Amoksiklav Quiktab - instructions for use, dose, side effects, contraindications

Component	Tablets 500 mg + 125 mg	Tablets 875 mg + 125 mg
Active Ingredients
Amoxicillin trihydrate (corresponds amoxicillin)	574.00 mg (500 mg)	1004.50 mg (875 mg)
Potassium clavulanate (corresponding to clavulanic acid)	148.87 mg (125 mg)	148.87 mg (125 mg)
Excipients
Aromatic Tropical Mixture	26.00 mg	38.00 mg
Aromatizer sweet orange	26.00 mg	38.00 mg
Aspartame	6.50 mg	9.50 mg
Silica dioxide colloidal anhydrous	13.00 mg	18.00 mg
Iron (III) oxide yellow, E 172	3.50 mg	5.13 mg
Talc	13.00 mg	18.00 mg
Castor oil, hydrogenated	26.00 mg	36.00 mg
Cellulose microcrystalline siliceous	Up to 1300.00 mg	Before 1940,00 mg

Description:Oblong octagonal pills of light yellow color with impregnations of brown color, with a fruity smell.

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,It has 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 effective against type I chromosomal beta-lactamases that are not inhibited by clavulanic acid.

The presence of clavulanic acid in the preparation 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.

Gram-positive aerobes: Bacillus anthracis, Enterococcus faecalis, Listeria monocytogenes, Nocardia asteroides, Streptococcus pyogenes¹² , Streptococcus agalactiae¹², other beta-hemolytic stethococci¹², Staphylococcus aureus (sensitive to methicillin)¹, Staphylococcus saprophyticus (sensitive to methicillin), coagulase-negative staphylococci (sensitive to methicillin).

Gram-negative aerobes: Bordetella pertussis, Haemophilus influenzae¹, Helicobacter pylori, Moraxella catarrhalis¹, Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae.

Other: Borrelia burgdorferi, Leptospira icterohaemorrhagiae, Treponema pallidum.

Gram-positive anaerobes: kinds kind Clostridium, Peptococcus niger, Peptostreptococcus magnus, Peptostreptococcus micros, kinds kind Peptostreptococcus.

Gram-negative anaerobes: Bacteroides fragilis, kinds kind Bacteroides, kinds kind Capnocytophaga, Eikenella corrodens, Fusobacterium nucleatum, kinds kind Fusobacterium, kinds kind Porphyromonas, kinds kind Prevotella.

Bacteria, for of which probable acquired resistance to combinations amoxicillin from clavulanate acid

Gram-negative aerobes: Escherichia coli¹, Klebsiella oxytoca, Klebsiella pneumoniae, species of genus Klebsiella, Proteus mirabilis, Proteus vulgaris, species of genus Proteus, species of genus Salmonella, species of genus Shigella.

Gram-positive aerobes: species of genus Corynebacterium, Enterococcus

faecium. Streptococcus pneumoniae¹² , group streptococci Viridans.

Bacteria, possessing natural sustainability to combinations amoxicillin from clavulanate acid

Gram-negative aerobes: species of genus Acinetobacter, Citrobacter freundii, species of genus Enterobacter, Hafnia alvei, Legionella pneumophila, Morganella morganii, species of genus Providencia, species of genus Pseudomonas, species of genus Serratia, Stenotrophomonas maltophilia, Yersinia enterocolitica

Other: Chlamydia pneumoniae, Chlamydia psittaci, kinds kind Chlamydia, Coxiella burnetii, kinds kind Mycoplasma.

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

²strains 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

The active substances of the preparation are quickly and completely absorbed from the gastrointestinal tract (GIT) after ingestion. Absorption of active substances is optimal in case of application of the preparation together with food.

Below are the pharmacokinetic parameters of amoxicillin and clavulanic acid after taking in a dose of 875 mg / 125 mg and 500 mg / 125 mg twice daily with healthy volunteers.

