Pharmacological properties of the drug Amikacin
An aminoglycoside antibiotic with a broad spectrum of activity against gram-positive and gram-negative bacteria. Has a bactericidal effect. It is obtained semi-synthetically from kanamycin A. After intramuscular administration, it is quickly absorbed and distributed in the body. It is excreted unchanged in the urine mainly due to glomerular filtration. About 20% of the antibiotic binds to blood plasma proteins. A number of gram-negative microorganisms are sensitive to amikacin, including Pseudomonas spp., E. coli, Proteus spp . (indole-positive and indole-negative strains), Klebsiella spp., Enterobacter spp., Serratia spp., Salmonella spp., Shigella spp., Mima Herellea, Citrobacter freundii, Providencia spp., as well as gram-positive microorganisms ( Staphylococcus spp. and some strains of Streptococcus pneumoniae ). The antibiotic does not affect most anaerobes. Many strains of gram-negative microorganisms resistant to gentamicin may be sensitive to amikacin. Staphylococci resistant to penicillin, methicillin, and some cephalosporins are sensitive to amikacin.
Amikacin solution for intravenous injection 250 mg/ml 2 ml N 10
pharmachologic effect
Semi-synthetic antibiotic of the aminoglycoside group with a broad spectrum of action. Has a bactericidal effect. Actively penetrating the bacterial cell membrane, it irreversibly binds to the 30S subunit of bacterial ribosomes and, thereby, inhibits the synthesis of the pathogen protein.
Highly active against aerobic gram-negative bacteria: Pseudomonas aeruginosa, Escherichia coli, Shigella spp., Salmonella spp., Klebsiella spp., Enterobacter spp., Serratia spp., Providencia stuartii.
Also active against some gram-positive bacteria: Staphylococcus spp. (including strains resistant to penicillin, methicillin, some cephalosporins), some strains of Streptococcus spp.
Inactive against anaerobic bacteria.
Pharmacokinetics
After intramuscular administration, it is quickly and completely absorbed. Distributed in all tissues of the body. Plasma protein binding is low (0-10%). Penetrates through the placental barrier.
Not metabolized. It is excreted unchanged in the urine. T1/2 - 2-4 hours.
Indications of the active substances of the drug Amikacin
Severe infectious and inflammatory diseases caused by microorganisms sensitive to amikacin: peritonitis, sepsis, neonatal sepsis, central nervous system infections (including meningitis), infections of bones and joints (including osteomyelitis), endocarditis, pneumonia, pleural empyema , lung abscess, purulent infections of the skin and soft tissues, infected burns, often recurrent urinary tract infections, biliary tract infections.
Dosage regimen
They are determined individually, taking into account the severity and localization of the infection and the sensitivity of the pathogen. Administer intramuscularly, possibly also intravenously (stream for 2 minutes or drip).
IM or IV for adults and adolescents - 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours for 7-10 days. For children, the initial dose is 10 mg/kg, then 7.5 mg/kg every 12 hours.
Maximum doses: for adults, the daily dose is 1.5 g.
Side effect
From the digestive system: increased activity of liver transaminases, hyperbilirubinemia, nausea, vomiting.
Allergic reactions: skin rash, itching, fever; rarely - Quincke's edema.
From the hematopoietic system: anemia, leukopenia, granulocytopenia, thrombocytopenia.
From the nervous system: headache, drowsiness, impaired neuromuscular transmission, hearing loss, up to the development of irreversible deafness, vestibular disorders.
From the urinary system: oliguria, proteinuria, microhematuria; rarely - renal failure.
Contraindications for use
Severe renal dysfunction, acoustic neuritis, pregnancy, hypersensitivity to aminoglycoside antibiotics.
Use during pregnancy and breastfeeding
Amikacin is contraindicated during pregnancy.
If it is necessary to use it during lactation, the issue of stopping breastfeeding should be decided.
Use for renal impairment
Contraindicated in severe renal impairment.
Patients with impaired renal excretory function require adjustment of the dosage regimen depending on the CC values.
The risk of nephrotoxicity increases when amikacin is used in high doses or in predisposed patients.
Use in children
For children, the initial dose is 10 mg/kg, then 7.5 mg/kg every 12 hours.
