Amikacin - instructions for use, dose, side effects, contraindications

Semisynthetic antibiotic of broad spectrum of action, possesses bactericidal activity. Communicating with 30S subunit of ribosomes, prevents the formation of a complex of transport and matrix RNA, blocks the synthesis of protein, and also destroys the cytoplasmic membranes of bacteria.

Highly active against 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 those resistant to penicillin, some cephalosporins); moderately active against Streptococcus spp.

When administered concomitantly with benzylpenicillin, it has a synergistic effect on strains Enterococcus faecalis.

Does not affect anaerobic microorganisms.

Amicacin does not lose activity under the action of enzymes that inactivate other aminoglycosides, and can remain active against strains Pseudomonas aeruginosa, resistant to tobramycin, gentamycin and netilmicin.

Pharmacokinetics:

After intramuscular (IM injection) is absorbed quickly and completely. The maximum concentration (Cmah) with a / m dose of 7.5 mg / kg - 21 μg / ml. Time to reach the maximum concentration (TCmax) - about 1.5 hours after the / m administration. Connection with plasma proteins - 4-11%.

It is well distributed in the extracellular fluid (the contents of abscesses, pleural effusion, ascitic, pericardial, synovial, lymphatic and peritoneal fluid); in high concentrations is found in the urine; in low - in bile, breast milk, watery eye moisture, bronchial secretion, sputum and cerebrospinal fluid (CSF).It penetrates well into all tissues of the body, where it accumulates intracellularly; high concentrations are noted in organs with good blood supply: lungs, liver, myocardium, spleen, and especially in the kidneys, where accumulates in the cortical layer, lower concentrations - in muscles, adipose tissue and bones.

At appointment in sredneverapepticheskih doses (in norm or rate) to adults amikacin does not penetrate the blood-brain barrier (BBB), with inflammation of the meninges, the permeability slightly increases. In newborns, higher concentrations are achieved in CSF than in adults; passes through the placenta - is found in the fetal blood and amniotic fluid. The volume of distribution in adults is 0.26 l / kg, in children 0.2-0.4 l / kg, in newborns less than 1 week old and weighing less than 1.5 kg to 0.68 l / kg , aged less than 1 week and body weight of more than 1.5 kg - up to 0.58 l / kg, in patients with cystic fibrosis _g 0.3-0.39 l / kg. The average therapeutic concentration with IV or IM injection is maintained for 10-12 hours.

It is not metabolized. The half-life (T1 / 2) in adults is 2-4 hours, in newborns - 5-8 hours, in older children - 2.5-4 hours. The final value of T1 / 2 is more than 100 hours (release from the intracellular depot).

It is excreted by the kidneys by glomerular filtration (65-94%), mainly unchanged. Kidney clearance - 79-100 ml / min.

T1 / 2 in adults with renal dysfunction varies depending on the degree of impairment - up to 100 h, in patients with cystic fibrosis - 1-2 h, in patients with burns and hyperthermia T1 / 2 may be shorter compared with the average due to increased clearance .

It is excreted during hemodialysis (50% for 4-6 hours), peritoneal dialysis is less effective (25% for 48-72 hours).

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to amikacin: gram-negative microorganisms (resistant to gentamycin, sisomycin and kanamycin) or associations of gram-positive and gram-negative microorganisms: respiratory tract (bronchitis, pneumonia, pleural empyema, lung abscess), sepsis, septic endocarditis, central nervous system (CNS) (including meningitis), abdominal cavity (including peritonitis), urinary tract (pyelonephritis, cystitis, urethritis), skin and soft tissues (including infected burns, infected ulcers and bedsores of various genesis), bile ducts, bones and joints (incl.osteomyelitis), wound infection, postoperative infections.

Contraindications:

Hypersensitivity (including to other aminoglycosides in the anamnesis), neuritis of the auditory nerve, severe chronic renal failure (CRF) with azotemia and uremia, pregnancy.

