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

It is active against gram-positive and gram-negative microorganisms: Staphylococcus, including penicillin and methicillin-resistant strains, Escherichia coli, Proteus spp., Providencia, microorganisms of the group Serratia, Klebsiella, Enterobacter, Citrobacter, Salmonella, Shigella, Pseudomonas aeruginosa, incl. gentamycin, tobramycin, and sizomycin-resistant strains. Moderately active against streptococci, enterococci, pneumococci. Inactive with respect to non-spore-forming gram-negative anaerobes and protozoa.

Amicacin is a polar structure, therefore it penetrates into bacterial cells through passive diffusion through the porins of the outer membrane. By active transport, the drug moves through the cytoplasmic membrane. This phase was called volatile. Divalent cations (Ca2 + or Mg2 +), hyperosmolar medium (eg urine), anaerobic conditions (abscess), low pH values slow the transport of amikacin through the cytoplasmic membrane of bacteria, which significantly reduces its antibacterial activity. In the cytoplasm of bacteria, the drug binds to the 30S subunit of the ribosome of the bacterial cell and disrupts the initial stages of protein synthesis on the ribosomes (the formation of the initiating complex is blocked) and the ribosome movement along the filament of the matrix RNA.

Amicacin also disrupts the process of reading the mRNA code, which leads to attachment "wrong" amino acids into the growing polypeptide chain and the synthesis of functionally inactive proteins. These aberrant proteins are embedded in the cytoplasmic membrane and damage it, thereby facilitating the transport of subsequent drug molecules. Thus, the permeability of the cytoplasmic membrane of microorganisms for ions and proteins increases.

Disturbance of protein synthesis in the early stages and increase in the permeability of the cytoplasmic membrane of bacteria ensure bactericidal action.

Pharmacokinetics:

Absorption is rapid and complete with intramuscular and topical application. Absorption at intake is low (almost not absorbed, therefore it is used only parenterally). Peak concentrations of amikacin for intramuscular administration of 7.5 mg / kg are 21 μg / ml (achieved one hour after administration of a dose of 500 mg, decreasing to 2 μg / ml 10 hours after injection), with intravenous administration of more than 30 minutes of dose 7, 5 mg / kg - 38 mcg / ml (decreasing to 18 mcg / ml after 1 h after intravenous infusion).

In patients in critical states, intramuscular absorption can be reduced [especially in conditions leading to impaired perfusion (shock), as a result of decreased plasma concentrations]. High concentrations in the urine, low in bile, sputum, CSF.

Relationship with plasma proteins 0-10%. Detect in therapeutic concentrations in the liver, kidneys, lungs, pleural, pericardial, synovial, peritoneal, ascitic and lymphatic fluids, urine, in segregated wounds, pus, granulation.Low concentrations are noted in adipose tissue, muscles, bones, bile, breast milk, watery eye moisture, bronchial secretion, sputum and cerebrospinal fluid. Aminoglycosides diffuse well into the perilymph of the inner ear. Biotransformation is absent. Elimination of the kidney 75-80% in unchanged form (glomerular filtration), in small amounts of bile. In patients with normal renal function, 70-95% is excreted in the first 24 hours, while concentrations of more than 100 μg / ml are created in the urine. The half-life in adults is 2-4 hours, in children from 1 weeks to 6 months of age - 3-3.5 hours, in newborns and premature infants with a body weight of more than 2 kg - 5.5 hours, with a body weight of less than 1, 5 kg - 11.5 hours, up to 2 kg - 8 hours, with renal insufficiency - up to 100 hours. Removed during hemodialysis (for every 4-6 hours the concentration of aminoglycosides decreases by 50%), peritoneal dialysis is less effective (removes ~ 25% dose for 48-72 hours).

Indications:Infectious-inflammatory diseases caused by gram-negative microorganisms (resistant to gentamycin, sisomycin and kanamycin) or associations of gram-positive and gram-negative microorganisms: respiratory tract infections (bronchitis, pneumonia, pleural empyema, lung abscess), sepsis (including those caused by strains Enterobacteriacea and Pseudomonas aeruginosa, resistant to other aminoglycosides), septic endocarditis, infections of the central nervous system (including meningitis), infections of the abdominal cavity (including peritonitis), urinary tract infections (pyelonephritis, cystitis, urethritis), prostatitis, gonorrhea, purulent skin and soft tissue infections (including infected burns, infected ulcers and bedsores of various genesis), bile duct infections, infections of bones and joints (including osteomyelitis), wound infection, postoperative infections, otitis media. Tuberculosis (reserve drug) - in combination with other reserve drugs.