The mean (± SD) pharmacokinetic		indicators
Active	Dose	FROMmOh	Tmoh (hour)	AUC (0-24h)	T "₂
matter	(mg)	(μg / ml)		(μg * h / ml)	(hour)
Amoxicillin / clav
ulanic acid
Amoxicillin
875 mg / 125 mg	875	11,64	1.50(1.0-2.5)	53,52	1.19
		±2,78		±12,31	±0.21
500 mg / 125 mg	500	7,19	1.5 (1.0-2.5)	53,52	1.15
		±2,26		±8,37	±0.20
Clavulanic acid
875 mg / 125 mg	125	2,18	1.25 (1.0-2.0)	10,16	0.96
		±0,99		±3,04	±0.12
500 mg / 125 mg	125	2,40	1.5 (1.0-2.0)	15,72	0.98
		±0,83		±3,86	±0.12

C_max - the maximum concentration in the blood plasma;

T_m_Oh - time to reach the maximum concentration in the blood plasma; AUC - area under the curve "concentration-time";

T1/2 - half-life

Metabolism

About 10-25% of the initial dose of amoxicillin is excreted by the kidneys in the form of an inactive metabolite (penicillic acid). Clavulanic acid in the human body undergoes intensive metabolism with the formation of 2,5-dihydro-4- (2-hydroxyethyl) -5-oxo-1 H -pyrrole-3-carboxylic acid and 1-amino-4-hydroxybutane-2 -one and is excreted by the kidneys, through the gastrointestinal tract, and also with exhaled air, in the form of carbon dioxide.

Distribution

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

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.

The distribution volume is about 0.3-0.4 l / kg for amoxicillin and about 0.2 l / kg for clavulanic acid. Amoxicillin and clavulanic acid do not penetrate hematoencephalic barrier in non-inflamed meninges. Amoxicillin (like most penicillins) is excreted in breast milk.

Traces of clavulanic acid can also be detected in breast milk. With the exception of the possibility of development sensitization, diarrhea and candidiasis of the oral mucosa, there is no known other adverse effects of amoxicillin and clavulanic acid on the health of infants fed by breast milk.

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.

Excretion

Amoxicillin is excreted mainly by the kidneys, whereas clavulanic acid is through both renal and extrarenal mechanisms. After a single oral intake of 875 mg / 125 mg or 500 mg / 125 mg of approximately 60-70% amoxicillin and 40-65% clavulanic acid for the first 6 hours is excreted unchanged in the kidneys. The mean half-life (T1_/2) amoxicillin / clavulanic acid is approximately 1 hour, the average total clearance is approximately 25 l / h in healthy patients.In various studies, it was found that excretion of amoxicillin by the kidneys within 24 hours is approximately 50-85%, clavulanic acid 27-60%. The greatest amount of clavulanic acid is excreted within the first 2 hours after administration.

The pharmacokinetics of amoxicillin / clavulanic acid does not depend on the patient's sex.

Patients with impaired renal function

The total clearance of amoxicillin / clavulanic acid decreases in proportion to the decrease in renal function. The decrease in clearance is more pronounced for amoxicillin than for clavulanic acid, because most of the amoxicillin is excreted by the kidneys. Doses of the drug for renal failure should be selected taking into account the undesirability of cumulation of amoxicillin against the background of maintaining a normal level of clavulanic acid.

Patients with impaired hepatic function

In patients with impaired liver function, the drug is used with caution, it is necessary to carry out constant monitoring of liver function.

Both components are removed by hemodialysis and minor amounts by peritoneal dialysis.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to amoxicillin / clavulanic acid:

- infections of the upper respiratory tract and ENT organs (including acute and chronic sinusitis, acute and chronic otitis media, retropharyngeal abscess, tonsillitis, pharyngitis);

- infection of the lower respiratory tract (acute bronchitis with bacterial superinfection, exacerbation of chronic bronchitis, pneumonia);

- urinary tract infections (eg, cystitis, urethritis, pyelonephritis);

- infection in gynecology and obstetrics;

- skin and soft tissue infections, including human and animal bites;

- infections of bone and connective tissues (eg, osteomyelitis);

- infection of the biliary tract (cholecystitis, cholangitis);

- odontogenic infections.