Carefully:

Myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause - a violation of the neuromuscular transmission, which leads to further weakening of the skeletal muscles), dehydration, renal failure, the period of newborns, prematurity of children, advanced age.

Pregnancy and lactation:

Use during pregnancy is contraindicated. In the presence of "vital" indications can be used during lactation (aminoglycosides penetrate breast milk in small amounts, but they are poorly absorbed from the gastrointestinal tract, and complications associated with them in infants were not recorded).

Dosing and Administration:

Intravenously (intravenously) (struyno for 2 min or drip), intramuscularly (IM). Adults and children over 6 years of age at 5 mg / kg every 8 hours or 7.5 mg / kg every 12 hours; bacterial urinary tract infections (uncomplicated) 250 mg every 12 hours; after the hemodialysis session, an additional dose of 3-5 mg / kg may be prescribed.

Maximum doses for adults up to 15 mg / kg / day, but not more than 1.5 g / day for 10 days. The duration of treatment with IV in the introduction of 3-7 days, with a / m - 7-10 days.

Preterm infants receive an initial dose of 10 mg / kg, then 7.5 mg / kg every 18-24 hours. Newborns and children under 6 years of age receive an initial dose of 10 mg / kg, then 7.5 mg / kg every 12 hours for 7 -10 days.

Patients with burns may need a dose of 5-7.5 mg / kg every 4-6 hours due to a shorter T1 / 2 (1-1.5 h) in these patients.

If the excretory function of the kidneys is impaired, a dose reduction or an increase in the intervals between administrations is necessary.

Increase the interval between administrations (the level of creatinine clearance is not known, and the patient's condition is stable) is established as follows:

Interval (h) = serum creatinine concentration x 9.

If the concentration of creatinine in the serum is 2 mg / 100 ml, then the recommended single dose (7.5 mg / kg) should be administered every 18 hours.

When the interval is increased, the single dose is not changed.

Reduction of a single dose with an unchanged interval between administrations:

The first dose to patients with renal insufficiency is 7.5 mg / kg.

Calculation of subsequent doses (every 12 hours):

the subsequent dose (mg) = the creatinine clearance found in the patient (ml / min) / creatinine clearance in norm (ml / min) x initial dose (mg).

For the / m introduction use a solution prepared ex tempore with the addition of 2-3 ml of water for injection to the contents of the bottle.

For IV introduction, the same solutions as for IM are used, previously diluted with 200 ml of a 5% solution of dextrose or 0.9 % solution of sodium chloride. The concentration of amikacin in the solution for intravenous administration should not exceed 5 mg / ml.

Side effects:

From the digestive system: nausea, vomiting, impaired liver function (increased activity of "liver" transaminases, hyperbilirubinemia).

From the hematopoiesis: anemia, leukopenia, granulocytopenia, - thrombocytopenia.

From the nervous system: headache, drowsiness, neurotoxic effect (muscle twitching, numbness, tingling, epileptic seizures), violation of neuromuscular transmission (respiratory arrest).

From the sense organs: ototoxicity (hearing loss, vestibular and labyrinthine disorders, irreversible deafness), toxic effect on the vestibular apparatus (discoordination of movements, dizziness, nausea, vomiting). From the urinary system: nephrotoxicity - a violation of kidney function (oliguria, proteinuria, microhematuria).

Allergic reactions: skin rash, itching and hyperemia of the skin, fever, angioedema.

Local reactions: soreness in the injection site, dermatitis.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Symptoms: toxic reactions (hearing loss, ataxia, dizziness, urination disorders, thirst, loss of appetite, nausea, vomiting, ringing or feeling in the ears, respiratory failure).

Treatment: for the removal of the blockade of the neuromuscular transmission and its consequences - hemodialysis - or peritoneal dialysis; anticholinesterase drugs, calcium salts, artificial respiration (IVL), and other symptomatic and supportive therapy.