Use in elderly patients
Use with caution in elderly people.
special instructions
Use with caution in patients with myasthenia gravis and parkinsonism, as well as in the elderly.
Patients with impaired renal excretory function require adjustment of the dosage regimen depending on the CC values.
It is not recommended to use amikacin in patients with hypersensitivity to other aminoglycosides due to the risk of developing cross-allergy.
The risk of developing ototoxic and nephrotoxic effects increases when amikacin is used in high doses or in predisposed patients.
Drug interactions
The risk of developing nephrotoxicity increases with simultaneous use of amikacin with amphotericin B, vancomycin, methoxyflurane, enflurane, NSAIDs, radiocontrast agents, cephalothin, cyclosporine, cisplatin, polymyxins.
The risk of developing ototoxicity increases with simultaneous use of amikacin with “loop” diuretics (furosemide, ethacrynic acid), cisplatin.
When used simultaneously with penicillins (in case of renal failure), the antimicrobial effect is reduced.
When used simultaneously with ethyl ether and neuromuscular transmission blockers, the risk of respiratory depression increases.
Amikacin in solution is incompatible with penicillins, cephalosporins, amphotericin B, chlorothiazide, erythromycin, heparin, nitrofurantoin, thiopentone, and also, depending on the composition and concentration of the solution, with tetracyclines, B vitamins, vitamin C and potassium chloride.
Use of the drug Amikacin
IM or IV. Adults and children are prescribed at a dose of 15 mg/kg body weight per day, dividing the daily dose into 2 administrations. In severe cases and for infections caused by Pseudomonas , the daily dose is divided into 3 administrations. The maximum daily dose is 1.5 g. The maximum course dose should not exceed 15 g. The duration of treatment is usually 3–7 days with intravenous administration and 7–10 days with intramuscular administration. Newborns, including premature infants, are prescribed an initial dose of 10 mg/kg, and then 7.5 mg/kg every 12 hours. When treating patients with impaired renal function, the daily dose should be reduced and/or the intervals between doses should be increased. The dose is reduced depending on the creatinine content in the blood plasma and the patient’s body weight. The interval between antibiotic administrations is calculated by multiplying the plasma creatinine level by 9; for example, if the creatinine level is 2 mg, the drug is prescribed every 18 hours. Administration of amikacin by intravenous infusion to adults and children should be carried out using a volume of fluid sufficient for drip infusion over 30–90 minutes (at a rate of 60 drops per 1 min), and for newborns - 1-2 hours. The concentration of p-ra amikacin when administered intravenously should not exceed 5 mg/ml. IV injection of amikacin should be given very slowly (over 2–7 minutes).
Pharmacokinetics
Suction
After intramuscular administration, it is absorbed quickly and completely. Cmax in blood plasma with intramuscular administration at a dose of 7.5 mg/kg is 21 mcg/ml, after 30 minutes of intravenous infusion at a dose of 7.5 mg/kg is 38 mcg/ml. After IM administration, Tmax is about 1.5 hours.
The average therapeutic concentration with intravenous or intramuscular administration lasts for 10-12 hours.
Distribution
Plasma protein binding is 4-11%. Vd in adults - 0.26 l/kg, in children - 0.2-0.4 l/kg, in newborns: less than 1 week old and weighing less than 1500 g - up to 0.68 l/kg, less than 1 week old and weighing more than 1500 g - up to 0.58 l/kg, in patients with cystic fibrosis - 0.3-0.39 l/kg.
Well distributed in extracellular fluid (abscess contents, pleural effusion, ascitic, pericardial, synovial, lymphatic and peritoneal fluid); found in high concentrations in urine; in low levels - in bile, breast milk, aqueous humor of the eye, bronchial secretions, sputum and cerebrospinal fluid. Penetrates well into all tissues of the body, where it accumulates intracellularly; high concentrations are observed in organs with good blood supply: lungs, liver, myocardium, spleen, and especially in the kidneys, where they accumulate in the cortex; lower concentrations are found in muscles, adipose tissue and bones.
When administered in moderate therapeutic doses (normally) to adults, amikacin does not penetrate the BBB; with inflammation of the meninges, permeability increases slightly. Neonates achieve higher concentrations in the cerebrospinal fluid than adults. Penetrates the placental barrier: found in fetal blood and amniotic fluid.
