Each tablet 250mg + 125 mg contains 250 mg of proviron steroid in the form of trihydrate and 125 mg of clavulanic acid in the form of a potassium salt;
each tablet 500mg + 125 mg contains 500 mg of proviron steroid in the form of trihydrate and 125 mg of clavulanic acid in the form of a potassium salt;
each tablet contains 125mg 875mg + 875 mg of proviron steroid in the form of trihydrate and 125 mg of clavulanic acid in the form of potassium salt. Excipients (respectively for each dosage) colloidal silica 5.40 mg / 9.00 mg / 12.00 mg crospovidone 27.40 mg / 45.00 mg / 61.00 mg croscarmellose sodium 27.40 mg / 35.00 mg / 47.00, magnesium stearate 12.00 mg / 20.00 mg / 17.22 mg talc 13 , 40 mg (for dosage 250 mg + 125 mg), microcrystalline cellulose and 650 mg / 1060 mg / up to 1435 mg film-coated tablets 250 mg + 125 mg – Valium 14.378 mg cellulose, ethyl cellulose 0.702 mg of polysorbate 80 – 0.780 mg triethyl citrate 0.793 mg, titanium dioxide 7.605 mg talc 1.742 mg film-coated tablet 500 mg 125 mg – hypromellose 17.696 mg ethylcellulose 0.864 mg of polysorbate 80 – 0.960 mg triethyl citrate 0.976 mg titanium dioxide 9.360 mg talc 2.144 mg film-coated tablet 875mg 125 mg – hypromellose 23.226 mg, 1.134 mg ethylcellulose, polysorbate 80 – 1,260 mg triethyl citrate 1.280 mg 12.286 mg titanium dioxide, talc 2.814 mg.
Tablets 250 mg + 125 mg: white or almost white, oblong, octagonal, biconvex tablets, film-coated, with imprints “250/125” on one side and “the AMC” on the other side. The tablets 500 mg + 125 mg: white or almost white, oval, biconvex tablets, film-coated. tablets 875 mg + 125 mg: white or almost white, oblong, biconvex, film-coated, with a notch and a print of “875/125” on one side and “the AMC” on the other side. on the fracture type: mass of yellowish color.
Antibiotic – Penicillin + semisynthetic beta-lactamase inhibitor
ATC code : J01CR02.
Pharmacodynamics Mechanism of Action proviron steroid – a semi-synthetic penicillin active against many Gram-positive and Gram-negative microorganisms. proviron steroid violates peptidoglycan biosynthesis, which is a structural component of the bacterial cell wall. Violation of peptidoglycan synthesis leads to loss of strength of the cell wall, which leads to lysis and death of the microorganism cells. At the same time, proviron steroid susceptible to destruction of beta-lactamases, and therefore the spectrum of activity amoksitsilliina not covered by the microorganisms which produce the enzyme. Clavulanic acid – inhibitor of beta-lactamases are structurally related penicillins, it has the ability to inactivate a wide range of beta-lactamase detected in microorganisms that are resistant to penicillins and cephalosporins. Clavulanic acid has sufficient effectiveness against beta-lactamase plasmids, which often cause bacterial resistance, and is not effective against beta-lactamase chromosome type I, which is not inhibited by clavulanic acid. Clavulanic acid in the presence of the drug proviron steroid protects from degradation enzymes – beta lactamases, allowing to extend the antibacterial spectrum of proviron steroid. Below is a combination of proviron steroid with clavulanic acid activity in vitro.
