Gentamycin sulfate

General characteristics. Structure:

1 ml of solution contains Gentamycini sulfas in terms of gentamycin and anhydrous substance - 40 mg;

Additional substances: sodium pyrosulphite, disodium salt of ethylene diamine tetraacetic acid (Trilonum of B), water for injections.

Main physical and chemical properties: transparent colourless or subtle shade liquid.

Pharmacological properties:

Pharmacodynamics. Gentamycin is an antibiotic of group of aminoglycosides with a broad spectrum of activity. The action mechanism connected with inhibition of ribosome subunits 30S. In vitro tests confirm its activity concerning different types of gram-positive and gram-negative microorganisms: Escherichia coli, Proteus spp. (indolpositive and indolnegative), Pseudomonas aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., Citrobacter spp., Salmonella spp., Shigella spp. and Staphylococcus spp. (including penicillin and metitsilinstoyky strains). Stated below microorganisms, as a rule, resistant to gentamycin: Streptococcus pneumoniae, majority of other types of streptococci, enterococci, Neisseria meningitidis, Treponema pallidum and anaerobic bacteria, such as Bacteroides spp. or Clostridium spp.

Pharmacokinetics. Gentamycin is easily absorbed, reaching the maximum concentration in a blood plasma in 30 - 60 min. after intramuscular introduction.
Therapeutic concentration in blood remain within 6-8 hours.
At intravenous drop administration concentration of an antibiotic in a blood plasma within the first hours exceeds concentration which is reached after intramuscular use of drug. Communication with proteins makes 0 - 10%.
In therapeutic concentration is defined in tissue of kidneys, lungs, in pleural and peritoneal exudates. Normal gentamycin at parenteral administration badly passes through a blood-brain barrier, but at meningitis concentration in cerebrospinal fluid increases. Drug is emitted with breast milk.
About 70% of gentamycin are within a day excreted in not changed look in urine by means of glomerular filtering. Plasma elimination half-life makes about 2 hours. At disturbance of secretory function of kidneys concentration significantly raises and increases a gentamycin elimination half-life.

Indications to use:

Considering the limited therapeutic width of gentamycin, it should be applied when rezistentna microorganisms to safer antibiotics. Gentamycini sulfas is appointed for treatment of infections which are caused by activators, sensitive to it, including:
• a septicaemia (including neonatal sepsis);
• persistent infections of urinary tract;
• infectious diseases of the lower respiratory tracts;
• infectious diseases of skin, bones, soft tissues; the infected burn
wounds;
• infectious diseases of TsNS (including meningitis) in a combination with
-laktamnymi antibiotics;
• infections of an abdominal cavity (including peritonitis);
• the infections which are followed by diseases which break resilience
human body (leukemia, diabetes, therapy by corticosteroids, etc.). In these
cases gentamycin is, as a rule, applied in a combination with a beta laktamnymi
antibiotics.
Use of Gentamycini sulfas is shown at acute and chronic conjunctivitis, a helcoma, a keratitis, a keratoconjunctivitis, an acute and chronic iritis, an acute and chronic blepharitis, a dacryocystitis and other infectious and inflammatory diseases of eyes, and also for prevention and treatment of purulent complications after operation in the eyes.

Route of administration and doses:

Gentamycini sulfas can be applied intramusculary or intravenously.
The dose, way of introduction and intervals between introductions depend on disease severity and a condition of the patient. The dose mode is calculated, proceeding from the body weight of the patient.
At a renal failure it is necessary to change the drug dosing mode so that it guaranteed therapeutic adequacy of treatment. At each opportunity it is necessary to control concentration of gentamycin in blood serum. In 30-60 minutes after intravenous or intramuscular administration serumal concentration have to make 5-10 mkg/ml. The initial single dose for patients with a stable chronic renal failure makes from 1 to 1,5 mg/kg of body weight, further the dose and an interval between introductions are defined depending on clearance of creatinine.

Clearance of creatinine  serum Creatinine   All the subsequent                      the Interval between
 ml/min.                        of blood,                      dose % mg (% of an initial dose)    introductions, hour

                                                                                     70 1,2 100                                         8
 
                                                                         40-69 2,2-1,3 100                                         12
 
                                         30-39 3-2,3                                                                              50 8
 
                                       20-29 4,2-3,1                                                                            50 12
 
                                         15-19 6-4,3                                                                             50 16
 
                                       10-14 8,5-6,1                                                                            50 24
 
                                          5-9 12 - 8,6                                                                            50 36

To adult patients with a bacterial infection for whom dialysis is necessary appoint 1 - 1,5 mg of gentamycin to body weight kg at the end of each dialysis. At peritoneal dialysis at adults add 1 mg of gentamycin to 2 l of dialysis solution.
At intravenous administration the usual volume of solvent (sterile normal saline solution or 5% glucose) makes 50 - 300 ml for adults, for children the volume of solvent has to be respectively reduced. Duration of intravenous infusion is 1-2 hours. (Concentration of gentamycin in solution should not exceed 1 mg/ml = 0,1%)
To children: To children up to 3 years Gentamycini sulfas is appointed only according to vital indications. Daily doses make: to newborns and children of chest age - 2 - 5 mg/kg, to children age from 1 year to 5 years - 1,5 - 3 mg/kg, 6-14 years - 3 mg/kg. The maximum daily dose for children of all age groups makes 5 mg/kg. The drug is administered by 2-3 times a day.
Adult
The usual daily dose of drug for patients with the average and heavy course of infectious process makes 3 mg/kg of body weight intramusculary or intravenously, divided into 2 - 3 introductions. The maximum daily dose for adults makes 5 mg/kg of body weight, divided into 3 - 4 introductions.
The usual duration of use of drug for all patients - 7 - 10 days. At the heavy and complicated infections the course of therapy can be continued as necessary. In such cases it is recommended to exercise control of function of kidneys, hearing and a vestibular mechanism as toxicity of drug is shown after its use of more than 10 days.
Calculation of body weight to which it is necessary to appoint gentamycin.
The dose is calculated on the actual body weight (ABW) if the patient has no excess weight (that is in addition no more than 20% to the ideal body weight (IBW)). If the patient has excess weight, the dose is calculated on such body weight (DMT) on a formula:
DMT = IMT + 0,4 (FMT - IMT).