Contraindications:

- increased sensitivity to amoxicillin, clavulanic acid, other components of the drug;

- severe hypersensitivity reactions (eg, anaphylactic reactions) in an anamnesis to other beta-lactam antibiotics (cephalosporins, carbapenems or monobactams);

- Cholestatic jaundice and / or other liver function disorders caused by amoxicillin / clavulanic acid, in history;

- children under 12 years of age with a body weight of less than 40 kg;

- phenylketonuria;

- renal failure (CK <30 ml / min) (for tablets dispersible 875 mg + 125 mg);

- Infectious mononucleosis;

- lymphocytic leukemia.

Carefully:

at a pseudomembranous colitis in the anamnesis, diseases of the gastrointestinal tract, hepatic insufficiency, severe renal dysfunction (for tablets dispersible 500 mg + 125 mg), pregnancy, lactation, with simultaneous use with anticoagulants.

Pregnancy and lactation:

Studies in animals have not revealed data on the dangers of taking Amoxiclav®Qwiktab during pregnancy and its effect on embryonic fetal development.

In one study in women with premature rupture of amniotic membranes, it was found that preventive therapy with amoxicillin / clavulanic acid may be associated with an increased risk of developing necrotizing enterocolitis in newborns. There is also information about the development in newborns of diarrhea and candidiasis of the mucous membranes of the oral cavity.

In pregnancy and during lactation, Amoxiclav® Quicact is used only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby.

Amoxicillin and clavulanic acid penetrate into breast milk in small amounts, so taking the drug during breastfeeding should be continued only if there are clear indications.

In infants receiving breastfeeding, it is possible to develop sensitization, diarrhea, candidiasis of the mucous membranes of the oral cavity. In such cases, breastfeeding should be discontinued.

Dosing and Administration:

Inside.

The dosage regimen is set individually depending on the age, body weight, function of the patient's kidneys and the severity of the infection. Tablets must be dissolved in half a glass of water (minimum 30 ml) and mix thoroughly, then drink, or hold the tablets in your mouth until completely dissolved, then swallow. To reduce the risk of side effects from the gastrointestinal tract, you should take the drug at the beginning of the meal.

Dispersible tablets of Amoxiclav®Quiktab 500 mg / 125 mg: Adults and children over 12 years of age with a body weight> 40 kg:

For the treatment of infections of mild and moderate severity - one tablet (500 mg / 125 mg) every 12 hours (2 times a day).

For the treatment of severe infections and respiratory infections - one tablet (500 mg / 125 mg) every 8 hours (3 times a day).

The maximum daily dose of Amoxiclav® Quicact is 1500 mg amoxicillin / 375 mg clavulan.

Patients with impaired renal function

In patients with creatinine clearance (CK) above 30 ml / min, there is no need for dose adjustment.

Adults and children over 12 years of age weighing> 40 kg (this dosing regimen is used for infections of medium and severe course):

Dispersible tablets of Amoxiclav®quicab 875 mg / 125 mg:

CK: 10-30 ml / min	500 mg / 125 mg twice a day (with an average and severe course of infection)
CK <10 ml / min	500 mg / 125 mg once a day (with an average and severe course of infection)
Hemodialysis	500mg / 125mg every 24 hours, plus 500mg / 125mg during the dialysis session, with repeated use at the end of the dialysis session (as the concentration of amoxicillin and clavulanic acid in the blood plasma is reduced)

Adults and children over 12 years of age with a body weight> 40 kg:

In severe infections and infections of the respiratory system - one tablet (875 mg / 125 mg) every 12 hours (2 times a day).

The daily dose of the drug Amoxiclav®Qviktab at application 2 times a day is 1750 mg amoxicillin / 250 mg clavulanic acid.

Patients with impaired renal function

In patients with a creatinine clearance (CK) of more than 30 ml / min, there is no need for correctiondose.

Patients with QC less than 30 ml / min use of dispersible tablets Amoxiclav® Quicactab, 875 mg / 125 mg it is contraindicated.

Such patients should take the drug at a dosage of 500 mg / 125 mg after the appropriate level of QC dose adjustment.

