Amikacin, 500 mg

A semisynthetic broad-spectrum antibiotic from the group of aminoglycosides, acts bactericidally. Binding to 30S ribosome subunit, it prevents formation of transport and matrix RNA complex, blocks protein synthesis and destroys 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).

It is moderately active against Streptococcus spp.

In concomitant administration with benzylpenicillin it shows synergistic action against strains of Enterococcus faecalis.

The drug is resistant to anaerobic microorganisms.

Amicacin 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.

Indications

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

Active ingredient

Composition

1 bottle contains amikacin (in the form of sulfate) 500 mg.

Auxiliary substances:

Sodium disulfite (sodium metabisulfite),

Sodium citrate d/i (sodium citrate pentasquihydrate),

sulfuric acid diluted,

water d/i.

How to take, the dosage

The drug is administered v/m, v/v (by stream, for 2 minutes or by drip) to adults and children over 6 years of age – 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours. In bacterial urinary tract infections (uncomplicated) – 250 mg every 12 hours; an additional dose of 3-5 mg/kg may be prescribed after a hemodialysis session.

The maximum dose for adults is 15 mg/kg/day, but not more than 1.5 g/day for 10 days. Duration of treatment when administered by injection is 3-7 days, when administered by injection is 7-10 days.

For premature infants the initial single dose is 10 mg/kg, then 7.5 mg/kg every 18-24 hours; for newborns and children under 6 years of age the initial dose is 10 mg/kg, then 7.5 mg/kg every 12 hours for 7-10 days.

In infected burns, a dose of 5-7.5 mg/kg every 4-6 h may be required due to the shorter T1/2 (1-1.5 h) in this patient category.

V/v Amikacin is administered by drip for 30-60 minutes, if necessary by jetting.

For intravenous administration (dropwise) the drug is first diluted with 200 ml of 5% dextrose (glucose) solution or 0.9% sodium chloride solution. The concentration of amikacin in the solution for intravenous injection should not exceed 5 mg/ml.

In case of impaired renal excretory function, the dose should be reduced or the intervals between injections should be increased. If the interval between injections is increased (if the CK value is unknown and the patient’s condition is stable), the interval between injections of the drug is established according to the following formula:

The interval (h) = serum creatinine concentration × 9.

If the serum creatinine concentration is 2 mg/dL, the recommended single dose (7.5 mg/kg) should be given every 18 hours. If the interval is increased, the single dose is not changed.

In case of decreased single dose with unchanged dosing regimen, the first dose for patients with renal insufficiency is 7.5 mg/kg. Subsequent doses are calculated using the following formula:

The subsequent dose (mg) administered every 12 h = CK (ml/min) in the patient × the initial dose (mg)/CK at normal (ml/min).

Interaction

It shows synergism in interaction with carbenicillin, benzylpenicillin, cephalosporins (in patients with severe chronic renal failure when combined with beta-lactam antibiotics may reduce the effectiveness of aminoglycosides).

Nalidixic acid, polymyxin B, cisplatin and vancomycin increase the risk of ototoxicity and nephrotoxicity.

Diuretics (especially furosemide), cephalosporins, penicillins, sulfonamides and NSAIDs, competing for active secretion in nephron tubules, block elimination of aminoglycosides and increase their serum concentrations, increasing nephro- and neurotoxicity.

Amikacin increases the myorelaxant effect of curare-like drugs.

When used concomitantly with amikacin methoxyflurane, polymyxins for parenteral administration, capreomycin and other drugs that block neuromuscular transmission (halogenated hydrocarbons – agents for inhaled anesthesia, opioid analgesics), transfusion of large amounts of blood with citrate preservatives increase the risk of respiratory arrest.

Parenteral administration of indomethacin increases the risk of aminoglycoside toxicity (increased T1/2 and decreased clearance).

Amikacin decreases the effectiveness of antimiasthenic drugs.

Pharmaceutical interactions

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

Special Instructions

The sensitivity of isolated pathogens is determined before use using discs containing 30 µg amikacin. When the diameter of the growth-free zone is 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 µg/ml (therapeutic concentration is 15-25 µg/ml).

The renal, auditory nerve and vestibular function should be monitored at least once a week during treatment.

The likelihood of nephrotoxicity is greater in patients with impaired renal function and when high doses are prescribed or for prolonged periods (daily monitoring of renal function may be necessary in this category of patients).

In case of unsatisfactory audiometric tests, the drug dose is reduced or treatment is stopped.

Patients with infectious inflammatory diseases of the urinary tract are advised to take increased fluids with adequate diuresis.

In the absence of positive clinical dynamics, the possibility of development of resistant microorganisms should be kept in mind. In these cases, treatment should be discontinued and appropriate therapy initiated.

The sodium disulfite in the drug may cause allergic complications (up to and including anaphylactic reactions) in patients, especially in those with a history of allergic reactions.

Features

Introduction

It is quickly and completely absorbed after intravenous administration. Cmax in blood plasma when administered in a dose of 7.5 mg/kg in the m/m, after 30 minutes of infusion in a dose of 7.5 mg/kg – 38 µg/ml. After intravenous administration, Tmax – about 1.5 h.

The average therapeutic concentration when administered v/v or intravenously is maintained for 10-12 hours.

Distribution

The binding to plasma proteins is 4-11%. Vd in adults – 0.26 l/kg, in children – 0.2-0.4 l/kg, in newborns: in age less than 1 week and body mass less than 1500 g – up to 0.68 l/kg, in those less than 1 week and with body mass more than 1500 g – 0.58 l/kg, in cystic fibrosis patients – 0.3-0.39 l/kg.

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

When administered in average therapeutic doses (normal) in adults amikacin does not penetrate through the BBB; in inflammation of the cerebral membranes permeability increases slightly. Neonates reach higher concentrations in cerebrospinal fluid than adults. Penetrates through the placental barrier: detected in fetal blood and amniotic fluid.

Metabolism

It is not metabolized.

Contraindications

The drug should be used with caution in myasthenia gravis, parkinsonism, botulism (aminoglycosides may cause disruption of neuromuscular transmission, which leads to further weakening of skeletal muscles), dehydration, renal failure, in the period of newborn, in premature children, in elderly patients, during lactation.

Side effects

Overdose

Symptoms: toxic reactions – hearing loss, ataxia, dizziness, urinary disorders, thirst, decreased appetite, nausea, vomiting, ringing or tinnitus, respiratory disorders.

Treatment: hemodialysis or peritoneal dialysis to relieve neuromuscular transmission blockade and its consequences; anticholinesterase agents, calcium salts, EVI, other symptomatic and supportive therapy.