Gentamicin

Instruction manual

For medical use of the drug

Structure:

Active ingredient: gentamіcin;

1 ml of the solution contains 40 mg gentamicin sulfate;

excipients: sodium metabisulfite (E 223), disodium edetate, water for injection.

Dosage form.

Injection.

Basic physical and chemical properties: transparent, colorless or slightly colored liquid.

Pharmacotherapeutic group.

Antibacterial agents for systemic use. aminoglycosides. gentamicin. code atx j01g b03.

Pharmacological properties.

Pharmacodynamics

Gentamicin is a broad-spectrum antibiotic of the aminoglycoside group. The mechanism of action is associated with the inhibition of 30S ribosomal subunits. In vitro tests confirm its activity against various types of gram-positive and gram-negative microorganisms: Escherichia coli, Proteus sp. (indolpositive and indolegative), Pseudomonas aeruginosa, Klebsiella sp., Enterobacter sp., Serratia sp., Citrobacter sp., Salmonella sp., Shigella sp. i Staphylococcus spr. (including penicillin- and methicillin-resistant strains). The following microorganisms are generally resistant to gentamicin: Streptococcus pneumoniae, most other types of streptococci, enterococci, Neisseria meningitidis, Treponema pallidum and anaerobic microorganisms such as Bacteroides sp. or Clostridium spr.

Pharmacokinetics

The maximum concentration in blood plasma after 0.5–2 hours after intramuscular injection of 80 mg of gentamicin is 4–12 μg / ml. Similar concentrations are achieved after intravenous administration. The elimination half-life is 2.5 hours and rises in case of impaired renal excretory function. Plasma protein binding is 20–30%. Distribution volume - 0.25 l / kg. Normally, gentamicin passes poorly through the blood-brain barrier, with meningitis, the concentration in the cerebrospinal fluid rises.

Gentamicin crosses the placenta. The concentration observed in the blood of the fetus is approximately 40% of the concentration, which is determined in the blood of the mother.

Gentamicin is not metabolized in the body. It is excreted unchanged in urine, mainly by glomerular filtration, and partially by glomerular secretion.

Clinical characteristics.

Indications.

Given the limited therapeutic breadth of gentamicin-darnica, it should be used in cases where microorganisms are resistant to safer antibiotics.

Bacterial infections caused by microflora sensitive to gentamicin, including: lower respiratory tract infections, complicated urogenital infections, bone and joint infections, including osteomyelitis, skin and soft tissue infections, infected burn wounds, abdominal infections (peritonitis), central nervous system infections systems, in particular meningitis in combination with β-lactam antibiotics, septicemia.

Contraindications

Hypersensitivity to the active substance or to other components of the drug; auditory nerve neuritis; chronic renal failure with azotemia and uremia; myasthenia gravis; parkinsonism; botulism (gentamicin can cause a violation of neuromuscular transmission, which can lead to further weakening of skeletal muscles); elderly age; pretreatment with ototoxic drugs. a limitation to the use of the drug is acute renal failure.

Interaction with other drugs and other types of interactions.

With the simultaneous use of the drug with other drugs, it is possible:

with ototoxic drugs (in particular capreomycin, cisplatin, teicoplanin, vancomycin, potent diuretics: furosemide, ethacrine acid) - increased ototoxic effect, this combination is not recommended;

with neurotoxic or nephrotoxic agents (particularly streptomycin, neomycin, kanamycin, capreomycin, tobramycin, cephaloridine, paromomycin, biomycin, polymyxin B, colistin, amikacin, vancomycin, teicoplanin, tacrolimus, amphotericin B, cyclosporine, clindamycin, piperacillin, methoxyflurane, foscarnet, radiopaque agents for intravenous administration, cisplatin) - increased neurotoxic or nephrotoxic effect, this combination is not recommended;

with non-depolarizing muscle relaxants - increased muscle relaxant effect of curariform drugs;

