Амикацин-Ферейн®

General characteristics. Structure:

Active ingredient: 0,5 g of amikacin (in the form of sulfate).

Semi-synthetic antibiotic of a broad spectrum of activity.

Pharmacological properties:

Pharmacodynamics. Works bakteritsidno. Communicating with 30ssubjedinitsey ribosomes, interferes with formation of a complex transport and template-RNA, blocks protein synthesis, and also destroys cytoplasmic membranes of bacteria.

It is highly active concerning aerobic gram-negative microorganisms - Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Serratia spp., Providencia spp., Salmonella spp., Shigella spp.; some gram-positive organisms - Staphylococcus spp. (including steady against penicillin, some cephalosporins); it is moderately active concerning Streptococcus spp.

At co-administration with benzylpenicillin has sinergidny effect concerning Enterococcus faecalis strains.

Does not affect anaerobic microorganisms.

Amikacin does not lose activity under the influence of the enzymes inactivating other aminoglycosides and can remain active concerning strains of Pseudomonas aeruginosa steady against Tobramycinum, gentamycin and a netilmitsin.

Pharmacokinetics. After intramuscular introduction it is soaked up quickly and completely. The maximum concentration (Cmax) at intramuscular introduction of 7,5 mg/kg - 21 mkg/ml, after 30 min. intravenous infusion of 7,5 mg/kg - 38 mkg/ml. Time of achievement of the maximum concentration (Tmax) - about 1,5 h after intramuscular introduction. Communication with proteins of plasma - 4-11%.

It is well distributed in extracellular liquid (contents of abscesses, a pleural exudate, ascitic, pericardiac, synovial, lymphatic and pepitonealny fluid); in high concentration it is found in urine; in low - in bile, breast milk, watery moisture of an eye, a bronchial secret, a phlegm and cerebrospinal fluid (SMZh).

Well gets into all body tissues where collects intracellularly; high concentration are noted in bodies with good blood supply: lungs, a liver, a myocardium, a spleen and especially - in kidneys where collects in cortical substance, lower concentration - in muscles, fatty tissue and bones.

At appointment in therapeutic doses (normal) as the adult amikacin does not get through the blood-brain barrier (BBB), at an inflammation of a meninx permeability increases a little. At newborns higher concentration in cerebrospinal fluid, than at adults are reached; passes through a placenta - it obnayoruzhivatsya in blood of a fruit and amniotic liquid. Distribution volume adults - 0,26 l/kg, at children have 0,2-0,4 l/kg, at newborns - at the age of less than 1 week and with a body weight less than 1500 - to 0,68 l/kg, at the age of less than 1 week and with a body weight more than 1500 - to 0,58 l/kg, at patients with a mucoviscidosis - 0,3-0,39 l/kg. Average therapeutic concentration at intravenous or intramuscular administration remains during 10-12ch.

It is not metabolized. The elimination half-life (T 1/2) at adults - 2-4 h, at newborns is 5-8 h, children of more advanced age have 2,5-4 h. The final size T of Ug - more than 100 h (release from intracellular depots).

It is removed by kidneys by glomerular filtering (65-94%) preferential in not changed look. Renal clearance - 79-100 ml/min. The t 1/2 at adults at a renal failure varies depending on extent of disturbance - to 100 h, patients with a mucoviscidosis have 1-2 h, at patients with burns and a hyperthermia of T 1/2 can be shorter in comparison with average values owing to the increased clearance.

It is removed at a hemodialysis (50 for 4-6 h), peritoneal dialysis is less effective (25% for 48-72 h).

Indications to use:

The infectious and inflammatory diseases caused by gram-negative microorganisms (steady against gentamycin, sisomicin and Kanamycinum) or associations of gram-positive and gram-negative microorganisms: respiratory infections (bronchitis, pneumonia, a pleura empyema, abscess of lungs), sepsis, a septic endocarditis, TsNS infections (including meningitis), infections of an abdominal cavity (including peritonitis), infections of urinogenital ways (pyelonephritis, cystitis, an urethritis), purulent infections of skin and soft tissues (including the infected burns infected ulcers and decubituses of various genesis), infections of bilious ways, bones and joints (including osteomyelitis), a wound fever, postoperative infections.

