile, urine, purulent, mokrote, in interstitial fluid).

Plasma protein binding is moderate: 25% for clavulanic acid and 18% amoxicillin.

Amoksiцillin (like most penicillins) excreted in breast milk. Breast milk also found trace amounts of clavulanic acid.

Isklyucheniem risk for sensitization, I do not know no other negative effects of amoxicillin and clavulanic acid on the health of infants, breastfed.

In experimental animal studies, that amoxicillin and clavulanic acid penetrate the placental barrier. However, it is not revealed impaired fertility or the adverse effects on the fetus.

Animal studies have not revealed cumulation ingredients Augmentin^® in any organ.

Metabolism and excretion

Amoxicillin is excreted mainly by the kidneys, whereas through the clavulanic acid as the kidney, and extrarenal mechanisms. After a single oral administration of one tablet 250 mg / 125 mg or 500 mg / 125 mg about 60-70% and amoksitsillina 40-65% clavulanic acid during the first 6 h excreted in the urine as unchanged. About 10-25% initial dose of amoxicillin is excreted in the urine as inactive penitsilloevoy acid. Clavulanic acid in the human body is exposed to intense metabolized to 2,5-dihydro-4-(2-hydroxyethyl)-5-oxo-1H-pyrrole-3-carboxylic acid and 1-amino-4-hydroxy-butan-2-one and excreted in the urine and feces.

Testimony

Infectious-inflammatory diseases, caused by susceptible to malaria infections:

- Infections of the upper respiratory tract and ENT (incl. recurrent tonsillitis, sinusitis, otitis media), usually caused by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes;

- Infections of the lower respiratory tract: exacerbation of chronic bronchitis, dolevaya pneumonia and bronchopneumonia, usually caused by Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis;

- Urinary tract infections: cystitis, uretrit, pyelonephritis, infections of female genital mutilation, usually caused by species of the family Enterobacteriaceae (predominantly Escherichia coli), Staphylococcus saprophyticus and species of the genus Enterococcus, and gonorrhea, caused by Neisseria gonorrhoeae;

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

- Bone and joint infections: osteomyelitis, usually caused by Staphylococcus aureus, When the need for long-term therapy;

- Other mixed infections, as septicheskiy abortion, obstetric sepsis, intra-abdominal infections.

Dosage regimen

The batch is individually depending on age, body weight, renal patients, as well as the severity of the infection.

For optimal absorption, and reduce potential side effects from the digestive system Augmentin^® it is recommended to take at the beginning of a meal.

Treatment should not continue more 14 days without a review of the clinical situation.

If necessary, may conduct sequential therapy (/ in the administration of the drug with a subsequent transition to oral).

Adults and children over 12 age or body weight over 40 kg

By 1 tablet (875 mg plus 125 mg) 2 times / day, or 1 tablet (500 mg + 125 mg) 3 times / day.

Children under 12 years

The dosage depends on the age and the body weight is indicated in mg / kg body weight per day, or ml suspension.

The recommended dosing regimen: 45 mg / kg / day 2 receiving or 40 mg / kg / day 3 admission. Multiplicity of reception depends on the release form.

For children weighing 40 kg or more the drug should be administered in the same doses, as adults.

Single doses of the drug Augmentin^® depending on the age and body weight are presented in Table.

* – for amoxicillin

Two tablets Augmentin^® (250 mg plus 125 mg) are not equivalent to one tablet (500 mg plus 125 mg), tk. the content of clavulanic acid 2 times.

For the correct dosage amount of suspension from children under 3 months We recommend using a syringe with graduations.

For convenience, reception at Children up to 2 years suspension can be diluted with water twice.

At treatment of infections of skin and soft tissue, as well as recurrent tonsillitis preparation can be administered in a dose of 20 mg / kg / day 3 admission (suspension 4:1) and 25 mg / kg / day 2 admission (suspension 7:1).

If the frequency of isolation of pneumococcus with a high level penicillin (IPC penicillin 2-4 mg / l) in the region (or a closed facility) more than 10%, amoksitsillina necessary application / clavulanate (Augmentin^®) dose 80-90 mg / kg / day, razdelennoy of 3 admission.

