Gentamicin - instructions for use, doses, side effects, contraindications

It penetrates the cell wall of microorganisms, irreversibly binds to receptors on subunits of 30 S ribosomes, violating their interaction with the information RNA. This leads to a violation of protein synthesis (sometimes to the formation of non-functional proteins), destruction of the cytoplasmic membrane, and lysis of the bacterial cell.

It works only on extracellular microorganisms. Highly sensitive to gentamycin (MIC of less than 4 mg / l) Gram-negative microorganisms - Proteus spp. (including indol-positive and indolotricative strains), Escherichia coli, Klebsiella spp., Salmonella spp ,, Shigella spp ,, Campylobacter spp., Gram-positive microorganisms - Staphylococcus spp. (including penicillin-resistant); sensitive with MPC 4-8 mg / l - Serratia spp., Klebsiella spp., Pseudomonas spp. (incl.Pseudomonas aeruginosa), Acinetobacter spp., Citrobacter spp., Providencia spp. Resistant (MIC of more than 8 mg / l) - Neisseria meningitidis, Treponema pallidum, Streptococcus spp. (including Streptococcus pneumoniae and strains of group D), Bacteroides spp., Clostridium spp., Providencia rettgeri. In combination with penicillins, it is active against Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Enterococcus avium, almost all strains of Streptococcus faecalis and their varieties (including Streptococcus faecalis liguifaciens, Streptococcus faecalis zymo genes), Streptococcus durans.

Resistance of microorganisms to gentamicin develops slowly, however, strains resistant to neomycin and kanamycin can also show resistance to gentamicin (incomplete cross-resistance). Antibacterial activity decreases in acidic medium (pH less than 7.4). Does not affect mushrooms, viruses, protozoa.

Pharmacokinetics:

After intramuscular injection absorbed quickly and completely. The time to reach the maximum concentration in plasma (TCmax) after intramuscular injection is 0.5-1.5 hours. The maximum concentration after intramuscular or intravenous administration of 1.5 mg / kg is 6 μg / ml.

The connection with plasma proteins is low (up to 10%). The volume of distribution in adults is 0.26 l / kg, in children 0.2-0.4 l / kg.

It is found in therapeutic concentrations in the liver, kidneys, lungs, in the pleural, pericardial, synovial, peritoneal, ascitic and lymphatic fluids, urine, in segregated wounds, pus, granulation.Low concentrations are found in adipose tissue, muscles, bones, bile, breast milk, watery eyes, bronchial secretion, sputum and cerebrospinal fluid (CSF).

In therapeutic concentrations in adults, almost does not penetrate the blood-brain barrier (BBB), with meningitis, its concentration in CSF increases. In newborns, higher concentrations are achieved in CSF than in adults. Penetrates through the placenta. Not exposed to metabolism. The half-life (T 1/2) in adults is 2-4 hours. It is excreted mainly by the kidneys in an unchanged form; in small quantities - with bile.

In patients with normal renal function, 70-95% is excreted in the first 24 hours, while concentrations of more than 100 μg / ml are created in the urine. In patients with reduced glomerular filtration, excretion is significantly reduced. It is excreted by hemodialysis - every 4-6 hours the concentration decreases by 50%. Peritoneal dialysis is less effective - for 48-72 hours, 25% of the dose is excreted. With repeated administration cumulates in the lymphatic space of the inner ear and in the proximal parts of the renal tubules.

Indications:Bacterial infections,caused by sensitive microflora: infections of the lower respiratory tract (including bronchitis, pneumonia, pleural empyema), complicated urogenital infections (including pyelonephritis, cystitis, urethritis, prostatitis, gonorrhea, endometritis), infections of bones and joints (in including osteomyelitis), skin and soft tissue infections, abdominal infections (peritonitis, pelvioperitonitis), central nervous system infections (meningitis, etc.), sepsis, wound infection, burn infection, otitis media.

Contraindications:Hypersensitivity (including to other aminoglycosides in anemnesis), neuritis of the auditory nerve, severe chronic renal failure with azotemia and uremia, pregnancy, lactation, neonatal period, including premature infants (due to a high risk of ototoxic and nephrotoxic action).

Carefully:Myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause disruption of neuromuscular transmission, which leads to further weakening of skeletal muscles), dehydration, renal insufficiency, and advanced age.

Dosing and Administration:

Parenteral. The daily dose for moderate diseases for adults with normal renal function is 3 mg / kg / day. Multiplicity of administration - 2-3 times a day.

In severe cases, the daily dose - 5 mg / kg, multiplicity - 3-4 times a day; after improving the condition, the dose is reduced to 3 mg / kg. Patients with infectious and inflammatory diseases of the urinary tract and normal kidney function are prescribed once a day at a dose of 120-160 mg for 7-10 days; with gonorrhea - 240-280 mg once. Children over 2 years are prescribed 3-5 mg / kg / day; multiplicity of administration - 3 times; children from 1 month. up to 2 years - 6 mg / kg with the frequency of administration 3 times a day.

Intravenously drip, for 1.5-2 hours in a 0.9% solution of NaCl or 5% dextrose solution, injected volume - 50-300 ml; in children, the volume of the injected fluid should be less (concentration should not exceed 1 mg / ml = 0.1%).