Route of administration and doses:

Intravenously (struyno, within 2 min. or kapelno), intramusculary, to adults and children 6 years on 5 mg/kg each 8 h or on 7,5 mg/kg each 12 h are more senior; bacterial infections of uric ways (uncomplicated) - 250 mg each 12 h; after the session of a hemodialysis the additional dose of-3-5 mg/kg can be appointed. The maximum doses for adults - 15 mg/kg/days, but no more than 1,5 g/days within 10 days.

Treatment duration at intravenous administration — 3 - 7 days, at intramuscular — 7 - 10 days.

To premature newborn children an initial dose - 10 mg/kg, then on 7,5 mg/kg each 18 - 24 h, to newborns and children up to 6 years an initial dose - 10 mg/kg, then - on 7,5 mg/kg each 12 h within 7-10 days.

The dose of 5 - 7,5 mg/kg each 4 - 6 h in connection with shorter elimination half-life (1 - 1,5 h) at these patients can be required by patients with burns.

For intramuscular introduction use the solution prepared by addition to contents of a bottle of 500 mg 2-3 ml of water for injections.

Intravenously amikacin is entered kapelno within 30 - 60 min., in case of need - struyno.

For intravenous administration (struyno) use the solution prepared by addition to contents of a bottle of 500 mg 2-3 ml of solvent (water for injections, either 0,9% chloride sodium solution, or 5% dextrose solution).

For intravenous administration (kapelno) contents of a bottle are dissolved in 200 ml of solvent (5% of solution of a dextrose or 0,9% of solution of sodium of chloride).
Concentration of amikacin in solution should not exceed 5 mg/ml.

At disturbance of secretory function of kidneys decrease in doses or increase in intervals between introductions is necessary.

In case of increase in an interval between introductions (if the level of clearance of creatinine is not known, and a condition of the patient stable), the interval between administrations of drug is established as follows: An interval (hours) = concentration of creatinine in blood serum x 9. If concentration of creatinine in serum of 2 mg / 100 ml, then the recommended single dose (7,5 mg/kg) it is necessary to enter each 18 hours. At increase in an interval the single dose is not changed.

In case of decrease in a single dose at the invariable mode of dosing the first dose by the patient with a renal failure makes 7,5 mg/kg. For calculation of the subsequent doses it is necessary to divide value of clearance (ml/min.) at patients into clearance of creatinine normal, then the received figure is multiplied by the size of an initial dose in mg:

The subsequent dose (mg) = (KK at sick (ml/min.) / KK is normal (ml/min.)) x the initial dose entered each 12 h (mg)

Features of use:

Before use define sensitivity of the allocated activators, using the disks containing 30 mkg of amikacin. With a diameter of a zone of 17 mm, free from growth, and more microorganism is considered sensitive, from 15 to 16 mm - moderately sensitive, less than 14 mm - steady.

Concentration of amikacin in plasma should not exceed 25 mkg/ml (concentration of 15-25 mkg/ml is therapeutic).

During treatment it is necessary at least 1 time a week to control function of kidneys, an acoustical nerve and vestibular mechanism.

The probability of development of nephrotoxicity is higher at patients with a renal failure, and also at purposes of high doses or for a long time (at this category of patients daily control of function of kidneys can be required).

At unsatisfactory audiometric tests the dose of drug is reduced or stop treatment.

In the presence "vital" indications it can be used at the feeding women (aminoglycosides get into breast milk in small amounts. However they are poorly soaked up from digestive tract, and the related complications at babies was not registered).

Patients with infectious and inflammatory diseases of urinary tract are recommended to apply the increased amount of liquid at an adequate diuresis.

In the absence of positive clinical dynamics it is necessary to remember a possibility of development of resistant microorganisms. In similar cases it is necessary to cancel treatment and to begin performing the corresponding therapy.

