Амикацин-Ферейн®

General characteristics. Structure:

Active ingredient: 250 mg, 500 mg or 1000 mg of amikacin in the form of sulfate in 1 bottle.

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:

Pregnancy and lactation. Use of drug at pregnancy is contraindicated. In need of use of drug in the period of a lactation, breastfeeding is stopped.

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 purpose 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.

Patients with infectious and inflammatory diseases of urinary tract are recommended to accept 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.

Influence on ability to manage vehicles and mechanisms. It is necessary to be careful at control of vehicles and occupations other potentially dangerous types of activity demanding the increased concentration of attention and speed of psychomotor reactions.

Side effects:

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

From a nervous system: headache, drowsiness, neurotoxic action (twitching of muscles, feeling of numbness, pricking; epileptic seizures), neuromuscular transmission disturbance (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). Frequency of emergence of vestibular and acoustical frustration increases at patients with a renal failure.

From an urinary system: nephrotoxicity, renal failure (oliguria, proteinuria, microhematuria, giperkreatininemiya, azotemia).

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

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

Local reactions: 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, benzylpenicillin, 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 нефро - and a neurotoxicity.

Amikacin strengthens myorelaxation action of not depolarizing muscle relaxants.

At simultaneous use with amikacin метоксифлуран, polymyxins for parenteral administration, капреомицин and other medicines blocking neuromuscular transmission (halogenated hydrocarbons - means for inhalation anesthesia, opioid analgetics), transfusion of a large amount of blood with nitrate preservatives increase risk of an apnoea.

Parenteral administration of indometacin increases risk of development of toxic effect of aminoglycosides (increase in T1/2 and decrease in clearance).

Amikacin reduces efficiency of anti-myasthenic medicines.

Contraindications:

Hypersensitivity to amikacin, drug components, other aminoglycosides in the anamnesis, neuritis of an acoustical nerve, a heavy chronic renal failure with an azotemia and uraemia, pregnancy, the breastfeeding period.

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

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; inhibitors of cholinesterase, salt of calcium (Sa2+), artificial ventilation of the lungs, other symptomatic and maintenance therapy.

Storage conditions:

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 - 3 years. Not to use drug after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Powder for preparation of solution for intravenous and intramuscular administration of 250 mg, 500 mg, 1000 mg. Packaging: on 250 mg, 500 mg, 1000 mg in the bottles with a capacity of 10 ml from glass which are hermetically corked by rubber bungs, pressed out by aluminum caps. On each bottle paste the label from paper for highly artistic editions or the self-adhesive label according to the specification of firm. 1 bottle with drug together with the application instruction is placed in a pack from a cardboard. On 5 bottles with drug place in a blister strip packaging from a film polyvinyl chloride. On 5 bottles with drug place in a blister strip packaging from a film of polyvinyl chloride and flexible packaging on the basis of aluminum foil or the packing material combined on a paper basis. 1 or 2 blister strip packagings with bottles together with the application instruction place in a pack from a cardboard. Packaging for hospitals: on 10 blister strip packagings with bottles together with the equal number of application instructions place in a box from a cardboard.