Patients with impaired hepatic function

Care should be taken when taking Amoxiclav® Quicactab. It is necessary to carry out regular monitoring of liver function. In the case of starting treatment with parenteral administration of the drug, It is possible to continue therapy with taking Amoxiclav® Quiquate tablets.

The duration of treatment is determined by the attending physician! The minimum course of antibiotic therapy is 5 days. Treatment should not last more than 14 days without reviewing the clinical situation.

Side effects:

According to the World Health Organization (WHO), adverse reactions are classified according to their frequency of development as follows: very frequent (> 1/10), frequent (> 1/100, <1/10), not frequent (> 1/1000, <1/100), rare (> 1/10000, <1/1000) and very rare (<1/10000). frequency is unknown - according to available data, it was not possible to establish the frequency of occurrence.

On the part of the organs of hematopoiesis and lymphatic system: rarely: reversible leukopenia (including neutropenia), thrombocytopenia; rarely: eosinophilia, thrombocytosis, reversible agranulocytosis, increased bleeding time and reversible increase in prothrombin time, anemia, including reversible hemolytic anemia.

From the immune system: frequency unknown: angioedema, anaphylactic reactions, allergic vasculitis, a syndrome similar to serum sickness.

From the nervous system: infrequently: dizziness, headache; rarely: insomnia, agitation, anxiety, behavior change, reversible hyperactivity, convulsions; seizures can be observed in patients with impaired renal function, as well as in those who receive high doses of the drug.

From the gastrointestinal tract often: loss of appetite, nausea, vomiting, diarrhea; Nausea is more often observed with ingestion of high doses. If violations of the GI tract are confirmed, they can be eliminated if you take the drug at the beginning of the meal. infrequently: indigestion disorder; rarely: antibiotic-associated colitis induced reception of antibiotics (including pseudomembranous and hemorrhagic colitis), black hairy tongue, gastritis, stomatitis.

In children, the discoloration of the surface layer of tooth enamel was very rare. Oral care helps prevent discoloration of tooth enamel.

From the skin infrequently: skin rash, itching, urticaria; rarely: multiforme exudative erythema;

frequency is unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis.

From the urinary system: rarely: crystalluria, interstitial nephritis, hematuria.

From the liver and biliary tract: infrequently: increased activity of alanine aminotransferase (ALT) and / or aspartate aminotransferase (ACT) (this phenomenon is observed in patients receiving beta-lactam antibiotic therapy, however, its clinical significance is unknown);

Undesirable liver side effects were observed mainly in men and elderly patients and may be associated with long-term therapy.These undesirable phenomena 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 phenomena, as a rule, are reversible. Unwanted phenomena on the part of the liver can be severe, in extremely rare cases there have been reports of fatal outcomes. In almost all cases, these were patients with severe concomitant pathologies or patients who received potentially hepatotoxic drugs at the same time. rarely: increased alkaline phosphatase, increased bilirubin, hepatitis, cholestatic jaundice (noted with concomitant therapy with other penicillins and cephalosporins).

Other often: Candidiasis of the skin and mucous membranes; frequency unknown: growth of insensitive microorganisms.

Overdose:

There are no reports of death or the occurrence of life-threatening side effects due to an overdose of Amoxiclav® Quicactab.

Symptoms of overdose include gastrointestinal disorders (abdominal pain, diarrhea, vomiting) and water-electrolyte balance disorders. Reports of crystalluria caused by amoxicillin have been reported, which, in some cases, led to the development of renal failure.

Possible development of seizures in patients with renal insufficiency or in patients receiving high doses of the drug.

In case of an overdose, the patient should be under the supervision of a physician, the treatment is symptomatic.

When an overdose of the drug recommended gastric lavage and intake of adsorbents (Activated carbon).

Hemodialysis is effective.

Interaction:

Antacids, glucosamine, laxative drugs, aminoglycosides slow absorption, ascorbic acid - increases absorption.

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).

Simultaneous application with allopurinol can lead to the development of skin allergic reactions.

