Pharmacological properties
Pharmacodynamics. Amikacin is a semi-synthetic antibiotic of the aminoglycoside group with a broad spectrum of action. It has a bactericidal effect. Actively penetrating the cell membrane of bacteria, it irreversibly binds to the 30S subunit of bacterial ribosomes, inhibiting the synthesis of the pathogen's protein.
It has high activity against aerobic gram-negative bacteria: Pseudomonas aeruginosa, Escherichia coli, Shigella spp., Salmonella spp., Klebsiella spp., Enterobacter spp., Serratia spp., Providencia stuartii.
It is also active against some gram-positive bacteria: Staphylococcus spp. (including strains resistant to penicillin, methicillin, some cephalosporins), some strains of Streptococcus spp.
Not active against anaerobic bacteria.
Pharmacokinetics
Absorption. After administration, it is absorbed quickly and completely. C max in blood plasma with i / m administration of the drug at a dose of 7.5 mg / kg of body weight is 21 μg / ml, after i / v infusion at a dose of 7.5 mg / kg for 30 minutes - 38 μg / ml. The time to reach C max in blood plasma after i / m administration is about 1.5.
Distribution. Evenly distributed in extracellular fluid (abscess contents, pleural effusion, ascitic, pericardial, synovial, lymphatic and peritoneal fluids); in high concentrations it is found in urine, in low - in bile, breast milk, aqueous humor, bronchial secretion, sputum and cerebrospinal fluid. Easily penetrates all tissues of the body, where it accumulates intracellularly. High concentrations are found in organs with intensive blood supply: lungs, liver, myocardium, spleen, and especially - in the cortical substance of the kidneys; lower concentrations - in muscles, adipose tissue and bones.
In adults, at average therapeutic doses (normal), amikacin does not cross the blood-brain barrier. Higher concentrations are achieved in the cerebrospinal fluid in newborns than in adults.
Amikacin penetrates the placental barrier - it is detected in fetal blood and amniotic fluid.
The volume of distribution (Vd) in adults is 0.26 l/kg, in children - 0.2-0.4 l/kg, in newborns aged 1 week and weighing 1.5 kg - up to 0.68 l/kg, in 1 week old infants weighing 1.5 kg - up to 0.58 l/kg, in patients with cystic fibrosis - 0.3-0.39 l/kg.
The average therapeutic concentration with intravenous or intramuscular administration is maintained for 10-12 hours.
Metabolism: Not metabolized.
Elimination. T ½ in the terminal (b) phase in adults is 2-4 hours, in newborns - 5-8 hours, in children - 2.5-4 hours. The final value of T ½ is 100 hours (release from intracellular depots).
It is excreted by the kidneys by glomerular filtration (65-94%), mainly in unchanged form. Renal clearance is 79-100 ml/min.
Pharmacokinetics in special clinical cases. In renal impairment in adults, T ½ 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, T ½ may be shorter compared to average values due to increased clearance.
It is removed by hemodialysis (50% in 4-6 hours) and peritoneal dialysis (25% in 48-72 hours).
Indication
Infections caused by amikacin-sensitive strains of microorganisms resistant to other aminoglycosides.
Application
Before administration, it is necessary to conduct a preliminary intradermal test for drug tolerance. Apply Amicyl IM or IV.
The usual dose for children aged 12 years and over and adults is 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours. The maximum dose for adults is 15 mg/kg/day. In severe cases and in infections caused by Pseudomonas, the daily dose should be divided into 3 doses. The maximum daily dose is 1.5 g. The maximum course dose should not exceed 15 g.
The duration of treatment with intravenous administration is up to 7 days, with intramuscular administration - 7-10 days.
Premature newborns should be given an initial loading dose of 10 mg/kg body weight, and then 7.5 mg/kg every 18-24 hours for 7-10 days.
Full-term newborns and children under 12 years of age should initially be prescribed 10 mg/kg of body weight, then 7.5 mg/kg of body weight every 12 hours for 7-10 days.
Patients with renal insufficiency require correction of the dosing regimen: reducing the dose or increasing the intervals between administrations without changing the single dose. The dose should be reduced depending on the creatinine content in the blood plasma and the patient's body weight. The interval between antibiotic administrations should be calculated by multiplying the value of the creatinine level in the blood plasma by 9, for example, if the creatinine level is 2 mg, the drug should be administered every 18 hours.
