Gentamycini sulfas

General characteristics. Structure:

Active agent - Gentamycini sulfas (in terms of gentamycin) - 80,0 mg.

Excipients: sodium metabisulphite, dinatrium эдетат, water for injections.

Pharmacological properties:

Pharmacokinetics. The drug is administered intramusculary or intravenously. It is quickly and completely soaked up at intramuscular introduction. After intramuscular introduction of Gentamycini sulfas peak plasma concentration are reached within 30 - 60 minutes, concentration can be defined in plasma from 6 to 12 hours. Linkng of gentamycin with proteins of plasma low from 0 to 30%. Gets into plasma, a lymph, fabrics, a phlegm, pleural, synovial and peritoneal liquids and through a placental barrier. Concentration in cortical substance of kidneys can sometimes surpass by eight times usual levels in plasma. In bile low concentration are defined that confirms insignificant removal of gentamycin with bile. Badly gets through a blood-brain barrier. Concentration of gentamycin in cerebrospinal fluid low also depend on a dose, the speed of penetration and expressiveness of a meningeal inflammation. Gentamycin can collect in plasma and tissues of patients at introduction of high doses for a long time, especially at a renal failure or at an underdevelopment of kidneys. As gentamycin is distributed in extracellular liquid, peak plasma concentration at patients with large volumes of extracellular liquid can be lower, than usually. Removal of gentamycin depends on post-natal age and clearance of creatinine. With increase in post-natal age and increase in a maturity of kidneys gentamycin is removed more quickly. Metabolic changes of gentamycin are minimum, removal happens by glomerular filtering. In several days of therapy the amount of the removed gentamycin is brought closer, but is not equal to quantity of the entered dose. A small part of the entered dose of gentamycin can remain in fabrics, in particular in kidneys. At some patients aminoglycosides were defined in insignificant quantity in urine in several weeks after the end of therapy. The renal clearance of gentamycin is similar to clearance of endogenous creatinine. It is not metabolized. About 90% of gentamycin are removed in not changed look by kidneys by means of glomerular filtering.

At adults the elimination half-life at normal function of kidneys makes 2-4 hours, at an impaired renal function – till 100 o'clock depending on extent of disturbance; at newborns at the age of less than 3 days about 10% of the entered dose it is removed in 12 hours, at children aged from 5 up to 40 days about 40% are removed. At the increased temperature and anemia the elimination half-life can be shortened. Dose adjustment usually is not required. At patients with heavy burns the elimination half-life can decrease considerably, causing decrease in plasma concentration  in comparison with expected when dosing in body weight mg/kg.

With urine it is removed - 70–95% of gentamycin and a small amount - with bile.

At patients with a heavy renal failure decrease in concentration of gentamycin in urine and its penetration into the struck parenchyma of kidneys is observed. It leads to decrease in removal of drug and increase in risk of nephrotoxic effect of aminoglycosides that it is necessary to take into account at treatment of patients with infections of urinary tract.

Pharmacodynamics. Gentamycini sulfas – an antibiotic of a broad spectrum of activity from group of aminoglycosides, antibacterial agent for topical and parenteral administration. Actively getting through a cellular membrane of bacteria, it is irreversible communicates with 30S in subunit of bacterial ribosomes and by that activator protein synthesis oppresses. Gentamycin has bactericidal effect concerning many gram-positive and gram-negative microorganisms, including so-called "steady microbes", resistant to other antibiotics. It is active concerning a wide number of pathogenic bacteriums, including Escherichia coli, Proteus spp., Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., Citrobacter spp., Staphylococcus spp. (including the strains steady against penicillin and Methicillinum).

Neisseria meningitides, Treponema pallidum, some strains of Streptococcus spp are steady against gentamycin., anaerobic bacteria. Does not affect mushrooms, viruses, the elementary.

Indications to use:

- lower respiratory tract infections, bronchitis, pneumonia, pleurisy, pleura empyemas;

- infections of the central nervous system, including meningitis, as a part of complex therapy;

- the heavy complicated infections of uric ways, pyelonephritis, cystitis, an urethritis, prostatitis;

- bacterial septicaemia, sepsis;

- acute cholecystitis, cholangitis, peritonitis;

- purulent infections of skin and soft tissues, burn infection;

- infections of bones and joints.

Route of administration and doses:

Gentamycini sulfas is entered intramusculary or intravenously (kapelno). The mode of dosing is set individually taking into account the body weight of the patient.

Adult: 3 mg/kg/days, at heavy infections - 5 mg/kg/days (to about 80 mg there are each 8 hours). The average duration of treatment – 6-7 days, as much as possible – 10 days. The recommended doses are identical both for intramuscular, and for intravenous administration.

Solution for injections of Gentamycini sulfas cannot be mixed with other drugs, it is necessary to enter separately according to ways of introduction and the mode of dosing.

Maximum single dose: 160 mg (for patients with normal function of kidneys). Maximum daily dose: 5 mg/kg/days.

