Amikacin, 500 mg

Pharmacological action – broad spectrum antibacterial, antituberculosis, bactericidal.

It actively penetrates through the cell membrane and irreversibly binds with specific receptor proteins on 30S ribosome subunit. Disrupts formation of the complex between matrix (informational) RNA and 30S ribosome subunit. This results in the misreading of information from RNA and the formation of incomplete proteins. The polyribosomes disintegrate and lose their ability to synthesize protein, which leads to the death of the microbial cell.

Active against the majority of Gram-negative and some Gram-positive microorganisms (MPC values, µg/ml are specified after the name of the microorganism): Pseudomonas aeruginosa (1.6-3.2), including those resistant to gentamic acid.including those resistant to gentamicin, tobramycin, sisomycin and netilmicin, Escherichia coli (1.6-3.2), Klebsiella spp. (1.6-6.4), Serratia spp. (1.6-6.4), Providencia spp. (1.6-6.4), Enterobacter spp. (1.6-3.2), Salmonella spp. (1.6-6.4), Shigella spp. (0.6-6.4), Streptococcus spp, Staphylococcus spp. (0.4-1.6), including those resistant to penicillin, methicillin and some cephalosporins, less active against enterococci. It is active against Mycobacterium tuberculosis and some atypical mycobacteria; it has bacteriostatic effect on Mycobacterium tuberculosis resistant to streptomycin, isoniazid, PASC and other anti-tuberculosis drugs (except viomycin and capreomycin). It has no effect on non-sporulating Gram-negative anaerobes and protozoa.

Resistance develops slowly, more than 70% of strains of Gram-negative and Gram-positive bacteria remain sensitive to amikacin. There is complete cross-resistance to the first generation aminoglycosides, to the rest – partial. Amikacin does not lose activity under the action of enzymes inactivating other aminoglycosides, due to which it can remain active against strains of Pseudomonas aeruginosa resistant to tobramycin, gentamicin and netilmicin.

It is practically not absorbed from the gastrointestinal tract. It is administered v/v or v/m. Cmax is reached 1 and 0.5 h after v/m and v/v administration at a dose of 7.5 mg/kg and is 21 and 38 µg/ml, respectively. Therapeutic concentration (15-25 µg/ml) is maintained for 10-12 hours in case of intravenous and intravenous administration. Along with netilmicin it is characterized by the most predictable Cmax and Cmin among aminoglycosides. Binding with plasma proteins is 4-11%.

The volume of distribution is 0.2-0.4 l/kg, in infants it is up to 0.68 l/kg. It easily passes through histohematic barriers and penetrates into lung tissue, liver, myocardium, spleen and bone tissue. It selectively accumulates in the cortical layer of kidneys and is distributed in extracellular fluid including serum, lymph, pleural, pericardial and peritoneal exudate, synovial fluid and abscess fluid.

In low concentrations it is determined in bile, bronchial secretion, muscle and fat tissue. It penetrates through the BBB, in case of inflammation of the cerebral membranes – to a greater extent. Higher concentrations in cerebrospinal fluid are achieved in newborns. It is not metabolized. T1/2 is 2-4 hours in adults and 5-8 hours in newborns. Renal clearance is 79-100 ml/min, with impaired renal function the T1/2 is increased to 70-100 hours. It is excreted mainly by kidneys (65-94%) in unchanged form by glomerular filtration, forms high concentrations in urine; a small amount is excreted with bile. It is excreted with hemodialysis (every 4-6 hours the concentration in plasma decreases by 50%) and to a lesser extent – with peritoneal dialysis (during 48-72 hours about 25% of dose is excreted).

When using amikacin the ototoxic effect is more pronounced (the auditory part of the VIII pair of cranial nerves is affected more often than the vestibular one) than the nephrotoxic effect. The probability of ototoxicity is higher with impaired renal function and dehydration, including burns. A single daily dose (80-100% of the standard dose) can reduce the risk of toxic effects while maintaining similar clinical efficacy.

The efficacy of intrathecal and intraventricular administration of amikacin in CNS infections has been reported, as well as the use of the solution for injection as inhalation.

In ophthalmology it can be used for local treatment of eye diseases – subconjunctival administration of amikacin solution (50 mg/ml); intravitreal 0.4 ml of solution (contains 0.4 mg/0.1 ml), the administration can be repeated at 3-day intervals.

