Instructions for Amikacin sulfate solution for injection 250 mg/ml ampoule 2 ml No. 1
Composition
active ingredient: amikacin;
1 ml of solution contains amikacin sulfate equivalent to amikacin 50 mg or 250 mg;
Excipients: sodium metabisulfite (E 223), sodium citrate, water for injections.
Dosage form
Solution for injection.
Main physicochemical properties: clear, colorless or slightly yellowish liquid.
Pharmacotherapeutic group
Antimicrobial agents for systemic use.
Aminoglycosides. Amikacin. ATX code J01G B06.
Pharmacological properties
Pharmacodynamics.
Amikacin is a semisynthetic aminoglycoside antibiotic with a broad spectrum of activity. Amikacin actively penetrates the bacterial cell membrane. By binding to the 30S subunit of ribosomes, it interferes with the formation of a complex of transfer and messenger RNA, blocks protein synthesis, and also disrupts the synthesis of the bacterial cytoplasmic membrane.
Active against aerobic gram-negative microorganisms: Pseudomonas aeruginosa, Escherichia coli, Shigella spp., Salmonella spp., Klebsiella spp., Enterobacter spp., Providencia spp., Proteus spp. (indole-positive and indole-negative strains), Serratia spp., Acinetobacter species, Citrobacter freundii.
Active against some gram-positive microorganisms: Staphylococcus spp., including staphylococci resistant to penicillin, methicillin, some cephalosporins and some strains of Streptococcus pyogenes, Streptococcus pneumoniae, Enterococcus. Amikacin can be used as basic therapy under certain conditions in cases of established diagnosis or suspicion of a disease caused by sensitive strains of staphylococci, in patients allergic to other antibiotics and in mixed staphylococcal-gram-negative infections. Amikacin is inactive against anaerobic pathogens.
Pharmacokinetics.
After intramuscular administration, amikacin is rapidly and completely absorbed. The maximum concentration is reached 0.5-1.5 hours after intramuscular administration and 0.5 hours after intravenous administration. Therapeutic concentrations of amikacin are maintained for 10-12 hours.
Distribution. Binding to blood proteins is 4-11%. Amikacin is well distributed in extracellular matter (abscess contents, pleural effusion, ascitic, pericardial, synovial, lymphatic and peritoneal fluids). Amikacin is found in high concentrations in urine, in low concentrations in bile, breast milk, aqueous humor, bronchial secretions, sputum and cerebrospinal fluid. Amikacin penetrates well into all tissues of the body, where it accumulates intracellularly. High concentrations of amikacin are observed in organs with increased blood supply: lungs, liver, myocardium, spleen and especially in the kidneys, where it accumulates in the cortical layer; lower concentrations are found in muscles, adipose tissue and bones.
In adults, at average therapeutic doses, amikacin practically does not penetrate the blood-brain barrier, but penetration increases suddenly in meningitis. Higher concentrations are achieved in the cerebrospinal fluid in newborns than in adults.
Amikacin crosses the placental barrier and is found in fetal blood and amniotic fluid.
Excretion. Amikacin is not metabolized, is excreted by the kidneys by glomerular filtration (65-94%) in an unchanged state, forming high concentrations in the urine. Renal clearance is 79-100 ml/min. The rate of excretion depends on the age, renal function and concomitant pathology of the patient.
In patients with fever, it increases, and in cases of decreased kidney function and in the elderly, it slows down significantly.
The half-life in adults with normal renal function is 2-4 hours, in newborns - 5-8 hours, in older children - 2.5-4 hours. In renal failure, the half-life can reach 70 hours or more, in cystic fibrosis - 1-2 hours. The final half-life is more than 100 hours (release from intracellular depots).
With hemodialysis, 50% is removed in 4-6 hours, with peritoneal dialysis - 25% in 48-72 hours.
Indication
Infections caused by amikacin-sensitive strains of microorganisms resistant to other aminoglycosides.
Contraindication
Kidney failure;
neuritis of the auditory nerve;
hypersensitivity to amikacin or to any other antibiotic of the aminoglycoside group and their derivatives;
hypersensitivity to any of the excipients included in the preparation;
myasthenia gravis;
vestibular dysfunction;
azotemia (residual nitrogen above 150 mg%);
previous treatment with ototoxic or nephrotoxic drugs.
Interaction with other medicinal products and other types of interactions
Concomitant administration of Amikacin sulfate with anesthetics and muscle relaxants may cause blockade of neuromuscular transmission and paralysis of the respiratory muscles.
