Gentamicin sulfate-Darnitsa solution for injection 40 mg/ml ampoule 2 ml No. 10

Instructions for Gentamicin sulfate-Darnitsa solution for injection 40 mg/ml ampoule 2 ml No. 10

Composition

active ingredient: gentamicin;

1 ml of solution contains gentamicin sulfate 40 mg;

Excipients: sodium metabisulfite (E 223), disodium edetate, water for injections.

Dosage form

Solution for injection.

Main physicochemical properties: clear colorless or slightly colored liquid.

Pharmacotherapeutic group

Antibacterials for systemic use. Aminoglycosides. Gentamicin. ATX code J01G B03.

Pharmacological properties

Pharmacodynamics.

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

Pharmacokinetics.

The maximum concentration in blood plasma 0.5-2 hours after intramuscular injection of 80 mg of gentamicin is 4-12 μg/ml. Similar concentrations are achieved after intravenous injection. The half-life is 2.5 hours and increases with impaired renal excretory function. Binding to plasma proteins is 20-30%. The volume of distribution is 0.25 l/kg. Normally, gentamicin does not penetrate the blood-brain barrier well, but in meningitis the concentration in the cerebrospinal fluid increases.

Gentamicin crosses the placenta. Concentrations observed in fetal blood are approximately 40% of those determined in the mother.

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

Indication

Given the limited therapeutic range of Gentamicin-Darnitsa, it should be used in cases where microorganisms are resistant to safer antibiotics.

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

Contraindication

Hypersensitivity to the active substance and to other components of the drug; acoustic neuritis; chronic renal failure with azotemia and uremia; myasthenia gravis; parkinsonism; botulism (gentamicin can cause neuromuscular transmission disorders, which can lead to further weakening of skeletal muscles); old age; previous treatment with ototoxic drugs. A limitation to the use of the drug is acute renal failure.

Interaction with other medicinal products and other types of interactions

When using the drug simultaneously with other drugs, it is possible:

with ototoxic agents (in particular capreomycin, cisplatin, teicoplanin, vancomycin, potent diuretics: furosemide, ethacrynic acid) – increased ototoxic effect, such a combination is not recommended;

with neurotoxic or nephrotoxic agents (in particular streptomycin, neomycin, kanamycin, capreomycin, tobramycin, cephaloridine, paromomycin, biomycin, polymyxin B, colistin, amikacin, vancomycin, teicoplanin, tacrolimus, amphotericin B, cyclosporine, clindamycin, piperacillin, methoxyflurane, foscarnet, intravenous radiocontrast agents, cisplatin) - increased neurotoxic or nephrotoxic effect, such a combination is not recommended;

with non-depolarizing muscle relaxants – increased muscle relaxant effect of curare-like drugs;

with methoxyflurane, polymyxins for parenteral administration, drugs that block neuromuscular transmission (inhalation agents for general anesthesia, narcotic analgesics, transfusion of large amounts of blood 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 - reduced effectiveness of the latter;

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

with penicillins – increased bactericidal effect;

with bisphosphonates - increased risk of hypocalcemia;

with indomethacin (parenteral administration) - increased risk of developing toxic effects of gentamicin due to increased half-life and decreased clearance.

Application features

Gentamicin is one of the main drugs for the treatment of severe purulent infections caused by resistant gram-negative flora. Due to its broad spectrum of action, gentamicin can be prescribed for mixed infections, as well as in cases where the pathogen is not identified, usually in combination with semi-synthetic penicillins: ampicillin, carbenicillin.

Treatment with the drug should be carried out only as prescribed by a doctor and under close clinical supervision due to the potential toxicity of gentamicin.

During treatment with gentamicin, regular blood tests should be performed to determine plasma drug concentrations to ensure adequate and potentially toxic levels of the drug in the blood.

During treatment, you should drink plenty of fluids.

Like other aminoglycosides, gentamicin is potentially nephrotoxic and neurotoxic. The risk of these side effects is higher in patients with impaired renal function, as well as when the drug is prescribed in high doses or for a long time. Therefore, renal function should be monitored regularly (1 or 2 times a week, and in patients receiving higher doses or those who are on treatment for more than 10 days - daily). 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 high-frequency hearing loss.

In some cases, hearing impairment may occur after the end of treatment.

You should inform your doctor if you experience any of the following symptoms: hearing loss, ringing or buzzing in the ears, dizziness, incoordination, numbness, tingling of the skin, muscle twitching, or seizures at any time during treatment. These may indicate the development of neurological side effects.

There is an increased risk of ototoxicity in patients with mitochondrial DNA mutations (particularly the 1555 A to G substitution in the 12S rRNA gene), even if aminoglycoside serum levels are within the recommended range during treatment. Alternative treatment options should be considered for these patients.

In patients with a maternal history of relevant mutations or aminoglycoside-induced deafness, alternative treatments or genetic testing should be considered before using the drug.