Features of use:

At patients with diseases of kidneys it is regularly necessary to control serumal concentration of gentamycin and function of kidneys, and also hearing.
Symptoms of a renal failure or damage of a hearing or vestibular mechanism demand the therapy termination by gentamycin or, in exceptional cases, only corrections of its dose.
Gentamycini sulfas should be applied with care at patients with dehydration, botulism, parkinsonism or a hypocalcemia, and also at patients of advanced age.
Patients with diseases of kidneys, a hearing loss, dizziness or a sonitus are especially sensitive to gentamycin.
Due to the brief clinical experience introduction of all daily dose of Gentamycini sulfas at such states is not recommended:
• burns more than 20%;
• цистофиброз;
• ascites;
• endocarditis;
• a chronic renal failure using a hemodialysis;
• sepsis.
At prolonged use the dose of drug has to be such which would provide the level of concentration of gentamycin in blood which does not exceed the most admissible. For this purpose at the patients carried to risk group during treatment it is necessary to control the level of concentration of gentamycin in blood.
Period of pregnancy and lactation. At appointment gentamycin can exert pregnant women an adverse effect on a fruit (ototoxicity) in this connection gentamycin is appointed to pregnant women only according to vital indications.
At pregnancy drug gets through a blood-brain barrier and into amniotic liquid.
When feeding the child breast milk and simultaneous need of appointment according to indications of Gentamycini sulfas of mother it is necessary or to stop feeding by a breast, or to cancel this antibiotic. Influence on ability to drive the car. There are no data on influence on ability to drive the car or mechanisms. However Gentamycini sulfas in high doses can cause disturbance of balance which is followed by nausea and dizziness, even after treatment cancellation in some patients.

Side effects:

Ototoxicity (damage of the eighth couple of cranial nerves): decrease in auditory acuity and damage of a vestibular mechanism (at symmetric damage of a vestibular mechanism these disturbances in certain cases at the first stages can even be unnoticed) can develop. The extra risk can cause the prolonged course of treatment gentamycin - 2 - 3 weeks.
Nephrotoxicity: frequency and severity of injuries of kidneys depend on the size of a single dose, duration of treatment and specific features of the patient, quality of control over therapy and a concomitant use of other nephrotoxic medicines. Damage of kidneys is shown by a proteinuria, an azotemia, is more rare - an oliguria, and, as a rule, has the return character.
Other side effects which are noted seldom: increase in level of serumal transaminases (ALT, ACT), bilirubin, reticulocytes, and also thrombocytopenia, a granulocytopenia, anemia, decrease in level of calcium in serum, skin rashes, urticaria, an itch, fever, a headache, vomiting, muscular pain. Very seldom there are such side effects: nausea, the raised slyunovydeleniye, appetite loss, loss of weight, purple, throat hypostasis, a joint pain, hypotension and drowsiness, are possible blockade of neuromuscular conductivity and respiratory depression.
In the place of intramuscular administration of gentamycin morbidity is possible, at intravenous administration - development of phlebitis and periphlebites.

Interaction with other medicines:

It is necessary to avoid co-administration with strong diuretics (furosemide, Acidum etacrynicum) as the last can strengthen ototoksichesky and nephrotoxic effects. Emergence of dysfunctions of breath is possible
owing to neuromuscular blockade at patients to whom along with gentamycin muscle relaxants (сукцинилхолин, tubocurarine, dekametony), anesthetics and the previous massive hemotransfusion with citrate anticoagulant are appointed.
Use of salts of calcium and antikholinesterazny means can eliminate the phenomena of neuromuscular blockade.
It is necessary to avoid simultaneous and/or consecutive system or topical administration of other neurotoxic and/or nephrotoxic means, such as Cisplatinum, Cefaloridinum, aminoglikozidny antibiotics, polymyxin B, colistin, Vancomycinum.
The risk of a renal failure increases at simultaneous use together with gentamycin of indometacin and other nonsteroid antiinflammatory medicines, and also quinidine, Cyclophosphanum, ganglioblokator, verapamil, Polyglucinum. Gentamycin increases toxicity of digoxin.
At simultaneous administration of aminoglycosides and penicillin the elimination half-life decreases and their content in blood serum decreases.
Decrease in an elimination half-life happens at patients to the expressed renal failures at the combined use of a karbenitsilin with gentamycin.
When mixing in one volume of aminoglycosides with antibiotics r-laktamnoy groups (penicillin, cephalosporins) the mutual inactivation is possible. Also pharmaceutical it is incompatible with Amphotericinum, heparin.

Overdose:

In case of overdose or at emergence of toxic reactions with signs or symptoms of nephrotoxicity or ototoxicity and neuromuscular blockade with respiratory insufficiency removal of gentamycin from a blood plasma can be promoted by a hemodialysis, at peritoneal dialysis the speed of removal of drug is much lower. At newborns carrying out exchange hemotransfusion is possible.

Storage conditions:

To store in protected from light and the place, unavailable to children, at a temperature from +15 °C to + 25 °C. A drug period of validity - 2 years. Not to use drug after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 2 ml in ampoules, on 10 ampoules in a box.