Amikacin

General characteristics. Structure:

Active ingredient: amikacin sulfate (in terms of amikacin) – 1000 mg.

Pharmacological properties:

The semi-synthetic antibiotic of a broad spectrum of activity from group of aminoglycosides, 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. (including steady against penicillin, some cephalosporins).

It is moderately active concerning Streptococcus spp.

At co-administration with benzylpenicillin shows an action synergism concerning Enterococcus faecalis strains.

Anaerobic microorganisms are steady against drug.

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. Absorption

After introduction in oil it is soaked up quickly and completely. Cmax in a blood plasma at introduction in oil in a dose of 7.5 mg/kg - 21 mkg/ml, after 30 min. in/in infusion in a dose of 7.5 mg/kg - 38 mkg/ml. After introduction of Tmax in oil - about 1.5 h.

Average therapeutic concentration at in/in or introduction in oil remains during 10-12 h.

Distribution

Linkng with proteins of plasma makes 4-11%. Vd 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.

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 cerebrospinal fluid. 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 GEB, at an inflammation of a meninx permeability increases a little. At newborns higher concentration in cerebrospinal fluid, than at adults are reached. Gets through a placental barrier: it is found in blood of a fruit and amniotic liquid.

Metabolism

It is not metabolized.

Removal

T1/2 adults have 2-4 h, newborns have 5-8 h, children of more advanced age have 2.5-4 h. Final T1/2 - 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.

Pharmacokinetics in special clinical cases

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).

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, pleura empyema, abscess of lungs);

— sepsis;

— septic endocarditis;

— TsNS infections (including meningitis);

— infections of an abdominal cavity (including peritonitis);

— infections of urinogenital ways (pyelonephritis, cystitis, urethritis);

— purulent infections of skin and soft tissues (including the infected burns infected ulcers and decubituses of various genesis);

— infections of bilious ways;

— infections of bones and joints (including osteomyelitis);

— wound fever;

— postoperative infections.

Route of administration and doses:

The drug is administered 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. At bacterial infections of uric ways (uncomplicated) - on 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.

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.

At the infected burns the dose of 5-7.5 mg/kg each 4-6 h in connection with shorter T1/2 (1-1.5 h) at this category of patients can be required.

Enter into amikacin kapelno within 30-60 min., in case of need - struyno.

For in/in introductions (kapelno) drug is previously diluted by 200 ml of 5% of solution of a dextrose (glucose) or 0.9% of solution of sodium of chloride. Concentration of amikacin in solution for in/in introductions should not exceed 5 mg/ml.

At disturbance of secretory function of kidneys the dose decline or increase in intervals between introductions is necessary. In case of increase in an interval between introductions (if KK value is unknown, and a condition of the patient stable) the interval between administration of drug is established on the following formula:

interval (ch) = concentration of serumal creatinine × 9.

If concentration of serumal creatinine makes 2 mg/dl, then the recommended single dose (7.5 mg/kg) needs to be entered each 18 h. At increase in an interval the single dose is not changed.

In case of decrease in a single dose at not changed dosing mode the first dose for patients with a renal failure makes 7.5 mg/kg. Calculation of the subsequent doses is made on the following formula:

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

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 system of a hemopoiesis: anemia, leukopenia, granulocytopenia, thrombocytopenia.

From TsNS and peripheral 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 reactions: morbidity in the place of an injection, dermatitis, phlebitis and a periphlebitis (at in introduction).

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.