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

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

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

Rapid direct intravenous administration of the drug may initially result in potentially neurotoxic concentrations of gentamicin, and it is important to administer the dose at the recommended time intervals.

Cross-hypersensitivity is possible among aminoglycoside antibiotics.

During 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 breastfeeding

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

The drug penetrates into breast milk, therefore, if it is necessary to prescribe gentamicin to the mother, breastfeeding should be stopped or the drug should be discontinued.

Ability to influence reaction speed when driving vehicles or other mechanisms

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

Method of administration and doses

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

Adults and children aged 14 and over.

The usual daily dose of gentamicin for patients with moderate to severe infections is 3 mg/kg body weight intramuscularly, divided into 2-3 injections. The maximum daily dose for adults is 5 mg/kg body weight, divided into 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 extended as necessary. In such cases, it is recommended to monitor the function of the kidneys, hearing and vestibular apparatus, since the toxicity of the drug appears after its use for more than 10 days.

The dose should be calculated based on actual body weight (AWB) if the patient is not overweight (i.e. no more than 20% more than ideal body weight (BMI)). If the patient is overweight, the dose should be calculated based on the following body weight (BW) using the formula:

DMT = BMI + 0.4 (FMT – BMI).

In case of impaired renal function, the dosage regimen of the drug should be changed to ensure therapeutic adequacy of treatment. The concentration of gentamicin in the blood serum should be monitored whenever possible. 30-60 minutes after intramuscular injection, serum concentrations should be 5-10 μg/ml.

The initial single dose for patients with stable CKD is 1-1.5 mg/kg body weight, and the subsequent dose and interval between administrations should be determined depending on creatinine clearance.

Adult patients with bacterial infections undergoing dialysis should be administered the drug at a dose of 1-1.5 mg/kg body weight at the end of each dialysis.

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

For intravenous administration, the dose of the drug should be diluted with a solvent. The usual volume of solvent (sterile saline or 5% glucose solution) for adults is 50-300 ml, for children the volume 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%).

For children.

Children under 3 years of age should be prescribed gentamicin sulfate only for vital indications.

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

Children.

The drug can be used in children. Gentamicin can be prescribed to children under 3 years of age only for vital indications.

Overdose

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

Treatment: adults should be given Prozerin intravenously, as well as a 10% solution of calcium chloride or a 5% solution of calcium gluconate. Before administering Prozerin, administer atropine intravenously at a dose of 0.5-0.7 mg, wait for the pulse to accelerate, and after 1.5-2 minutes, administer 1.5 mg (3 ml of a 0.05% solution) of Prozerin intravenously. If the effect of this dose is insufficient, re-administer the same dose of Prozerin (if bradycardia occurs, give an additional injection of atropine). In severe cases of respiratory depression, artificial ventilation of the lungs is necessary. It can be removed by hemodialysis (more effective) and peritoneal dialysis.

Side effects

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

Respiratory, thoracic and mediastinal disorders: sore throat, shortness of breath.

Gastrointestinal: 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.

On the part of the kidneys and urinary system: nephrotoxicity (impaired kidney function) - oliguria, azotemia, proteinuria, microhematuria, interstitial nephritis, renal failure, in some cases - renal tubular necrosis.

From the side of metabolism: hypomagnesemia, hypocalcemia, hypokalemia, hyponatremia.

From the nervous system: headache, drowsiness, confusion, muscle twitching, paresthesia, numbness, convulsions, epileptic seizures, peripheral neuropathy, encephalopathy, neuromuscular transmission disorders.

On the part of the psyche: depression, hallucinations, in children - psychosis.

From the cardiovascular system: decreased blood pressure.

From the blood and lymphatic system: anemia, leukopenia, granulocytopenia, thrombocytopenia, eosinophilia, purpura.

On the part of the immune system: hypersensitivity reactions, including rash, itching, hyperemia, urticaria, angioedema, anaphylactic shock, development of superinfections.

General disorders and administration site reactions: general weakness, muscle pain, edema, fever, chills, increased salivation, disorders at the injection site (including hyperemia, skin induration, atrophy or necrosis of subcutaneous tissue, with intravenous administration - development of phlebitis and periphlebitis).

Expiration date

3 years.

Do not use the medicine after the expiry date stated on the packaging.

Storage conditions

Store in the original packaging at a temperature not exceeding 25 ° C. Do not freeze. Keep out of the reach of children.

Incompatibility

The drug should not be mixed with other drugs. Pharmaceutically incompatible with other aminoglycosides, amphotericin B, heparin, ampicillin, benzylpenicillin, cloxacillin, carbenicillin, capreomycin.

Packaging

2 ml in an ampoule; 5 ampoules in a contour blister pack; 2 contour blister packs in a pack.

Vacation category

According to the recipe.

Producer

PrJSC "Pharmaceutical Company "Darnitsa".

Location of the manufacturer and its business address.

Ukraine, 02093, Kyiv, Boryspilska St., 13.