The optimal dosage form of Augmentin^® to children from 6 to 12 years are tablets 500 mg plus 125 mg, Accepted 2 times / day.

Patients with impaired renal function

Correction dose is based on the maximum recommended dose of amoxicillin and carried out taking into account the values ​​QC.

Adult

Pills 875 mg plus 125 mg should be used only in patients with CC >30 ml / min.

Children

In most cases the possible preference should be given parenteral therapy.

Patients, on hemodialysis

Dosage adjustments based on the maximum recommended dose of amoxicillin.

Adults appointed 1 tab. (500 mg plus 125 mg) or 2 tab. (250 mg plus 125 mg) every 24 no.

Additionally appoint 1 dose during dialysis and 1 dose after dialysis (to compensate for lowering of serum concentrations of amoxicillin and clavulanic acid).

Pills (875 mg plus 125 mg) It should only be used in patients with CC>30 ml / min.

Babies appointed 15 mg ± 3.75 mg / kg 1 time / day.

Before hemodialysis enter one additional dose 15 mg ± 3.75 mg / kg. To restore the concentrations of active ingredients Augmentin^® in the blood of a second additional dose 15 mg ± 3.75 mg / kg should be entered after hemodialysis.

Patients with impaired hepatic function

Treatment is carried out with caution; regularly monitor liver function. Insufficient data for correct dosing regimen in this patient.

Elderly patients

Reduce the dose of Augmentin^® not required; the same dose, for adults. In elderly patients with impaired renal function dose should be adjusted so, as stated above for adults with impaired renal function.

Rules suspension

The suspension was prepared immediately before the first use. The powder should be dissolved with boiled water, cooled to room temperature, gradually shaking and adding water to the mark on the bottle. Then let stand about 5 m, to ensure complete dissolution. The vial should be shaken well before each use. For exact dosage of the drug should be used capful-cover, which should be rinsed well with water after each use. Once reconstituted suspension should be stored no more than 7 days in a refrigerator, but do not freeze.

Side effect

Determining the incidence of side effects: Often (>10%), often (>1% and <10%), sometimes (>0.1% and <1%), rarely (>0.01% and <0.1%), rarely (<0.01%).

From the hematopoietic system: rarely – reversible leukopenia (including neutropenia), thrombocytopenia; rarely – obratimыe gemoliticheskaya anemia and agranulocytosis, increase in bleeding time and prothrombin time.

Allergic reactions: rarely – angioedema, anaphylaxis, syndrome, similar to serum sickness, sensitization vasculitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, Acute generalized exanthematous pustulosis.

In case of any form of treatment of atopic dermatitis Augmentin^® must stop.

Dermatological reactions: sometimes – skin rash, hives; rarely – erythema multiforme.

CNS: sometimes – dizziness, headache; rarely – Reversible hyperactivity and convulsions. Seizures may occur in patients with impaired renal function and in patients, receiving the drug at high doses.

From the digestive system: Often – diarrhea (adult); often – diarrhea (children), nausea (often while taking the drug at high doses), vomiting; sometimes – dyspepsia; rarely – discoloration of the surface layer of the tooth enamel (children, receiving suspension).

Liver: sometimes in the treatment of beta-lactam antibiotics is observed a moderate increase in ACT levels and / or ALT (the clinical significance is not installed); rarely – hepatitis, cholestatic jaundice. These side effects occur when taking other cephalosporins, penicillins, or.

Side effects are reversible liver, occur during or shortly after treatment. Children are developing very rarely. Occurs predominantly in males and elderly patients and may be associated with prolonged therapy.

In very rare cases, patients with serious previous illness or those, who received potentially hepatotoxic drugs, Side effects may be severe and result in death.

From the urinary system: rarely – interstitial nephritis, kristallurija.

Effects, caused by microbiological action: often – mucosal candidiasis; rarely – psevdomembranoznыy and gemorragicheskiy colitis.

Upon receipt of Augmentin^® Side effects are rare and are mostly mild and transient.