ICD-10

I.A30-A49.A41 Other septicemia

I.A30-A49.A40 Streptococcal septicemia

VI.G00-G09.G00 Bacterial meningitis, not elsewhere classified

IX.I30-I52.I33 Acute and subacute endocarditis

X.J10-J18.J15 Bacterial pneumonia, not elsewhere classified

X.J85-J86.J85 Abscess of the lung and mediastinum

X.J85-J86.J86 Pythothrace

XI.K65-K67.K65 Peritonitis

XI.K80-K87.K81.1 Chronic cholecystitis

XI.K80-K87.K81.0 Acute cholecystitis

XI.K80-K87.K83.0 Cholangitis

XII.L00-L08.L02 Abscess of skin, boil and carbuncle

XII.L00-L08.L03 Phlegmon

XII.L00-L08.L08.0 Pyoderma

XIII.M00-M03.M00 Pyogenic arthritis

XIII.M86-M90.M86 Osteomyelitis

XIV.N10-N16.N11.1 Chronic obstructive pyelonephritis

XIV.N10-N16.N11.0 Non-structural chronic pyelonephritis associated with reflux

XIV.N30-N39.N30 Cystitis

XIV.N30-N39.N34 Urethritis and urethral syndrome

XVI.P35-P39.P36 Bacterial sepsis of newborn

XIX.T79.T79.3 Post-traumatic wound infection, not elsewhere classified

Contraindications:Hypersensitivity, including other aminoglycosides; damage to the auditory and vestibular apparatus of non-tuberculous etiology, including the neuritis of the auditory nerve; impaired renal function (renal failure, uremia, azotemia); severe heart disease and hematopoiesis; pregnancy.

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

Pregnancy and lactation:

FDA recommendation category D, the risk of complete irreversible deafness of the fetus. All aminoglycosides penetrate the placenta, sometimes accumulating in high concentrations in the cord blood and / or amniotic fluid. Aminoglycosides may be nephrotoxic to the fetus.Adequate and well-controlled studies in humans have not been conducted.

It is necessary to correlate the benefits and risks when treatment is necessary in life-threatening conditions or serious diseases, if other methods of treatment can not be used or they are ineffective.

Dosing and Administration:

Intramuscularly or intravenously (streamwise, for 2 minutes, or drip, at a rate of 60 drops per minute). Adults and children: 5 mg / kg every 8 hours or 7.5 mg / kg every 12 hours; the maximum dose is 15 mg / kg in day, the course dose is not more than 15 g. Premature neonates: in the initial dose - 10 mg / kg, then at 7.5 mg / kg every 18-24 h; newborns the initial dose is 10 mg / kg, then 7.5 mg / kg every 12 hours. Duration of treatment at intravenous introduction - 3-7 days, with intramuscular - 7-10 days. Maximum doses: for adults, the daily dose is 1.5 g.

Side effects:

From the nervous system and sensory organs: headache, paresthesia, muscle twitching, convulsions, tremor, drowsiness, impaired neuromuscular transmission (muscle weakness, difficulty breathing, apnea), psychosis, hearing impairment (feeling of "laying" or tinnitus, hearing loss with decreased perception of high tones , irreversible deafness) and balance (uncoordinated movements, dizziness,instability).

From the cardiovascular system and hematopoiesis: heart beat, arterial hypotension, anemia, leukopenia, thrombocytopenia, granulocytopenia, eosinophilia.

On the part of the organs of the gastrointestinal tract: nausea, vomiting, diarrhea, dysbiosis, increased activity of hepatic transaminases, hyperbilirubinemia.

From the genitourinary system: renal damage (albuminuria, hematuria, oliguria, renal insufficiency).

Allergic reactions: skin itching, urticaria, arthralgia, Quincke's edema, anaphylactic shock.

Other: drug fever, soreness at the injection site, dermatitis, phlebitis and periphlebitis (with intravenous administration).