The solution for parenteral administration should be prepared immediately before administration.
Amicyl should be administered by intravenous infusion to adults and children, using a volume of fluid sufficient for drip infusion, over 60-90 minutes (at a rate of 50 drops per minute), and to newborns over 1-2 hours.
For intravenous infusions, dissolve the contents of the vial in 100-200 ml of 0.9% sodium chloride solution or 5% glucose solution.
The concentration of the amikacin solution for intravenous administration should not exceed 5 mg/ml. Intravenous injection of Amicyl should be performed very slowly (over approximately 7 minutes).
For intramuscular injections, dissolve the contents of the vial in 2-3 ml of water for injection and inject deeply into the upper outer quadrant of the buttock.
Children. Amicyl should be used with caution in premature and full-term newborns, since due to the underdevelopment of the excretory system, the excretion of aminoglycosides may be prolonged, causing toxicity.
Hypersensitivity to amikacin, to other components of the drug or to any other antibiotic of the aminoglycoside group and their derivatives; renal failure; auditory neuritis; myasthenia gravis; vestibular dysfunction; azotemia (residual nitrogen 150 mg%); previous treatment with oto- or nephrotoxic drugs.
Side effects
On the part of the digestive system: nausea, vomiting, liver dysfunction (increased activity of hepatic transaminases, hyperbilirubinemia).
From the hematopoietic system: anemia, leukopenia, granulocytopenia, thrombocytopenia.
Cardiovascular system: vasculitis, arterial hypotension.
From the side of the central nervous system and peripheral nervous system: headache, drowsiness, neurotoxic effects (muscle twitching, numbness, tingling, epileptic seizures), neuromuscular transmission disorders (respiratory arrest).
From the sensory organs: ototoxicity (hearing loss, tinnitus, vestibular and labyrinth disorders, reversible deafness), toxic effect on the vestibular apparatus (discoordination of movements, dizziness, nausea, vomiting).
From the urinary system: nephrotoxicity - impaired renal function (oliguria, proteinuria, hematuria, albuminuria, cylindruria, hyperazotemia), renal failure.
Allergic reactions: skin rash, itching, skin hyperemia, fever, angioedema.
Other: injection site reactions, injection site pain, paraesthesia, tremor.
Special instructions
Before using the drug, the sensitivity of the isolated pathogens should be determined.
Do not use Amicyl in patients with hypersensitivity to other aminoglycosides due to the risk of cross-allergy.
The drug should be used with caution in myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause neuromuscular transmission disorders, which leads to further weakening of skeletal muscles), dehydration, renal failure, as well as in infants (especially premature infants), and in elderly patients.
During treatment, it is necessary to monitor the function of the kidneys, auditory nerve and vestibular apparatus at least once a week.
The likelihood of developing nephrotoxicity is higher in patients with impaired renal function, as well as when using the drug in high doses or for a long time (this category of patients requires daily monitoring of renal function).
In case of unsatisfactory audiometric tests, the dose of the drug should be reduced or treatment should be discontinued.
Patients with infectious and inflammatory diseases of the urinary tract are recommended to drink plenty of fluids.
The main toxic effect of the drug when administered parenterally is its effect on the VIII pair of cranial nerves, which is initially manifested by 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, the patient's water and electrolyte balance should be corrected. During treatment with amikacin sulfate, a sufficient amount of fluid should be consumed, the concentration of creatinine in the blood plasma should be frequently determined and, if necessary, the dosage regimen should be adjusted.
Elderly patients should reduce the dose of Amicyl due to decreased renal function and possible weight loss. Renal function should be assessed regularly. Urinalysis should be performed before or during treatment.
The use of Amicyl may change the following laboratory parameters: serum ALT, AST, bilirubin, LDH, alkaline phosphate, urine nitrogen, creatinine, calcium, magnesium, potassium, sodium ions.
In patients with impaired renal function, the daily dose should be reduced and/or the dose interval should be increased according to serum creatinine concentration to prevent accumulation of the drug in the blood and to minimize the risk of ototoxicity. If signs of renal irritation (albuminuria, microhematuria, leukocyturia) appear, hydration should be increased and the dosage reduced. These manifestations usually disappear after the end of treatment. If signs of ototoxicity (e.g. dizziness, tinnitus, tinnitus or hearing loss) or nephrotoxicity (e.g. decreased creatinine clearance, oliguria) appear, the use of Amicyl should be discontinued or the dose reduced. If signs of azotemia occur or oliguria increases, treatment should be stopped.