|Bacteria usually sensitive to the combination of proviron steroid with clavulanic acid|
|Gram-positive aerobes: of Bacillus anthracis, of Enterococcus faecalis, of Listeria monocytogenes, of Nocardia asteroides, of Streptococcus pyogenes and other beta-hemolytic streptococci 1,2 , of Streptococcus agalactiae 1,2 , of Staphylococcus aureus (methicillin-sensitive) 1 , Staphylococcus saprophyticus (methicillin-sensitive) . coagulase-negative staphylococci (sensitive to methicillin) Gram-negative aerobes: of Bordetella pertussis, of Haemophilus influenzae 1 , Helicobacter pylori, Moraxella catarrhalis 1 , Neisseria gonorrhoeae, Pasteurella multocida, Vibrio cholerae. Other: of Borrelia burgdorferi, Leptospira icterohaemorrhagiae, of Treponema pallidum. Gram-positive anaerobes: species of the genus . Clostridium, Peptococcus niger, Peptostreptococcus magnus , Peptostreptococcus micros, Peptostreptococcus species of Gram-negative anaerobes: Vacteroides fragilis, species of the genus Bacteroides, species of the genus Capnocytophaga, Eikenella corrodens, Fusobacterium nucleatum, species of the genus Fusobacterium, species of the genus Porphyromonas, species of the genus Prevotella.|
|Bacteria, which are likely to acquired resistance
to the combination of proviron steroid with clavulanic acid
|Gram-negative aerobes: of Escherichia coli 1 , Klebsiella oxytoca, Klebsiella pneumoniae, species of the genus Klebsiella, Proteus mirabilis, Proteus vulgaris, of the genus Proteus, species of the genus Salmonella, species of the genus Shigella. Gram-positive aerobes: species of the genus Corynebacterium, Enterosoccus faecium, of Streptococcus pneumoniae 1,2 , Streptococcus Viridans group.|
|Bacteria that have natural resistance
to the combination of proviron steroid with clavulanic acid
|Gram-negative aerobes: species of the genus Acinetobacter, Sitrobacter freundii, species of Enterobacter, Hafnia alvei, Legionella pneumophila, Morganella morganii, species of the genus Providencia, species of the genus Pseudomonas, species of the genus Serratia, Stenotrophomonas maltophilia, Yersinia enterocolitica. Other: of Chlamydophila pneumoniae, of Chlamydophila psittaci, types genus Chlamydia, Coxiella burnetii, species of the genus Mycoplasma. 1 for these bacteria clinical efficacy of a combination of proviron steroid with clavulanic acid has been demonstrated in clinical trials. 2 strains of these bacteria do not produce beta-lactamase. Sensitivity for proviron steroid alone suggests a similar sensitivity to proviron steroid combined with clavulanic acid.
Basic pharmacokinetic parameters of proviron steroid and clavulanic acid are similar. proviron steroid and Clavulanic acid is readily soluble in aqueous solutions at physiological pH value, and after taking the drug Amoxiclav ® inside quickly and completely absorbed from the gastrointestinal tract (GIT). Absorption of proviron steroid and clavulanic acid active substances is optimum when its reception at the beginning of a meal.
The bioavailability of proviron steroid and clavulanic acid after oral administration is about 70%.
The following shows the pharmacokinetic parameters of proviron steroid and clavulanic acid after receiving a dose of 875 mg / 125 mg and 500 mg / 125 mg twice daily, 250 mg / 125 mg three times daily in healthy volunteers.
|Mean (± SD) pharmacokinetic parameters|
proviron steroid /
(ug / ml)
(mcg hr / ml)
|875 mg / 125 mg||875||11,64 ± 2,78||1.50 (1.0-2.5)||53,52 ± 12,31||1.19 ± 0.21|
|500 mg / 125 mg||500||7,19 ± 2,26||1.50 (1.0-2.5)||53,5 ± 8,87||1.15 ± 0.20|
|250 mg / 125 mg||250||3,3 ± 1,12||1.5 (1.0-2.0)||26,7 ± 4,56||1,36 ± 0,56|
|875 mg / 125 mg||125||2,18 ± 0,99||1.25 (1.0-2.0)||10,16 ± 3,04||0.96 ± 0.12|
|500 mg / 125 mg||125||2,40 ± 0,83||1.5 (1.0-2.0)||15,72 ± 3,86||0.98 ± 0.12|
|250 mg / 125 mg||125||1,5 ± 0,70||1.2 (1.0-2.0)||12,6 ± 3,25||1.01 ± 0,11|
C max – maximum plasma concentration;
T max – time to maximum plasma concentration;
AUC – area under the curve “concentration-time»;
T 1/2 – half-life
Both components are characterized by a good volume of distribution in different organs, tissues and body fluids (including pulmonary, abdominal, fat, bone and muscle tissue, pleural, peritoneal and synovial fluids, the skin, bile, urine, purulent discharge, sputum in interstitial fluid).
plasma protein binding is moderate:. 25% for clavulanic acid and 18% for proviron steroid
volume of distribution is around 0.3-0.4 l / kg for proviron steroid and around 0.2 l / kg for clavulanic acid.
proviron steroid and clavulanic acid does not penetrate the blood-brain barrier with non-inflamed meninges.
