Amikacin sulfate 1000mg bottle №1

Mechanism of action

Pharmacodynamics
Amikacin - semisynthetic broad-spectrum antibiotic, bactericidal. By binding to the 30S subunit of ribosomes, it prevents the formation of a complex of transport and messenger RNA, blocks protein synthesis, 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 and some cephalosporins); moderately active against Streptococcus spp. With simultaneous appointment with benzylpenicillin has a synergistic effect against strains of Enterococcus faecalis. Does not affect anaerobic microorganisms. Amikacin does not lose activity under the action of enzymes that inactivate other aminoglycosides, and may remain active against strains of Pseudomonas aeruginosa resistant to tobramycin, Gentamicin and netilmicin.

Pharmacokinetics 
After intramuscular injection is absorbed quickly and completely. The maximum concentration (Cmax) for intramuscular injection of 7.5 mg / kg is 21 μg / ml, after 30 minutes of the infusion of 7.5 mg / kg by 38 mg / kg. The time to reach the maximum concentration (Tcmax) is about 1.5 h after intramuscular injection. Communication with plasma proteins - 4-11%.Well distributed in the extracellular fluid (contents of abscesses, pleural effusion, ascitic, pericardial, synovial, lymphatic and peritoneal fluid); found in high concentrations in the urine; in low - in the bile, breast milk, watery moisture of the eye, bronchial secretions, sputum and cerebrospinal fluid (CSF). It penetrates well into all tissues of the body, where it accumulates intracellularly; high concentrations are found in organs with good blood supply: lungs, liver, myocardium, spleen, and especially in the kidneys, where it accumulates in the cortex, lower concentrations in muscles, adipose tissue and bones.

When prescribed in average therapeutic doses (normal) to adults, amikacin does not penetrate the hemato-encephalic barrier (BBB), and during inflammation of the meninges, the permeability increases slightly. Newborns achieve higher concentrations in the CSF than in adults; passes through the placenta - is found in the blood of the fetus and amniotic fluid. The volume of distribution in adults is 0.26 l / kg, in children - 0.2-0.4 l / kg, in newborns - at the age of less than 1 week and weighing less than 1500 g - up to 0.68 l / kg, at the age of less than 1 week and weighing more than 1500 g - up to 0.58 l / kg, in patients with cystic fibrosis - 0.3-0.39 l / kg. The average therapeutic concentration when in / in or in / m the introduction is maintained for 10-12 hours. Not metabolized.

The elimination half-life (T1 / 2) in adults is 2-4 hours, in newborns 5-8 hours, in older children 2.5-4 hours.The final T1 / 2 value is more than 100 hours (release from intracellular depots). Excreted by the kidneys by glomerular filtration (65-94%) mostly unchanged. Renal clearance - 79-100 ml / min. T1 / 2 in adults with impaired renal function varies depending on the degree of impairment - up to 100 hours, in patients with cystic fibrosis - 1-2 hours, in patients with burns and hyperthermia, T1 / 2 may be shorter compared to the average values ​​due to increased clearance. It is removed during hemodialysis (50% in 4-6 hours), peritoneal dialysis is less effective (25% in 48-72 hours).

Indications

Infectious and inflammatory diseases caused by gram-negative microorganisms (resistant to gentamicin, sizomycin and kanamycin) or by associations of gram-positive and gram-negative microorganisms:

• respiratory tract infections (bronchitis, pneumonia, pleural empyema, lung abscess),
• sepsis,
• septic endocarditis,
• infections of the central nervous system (CNS) (including meningitis),
• infections of the abdominal cavity (including peritonitis),
• urinary tract infections (pyelonephritis, cystitis, urethritis),
• purulent infections of the skin and soft tissues (including infected burns, infected ulcers and bedsores of various origins),
• infections of the biliary tract, bones and joints (including osteomyelitis),
• wound infection
• postoperative infections.

Contraindications

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

With care - myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause impaired neuromuscular transmission, which leads to a further weakening of skeletal muscles), dehydration, renal failure, neonatal period, prematurity of children, old age, lactation.

Special notes

Before use, determine the sensitivity of isolated pathogens using disks containing 30 μg of amikacin. With a diameter free from growth zone of 17 mm and more, the microorganism is considered sensitive, from 15 to 16 mm is moderately sensitive, less than 14 mm is stable. The concentration of amikacin in the plasma should not exceed 25 µg / ml (therapeutic is a concentration of 15-25 µg / ml).

During the period of treatment, 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 prescribing high doses or for a long time (in this category of patients, daily monitoring of renal function may be required). In case of unsatisfactory audiometric tests, the dose of the drug is reduced or discontinued treatment.