The simultaneous use of amikacin sulfate and fast-acting diuretics, such as ethacrynic acid derivatives, furosemide, mannitol (especially if the diuretic is administered intravenously), may lead to the development of irreversible deafness.
Two aminoglycosides should not be used simultaneously or one drug should be replaced by another if the first aminoglycoside was used for 7-10 days. A repeat course can be carried out no earlier than after 4-6 weeks.
In the absence of positive clinical dynamics, it is worth remembering the possibility of the development of resistant microorganisms. In such cases, it is necessary to cancel the treatment and start appropriate therapy.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms. The drug generally does not affect the reaction rate, but the likelihood of such side effects from the central nervous system as drowsiness, impaired neuromuscular transmission should be taken into account.
Interactions
Pharmaceutically incompatible with penicillins, heparin, cephalosporins, capreomycin, amphotericin B, hydrochlorothiazide, erythromycin, nitrofurantoin, vitamins B and C, potassium chloride.
Amikacin exhibits synergy when interacting with carbenicillin, benzylpenicillin, cephalosporins (in patients with severe chronic renal failure, simultaneous use with beta-lactam antibiotics may reduce the effectiveness of aminoglycosides). Nalidixic acid, polymyxin B, cisplatin and vancomycin increase the risk of oto- and nephrotoxicity.
With simultaneous use with penicillins, cephalosporins, sulfonamides, vancomycin, methoxyflurane, enflurane, NSAIDs, radiocontrast agents, cyclosporine, cisplatin, amphotericin B, cephalothin, polymyxin and diuretics (especially furosemide) the risk of nephrotoxic effects increases.
Indomethacin, phenylbutazone and other non-steroidal anti-inflammatory drugs that impair renal blood flow may slow the rate of excretion of Amicyl. If amikacin is used simultaneously with the administration of indomethacin by intravenous administration to premature infants, an increase in the concentration of the drug in the blood plasma occurs and there is a risk of toxicity.
Enhances the muscle relaxant effect of curare-like drugs.
Methoxyflurane, polymyxins for parenteral administration, capreomycin and other drugs that block neuromuscular transmission (halogenated hydrocarbons as drugs for inhalation anesthesia, opioid analgesics), transfusion of a large volume of blood with citrate preservatives - increase the risk of respiratory arrest. Parenteral administration of indomethacin increases the risk of developing the toxic effects of aminoglycosides (increase in T ½ and decrease in clearance).
Amikacin reduces the effectiveness of drugs used for myasthenia gravis.
With simultaneous use with ethyl ether and neuromuscular blockers, the risk of respiratory depression increases.
The risk of developing ototoxic effects increases with the simultaneous use of Amicil with furosemide and ethacrynic acid.
The antibiotic combinations - amikacin + ceftazidime and amikacin + cefoperazone - show the most additive and synergistic effect against Pseudomonas aeruginosa.
When using multiple antibiotics, Amicyl should not be mixed in the same syringe or vial with other antibacterial agents.
Incompatibility. Amikacin sulfate solution should not be directly mixed with other aminoglycosides, penicillins, heparin, cephalosporins, capreomycin, amphotericin B, thiopental, hydrochlorothiazide, erythromycin, nitrofurantoin, vitamins B and C, potassium chloride. If necessary, the two drugs are administered separately, sequentially.
Overdose
The appearance of ototoxic and nephrotoxic effects of the drug and signs of neuromuscular blockade is possible: tinnitus, hearing disorders, skin rashes, headache, dizziness, fever, paresthesias, decreased kidney function (up to renal failure), respiratory depression or paralysis, toxic reactions (ataxia, urination disorders, thirst, decreased appetite, nausea, vomiting).
Treatment: to relieve neuromuscular blockade and its consequences - hemodialysis or peritoneal dialysis; anticholinesterase agents, calcium salts, artificial lung ventilation, other symptomatic and supportive therapy.
Storage conditions
In the original packaging at a temperature not exceeding 25 °C.