Patients with impaired renal excretory function and elderly patients, as well as with severe burn disease, need to determine the concentration of gentamicin in plasma for an adequate choice of dosing regimen. The interval between the administration of average doses of gentamicin (in hours) is determined by the formula: interval (h) = creatinine concentration (mg / 100 ml) x 8. In severe infections, it is recommended to administer smaller single doses with a higher frequency of administration; the reduction in the single dose should be a multiple of the ratio of the interval calculated according to the above formula to the value of the normal interval between administrations (8 h).The dose should be selected in such a way that Cmax does not exceed 12 μg / ml (reduced risk of developing nephro-, oto- and neurotoxicity). With edema, ascites, obesity, the dose is calculated by the "ideal" or "dry" body weight. If the kidney function is disrupted and hemodialysis is performed, the recommended dose after the adult session is 1-1.7 mg / kg (depending on the severity of the infection), children - 2-2.5 mg / kg.

Side effects:

From the digestive system: nausea, vomiting, increased activity of "liver" transaminases, hyperbilirubinemia.

On the part of the hemopoiesis: anemia, leukopenia, granulocytopenia, thrombocytopenia.

From the nervous system: twitching of muscles, paresthesia, sensation of numbness, epileptic seizures, headache, drowsiness, in children - psychosis.

From the urinary system: nephrotoxicity - a violation of kidney function (oliguria, proteinuria, microhematuria), in rare cases - renal tubular necrosis.

From the sense organs: ototoxicity - noise in the ears, hearing loss, irreversible deafness; vestibular disorders - dizziness, impaired coordination.

Allergic reactions: skin rash, itching, fever, angioedema, eosinophilia. Laboratory indicators: in children - hypocalcemia, hypokalemia, hypomagnesemia.

Other: fever, development of superinfection.

Overdose:

Symptoms: decrease in neuromuscular conduction (respiratory arrest).

Treatment: adults are injected intravenously with anticholinesterase drugs (proserin), as well as calcium preparations (calcium chloride 10% 5-10 ml, calcium gluconate 10% 5-10 ml). Before the introduction of proserine, intravenously atropine in a dose of 0.5-0.7 mg, the pulse is expected to accelerate and 1.5 mg (3 ml 0.05% solution) of prozerol is injected 1.5-2 minutes intravenously. If the effect of this dose was insufficient, re-inject the same dose of prosirin (with the appearance of bradycardia, an additional injection of atropine). Children are given preparations of calcium ions. In severe cases of respiratory depression, artificial ventilation is necessary. Can be excreted by hemodialysis (more effective) and peritoneal dialysis.

Interaction:

Pharmaceutically incompatible (it is impossible to mix in one syringe) with other medicinal products (including with others.aminoglycosides, amphotericin B, heparin, ampicillin, benzyl-penicillin, cloxacillin, capreomycin).

Increases the muscle relaxant effect of curare-like drugs.

Reduces the effect of antimiasthenic drugs.

Methoxyflurane, polymyxins for parenteral administration, and other drugs that block neuromuscular transmission (halogenated hydrocarbons as drugs for inhalation anesthesia, narcotic analgesics, transfusion of large amounts of blood with nitrate preservatives), increase the risk of nephroxia and respiratory arrest (as a result of nerve enhancement muscular blockade).

"Loop" diuretics increase oto and nephotoxicity (decrease in tubular secretion of gentamicin).

Toxicity is enhanced when co-administered with cisplatin and other oto- and nephrotoxic drugs.
Antibiotics of the penicillin series (ampicillin, carbenicillin) enhance the antimicrobial effect by expanding the spectrum of activity.

Parenteral administration of indomethacin increases the risk of toxic actions of aminoglycosides (an increase in T1 / 2 and a decrease in clearance)

Special instructions:

Patients with infectious and inflammatory diseases of the urinary tract is recommended to take an increased amount of liquid.

During treatment with gentamicin, the concentration of the drug in serum should be determined (to prevent the administration of low ineffective doses or, conversely, drug overdose), and to monitor the clearance of creatinine, especially in the elderly. The likelihood of developing nephrotoxicity is higher in patients with impaired renal function, as well as in the administration of high doses or for a long time, so regularly (1 or 2 times a week, and in patients receiving high doses or being treated for more than 10 days, every day ), kidney function should be monitored.

In order to avoid the development of hearing disorders, it is recommended to conduct audiometry regularly (1 or 2 times a week) to determine hearing loss at high frequencies (in case of unsatisfactory audiometric tests, the dose of the drug is reduced or discontinued).

The disulfite contained in ampoules of sodium can cause the development of allergic reactions in patients, especially in patients with allergic diseases.

Against the background of treatment, resistance of microorganisms can develop. In such cases, it is necessary to cancel the drug and prescribe a treatment based on the antibioticogram.

Form release / dosage:Solution for intravenous and intramuscular administration 40 mg / ml in ampoules of 1 ml or 2 ml.

Packaging:

10 ampoules are placed in a box. 5 or 10 ampoules are placed in a contour mesh package.

1, 2 contour packs are placed in a pack of cardboard. The instructions for use, the ampoule knife or the scarifier ampoule (in the case of packing ampoules with notches, rings and points for opening the ampoules or scarifiers do not put into the box and pack).

Storage conditions:List B. In a place protected from light and inaccessible to children, at a temperature of 2 to 25 ° C.

Shelf life:2 years. Do not use after the expiration date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LSR-008633/08

Date of registration:30.10.2008

Expiration Date:Unlimited

The owner of the registration certificate:PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC Russia

Manufacturer: & nbsp

PHARMSTANDART-UFIM VITAMIN FACTORY, OJSC Russia

Information update date: & nbsp23.03.2017

Illustrated instructions

Instructions

Gentamicin (Gentamicin)