with methoxyflurane, parenteral polymyxins, drugs that block neuromuscular transmission (inhalants for general anesthesia, narcotic analgesics, large amounts of blood transfusion with citrate preservatives) - increased risk of respiratory arrest due to increased neuromuscular blockade;

with botulinum toxin - increased risk of toxicity due to increased neuromuscular blockade;

with drugs that increase muscle tone - a decrease in the effectiveness of the latter;

with cephalosporins - increased nephrotoxic effect; during therapy, monitoring of renal function is recommended;

with penicillins - increased bactericidal effect;

with bisphosphonates - an increased risk of hypocalcemia;

with indomethacin (parenteral administration) - an increase in the risk of toxic effects of gentamicin due to an increase in half-life and a decrease in clearance.

Features of the application.

Gentamicin is one of the main treatments for severe suppurative infections caused by resistant gram-negative flora. due to the wide spectrum of action, gentamicin can be prescribed for mixed infections, as well as in cases where the pathogen is not installed, usually in combination with semisynthetic penicillins: ampicillin, carbenicillin.

Drug treatment should be carried out only as prescribed by the doctor and under close clinical supervision due to the potential toxicity of gentamicin.

In the treatment with gentamicin, it is necessary to regularly conduct a blood test to determine the plasma concentrations of the drug in order to ensure adequate and avoid the potentially toxic level of the drug in the blood.

During treatment, a sufficient amount of liquid should be consumed.

Like other aminoglycosides, gentamicin is potentially nephro- and neurotoxic. The risk of developing these side effects is higher in patients with impaired renal function, as well as when prescribing a drug in large doses or for a long time. Therefore, regularly (1 or 2 times a week, and in patients receiving high doses or being treated for more than 10 days - daily), it is necessary to monitor renal function. In order to avoid the development of hearing impairment, it is recommended to regularly (1 or 2 times a week) conduct a study of vestibular function or determine hearing loss at high frequencies.

In some cases, auditory impairment may occur after treatment.

It is necessary to inform the doctor about the presence of the following symptoms: a sensation of any loss of hearing, a sensation of tinnitus or tinnitus, dizziness, impaired coordination of movements, numbness, tingling of the skin, muscle twitching, cramps at any time during treatment. This may indicate the development of neurological side effects.

Symptoms of impaired renal function or damage to the auditory or vestibular apparatus require cessation of gentamicin therapy or, in exceptional cases, only dose adjustment.

The drug should be used with caution in patients with dehydration, hypocalcemia, patients with impaired renal function, and obesity.

Due to the small clinical experience, it is not recommended to administer the entire daily dose of gentamicin in such conditions: burns with an area of ​​more than 20%, cystofibrosis, ascites, endocarditis, chronic renal failure with hemodialysis, sepsis.

Rapid, direct administration of the drug may initially lead to a potentially neurotoxic concentration of gentamicin, and it is very important to administer the dose at recommended intervals.

Among antibiotics of the aminoglycoside group, cross-hypersensitivity is possible.

Against the background of treatment, resistance of microorganisms may develop. In such cases, it is necessary to cancel the drug and conduct a study of the sensitivity of microorganisms to the antibiotic.

Use during pregnancy or lactation.

Due to the fact that gentamicin sulfate crosses the placenta and may have a nephrotoxic effect on the fetus, the drug is contraindicated for use during pregnancy.

The drug penetrates into breast milk, so if necessary, the appointment of gentamicin mother should either stop breastfeeding, or abandon the use of the drug.

The ability to influence the reaction rate when driving vehicles or other mechanisms.

The drug affects the speed of neuromuscular conduction, and therefore, when treating with the drug, one should refrain from driving vehicles and working with mechanisms that require increased attention.

Dosage and administration.

Gentamicin should be administered intramuscularly or intravenously. the dose, route of administration and intervals between doses depend on the severity of the disease and the condition of the patient. dose regimen is calculated based on the patient’s body weight.

Adults and children from 14 years.