Interaction:

Pharmaceutically incompatible with penicillins, heparin, cephalosporins, capreomycin, amphotericin B, hydrochlorothiazide, erythromycin, nitrofurantoin, vitamins of group B and C, potassium chloride.

It shows a synergy with carbenicillin, benzylpenicillin, cephalosporins (in patients with severe CRF, beta-lactam antibiotics can reduce the effect of aminoglycosides).

Nalidixic acid, polymyxin AT, cisplatin and vancomycin increase the risk of oto and nephrotoxicity.

Diuretics (especially furosemide), cephalosporins, penicillins, sulfonamides and non-steroidal anti-inflammatory drugs (indomethacin), competing for active secretion in the tubules of the nephron, block the elimination of aminoglycosides, increase their concentration in the serum, enhancing nephro- and neurotoxicity.

Strengthens the muscle relaxant effect of curare like medicines. Methoxyflurane, polymyxins for parenteral administration, capreomycin and other medicines that block neuromuscular transmission (halogenated hydrocarbons as drugs for inhalation anesthesia, narcotic analgesics), transfusion of large amounts of blood with nitrate preservatives increase the risk of stopping breathing.

Reduces the effect of antimiasthenic drugs.

If you are taking other drugs, consult a doctor.

Special instructions:

Before use, the sensitivity of the isolated pathogens is determined using discs containing 30 μg of amikacin. With a diameter of a growth free zone of 17 mm or more, the microorganism is considered sensitive, from 15 to 16 mm - moderately sensitive, less than 14 mm - resistant.

The concentration of amikacin in plasma should not exceed 25 mcg / ml (the therapeutic concentration is 15-25 mcg / ml).

During the treatment period, it is necessary to monitor the function of the kidneys, the auditory nerve and the vestibular apparatus at least once a week.

The likelihood of developing nephrotoxicity is higher in patients with impaired renal function, as well as when administered at high doses or for a long time (this category of patients may require daily monitoring of kidney function).

When unsatisfactory audiometric tests, the dose of the drug is reduced or discontinued.

Patients with infectious and inflammatory diseases of the urinary tract is recommended to take the increased amount of fluid at adequate diuresis.

In the absence of positive clinical dynamics should be remembered the possibility of developing resistant microorganisms.In such cases, it is necessary to cancel treatment and begin appropriate therapy.

Effect on the ability to drive transp. cf. and fur:

Use caution to drivers of vehicles and people whose activities require increased concentration of attention and good coordination of movements.

Form release / dosage:Powder for solution for intravenous and intramuscular injection 500 mg.

Packaging:

500 mg of active substance in glass vials with a capacity of 10 ml.

1 bottle with instructions for use in a pack of cardboard.

10 bottles with instructions for use in a cardboard box.

For hospitals:

1) 50 bottles with an equal number of instructions for use in a cardboard box;

2) from 1 to 50 bottles with an equal number of instructions for use in a cardboard box.

Complete with solvent

Solvent: 5 ml of water for injection in ampoules of glass.

1 vial and 1 ampoule in a contoured cell package (KNU) with instructions for use in a pack of cardboard.

5 bottles and 5 ampoules in separate KNU with instructions for use in a pack of cardboard.

In the pack put a knife to open the ampoules or a scarifier ampoule.When using ampoules with notches, rings or break points, the ampoule opener opener or ampoule scarifier is allowed not to be inserted.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

After the expiry date of the drug, unused vials should be carefully opened, the contents dissolved in a large amount of water and drained into the drain.

Shelf life:

2 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LS-000772

Date of registration:31.05.2010 / 05.11.2014

Expiration Date:Unlimited

The owner of the registration certificate:KRASFARMA, JSC KRASFARMA, JSC Russia

Manufacturer: & nbsp

KRASFARMA, JSC Russia

Information update date: & nbsp03.08.2017

Illustrated instructions

Instructions

Amikacin (Amikacin)