Amikacin sulfate is incompatible in solution with penicillins, cephalosporins, amphotericin, hydrochlorothiazide, erythromycin, heparin, nitrofurantoin, thiopentone, warfarin, tetracyclines, B vitamins, vitamin C, and potassium chloride.
Indomethacin, phenylbutazone, and other NSAIDs that impair renal blood flow may slow the rate of amikacin sulfate elimination. When amikacin sulfate is administered to premature infants concurrently with intravenous indomethacin, plasma concentrations of the drug are increased and there is a risk of toxicity.
The antibiotic combinations amikacin + ceftazidime and amikacin + cefotaxime exhibit the most additive and synergistic effect against Pseudomonas aeruginosa.
Application features
Due to the potential ototoxicity and nephrotoxicity of aminoglycosides, patients should be under special medical supervision.
It is not recommended to prescribe amikacin sulfate to patients with hypersensitivity to other aminoglycosides due to the risk of cross-allergy.
It should be used with caution in patients with myasthenia gravis and parkinsonism, as well as in the elderly and patients with neuromuscular conduction disorders, due to the possibility of a curare-like effect.
In the presence of difficult-to-treat infections or complicated infections, after 10 days it is necessary to evaluate the treatment with the drug and before prescribing the next course, check kidney function, hearing, vestibular apparatus and serum drug concentration. If there is no expected clinical effect after 3-5 days, treatment should be stopped and the pathogen's sensitivity to antibiotics should be determined.
Patients with impaired renal function should adjust the dosage regimen depending on creatinine clearance. The risk of ototoxic and nephrotoxic effects increases with the administration of large doses of the drug. To prevent ototoxic and nephrotoxic complications and reduce their incidence, it is recommended to monitor renal function, hearing and vestibular function at least once a week when using the drug.
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, it is necessary to correct the patient's water and electrolyte balance. During treatment with amikacin sulfate, it is necessary to drink a sufficient amount of fluid, frequently determine the concentration of creatinine in the blood plasma and, if necessary, adjust the dosage regimen.
Elderly patients should reduce the dose of amikacin sulfate due to decreased renal function and possible weight loss. Renal function should be assessed regularly. Urinalysis should be performed before or during treatment. Periodic examination and recording of audiograms and determination of vestibular function are necessary. If renal, vestibular, or auditory impairment is observed, the dose of amikacin sulfate should be reduced or amikacin sulfate should be discontinued.
In patients with impaired renal function, the daily dose should be reduced and/or the dosing 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 damage appear (e.g. albuminuria, microhematuria, leukocyturia), hydration should be increased and the dosage reduced. These signs 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 amikacin sulfate should be discontinued or the dose reduced. However, if signs of azotemia occur or oliguria increases, treatment should be stopped.
Ototoxicity caused by aminoglycoside antibiotics can develop even after discontinuation of the drug and is usually irreversible. The risk of developing ototoxicity is increased in patients with impaired renal function, as well as when using high doses or with prolonged treatment with the drug.
Patients with mitochondrial DNA mutations (particularly the 12S rRNA gene 1555 A to G substitution) are at increased risk of ototoxicity, even if serum aminoglycoside levels are within the recommended range during treatment. Alternative treatments should be considered for these patients.
Also, before prescribing the drug to patients with a family history of mitochondrial DNA mutations or patients with aminoglycoside-induced deafness, alternative treatments or genetic testing should be considered.
In dehydrated patients, the risk of toxicity is increased due to increased serum drug concentrations.
Two aminoglycosides should not be prescribed simultaneously or one drug should be replaced by another if the first aminoglycoside has been used for 7-10 days. A repeat course can be carried out no earlier than after 6 weeks.
The drug contains sodium metabisulfite, which may cause allergic-type reactions, including symptoms of anaphylaxis and asthma attacks of varying severity, especially in patients with bronchial asthma.
When used simultaneously with cephalosporins, it is advisable to administer them in different places (with intramuscular administration) with an interval of at least 1 hour.
The use of amikacin sulfate may alter the following laboratory parameters: serum alanine aminotransferase, aspartate aminotransferase, bilirubin, lactate dehydrogenase, alkaline phosphate, urine nitrogen, creatinine, calcium, magnesium, potassium, sodium ions.
Use during pregnancy or breastfeeding
The drug is contraindicated during pregnancy and breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
Experience with the drug indicates that it does not affect the ability to drive or operate machinery, but the likelihood of such side effects from the central nervous system as drowsiness and impaired neuromuscular transmission should be taken into account.