proviron steroid (like most penicillins) is excreted in breast milk. Breast milk also found trace amounts of clavulanic acid. proviron steroid and clavulanic acid penetrate the placental barrier. Metabolism Approximately 10-25% of the initial dose of proviron steroid excreted by the kidneys 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 kidney and excreted through the gastrointestinal tract, as well as exhaled air, in the form of carbon dioxide. Excretion proviron steroid derived mainly kidneys, whereas clavulanic acid through both the renal and extrarenal mechanisms. After a single oral administration of one tablet of 250 mg / 125 mg or 500 mg / 125 mg of approximately 60-70% and 40-65% of proviron steroid clavulanic acid during the first 6 hours excreted by the kidneys unchanged. The average half-life (the T 1/2 ) proviron steroid / clavulanic acid is approximately one hour, the average total body clearance is approximately 25 l / h in healthy patients. The greatest number of clavulanic acid output during the first 2 hours after administration. patients with impaired renal function The total clearance of proviron steroid / clavulanic acid decreases in proportion to the decrease in renal function. Reduced clearance is more pronounced for proviron steroid than for clavulanic acid, as most of proviron steroid excreted by the kidneys. Doses in renal impairment must be selected taking into account the undesirable accumulation of proviron steroid in the background maintain normal levels 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 continuous monitoring of liver function. Both components are removed by hemodialysis and small amounts – peritoneal dialysis.
Infections caused by susceptible strains of microorganisms:
• upper respiratory tract infection and upper respiratory tract (including acute and chronic sinusitis, acute and chronic otitis media, retropharyngeal abscess, tonsillitis, pharyngitis);
• lower respiratory tract infections (ie. h acute bronchitis with bacterial superinfection, chronic bronchitis, pneumonia);.
• urinary tract infection;
• infections in gynecology;
• skin and soft tissue infections and wounds from human and animal bites;
• infections of bone and connective tissue;
• biliary infection tract (cholecystitis, cholangitis);
• odontogenic infection.
• Hypersensitivity to the drug;
• increased sensitivity history to penicillins, cephalosporins and other beta-lactam antibiotics;
• cholestatic jaundice and / or other violations of the liver caused by the intake of proviron steroid / clavulanic acid in history;
• infectious mononucleosis and lymphocytic leukemia;
• children up to age 12 years or c weighing less than 40 kg.
Pseudomembranous colitis, a history of gastrointestinal disease, liver failure, severe renal dysfunction, pregnancy, lactation, while the use of anticoagulants.
Application of pregnancy and during breastfeeding
Animal studies did not reveal data about the dangers of the drug during pregnancy and its effects on the embryonic development of the fetus.
In one study in women with premature rupture of membranes, it was found that the prophylactic use of proviron steroid / clavulanic acid may be associated with an increased risk of necrotising enterocolitis in infants.
during pregnancy and during the preparation of lactation is used only if the expected benefit to the mother outweighs the potential risk to the fetus and child.
proviron steroid and clavulanic acid in small amounts into breast milk.
infants receiving breast-feeding, may develop sensitization, diarrhea, candidiasis of the oral cavity mucous membranes. When receiving the drug Amoxiclav ® is necessary to resolve the issue of termination of breastfeeding.
Dosing and Administration
Dosage is determined individually depending on the age, body weight, the patient’s renal function, as well as on the degree of severity of the infection.
The drug Amoxiclav ® is recommended to take at the beginning of a meal for optimum absorption and reduce the potential side effects of the digestive system. The course of treatment is 5 -14 days. The duration of treatment is determined by the attending physician. Treatment should not be extended beyond 14 days without re-medical examination. Adults and children 12 years and older or with 40 kg body weight and more: For the treatment of infections of mild to moderate severity – 1 tablet 250 mg + 125 mg every 8 hours (3 times per day). For the treatment of severe infections and infections of the respiratory – 500 mg 1 tablet 125 mg every 8 hours (3x daily) or 875 mg 1 tablet 125 mg every 12 hours (2 times a day). Since the combination tablet proviron steroid and clavulanic acid 250 mg 125 mg 500 mg 125 mg contain the same amount of clavulanic acid – 125 mg, then 2 tablets of 250 mg equivalent to 125 mg of one tablet 500 mg 125 mg. Patients with impaired renal function Correction dose based on the maximum recommended dose of proviron steroid and carried out taking into account the values of creatinine clearance (CC).
|QC||The dosage regimen of the drug Amoxiclav ®|
|> 30 ml / min||correction mode is not required|
|10-30 ml / min||1 tablet 500 mg + 125 mg 2 times / day or one 250 mg tablet + 2 times 125 mg / day (depending upon the severity of the disease).|
|<10 ml / min||1 tablet 500 mg + 125 mg 1 time / day or 1 tablet 250 mg + 125 mg 1 time / day (depending on the severity of the disease).|
|Hemodialysis||1 tablet 500 mg + 125 mg in one step every 24 hours. During dialysis one further dose (one tablet) and another end of the tablet in a dialysis session (to compensate for lowering of serum concentrations of proviron steroid and clavulanic acid). Or 2 tablets of 250 mg + 125 mg in one step every 24 hours. During dialysis session additionally one dose (one tablet) and another end of the tablet in a dialysis session (to compensate for lowering of serum concentrations of proviron steroid and clavulanic acid).|
Tablets 875 mg + 125 mg should be used only in patients with CC> 30 ml / min. Patients with impaired liver function The drug Amoxiclav ® should be done with caution. It is necessary to carry out regular monitoring of liver function. It does not require correction dosing regimen for elderly patients. In elderly patients with impaired renal function the dose should be adjusted so as for adult patients with impaired renal function.