Contraindications

- Jaundice or abnormal liver function during treatment with Augmentin^® history;

- Hypersensitivity to beta-lactam antibiotics (incl. to penicillins and cephalosporins).

Not recommended apply Augmentin^® with suspected infectious mononucleosis, since in such cases amoxicillin can cause skin rashes, making it difficult to diagnose the disease.

Pregnancy and lactation

In reproduction studies in animals while taking Augmentin^® shows, that oral and parenteral administration of the drug did not cause teratogenic effects.

In a single study in women with premature rupture of membranes has been found, that preventive therapy augmentin^® It may be associated with an increased risk of necrotising enterocolitis in newborns. AUGMENTIN^® not recommended for use during pregnancy, except, where, According to the doctor, it's necessary.

AUGMENTIN^® It can be used during breastfeeding. Isklyucheniem risk for sensitization, associated with the release of the breast milk of active drug substances in trace amounts, no other adverse effects in infants, breastfed, not observed.

Cautions

Before starting treatment with Augmentin^® You need to collect detailed history, concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens.

Describes serious, and occasionally fatal hypersensitivity reactions (anaphylactic reactions) of penitsillinы. The risk of these reactions is greatest in patients, with a history of hypersensitivity reactions to the antibiotics of this group. In the event of an allergic reaction, you must stop treatment Augmentin^® and start alternative therapy. If severe hypersensitivity reactions should be immediately put adrenaline (epinephrine). There may also need oxygen therapy, in / with the introduction of steroids and airway management, vklюchaющee intubaciю.

Be wary of Augmentin^® in patients with impaired hepatic function.

Intensity of side effects from the digestive system can be reduced by taking Augmentin^® at the beginning of a meal.

Oral care helps to prevent discoloration of the teeth, since it is enough to brush your teeth.

Patients, receiving Augmentin^®, occasionally there is an increase in prothrombin time, and therefore the concomitant use of Augmentin^® and anticoagulants should be carried out appropriate monitoring.

In patients with reduced urine output crystalluria occur very rarely, predominantly with parenteral therapy. When taken in high doses of amoxicillin it is recommended to take plenty of fluids and to maintain an adequate urine output to reduce the likelihood of formation of crystals of amoxicillin.

Prolonged treatment with Augmentin^® It may be accompanied by excessive growth of non-susceptible organisms.

Generally, AUGMENTIN^® is well tolerated and has a characteristic of all penicillins low toxicity. During long-term therapy augmentin^® it is recommended to periodically monitor renal function, liver, hematopoiesis.

Suspension soderzhat aspartame, which is the source of phenylalanine, and thus these dosage forms should be used with caution in patients with phenylketonuria.

In the medical literature there is no data on the abuse of Augmentin^® and depending on the drug.

Effects on ability to drive vehicles and management mechanisms

AUGMENTIN^® no negative effect on the ability to drive vehicles and operate machinery.

Overdose

Symptoms: possible gastro-intestinal disorders and water and electrolyte balance. Amoksitsillinovaya described kristalluriya, in some cases leading to the development of renal failure.

Treatment: symptomatic therapy, Correction fluid and electrolyte balance. Amoxicillin and clavulanic acid derived from blood via hemodialysis.

Drug Interactions

Augmentin is not recommended^® concurrently with probenecid. Probenecid reduces the tubular secretion of amoxicillin, and, therefore, the simultaneous use of Augmentin^® and probenecid may increase and persistence in the blood levels of amoxicillin, but not clavulanic acid.

With simultaneous use of allopurinol and amoxicillin may increase the risk of allergic reactions. Data on concomitant use of Augmentin^® and allopurinol currently available.

As with other broad-spectrum antibiotics, AUGMENTIN^® may reduce the effectiveness of oral contraceptives (it is necessary to inform patients).

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored in a dry, inaccessible to children at temperature not exceeding 25 ° C. Shelf life Tablets (250 mg plus 125 mg) and (875 mg plus 125 mg) – 2 year, tablets (500 mg plus 125 mg) – 3 year. Shelf life of the powder for suspension – 2 year.

The obtained suspension should be stored in a refrigerator at 2 ° to 8 ° C for 7 days.