Азтреабол®

General characteristics. Structure:

Active ingredient: 0,5 g and 1,0 g of an aztreonam.
 
Excipient: L-arginine.

Pharmacological properties:

Pharmacodynamics. Aztreonam is synthetic monocyclic beta лактамным an antibiotic for parenteral use. Structurally differs from others beta лактамных antibiotics (such as penicillin, cephalosporins); a kernel of a molecule is alpha methyl-3-amino-mono-baktamnaya acid. Works bakteritsidno: contacts transpeptidases and breaks the final stages of synthesis of a cell wall of bacteria. Has high affinity to penicillin - to the connecting protein 3. Высокоустойчив to beta lactamelements (including to penicillinases and tsefalosporinaza) gram-negative bacteria.

Has powerful and specific activity of in vitro concerning gram-negative aerobic activators, including Pseudomonas aeruginosa. Bactericidal action is shown in a wide interval of values рН and in anaerobic conditions.

It is active concerning the following microorganisms both in vitro, and in vivo: Citrobacter spp., including S. of freundii, Enterobacter spp., including E. cloacae, Escherichia coli, Haemophilus influenzae (including ampicillin - steady, etc. penitsillinazoprodutsiruyushchy strains), Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Serratia spp., including S. marcescens.

The following strains were in vitro are sensitive, however, clinical value of these data is unknown: Aeromonas hydrophila, Morganella morganii, Neisseria gonorrhoeae (including penitsillinazoprodutsiruyushchy strains), Pasteurella multocida, Proteus vulgaris, Providencia stuartii, Providencia rettgeri, Yersinia enterocolitica. Are steady against Aztreabolu®: gram-positive aerobic cocci and bacteria, Acinetobacter spp., anaerobic microorganisms, mycoplasmas and other intracellular pathogens, Mycobacterium spp.

Use of Aztreabola® at an allergy to penicillin, cephalosporins and karbapenema is possible. Seldom causes dysbacteriosis.

Pharmacokinetics. The maximum serumal concentration (Cmax) after single to 30 minute intravenous (in/in) infusion of 0,5 g and 1 g of an aztreonam are observed at once after introduction and make, on average, 54 mkg/ml and 90 mkg/ml, respectively. At an intravenous bolyusny injection within 3 min. average Cmax values, equal 58 and 125 mkg/ml, are reached in 5 min. after introduction.

After an intramuscular injection of 0,5 g (in oil) and 1 g of Cmax are defined in an hour after introduction and make, on average, 21 mkg/ml and 46 mkg/ml, respectively.

Later in/in or introductions in oil to aztreona it is well distributed in many bodies and fabrics. Therapeutic the significant concentration exceeding the minimum overwhelming concentration (MOC) for sensitive microorganisms myometriums, skeletal muscles, tissue of a liver and a wall of a gall bladder, a wall of a small and large intestine are defined in synovial fluid, bile, pericardium liquid, a bronchial secret, intersticial liquid, peritoneal exudate, kidneys, a prostate, lungs, skin, bones, ovaries, an endometria. Passes through a placenta; in low concentration gets into breast milk. At introduction as a part of liquid for peritoneal dialysis quickly reaches therapeutic concentration in blood serum. 

The seeming distribution volume in an equilibrium state - about 13 l that is approximately equivalent to the volume of extracellular liquid.

Extent of linkng with proteins of a blood plasma - 56%. It is removed preferential by kidneys by glomerular filtering and tubular secretion. Serumal clearance - about 91 ml/min., renal clearance - 56 ml/min. The elimination half-life (Т½) makes 1,5-2 hours. Slightly (less than 6% of the entered dose) it is metabolized in a liver. 60-70% are removed by kidneys in not changed look and in the form of an inactive hydrolysate beta лактамного rings, 12% - through intestines. 

At patients with reduced function of kidneys Т½ the aztreonama considerably increases owing to what correction of a dose is recommended.

Serumal concentration of an aztreonam quickly decrease at haemo - or peritonalny dialysis.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to an aztreonam:
 
- lower respiratory tract infections, including pneumonia, acute and exacerbations of chronic bronchitis;
 
- intraabdominal infections, including peritonitis;
 
- the uncomplicated and complicated infections of urinary tract, including pyelonephritis and cystitis (including recuring);
 
- gynecologic infections, including an endometritis and a parametritis;
 
- infections of skin and soft tissues;
 
- septicaemia.
 