Overdose:

Hearing loss, ataxia, dizziness, urination disorders, thirst, anorexia, nausea, vomiting, ringing or feeling in the ears, impaired breathing.

Treatment: adults are injected intravenously with anticholinesterase drugs, as well as preparations of Ca2+ (calcium chloride 10% 5-10 ml, calcium gluconate 10% 5-10 ml). Before the introduction of neostigmine methyl sulfate, intravenously, atropine sulfate is administered at a dose of 0.5-0.7 mg, the pulse is expected to increase and 1.5 mg (3 ml of 0.05% solution) of neostigmine methyl sulfate is injected 1.5-2 minutes intravenously.If the effect of this dose was insufficient, re-inject the same dose of neostigmine (with the appearance of bradycardia, an additional injection of atropine). Children are injected with Ca2+. In severe cases of respiratory depression, artificial ventilation is necessary. Can be excreted by hemodialysis (more effective) and peritoneal dialysis.

Interaction:

Beta-lactam antibiotics: synergism with many gram-negative microorganisms.

Ticarcillin: synergism in relation to Pseudomonas aeruginosa and other non-fermenting gram-negative bacteria.

Azlocillin: synergism in relation to Pseudomonas aeruginosa and other non-fermenting gram-negative bacteria.

Piperacillin: synergism in relation to Pseudomonas aeruginosa and other non-fermenting gram-negative bacteria.

Penicillins: with renal insufficiency, a decrease in antimicrobial activity.

Amyloride: a decrease in the toxicity of amikacin.

Amphotericin B: increased risk of developing nephrotoxic action.

Vancomycin: increased risk of developing nephrotoxic action.

Methoxyflurane: increased risk of developing nephrotoxic action, increased neuromuscular blockade.

Enflurane: increased risk of nephrotoxic action, increased neuromuscular blockade.

Non-steroidal anti-inflammatory drugs: increased risk of developing nephrotoxic action.

Radiopaque means: increased risk of developing nephrotoxic action.

Cephalothin: increased risk of developing nephrotoxic and ototoxic action.

Cyclosporine: increased risk of developing nephrotoxic action.

Cisplatin: increased risk of developing nephrotoxic and ototoxic effects.

Polymyxins: increased risk of developing nephrotoxic action, with parenteral injection, increased neuromuscular blockade.

"Loop" diuretics (furosemide, ethacrynic acid): increased risk of ototoxic action.

Nalidixic acid: increased risk of developing nephrotoxic action.

Anti-asthma drugs: a decrease in their effectiveness.

Opioid analgesics: increased neuromuscular blockade.

Kurarepodobnye drugs: strengthening neuromuscular blockade.

Magnesium sulphate: strengthening neuromuscular blockade.

Ethyl ether: increased risk of respiratory depression.

Blockers of neuromuscular transmission: increased risk of respiratory depression.

Other aminoglycosides: weakening of their antibacterial action (competition for one mechanism of "capture" by a microbial cell), intensification of toxic effects.

Special instructions:

Amicacin is not compatible in solution with penicillins, cephalosporins, amphotericin B, chlorothiazide, erythromycin, heparin, nitrofurantoin, thiopentone, and, depending on the composition and concentration of the solution, with tetracyclines, group B vitamins, vitamin C and potassium chloride.

Before use, determine the sensitivity of microorganisms. Solution for injections and infusions are prepared immediately before use. The contents of the vial (0.25-0.5 g) are dissolved in 2-3 ml of sterile water for injection; for intravenous infusion, the resulting solution is diluted in 200 ml of a 0.9% solution of sodium chloride or 5% solution of dextrose. Amicacin disrupts the auditory (cochlear) function more than gentamicin.

When transfusing large volumes of blood with citrated preservatives, neuromuscular blockade may be enhanced.

Patients with renal failure need to reduce the dose or increase the intervals between the administrations without changing the single dose. The interval is calculated by the formula: concentration of creatinine in serum × 9.The first dose for patients with renal insufficiency is 7.5 mg / kg, the following formula is used to calculate the subsequent doses: Cl creatinine (ml / min) × initial dose (mg) / Cl Creatinine normal (ml / min).

Instructions

Amikacin (Amikacinum)