Patients with infectious and inflammatory diseases of the urinary tract are advised to take an increased amount of fluid. In the absence of positive clinical dynamics, one should be aware of the possibility of developing resistant microorganisms.In such cases, it is necessary to cancel treatment and initiate appropriate therapy. In the presence of vital indications, the drug can be used in lactating women (aminoglycosides enter breast milk in small amounts, however, they are poorly absorbed from the gastrointestinal tract, and there are no complications associated with them in infants).

Composition

Active substance: amikacin sulfate (in terms of amikacin) - 1000 mg.

Dosage and administration

Intramuscularly, intravenously (struino, for 2 minutes, or drip), adults and children over 6 years of age - at 5 mg / kg every 8 hours or 7.5 mg / kg every 12 hours; bacterial infections of the urinary tract (uncomplicated) - 250 mg every 12 hours; After the hemodialysis session, an additional dose of 3-5 mg / kg may be prescribed.
The maximum dose for adults is 15 mg / kg / day, but not more than 1.5 g / day for 10 days.
The duration of treatment with a / in the introduction - 3-7 days, with a / m - 7-10 days.
For preterm infants, the initial dose is 10 mg / kg, then 7.5 mg / kg every 18-24 hours; for newborns and children up to 6 years old, the initial dose is 10 mg / kg, then 7.5 mg / kg every 12 hours for 7-10 days.

Patients with burns may require 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.
For intramuscular administration, a solution prepared by adding to the contents of the vial 250 mg or 500 mg of 2-3 ml of water for injection is used.
Intravenous amikacin is administered driply for 30-60 minutes, if necessary - jet

For intravenous administration (streak), use a solution prepared by adding to the contents of the vial 250 mg or 500 mg of 2-3 ml of water for injection or 0.9% sodium chloride solution or 5% dextrose solution.
For intravenous (drip) administration, the contents of the vial are dissolved in 200 ml of 5% dextrose solution or 0.9% sodium chloride solution.
The concentration of amikacin in the solution for intravenous administration should not exceed 5 mg / ml.

Side effects

On the part of the digestive system: nausea, vomiting, abnormal liver function (increased activity of “liver” transaminases, hyperbilirubinemia).

From the side of blood-forming organs: anemia, leukopenia, granulocytopenia, thrombocytopenia.

Nervous system disorders: headache, drowsiness, neurotoxic action (muscle twitching, numbness, tingling, epileptic seizures), neuromuscular transmission disorder (respiratory arrest).

On the part of the senses: ototoxicity (hearing loss, vestibular and labyrinth disorders, irreversible deafness), toxic effect on the vestibular apparatus (discoordination of movements, dizziness, nausea, vomiting).

On the part of the urinary system: nephrotoxicity - impaired renal function (oliguria, proteinuria, microhematuria).

Allergic reactions: skin rash, itching, skin flushing, fever, angioedema.

Local: soreness at the injection site, dermatitis, phlebitis and periphlebitis (when administered intravenously).

Drug interaction

Pharmaceutically incompatible with penicillins, Heparin , cephalosporins, capreomycin, amphotericin B, hydrochlorothiazide, Erythromycin , nitrofurantoin, Vitamins B and C, potassium chloride. Shows synergism when interacting with carbenicillin, benzylpenicillin, cephalosporins (in patients with severe chronic renal failure when used together with beta-lactam antibiotics, it is possible to reduce the effectiveness of aminoglycosides).

Nalidixic acid, polymyxin B, Cisplatin and Vancomycin increase the risk of developing oto- and nephrotoxicity. Diuretics (especially furosemide), cephalosporins, penicillins, sulfonamides and nonsteroidal anti-inflammatory drugs, competing for active secretion in the tubules of the nephron, block the elimination of aminoglycosides, increase their concentration in serum, increasing the nephro and neurotoxicity. Strengthens the muscle relaxant effect of kurarepodobny drugs.

Methoxyflurane, parenteral polymyxins, capreomycin and other drugs that block neuromuscular transmission (halogenated hydrocarbons as drugs for inhalation anesthesia, opioid analgesics), the transfusion of large quantities of blood with citrate preservatives increase the risk of respiratory failure. Parenteral administration of Indomethacin increases the risk of the development of the toxic effects of aminoglycosides (increased half-life and decreased clearance). Reduces the effect of anti-myasthenic drugs.

Overdose

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

Treatment: for removal of the blockade of neuromuscular transmission and its consequences - hemodialysis or peritoneal dialysis; anticholinesterase agents, Calcium salts (Ca2 +), artificial lung ventilation, other symptomatic and supportive therapy.

In a dry, dark place at a temperature not higher than 25 ° C. Keep out of reach of children.