Азтреабол® it is shown for a perioperatsionny antibiotikoprofilaktika, and also for therapy of postoperative infectious complications, including abscesses of various localizations, infectious complications at perforation of hollow bodies, infections of skin and soft tissues.

For empirical therapy of multi-infections when it is impossible to exclude an etiological role of gram-positive aerobic microorganisms and/or anaerobe bacterias, it is recommended to combine Aztreabol® with antistaphylococcal antibiotics (penicillin, cephalosporins, Vancomycinum, aminoglycosides) and/or antianaerobic antibiotics (metronidazole, linkozamida).

Азтреабол® is considered as an alternative antibiotic for treatment of infections at patients with an allergy to penicillin, cephalosporins and karbapenema.

Route of administration and doses:

Азтреабол® enter intravenously (struyno, kapelno) and intramusculary. In/in a way of introduction it is recommended at patients for whom single doses more than 1 g are required, and also at a septicaemia, at peritonitis or other heavy system or zhizneugrozhayushchy infections.

To adults and children 12 years for treatment of infections of urinary tract of Aztreabol® are more senior appoint in a dose 0,5-1,0 g in/in or each 8-12 hours in oil. For therapy of medium-weight infections of other localizations each 8 or 12 hours enter in a dose 1 g or 2 g. In cases of the heavy or life-threatening infections and infections caused by P.aeruginosa, the single dose is increased to 2,0 g and entered in/in bucketed at 6 or 8 hours. The maximum daily dose of drug should not exceed 8 g. Duration of antibacterial therapy is established individually, proceeding from weight of an infection and the allocated activators. The course of treatment depends on weight of an infection; administration of drug has to be continued by at least 48 h after disappearance of clinical symptoms of an infection. 

At a renal failure dose adjustment is required at clearance of creatinine of smaller or equal 30 ml/min./1,73 sq.m. Treatment is begun with a load (first) dose which depends on localization and weight of an infection (see below):
 
- the clearance of creatinine, ml/min. of/1,73 sq.m more than 30 - dose adjustments is not required;
 
- clearance of creatinine, ml/min. of/1,73 sq.m 10-30 - a load dose of 1-2 g, then 1/2 from a load dose each 6, 8 or 12 hours;
 
- clearance of creatinine, ml/min. of/1,73 sq.m less than 10 - a load dose 0,5, 1 g or 2 g, then 1/4 from a load dose each 6, 8 or 12 hours;
 
- a hemodialysis - a load dose 0,5, 1 g or 2 g, then 1/4 from a load dose each 6, 8 or 12 hours. At a heavy infection - in addition 1/8 from a load dose after each session of a hemodialysis.

Usual dosages of Aztreabola® at children from 9 months to 12 years make 30 mg/kg each 8 hours in / century. For treatment of heavy and life-threatening infections enter 30 mg/kg each 6-8 hours in / century. The maximum dose of Aztreabola® - 120 mg/kg/days.

Rules of preparation of solutions for in/in and introductions in oil.
 
Intramuscular introduction.
For introduction in oil the sterile powder Aztreabola® is dissolved in sterile water for injections or in 0,9% chloride sodium solution. The following minimum quantities of solvent add directly to a bottle with dry powder of an antibiotic:
in the bottle containing
0,5  g Азтреабола® 1,5 ml
in the bottle containing
1,0  g Азтреабола® 3,0 ml

Enter deeply intramusculary into body parts with the expressed muscular layer (an upper outside quadrant of a buttock or the lateral surface of a hip). It is recommended to carry out the test for aspiration to avoid undesirable administration of solution in a blood vessel.

Intravenous administration.
For in/in jet introductions of Aztreabol® dissolve in sterile water for injections. The following minimum quantities of solvent add directly to a bottle with dry powder of an antibiotic:
in the bottle containing
0,5  g Азтреабола® 6 ml
in the bottle containing
1,0  g Азтреабола® 10 ml

Enter in/in slowly, within 3-5 min.; introduction through a special node or port for system injections for in/in infusions is possible if the patient receives liquids, compatible to Aztreabolom®, parenterally.