Metabolism
Not metabolized.
Removal
T1/2 in adults - 2-4 hours, in newborns - 5-8 hours, in older children - 2.5-4 hours. Final T1/2 —
more than 100 hours (release from intracellular depots).
It is excreted by the kidneys by glomerular filtration (65-94%), mainly unchanged. Renal clearance - 79-100 ml/min.
Pharmacokinetics in special clinical situations
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 than the average due to increased clearance .
It is eliminated by hemodialysis (50% in 4-6 hours), peritoneal dialysis is less effective (25% in 48-72 hours).
Side effects of the drug Amikacin
Possible albuminuria, hematuria, cylindruria, hyperazotemia and oliguria; manifestations of ototoxicity (partially reversible or irreversible deafness, tinnitus, vestibular disorders), increased activity of liver transaminases and bilirubin concentration in the blood serum, allergic reactions (skin rash, itching, fever, less often - Quincke's edema), changes in the composition of peripheral blood (anemia , leukopenia, granulocytopenia, thrombocytopenia), nausea, vomiting, headache, drowsiness, very rarely - disturbance of neuromuscular transmission.
Special instructions for the use of Amikacin
The main toxic effect of amikacin when administered parenterally is its effect on the VIII pair of cranial nerves, which initially manifests itself as deafness in the range of high-frequency sounds. In patients with impaired renal function, the risk of developing ototoxic complications is significantly higher. Before starting treatment, it is necessary to correct the patient's water and electrolyte balance. During treatment with amikacin, it is necessary to take a sufficient amount of fluid, frequently determine the concentration of creatinine in the blood plasma and, if necessary, adjust the dosage regimen. If signs of nephrotoxicity occur, fluid administration should be increased and the amikacin dose reduced. If hyperazotemia or oliguria develops, treatment should be discontinued.
Contraindications for use
- acoustic neuritis;
- severe chronic renal failure with azotemia and uremia;
- pregnancy;
- hypersensitivity to the components of the drug;
- history of hypersensitivity to other aminoglycosides.
Carefully _
the drug should be used for myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause disruption of neuromuscular transmission, which leads to further weakening of skeletal muscles), dehydration, renal failure, in the neonatal period, in premature infants, in elderly patients, during lactation.
Drug interactions Amikacin
The simultaneous administration of amikacin with anesthetics and muscle relaxants can cause blockade of neuromuscular transmission and paralysis of the respiratory muscles. Do not simultaneously use other ototoxic and/or nephrotoxic drugs, in particular antibiotics such as streptomycin, polymyxin B, neomycin, gentamicin. The simultaneous use of amikacin and fast-acting diuretics, for example derivatives of ethacrynic acid, furosemide, mannitol (especially if the diuretic is administered intravenously), can lead to the development of irreversible deafness. Amikacin should not be mixed with other antibacterial agents in the same volume.
Drug interactions
Shows synergism when interacting with carbenicillin, benzylpenicillin, cephalosporins (in patients with severe chronic renal failure, when used together with beta-lactam antibiotics, the effectiveness of aminoglycosides may be reduced).
Nalidixic acid, polymyxin B, cisplatin and vancomycin increase the risk of oto- and nephrotoxicity.
Diuretics (especially furosemide), cephalosporins, penicillins, sulfonamides and NSAIDs, competing for active secretion in the nephron tubules, block the elimination of aminoglycosides, increase their concentration in the blood serum, increasing nephro- and neurotoxicity.
Amikacin enhances the muscle relaxant effect of curare-like drugs.
When used simultaneously with amikacin, methoxyflurane, polymyxins for parenteral administration, capreomycin and other drugs that block neuromuscular transmission (halogenated hydrocarbons - inhalation 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 developing toxic effects of aminoglycosides (increased T1/2 and decreased clearance).
Amikacin reduces the effectiveness of antimyasthenic drugs.
Pharmaceutical interactions
Pharmaceutically incompatible with penicillins, heparin, cephalosporins, capreomycin, amphotericin B, hydrochlorothiazide, erythromycin, nitrofurantoin, vitamins B and C, potassium chloride.