Simultaneous use of Amoxiclav® Quicactab and methotrexate increases the toxicity of methotrexate. The simultaneous use of disulfiram.

Increases the effectiveness of indirect anticoagulants (suppressing the intestinal microflora, reduces the synthesis of vitamin K and prothrombin index). In some cases, taking the drug may prolong prothrombin time, therefore, care should be taken when applying simultaneously anticoagulants and Amoxiclav® Quicactab.

In the literature, rare cases of an increase in the international normalized ratio (INR) in patients with simultaneous application acenocoumarol or warfarin and amoxicillin. If it is necessary to simultaneously use anticoagulants, prothrombin time or INR should be closely monitored when the drug is prescribed or withdrawn, and correction of the dose of anticoagulants for oral administration may be required.

When combined with rifampicin there is a mutual weakening of the antibacterial effect.

Amoxiclav®Qviktab should not be used concomitantly with bacteriostatic antibiotics (macrolides, tetracyclines), sulfonamides due to a possible decrease in the effectiveness of Amoxiclav® Quicactab.

Probenecid reduces the excretion of amoxicillin, increasing its serum concentration. Antibiotics reduce the effectiveness oral contraceptives.

Reduces the effectiveness of drugs, in the metabolism of which is formed p-aminobenzoic acid, ethinyl estradiol - risk of bleeding "breakthrough".

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 of 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, it is necessary to interview the patient to identify in a history of hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics.

In patients who are hypersensitive to penicillins, there may be cross-allergic reactions with cephalosporin antibiotics. In course treatment it is necessary to monitor the function of the organs of hematopoiesis, liver, kidneys.

Patients with severe renal dysfunction require adequate dose adjustment or an increase in the intervals between doses.

To reduce the risk of side effects from the GI tract, you should take the drug before or during meals.

When using high doses of Amoxiclav® Quiquate, patients with crystalluria should adequately compensate for fluid loss. Perhaps the development of superinfection due to the growth of microflora insensitive to amoxicillin, which requires a corresponding change in antibacterial therapy.

If antibiotic-associated colitis occurs, immediately discontinue Amoxiclav® Quicact, consult a doctor and begin appropriate treatment. Drugs that inhibit peristalsis are contraindicated in such situations.

Treatment necessarily continues for another 48-72 hours after the disappearance of clinical signs of the disease.When using estrogen-containing oral contraceptives and amoxicillin concomitantly, other or additional methods of contraception should be used whenever possible.

Amoxicillin and clavulanic acid can provoke non-specific binding of immunoglobulins and albumins to the erythrocyte membrane, which can be the cause of a false positive reaction in the Coombs sample.

The use of amoxicillin and clavulanic acid is contraindicated in infectious mononucleosis, as it can provoke the appearance of a measles-like rash.

Lab tests: high concentrations of amoxicillin give a false positive reaction to urine glucose when using a Benedict reagent or Felling solution. It is recommended to use enzymatic reactions with glucosidase.

Special precautions for the destruction of unused medicinal product

There is no need for special precautions when destroying an unused Amoxiclav® Quiquate.

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

Data on negativeThe effect of Amoxiclav® Quicact in recommended doses on the ability to drive a car or work with mechanisms is not. However, because of the potential for side effects from the side of the central nervous system, such as dizziness, headache, convulsions, during treatment should be careful when driving and doing other activities that require concentration and speed of psychomotor reactions. When these undesirable phenomena appear, one should refrain from performing these activities.

Form release / dosage:

Tablets are dispersible 500 mg + 125 mg or 875 mg + 125 mg.

Packaging:

2 tablets per blister of aluminum / aluminum.

For 5 or 7 blisters together with instructions for medical use in a pack of cardboard.

Storage conditions:

In a place protected from moisture 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.

Terms of leave from pharmacies:On prescription

Registration number:LSR-005243/08

Date of registration:04.07.2008

The owner of the registration certificate: Lek dd Lek dd Slovenia

Manufacturer: & nbsp

LEK d.d. Slovenia

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp22.07.2014

Illustrated instructions

Instructions

Amoxiclav® Quicactab (Amoksiklav® Quicktabs)