To children up to 3 years drug is appointed only according to vital indications at heavy infections. A dosage for children of various age taking into account body weight: to children of chest age and newborns: 2 - 5 mg/kg/days, frequency rate of introduction 2 times a day; to children 3 years are more senior: a daily dose of 3 - 5 mg/kg, frequency rate of introduction 3 times a day.

At a renal failure correction of the mode of dosing is required. Whenever possible it is necessary to carry out control of gentamycin level in plasma.

Intravenous administration. Doses are same, as for intramuscular introduction. The usual volume of solvent (sterile normal saline solution or 5% glucose solution) makes 100-200 ml for adults; for children the volume of solvent has to be reduced in proportion. Concentration of Gentamycin in solution should not exceed 1 mg/ml (0.1%). Solution is entered in the form of slow infusion within 1-2 hours. In the syringe Gentamycini sulfas cannot be mixed with any other medicine.

Features of use:

Whenever possible carry out monitoring of plasma concentration of gentamycin. Increase in an interval between introductions can be required. In view of the fact that concentration of creatinine of plasma have close correlation with a gentamycin elimination half-life, laboratory tests on creatinine can serve as the management for establishment of an interval between introductions.

At use of drug it is necessary to control functions of kidneys, acoustical and vestibular devices.

It is necessary to be careful at patients with dehydration, a hypocalcemia, at patients of advanced age.

It is not recommended for treatment of not hospital pneumonia both in out-patient, and in stationary conditions.

To children up to 3 years only according to vital indications at heavy infections.

Considering side effects of drug it is necessary to be careful at control of motor transport or potentially dangerous mechanisms.

Side effects:

- a headache, drowsiness, disturbance of neuromuscular conductivity, muscular pains, spasms, vestibular frustration, decrease in hearing, in certain cases – irreversible deafness;

- nausea, vomiting, appetite loss;

- increase in activity of hepatic transaminases, hyperbilirubinemia;

- anemia, leukopenia, granulocytopenia, thrombocytopenia;

- oliguria, proteinuria, microhematuria;

- renal failure;

- skin rash, an itch, a small tortoiseshell, fever, sometimes – a Quincke's edema.

In rare instances:

- tubular necrosis;

- acute anaphylaxis;

- morbidity in the place of intramuscular introduction;

- phlebitis and thrombophlebitises at intravenous administration.

Interaction with other medicines:

It is necessary to take into account a possibility of development of neuromuscular blockade and paralysis of breath at any way of administration of aminoglycosides at the patients receiving the anesthetics or means causing neuromuscular blockade such as сукцинилхолин, tubocurarine, dekametony, and also at patients to whom massive transfusions of a citrated blood are carried out. At approach of neuromuscular blockade enter calcium salts. Simultaneous or subsequent system or topical administration of other potentially neurotoxic or nephrotoxic drugs, such as Cisplatinum, Cefaloridinum, Kanamycinum, amikacin, Neomycinum, polimiksin-V, colistin, паромомицин, streptomycin, Tobramycinum, Vancomycinum and Viomycinum is not recommended. At simultaneous use of a hydrocortisone and indometacin nephrotoxic effect of gentamycin can amplify. 

It is not necessary to apply along with furosemide and Acidum etacrynicum because strengthening of ototoksichesky action is possible. Besides, at intravenous use of diuretics change of concentration of an antibiotic in plasma and fabrics is possible that leads to strengthening of the toxic reactions caused by aminoglycosides.

At the patients with a heavy renal failure receiving at the same time карбенициллин and gentamycin, decrease in an elimination half-life of gentamycin from plasma was observed.

Pharmaceutical it is incompatible with a beta laktamnymi antibiotics, heparins, Amphotericinum.

Contraindications:

- hypersensitivity to components of drug and other antibiotics of group of aminoglycosides;

- neuritis of an acoustical nerve;

- diseases of a vestibular mechanism;

- heavy renal failures, uraemia;

- pregnancy and period of a lactation;

- myasthenia, parkinsonism;

- azotemia;

- children's age up to 3 years.

Overdose:

Symptoms: nausea, vomiting, increase in activity of hepatic transaminases, a hyperbilirubinemia, anemia, a leukopenia, a granulocytopenia, thrombocytopenia, an oliguria, a proteinuria, a microhematuria, a renal failure, a headache (migraine), drowsiness, disturbance of neuromuscular conductivity, vestibular frustration, irreversible deafness, skin rash, an itch, a small tortoiseshell, fever, sometimes – a Quincke's edema.

Treatment: it is necessary to cancel drug, for removal of gentamycin from the circulating blood the hemodialysis, especially can help with cases when function of kidneys is broken. Extent of removal of gentamycin from an organism at peritoneal dialysis is significantly lower, than at a hemodialysis.

Storage conditions:

To store in the place protected from light, at a temperature not above 30 °C .

To store in the place, unavailable to children!

Issue conditions:

According to the recipe

Packaging:

On 2 ml in ampoules. On 5 or 10 ampoules pack into a blister strip packaging from a polyvinyl chloride film. On 10 ampoules place in a box from a cardboard. Boxes with ampoules or planimetric packagings together with instructions on a medical use in the state and Russian languages place in boxes from a cardboard.