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

Active substance: Gentamycin sulfate in terms of gentamicin base - 40 mg, Excipients: sodium disulphite -3.2 mg, disodium edetate dihydrate 0.1 mg, water for injection up to 1 ml.

Description:Colorless transparent liquid.

Pharmacotherapeutic group:Antibiotic, aminoglycoside

ATX: & nbsp

J.01.G.B.03 Gentamicin

Pharmacodynamics:

Bactericidal broad-spectrum antibiotic from the group of aminoglycosides. It binds to the 30S subunit of the ribosomes and disrupts protein synthesis, preventing the formation of a complex of transport and information ribonucleic acids, with an erroneous reading of the genetic code and the formation of non-functional proteins. Has bactericidal action - in high concentrations reduces the barrier functions of cell membranes and causes the death of microorganisms. Highly sensitive to gentamycin (minimum inhibitory concentration less than 4 mg / l), gram-negative microorganisms - Proteus spp. (including indol-positive and indolotricate strains), Escherichia coli, Klebsiella spp., Salmonella spp., Shigella spp., Campylobacter spp .; gram-positive microorganisms - Staphylococcus spp. (including penicillin-resistant); sensitive at a minimum inhibitory concentration of 4-8 mg / l - Serratia spp., Klebsiella spp., Pseudomonas spp. (incl.Pseudomonas aeruginosa), Acinetobacter spp., Citrobacter spp., Providencia spp. Resistant (the minimum suppressive concentration is 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 (including benzylpenicillin, ampicillin, carbenicillin, oxacillin), acting on the synthesis of the cell wall of microorganisms, shows activity against Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Enterococcus avium, almost all strains of Streptococcus faecalis and their varieties (including Streptococcus faecalis liguifaciens, Streptococcus faecalis zymogenes), Streptococcus faecium, 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). Does not affect mushrooms, viruses, protozoa.

Pharmacokinetics:

After intramuscular (IM) or intravenous (IV) administration, therapeutic concentrations in the blood are created after about 0.5-1.5 hours and persist for 8-12 hours.

Absorption when taken orally - low (almost not absorbed, therefore only applied parenterally). After the / m introduction is absorbed quickly and completely. The time to reach the maximum concentration in the plasma after the / m administration is 0.5-1.5 h, after 30 min IV infusion - 30 min,after 60 min IV infusion - 15 min; the maximum plasma concentration after IM or IV injection 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, in newborns under the age of 1 week and in body weight less than 1.5 kg - up to 0.68 l / kg, in age to 1 week and a body weight of more than 1.5 kg - up to 0.58 l / kg. It is found in therapeutic concentrations in the liver, kidneys, lungs, 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.

In therapeutic concentrations in adults, almost does not penetrate the blood-brain barrier, with meningitis, its concentration in the cerebrospinal fluid increases. Newborns have higher concentrations in the cerebrospinal fluid than in adults. Penetrates through the placenta.

Not exposed to metabolism. The half-life of the drug in adults is 2-4 hours, in children from 1 week to 6 months - 3-3.5 hours, in newborns and premature babies with a body weight of more than 2 kg - 5.5 hours, with a body weight less than 1.5 kg - 11.5 h, up to 2 kg - 8 h.

It is excreted mainly by the kidneys in 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, mainly in the lymphatic space of the inner ear and in the proximal sections of the renal tubules.

Indications:Bacterial infections caused by gentamicin-sensitive microorganisms: upper and lower respiratory tract infections (including bronchitis, pneumonia, pleural empyema), complicated urogenital infections (including pyelonephritis, cystitis, urethritis, prostatitis, gonorrhea, endometritis), bone infections and joints (including osteomyelitis), skin and soft tissue infections, abdominal infections (peritonitis, pelvioperietitis), central nervous system infections (including meningitis), sepsis, wound infection, burn infection, otitis media.

Contraindications:Hypersensitivity to gentamycin (including other aminoglycosides in the anamnesis), neuritis of the auditory nerve, severe chronic renal failure with azotemia and uremia, newborns (up to 1 month).

Carefully:Myasthenia, parkinsonism, botulism (aminoglycosides can cause a breakdown of the neuromuscular transmission, which leads to further weakening of the skeletal muscles), dehydration, renal insufficiency, prematurity of children, advanced age, pregnancy, lactation.

Pregnancy and lactation:

In the presence of "vital" evidence can be used in pregnant and lactating women.

In pregnancy and during lactation apply only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby.

Dosing and Administration:

Parenteral. The daily dose for intravenous and / or intramuscular injection for moderate to severe diseases is the same for adults with normal renal function - 3 mg / kg / day.Multiplicity of administration - 2-3 times a day. In / in the drip, for 1.5-2 hours in a 0.9% solution of sodium chloride or 5% solution of dextrose, 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%).

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. Preterm infants - 6 mg / kg / day, multiplicity of administration - 2 times; children from 1 month. up to 2 years - 6 mg / kg / day, multiplicity of administration - 3 times; Children over 2 years are prescribed 3-5 mg / kg / day, the frequency of administration is 3 times.

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.