For in/in drop introductions Aztreabol ® dissolve in two stages:
1) for primary dissolution use sterile water for injections at the rate of 3 ml of solvent on each gram of Aztreabola®;
2) the received solution is transferred to the bottle containing 50-100 ml of the compatible infusional environment. Enter through system for in/in infusions within not less than 30 minutes. Aztreabola® solutions are compatible from 0,9% solution of sodium of chloride it (is recommended), 5% (are recommended) by solution of a dextrose, 10% dextrose solution; the aqueous solution containing 0,45% of sodium of chloride and 5% of a dextrose; the aqueous solution containing 0,9% of sodium of chloride and 5% of a dextrose; the aqueous solution containing 0,2% of sodium of chloride and 5% of a dextrose; Ringer's solution; laktirovanny solution of Ringer; lactate sodium solution for injections; solutions Normozol, Normozol-R, Normozol-M from 5% glucose; 5% and 10% Mannitolum solutions; 10% solution of invert sugar; solution Ionozol from 5% glucose; solutions of Isolithic lines E and Isolithic lines of M from 5% glucose.

Features of use:

In spite of the fact that to aztreona practically does not put the selection pressure upon anaerobic intestinal microflora, when developing diarrhea during treatment of Aztreabolom® it is necessary to show vigilance in view of possible development of pseudomembranous colitis. If the diagnosis an antibiotic - the associated diarrhea or pseudomembranous colitis is established, it is necessary to stop immediately introduction of Aztreabola® and to appoint the corresponding treatment.

As well as in case of other antibiotics, use of Aztreabola® can lead to colonization by insensitive microflora and to development of superinfection.

Side effects:

Allergic reactions: bronchospasm, Quincke's disease, acute anaphylaxis.

From bodies of a hemopoiesis: leukopenia, neutropenia, granulocytopenia, thrombocytopenia, anemia, eosinophilia, leukocytosis, thrombocytosis.

From the alimentary system: spastic abdominal pains, nausea, it is very rare - jaundice, stomatitis, a glossitis, taste disturbances, an unpleasant smell from a mouth, the diarrhea caused by S. difficile including pseudomembranous colitis or bleedings from a GIT.

From integuments: small tortoiseshell, petechias, skin itch, toxic epidermal necrosis, multiformny erythema, exfoliative dermatitis, plentiful sweating.

From a nervous system: paresthesias, spasms, sleeplessness, headache, dizziness.

From sense bodys: sonitus, diplopia, food faddism, numbness of language, sneezing, nose congestion.

From respiratory system: asthma, thorax pains, goose breathing.

From cardiovascular system: a lowering of arterial pressure, the taking place changes on an ECG (a ventricular bigeminal pulse, ventricular premature ventricular contraction), "inflows".

From skeletal muscles: muscle pain.

Changes of laboratory indicators: seldom - increase in activity of "hepatic" transaminases, an alkaline phosphatase, a hyperbilirubinemia, false positive test of Koombs, increase in creatinine of blood serum, increase in a prothrombin time and partial tromboplastinovy time.

Local reactions: phlebitis, morbidity on the vein course, unpleasant feelings in the place in oil of introduction.

Others: mycotic vulvovaginitis, fervescence, morbidity of mammary glands, weakness, indisposition.

Interaction with other medicines:

At co-administration of Aztreabola® with anti-pyocyanic penicillin, ampicillin, cephalosporins (except a tsefoksitin), aminoglycosides and ftorkhinolona are observed sinergidny effect concerning some enterobakteriya and P.aeruginosa.

In solution pharmaceutical it is incompatible with naftsilliny, Cefradinum and metronidazole. At simultaneous use it is not necessary to mix them in one syringe or one infusional environment; at introduction in oil to enter into different body parts; at intravenous administration to enter separately, observing a certain sequence with as it is possible a big time interval between injections (infusions), or to use separate intravenous catheters.

Contraindications:

Hypersensitivity to an aztreonam or L-arginine, the lactation period, children's age (up to 9 months).

Overdose:

Data on overdose of an aztreonam are absent.
If necessary, concentration of an aztreonam in blood serum can be reduced by means of haemo - and peritoneal dialysis.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. To store in the places unavailable to children.

Issue conditions:

According to the recipe

Packaging:

0,5 g or 1,0 g of active agent place glass with a capacity of 10 ml in bottles
 
1 bottle with drug and the application instruction is placed in a pack from a cardboard.