The usual daily dose of gentamicin for patients with moderate to severe infections is 3 mg / kg of body weight intramuscularly, divided into 2-3 injections. The maximum daily dose for adults is 5 mg / kg body weight, distributed over 3-4 injections. The usual duration of use of the drug for all patients is 7-10 days.

In severe and complicated infections, the course of therapy can be continued as necessary. In such cases, it is recommended to monitor the function of the kidneys, hearing and the vestibular apparatus, since the toxicity of the drug appears after its use for more than 10 days.

Calculation of body weight for which gentamicin must be prescribed.

The dose should be calculated based on the actual body weight (BMI) if the patient does not have excess weight (that is, an additional no more than 20% of ideal body weight (BMI)). If the patient has excess body weight, the dose is calculated on the basis of the following body mass (DMT) formula: DMT = BMI + 0.4 (FMT - BMI).

In case of impaired renal function, it is necessary to change the dosage regimen of the drug so that it guarantees the therapeutic adequacy of the treatment. At every opportunity, the concentration of gentamicin in the blood serum should be monitored. 30-60 minutes after intramuscular administration, serum concentrations should be 5-10 μg / ml.

The initial single dose for patients with stable chronic renal failure is 1–1.5 mg / kg body weight, in the future the dose and the interval between administrations is determined depending on the creatinine clearance.

For adult patients with a bacterial infection who are on dialysis, the drug is prescribed in a dose of 1-1.5 mg / kg of body weight at the end of each dialysis.

For peritonial dialysis in adults, add 1 mg of gentamicin to 2 liters of dialysis solution.

For intravenous administration, dilute the dose of the drug with a solvent.The usual volume of solvent (sterile saline or 5% glucose solution) for adults is 50–300 ml, for children, the amount of solvent should be reduced accordingly. The duration of intravenous infusion is 1-2 hours.

The concentration of gentamicin in the solution should not exceed 1 mg / ml (0.1%).

To the children.

Children up to 3 years of age should be prescribed gentamicin sulfate solely for health reasons.

The usual daily dose of gentamicin is: 2–5 mg / kg body weight for infants and children up to 1 year old, 1.5–3 mg / kg body weight for children 1–5 years old, and 3 mg / kg body weight for children 6–14 years old body. The maximum daily dose for children of all age-old groups is 5 mg / kg body weight, divided into 2-3 injections. The average duration of treatment is 7-10 days.

Children.

The drug can be used in children. for children under 3 years of age, gentamicin can be prescribed only for health reasons.

Overdose.

Symptoms: dizziness, nausea, vomiting, nephrotoxic and ototoxic manifestations, blockade of neuromuscular conduction (respiratory arrest).

Treatment: Administer intravenously proserin, as well as a 10% solution of calcium chloride or 5% solution of calcium gluconate. Before administering proserin, atropine should be administered intravenously at a dose of 0.5–0.7 mg, pulse rate should be expected, and after 1.5–2 minutes, 1.5 mg (3 ml of a 0.05% solution) of proserin is administered intravenously. If the effect of this dose was insufficient, re-introduce the same dose of proserin (if bradycardia appears, give an additional injection of atropine). In severe cases of respiratory depression, mechanical ventilation is necessary. It can be excreted by hemodialysis (more effective) and peritoneal dialysis.

Adverse Reactions

On the part of the hearing organs and the vestibular apparatus: ototoxicity (damage to the viii pair of cranial nerves, especially if the duration of treatment lasts 2-3 months) - tinnitus, hearing loss, vestibular and labyrinth disorders, irreversible deafness.

From the respiratory system, chest and mediastinal organs: sore throat, shortness of breath.

From the gastrointestinal tract: nausea, vomiting, increased thirst, loss of appetite, stomatitis, in some cases - pseudomembranous colitis.

From the liver and biliary tract: increased activity of hepatic transaminases, hyperbilirubinemia.

From the kidneys and urinary system: nephrotoxicity (impaired renal function) - oliguria, azotemia, proteinuria, micr