Indications

Infectious and inflammatory diseases caused by Gram-negative microorganisms (resistant to gentamicin, Sisomycin and Kanamycin) or associations of Gram-positive and Gramnegative microorganisms: Respiratory tract infections (bronchitis, pneumonia, pleural empyema, pulmonary abscess), sepsis (includingч. caused by strains of Enterobacteriaceae and Pseudomonas aeruginosa resistant to other aminoglycosides), septic endocarditis, CNS infections (including meningitis), abdominal infections (including peritonitis), urinary tract infections (pyelonephritis, cystitis, urethritis), prostatitis, gonorrhea, purulent skin and soft tissue infections (including infected burns).including infected burns, infected ulcers and bedsores of various genesis), biliary tract infections, bone and joint infections (including osteomyelitis), wound infections, postoperative infections, otitis media.

Tuberculosis (reserve drug) – in combination with other reserve drugs.

Active ingredient

Composition

Amicacin (in the form of sulfate) – 500 mg

How to take, the dosage

I/m, intravenously (by jetting for 2 minutes or by 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; maximum dose is 15 mg/kg/day, the course dose is not more than 15 g.

In premature infants: initial dose is 10 mg/kg, then 7.5 mg/kg every 18-24 hours; neonates initial dose is 10 mg/kg, then 7.5 mg/kg every 12 hours.

The duration of treatment by intravenous injection is 3-7 days, by intravenous injection – 7-10 days. Patients with renal insufficiency need to correct the dosage regimen in accordance with creatinine clearance.

Interaction

Physicochemical incompatibility with penicillins, especially carbenicillin has been noted. Pharmaceutically incompatible with heparin, cephalosporins, amphotericin B, chlorthiazid, erythromycin, vitamins C and group B, potassium chloride.

It shows synergism with beta-lactam antibiotics against many gram-negative microorganisms, with ticarcillin, azlocillin and piperacillin against Pseudomonas aeruginosa and other non-fermentative gram-negative bacteria. When two or more aminoglycosides (neomycin, streptomycin, kanamycin, gentamicin, monomycin, tobramycin, netilmicin) are used simultaneously and/or sequentially their antibacterial effect is weakened (competition for one mechanism of “capture” by the microbial cell) and their toxic effects are enhanced.

Amiloride reduces nephrotoxicity of amikacin (by reducing penetration into the proximal tubules). When concomitant administration with amphotericin B, cephalothin, polymyxin, cisplatin, vancomycin and nalidixic acid increases the risk of nephrotoxicity.

Petal diuretics (furosemide, etacrynic acid) and cephalothin increase ototoxicity. Indomethacin, when administered intravenously, decreases renal clearance of amikacin and increases its plasma concentration and risk of toxicity.

Concomitant use with agents for inhalation anesthesia, curare-like drugs, opioid analgesics, magnesium sulfate and polymyxins for parenteral administration, as well as transfusion of large amounts of blood with citrate preservatives increases neuromuscular blockade. Reduces the effectiveness of antimiasthenic drugs (requires adjustment of their dose).

Special Instructions

Sensitivity of microorganisms should be determined before use.

The solution for injection and infusion is prepared immediately before use. The contents of the vial (0.25-0.5 g) is dissolved in 2-3 ml of sterile water for injection; for infusion the obtained solution is diluted in 200 ml of 0.9% sodium chloride solution or 5% dextrose solution.

Contraindications

Hypersensitivity, including to other aminoglycosides; lesions of the auditory and vestibular apparatus of nontuberculous etiology, including neuritis of the auditory nerve, renal disorders (renal failure, uremia, azotemia), severe diseases of the heart and blood forming organs.

Side effects

Nervous system and sensory organs: Headache, paresthesia, muscle twitching, seizures, tremors, somnolence, impaired neuromuscular transmission (muscle weakness, difficulty breathing, apnea), psychosis, hearing disorders (feeling of “blocking” or tinnitus, reduced hearing with decreased perception of high tones, permanent deafness) and balance (uncoordinated movements, dizziness, instability).

Cardiovascular system and blood (hematopoiesis, hemostasis): palpitation, arterial hypotension, anemia, leukopenia, thrombocytopenia, granulocytopenia, eosinophilia.

Gastrointestinal system disorders: nausea, vomiting, diarrhea, dysbacteriosis, increased liver transaminase activity, hyperbilirubinemia.

Urinary system disorders: kidney damage (albuminuria, hematuria, oliguria, renal failure).

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

Others: drug fever, pain at the injection site, dermatitis, phlebitis and periphlebitis (when injected intravenously).

Overdose

Symptoms: toxic reactions, neuromuscular blockage up to respiratory arrest, in infants – CNS depression (lethargy, stupor, coma, deep respiratory depression).

Treatment: calcium chloride v/v, anticholinesterase agents (neostigmine p/k), m-cholinoblockers (atropine), symptomatic therapy, if necessary – EVI. Hemodialysis, peritoneal dialysis are effective in cases of impaired renal function, and exchange blood transfusions are given to newborns.