Side effects:

From the alimentary system: nausea, vomiting, abnormal liver function (increase in activity of "hepatic" transaminases, hyperbilirubinemia).

From bodies of a hemopoiesis: anemia, leukopenia, granulocytopenia, thrombocytopenia.

From the central nervous system: a headache, drowsiness, neurotoxic action (twitching of muscles, feeling of numbness, a pricking, epileptic seizures), disturbances nervously - muscular transfer (apnoea).

From sense bodys: ototoxicity (decrease in hearing, vestibular and labyrinth disturbances, irreversible deafness), toxic action on a vestibular mechanism (a diskoordination of movements, dizziness, nausea, vomiting).

From mocheeydelitelny system: nephrotoxicity – a renal failure (an oliguria, a proteinuria, a microhematuria).

Allergic reactions: skin rash, itch, dermahemia, fever, Quincke's edema.

Local: morbidity in the place of an injection, dermatitis, phlebitis and a periphlebitis (at intravenous administration).

Interaction with other medicines:

Pharmaceutical it is incompatible with penicillin, heparin, cephalosporins, kapreomitsiny, Amphotericinum In, a hydrochlorothiazide, erythromycin, nitrofurantoin, vitamins of group B and C, potassium chloride.

Shows a synergism at interaction with karbenitsilliny, Benzylium penicillin, cephalosporins (at patients with a heavy chronic renal failure at combined use with a beta laktamnymi with antibiotics decrease in efficiency of aminoglycosides is possible).

Acidum nalidixicum, polymyxin B, Cisplatinum and Vancomycinum increase risk of development from - and nephrotoxicity.

Diuretics (especially furosemide), cephalosporins, penicillin, streptocides and non-steroidal anti-inflammatory drugs, competing for active secretion in nephron tubules, block elimination of aminoglycosides, increase their concentration in blood serum, strengthening nefro-and a neurotoxicity.

Strengthens myorelaxation effect of kurarepodobny drugs.

Metoksifluran, polymyxins for parenteral administration, капреомицин and other medicines blocking neuromuscular transmission (halogenated hydrocarbons as drugs for inhalation anesthesia, opioid analgetics), transfusion of large amounts of blood with citrate preservatives increase risk of an apnoea.

Parenteral administration of indometacin increases risk of development of toxic effects of aminoglycosides (increase in an elimination half-life and decrease in clearance). Reduces effect anty and asthenic medicines.

Contraindications:

Hypersensitivity (including to other aminoglycosides in the anamnesis), neuritis of an acoustical nerve, a heavy chronic renal failure with an azotemia and uraemia, pregnancy.

With care. A myasthenia, parkinsonism, botulism (aminoglycosides can cause neuromuscular transmission disturbance that leads to further weakening of skeletal muscles), dehydration, a renal failure, the period newborn prematurity of children, advanced age, the lactation period.

Overdose:

Symptoms: toxic reactions (a hearing loss, an ataxy, dizziness, frustration of an urination, thirst, a loss of appetite, nausea, vomiting, a ring or feeling of a mortgaging in ears, breath disturbance).

Treatment: for lifting the siege of neuromuscular transmission and its effects - a hemodialysis or peritoneal dialysis; antikholinesterazny means, calcium salts, artificial ventilation of the lungs, other symptomatic and maintenance therapy.

Storage conditions:

List B. In the dry, protected from light place, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Lyophilisate for preparation of solution for intravenous and intramuscular administration on 0,5 g in bottles with a capacity of 10 ml. Each bottle together with the application instruction - in a pack from a cardboard. 5 bottles - in a blister strip packaging from a film polyvinyl chloride. 5 bottles - in a blister strip packaging from a film of the polyvinyl chloride and aluminum foil varnished or a packing material. 1 blister strip packaging with the application instruction - in a pack from a cardboard. 5 bottles together with the application instruction - in a pack from a cardboard with an insert with cells for bottles. 10, 20, 30, 40, 50, 70, 100, 200 blister strip packagings with application instructions in a box from a cardboard (for hospitals). 50, 108, 115, 888 bottles with application instructions in a box from a cardboard (for hospitals).