Method of administration and doses
The drug is administered intramuscularly or intravenously (by jet or drip). The dose and method of administration of the drug are determined individually for each patient depending on the severity of the disease, the sensitivity of the pathogen, kidney function and the patient's body weight. Adults and children over 12 years of age are prescribed 10-15 mg/kg per day. The daily dose is divided into 2 doses. The maximum daily dose for adults is 1.5 g. The duration of treatment with intravenous administration is 3-7 days, with intramuscular administration – 7-10 days.
For uncomplicated infections of the genitourinary system (except infections caused by Pseudomonas aeruginosa), the drug is administered intramuscularly at 250 mg 2 times a day for 5-7 days.
For infections caused by Pseudomonas aeruginosa and life-threatening infections, the drug is prescribed at a dose of 15 mg/kg per day, divided into 3 administrations.
For newborns and premature infants, the initial loading dose is 10 mg/kg per day, followed by a daily dose of 15 mg/kg, divided into 2 doses, for 7-10 days.
In patients with impaired renal function, the daily dose should be reduced or the interval between administrations should be increased to avoid antibiotic cumulation. The dosage regimen should be adjusted depending on creatinine clearance.
| Creatinine clearance, mg/ml | Number of entries | Dose, mg/kg |
| 80 | 1 time in 24 hours | 15 |
| 60-80 | –//– | 12 |
| 40-60 | –//– | 7.5 |
| 30-40 | –//– | 4 |
| 20-30 | Once every 48 hours | 7.5 |
| 10-20 | –//– | 4 |
| Less than 10 | –//– | 3 |
To prepare the infusion solution, use isotonic sodium chloride solution, 5% glucose solution, Ringer's solution. The concentration of amikacin solution for intravenous administration should not exceed 5 mg/ml. The duration of infusion is 30-90 minutes. Intravenous injection should be performed slowly, within 7 minutes.
Children. The drug is used in pediatric practice.
Amikacin sulfate is used with caution in the treatment of premature and full-term infants, since due to the underdevelopment of the excretory system, the excretion of aminoglycosides may be prolonged, causing toxicity.
Overdose
The drug may cause oto- and nephrotoxic effects and signs of neuromuscular blockade: tinnitus, hearing disorders, skin rashes, headache, dizziness, fever, paresthesias, decreased kidney function (up to renal failure), respiratory depression or paralysis.
If necessary, the drug is removed from the body by parenteral dialysis or hemodialysis. The drug level is reduced by continuous arteriovenous hemofiltration. Exchange hemotransfusion is also used to remove the drug from the body in newborns.
At the first signs of neuromuscular blockade, it is necessary to stop the administration of amikacin sulfate and immediately administer an intravenous solution of calcium chloride or a subcutaneous solution of proserin and atropine. If necessary, the patient is transferred to controlled respiration.
Side effects
From the digestive tract: nausea, vomiting, diarrhea.
On the part of the hearing organs: partially reversible or irreversible deafness, tinnitus.
From the side of the central nervous system: headache, drowsiness, possible hearing loss, vestibular disorders, dizziness, paresthesias, tremor, convulsions, encephalopathy; in rare cases - impaired neuromuscular conduction, possible occurrence of neuromuscular blockade (muscle paralysis, respiratory depression).
From the urinary system: nephrotoxicity - impaired renal function (oliguria, albuminuria, cylindruria, hyperazotemia, proteinuria, microhematuria, hematuria, increased creatinine levels); rarely - acute necrosis, interstitial nephritis, acute renal failure.
Cardiovascular system: vasculitis, arterial hypotension.
Endocrine and metabolic disorders: hypomagnesemia.
Musculoskeletal system: arthralgia.
Allergic reactions: skin rashes, itching, fever; in rare cases - Quincke's edema.
Others: pain at the injection site, hyperemia, edema, hyperthermia, hyperbilirubinemia, increased blood transaminase levels.
Expiration date
2 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
Solution for injection 50 mg/ml – 2 ml in ampoules.
Solution for injection 250 mg/ml – 2 ml or 4 ml in ampoules.
1 ampoule in a pack. 5 ampoules in a blister, 1 or 2 blisters in a pack.
Vacation category
According to the recipe.
Producer
Private Joint-Stock Company "Lekhim-Kharkiv".
Address
Ukraine, 61115, Kharkiv region, Kharkiv city, Severyna Pototskoho street, building 36.
