Amikacin

General characteristics. Structure:

Powder for preparation of solution for in/in and introductions of white or almost white color in oil, is hygroscopic.

Active ingredient: amikacin sulfate (in terms of amikacin) – 250 mg, 500 mg.

Pharmacological properties:

Pharmacodynamics. The semi-synthetic antibiotic of a broad spectrum of activity, works bakteritsidno. Communicating with 30S in subunit of 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., Enterobacter spp., Salmonella spp., Shigella spp.; some gram-positive microorganisms - Staphylococcus spp. (in т.ч steady against penicillin, some cephalosporins); it is moderately active concerning Streptococcus spp. At co-administration with benzylpenicillin has synergy 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 (in oil) it is soaked up quickly and completely. The maximum concentration (Cmax) at introduction of 7.5 mg/kg in oil – 21 mkg/ml, after 30 min. in/in infusion of 7.5 mg/kg – 38 mkg/ml. Time of achievement of the maximum concentration (Tcmax) – about 1.5 h after introduction in oil. 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 peritoneal 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 the medullispinal liquid (ML). 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 sredneterapevtichesky 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 SMZh, than at adults are reached; passes through a placenta - it is found 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 in/in or introduction in oil remains during 10-12 h. It is not metabolized. An elimination half-life (T1/2) adults – 2-4 h, at newborns have 5-8 h, children of more advanced age have 2.5-4 h. The final size T1/2 is more than 100 h (release from intracellular depots). It is removed by kidneys by glomerular filtering (65-94%) preferential in not changed look. The renal clearance - 79-100 ml/min. of T1/2 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 T1/2 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). п

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, infections of the central nervous system (CNS) (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:

In oil, in/in (struyno, within 2 min., or kapelno), 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 - 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 in introduction - 3-7 days, at in oil - 7-10 days.
The premature newborn 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 T1/2 (1-1.5 h) at these patients can be required by patients with burns.
For introduction in oil use the solution prepared by addition to contents of a bottle of 250 mg or 500 mg 2-3 ml of water for injections. 
Intravenously amikacin is entered kapelno within 30-60 min., in case of need – struyno 
For in/in introductions (struyno) use the solution prepared by addition to contents of a bottle of 250 mg or 500 mg 2-3 ml of water for injections or 0,9% of solution of sodium of chloride or 5% of solution of a dextrose. 
For in/in introductions (kapelno) contents of a bottle dissolve 5% of solution of a dextrose or 0.9% of solution of sodium of chloride in 200 ml. 
Concentration of amikacin in solution for in/in introductions should not exceed 5 mg/ml.

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 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.

The disulphite which is contained in composition of drug of sodium can cause development in sick allergic complications (up to anaphylactic reactions), especially at patients with the allergological anamnesis.

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 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). From an urinary 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:

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 NPVS, competing for active secretion in nephron tubules, block elimination of aminoglycosides, increase their concentration in blood serum, strengthening nefro-and a neurotoxicity.

Amikacin strengthens myorelaxation effect of kurarepodobny drugs.

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 citrate 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.

Pharmaceutical interaction

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

Contraindications:

— neuritis of an acoustical nerve;

— a heavy chronic renal failure with an azotemia and uraemia;

— pregnancy;

— hypersensitivity to drug components;

— hypersensitivity to other aminoglycosides in the anamnesis.

With care it is necessary to use drug at a myasthenia, parkinsonism, botulism (aminoglycosides can cause neuromuscular transmission disturbance that leads to further weakening of skeletal muscles), dehydrations, a renal failure, in the neonatality period, at premature children, at patients of advanced age, in the period of a lactation.

Use of the drug AMIKACIN at pregnancy and feeding by a breast

Drug is contraindicated at pregnancy.

In the presence of vital indications drug can be used at the feeding women. It must be kept in mind that aminoglycosides are emitted with breast milk in small amounts. They are poorly soaked up from a GIT, and the related complications at babies is not registered.

Use at renal failures

Use at a chronic renal failure of heavy degree with an azotemia and uraemia is contraindicated.

At disturbance of secretory function of kidneys correction of the mode of dosing is required.

Use for elderly patients

With care it is necessary to use drug at patients of advanced age.

Use for children

For premature newborn children the initial single dose makes 10 mg/kg, then on 7.5 mg/kg each 18-24 h; for newborns and children under 6 years an initial dose - 10 mg/kg, then on 7.5 mg/kg each 12 h within 7-10 days.

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, salts of calcium, IVL, other symptomatic and maintenance therapy.

Storage conditions:

List B. Drug should be stored in the unavailable to children, dry, protected from light place at a temperature from 5 to 25 °C. A period of validity - 2 years.

Issue conditions:

According to the recipe

Packaging:

Bottles with a capacity of 10 ml (1) - packs cardboard.
Bottles with a capacity of 10 ml (5) - packs cardboard.
Bottles with a capacity of 10 ml (10) - packs cardboard.