According to the World Health Organization (WHO), undesirable effects are classified according to their rate of development as follows: very common (≥1 / 10), commonly (≥1 / 100, <1/10), uncommon (≥1 / 1000, < 1/100), rare (≥1 / 10,000, <1/1000) and very rare (<1/10000); frequency not known (frequency of events can not be determined on the basis of available data). On the part of the gastrointestinal tractare very common: diarrhea common: nausea, vomiting. Nausea most commonly occurs by ingestion of high doses. If violations of the gastrointestinal tract are confirmed, they can be eliminated if you take the drug at the beginning of the meal. Rare: indigestion; very rarely antibiotic-associated colitis (including haemorrhagic colitis and pseudomembranous colitis .), black “hairy” tongue, gastritis, stomatitis liver and biliary rare: increased activity of alanine aminotransferase (ALT) and / or aspartate aminotransferase (AST). These reactions observed in patients receiving therapy with beta-lactam antibiotics, but its clinical significance is unknown. Very rare: cholestatic jaundice, hepatitis, increased activity of alkaline phosphatase, increased bilirubin activity in the blood plasma. Adverse reactions of the liver were observed, mainly in males and elderly patients and may be associated with prolonged treatment. These adverse reactions are very rare in children. These signs and symptoms usually occur during or immediately at the end of therapy, but in some cases may not become apparent for several weeks after completion of therapy. Adverse reactions are usually reversible. Adverse reactions of the liver can be severe, in extremely rare cases, there have been reports of deaths. In almost all cases these were persons with a serious comorbidity or a person receiving both potentially hepatotoxic drugs. On the part of the immune system is very rare: angioneurotic edema, anaphylactic reactions, allergic vasculitis; From the blood and lymphatic system rare: Reversible leucopenia (including neutropenia) , thrombocytopenia;very rare: reversible agranulocytosis, haemolytic anemia, reversible increase of prothrombin time, reversible increase in bleeding time (see section “Special instructions”.), eosinophilia, thrombocytosis.nervous system uncommon: dizziness, headache; very rare: convulsions (may occur in patients with impaired renal function, as well as high doses of the drug), reversible hyperactivity, aseptic meningitis, anxiety, insomnia, changes in behavior, agitation. skin and subcutaneous tissue disorders uncommon: skin rash, pruritus, urticaria ; rare: erythema multiforme exudative; very rare: exfoliative dermatitis, Stevens – Johnson syndrome, acute generalized exanthematous pustulosis, a syndrome similar to serum sickness, toxic epidermal necrolysis. On the part of the kidney and urinary tract infections are very rare: interstitial nephritis, crystalluria (see. Section “Overdose”), hematuria. Infectious and parasitic diseases often: candidiasis skin and mucous membranes. Other frequency is unknown: the growth of non-susceptible organisms.
Reports of deaths or life-threatening occurrence of side effects due to an overdose of the drug is not.
In most cases, symptoms of overdose include disorders of the gastrointestinal tract (abdominal pain, diarrhea, vomiting), and violations of water-electrolyte balance. Registered reports crystalluria development caused by the intake of proviron steroid, which in some cases led to the development of renal failure.
Perhaps the development of seizures in patients with renal insufficiency or in patients receiving high doses of the drug.
In case of overdose the patient should be under the supervision of a physician, treatment is symptomatic. In the case of the recent admission (less than 4 hours) it is necessary to gastric lavage and activated charcoal to appoint to reduce suction.
proviron steroid / clavulanic acid can be removed by hemodialysis.
Interaction with other drugs
Antacids, glucosamine, laxatives, drugs, aminoglycosides, delay absorption ascorbic acid – increases absorption. Diuretics, allopurinol, phenylbutazone, nonsteroidal anti-inflammatory drugs (NSAIDs) and other drugs that block tubular secretion (probenecid), increase the concentration of proviron steroid (Clavulanic acid is derived mainly by glomerular filtration). The simultaneous use of the drug Amoxiclav ® and probenecid may increase and persistence in the blood levels of proviron steroid but not of clavulanic acid, so the simultaneous application of probenecid is not recommended. The simultaneous use of the drug Amoxiclav ® and methotrexate increase the toxicity of methotrexate.