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 medium doses of gentamicin (in hours) is determined by the formula: interval (h) = creatinine concentration (mg / 100 ml) x 8.

In severe infections, the recommended use of smaller single doses with a higher multiplicity; decrease in the single doseshould be a multiple of the ratio calculated from the above formula of the interval to the value of the normal interval between administrations (8 h). The dose should be selected in such a way that the maximum concentration in the plasma does not exceed 12 μg / ml (reduced risk of nephro-, oto- and neurotoxicity).

With edema, ascites, obesity, the dose is determined by the "ideal" or "dry" mass of the body. 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.

From the hematopoiesis: 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 - renal dysfunction (oliguria, proteinuria, microhematuria), renal tubular necrosis.

From the sense organs: ototoxicity - noise in the ears, hearing loss, vestibular and labyrinthine disorders, irreversible deafness. Allergic reactions: skin rash, itching, fever, angioedema, eosinophilia.

Laboratory indicators: in children - hypocalcemia, hypokalemia, hypo-magnesium.

Other: fever, development of superinfection.

Overdose:

Symptoms: decrease in neuromuscular conduction (respiratory arrest).

Treatment: adult intravenously injected cholinesterase inhibitors (neostigmine methyl sulfate), as well as calcium preparations (calcium chloride 10% 5-10 ml, calcium gluconate 10% 5-10 ml). Before the introduction of neostigmine methyl sulfate, pre-IV injection 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 neostigmine methyl sulfate is injected 1.5-2 minutes later. If the effect of this dose is insufficient, re-inject the same dose of methyl isosulfate neostigmine (with the appearance of bradycardia, an additional injection of atropine). Children are given calcium preparations. In severe cases of respiratory depression, artificial ventilation is necessary. Can be excreted by hemodialysis (more effective) and peritoneal dialysis.

Interaction:

Pharmaceutically compatible (can not be mixed in the same syringe) with other drugs (including with others. Aminoglycosides, amphotericin B, heparin, ampicillin, benzylpenicillin, cloxacillin, carbenicillin, capreomycin).

Increases the muscle relaxant effect of curare-like medicines.

Reduces the effect of antimiasthenic drugs.

Methoxyflurane, polymyxins for parenteral administration, and other drugs that block neuromuscular transmission (halogen-ized hydrocarbons as medicaments for inhalation anesthetic, narcotic analgesics, transfusion of large amounts of blood to citrate preservatives), increase the risk of nefroksicheskogo action and respiratory arrest ( as a result of increased neuromuscular blockade).

"Loop" diuretics increase oto and nephrotoxicity (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 the half-life of the drug and a decrease in clearance).

Special instructions:

In the presence of "vital" evidence can be used in pregnant and lactating women.

Aminoglycosides penetrate into breast milk in small amounts. However, they are poorly absorbed from the gastrointestinal tract, and complications associated with them in infants have not been reported. The sodium bisulfite contained in the ampoules of sodium can cause the development of allergic complications in patients, especially in patients with allergic anamnesis.

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

During treatment with aminoglycosides, the serum concentration of the drug 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 probability of developing nephrotoxicity is higher in patients with impaired renal function, as well as in appointments in 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 - daily), kidney function should be monitored.

In order to avoid the development of hearing impairment, it is recommended that a vestibular function be performed regularly (1 or 2 times a week) to determine hearing loss at high frequencies (in poor audio metric tests, the dose of the drug is reduced or discontinued).

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.

Effect on the ability to drive transp. cf. and fur:Care must be taken when managing vehicles, mechanisms and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:Solution for intravenous and intramuscular injection 40 mg / ml.

Packaging:

2 ml of the drug into neutral glass ampoules.

Each label is labeled with label paper or writing paper, or self-adhesive, or the label text is applied to the ampoule by gravure printing with a fast-fixing ink.

5 ampoules are placed in a contiguous cell pack of a polyvinylchloride film without coating.

1 or 2 contour squares are placed in a pack of cardboard for consumer packaging or cardboard chromium-ersatz waste.

5,10 ampoules are placed in a pack of cardboard for consumer packaging or cardboard chromium-ersatz recycled paper with baffles or gratings, or a paperboard separator for consumer packaging or cardboard, chromium-ersatz recycled paper, or paper bag.

10 ampoules are placed in a box of cardboard for consumer packaging or cardboard chromium-ersatz recycled paper and with a liner of paper paste. A box is pasted with a label - a parcel of paper label or coated.

Each instruction pack or box is supplied with instructions for use, an ampoule knife or ampoule scarifier.

In the case of using ampoules with incisions, rupture rings or break points, the ampoule opener or ampoule ampoule opener is not inserted.Boxes and bundles are placed in a group package.

Storage conditions:In a place protected from light, inaccessible to children, at a temperature not exceeding 25 ° С.

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

Terms of leave from pharmacies:On prescription

Registration number:LS-001914

Date of registration:09.08.2011 / 02.10.2015

Expiration Date:Unlimited

The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Information update date: & nbsp23.03.2017

Illustrated instructions

Instructions

Gentamicin (Gentamicin)