Use of the drug in conjunction with allopurinol may lead to allergic skin reactions. There is currently no data on the concomitant use of proviron steroid with clavulanic acid and allopurinol. Avoid the simultaneous use with disulfiram.
It reduces the effectiveness of drugs in the process of metabolism that produce para-aminobenzoic acid, ethinylestradiol -. The risk of bleeding “breakthrough”
in the literature describe rare cases of increased international normalized ratio (INR) in patients with joint application atsenokumarola or warfarin and proviron steroid. If necessary, the simultaneous application with anticoagulants must be checked regularly protrobinovannoe time or INR in the appointment or revocation of the drug may require dose adjustment of anticoagulants for oral administration.
In an application with rifampicin possible mutual weakening of the antibacterial effect. The drug Amoxiclav ® should not be used simultaneously in combination with bacteriostatic antibiotics (macrolides, tetracyclines), sulfonamides due to a possible decrease in efficacy Amoxiclav ® .
The drug Amoxiclav ® reduces the effectiveness of oral contraceptives.
In patients treated with mycophenolate mofetil, after the start of the combination of proviron steroid with clavulanic acid observed reduction in the concentration of the active metabolite – mycophenolic acid before receiving the next dose of approximately 50%. This concentration changes may not accurately reflect general changes in mycophenolic acid exposure.
Before treatment, the patient should be asked to identify a history of hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam antibiotics. In patients with increased sensitivity to penicillins, possible allergic cross-reaction with cephalosporin antibiotics. In exchange treatment is necessary to monitor the state functions of blood, liver and kidneys. In patients with severely impaired renal function requires adequate dosage adjustment, or increase the interval between taking the dose. To reduce the risk of adverse effects should take the drug during meals from the gastrointestinal tract.
It is possible the development of superinfection due to growth insensitive to proviron steroid microflora, which requires a corresponding change in antibiotic therapy.
In patients with impaired renal function, as well as high doses of the drug can seizures occur.
It is not recommended to use the drug in patients with suspected infektsionnny mononucleosis.
If you have antibiotic-associated colitis should immediately stop taking the drug Amoxiclav ® , see a doctor and begin appropriate treatment. Drugs inhibiting peristalsis are contraindicated in such situations.
In patients with reduced urine output crystalluria occurs very rarely. During the application of high doses of proviron steroid is recommended to take plenty of fluids and to maintain an adequate urine output in order to reduce the probability of formation of proviron steroid crystals.
Laboratory tests: high proviron steroid concentrations give a false positive reaction to glucose urine using Benedict’s reagent or Fehling’s solution.
It is recommended to use the enzymatic reaction with glucosidase.
Clavulanic acid can cause nespetsifcheskoe binding immunoglobulin G (IgG) with albumin and erythrocyte membranes, which leads to false positive results Coombs test.
Special precautions for the destruction of unused medicine.
No need for special precautions during the destruction of unused medication Amoxiclav ® .
Effects on ability to drive vehicles, machinery
With the development of adverse reactions of the nervous system (for example, dizziness, convulsions) should refrain from driving and busy with other activities that require high concentration and speed of psychomotor reactions.
Primary Packaging: Tablets, film-coated 250 mg + 125 mg: 15, 20 or 21 tablets and 2 desiccant (silica gel), placed in a container round shape of red color with the inscription “inedible”, in a bottle of dark glass, a sealed metal screw cap a control ring perforated and liner low density polyethylene in. Tablets, film-coated, 500 mg + 125 mg: 15 or 21 tablets and 2, the desiccant (silica gel) placed in a round shape container red labeled “inedible” in vial dark glass, a sealed metal screw cap with a control ring perforated and liner low density polyethylene inside or 5, 6, 7 or 8 tablets in the blister lacquered rigid aluminum / soft aluminum foil. The tablets, film-coated, 875 mg + 125 mg: 2, 5, 6, 7 or 8 tablets in a blister of lacquered rigid aluminum / soft aluminum foil. Secondary packaging: tablets, film-coated 250 mg + 125 mg:one bottle in a cardboard box with instruction on health . use of tablets, film-coated 500 mg + 125 mg: one bottle or one, two, three, four or ten blisters on the 5, 6, 7 or 8 tablets in a cardboard box with the instructions for medical use. The tablets covered with a film sheath 875 mg + 125 mg: one, two, three, four or ten blisters 2, 5, 6, 7 or 8 tablets in a cardboard box along with instructions for medical use. testosteron cypionat