Gentamycin

General characteristics. Structure:

Active ingredient: 40 g of Gentamycini sulfas (in terms of gentamycin the basis) in 1 l of solution.

Excipients: sodium of a sulfite feast (sodium disulphite), disodium salt of ethylene diamine tetraacetic acid (Trilonum of B) (эдетат dinatrium), waters for injections.

Bactericidal antibiotic of a broad spectrum of activity from group of aminoglycosides.

Pharmacological properties:

Pharmacodynamics. Communicates with 30S in subunit of ribosomes and breaks protein synthesis, interfering with formation of a complex of transport and information RNA, at the same time there is a wrong reading of RNA and formation of nonfunctional proteins. Possesses bactericidal action - in big concentration reduces barrier functions of cytoplasmic membranes and causes death of microorganisms.

Gram-negative microorganisms - Proteus spp are highly sensitive to gentamycin (MPK less than 4 mg/l). (including indolpositive and indolnegative strains), Escherichia coli, Klebsiella spp., Salmonella spp., Shigella spp., Campylobacter spp.; gram-positive microorganisms - Staphylococcus spp. (including penitsillinorezistentny); are sensitive at MPK of 4-8 mg/l - Serratia spp., Klebsiella spp., Pseudomonas spp. (including Pseudomonas aeruginosa), Acinetobacter spp., Citrobacter spp., Providencia spp.

Rezistentna (MPK more than 8 mg/l) - Neisseria meningitidis, Treponema pallidum, Strep-tococcus spp. (including Streptococcus pneumoniae and strains of group D), Bacteroides spp., Clostridium spp., Providencia rettgeri.

In a combination with the penicillin (including with benzylpenicillin, ampicillin, karbenitsilliny, Oxacillinum) operating on synthesis of a cell wall of microorganisms shows activity concerning Enterococcus faecalis, Enterococcus faecium, Enterococcus durans, Enterococcus avium, practically all strains of Streptococcus faecalis and their versions (including Str.faecalis liguifa-ciens, Str.faecalis zymogenes), Streptococcus faecium, Streptococcus durans.

Resistance of microorganisms to gentamycin develops slowly, however the strains steady against Neomycinum and Kanamycinum can show stability as well to gentamycin (incomplete cross stability). Does not affect mushrooms, viruses, the elementary.

Pharmacokinetics. After intramuscular introduction (in oil) it is soaked up quickly and completely. Time of achievement of the maximum concentration (TCmax) after introduction in oil - 0.5-1.5 h, after 30 min. intravenous (in/in) infusion - 30 min., after 60 min. in/in infusion of-15 min.; the size Cmax after in oil or in/in introductions of 1.5 mg/kg makes 6 mkg/ml.

Communication with proteins of plasma - low (to 10%). Distribution volume adult-0.26 l/kg, at children have 0.2-0.4 l/kg, at newborns aged to 1 week and with a body weight less than 1.5 kg - to 0.68 l/kg, aged to 1 week and with a body weight more than 1.5 kg - to 0:58 l/kg.

It is found in therapeutic concentration in a liver, kidneys, lungs, in pleural, pericardiac, synovial, peritoneal, ascitic and lymphatic liquids, urine, in separated wounds, pus, granulations. Low concentration are noted in fatty tissue, muscles, bones, bile, breast milk, watery moisture of an eye, a bronchial secret, a phlegm and cerebrospinal fluid (SMZh). In therapeutic concentration at adults practically does not get through a blood-brain barrier (GEB), at meningitis its concentration in SMZh increases. At newborns higher concentration in SMZh, than at adults are reached. Gets through a placenta.

Is not exposed to metabolism. An elimination half-life (T1/2) adults - 2-4 h, at children aged from 1 week up to 6 months have 3-3.5 h, newborn and premature children with body weight have more than 2 kg - 5.5 h, with body weight less than 1.5 kg - 11.5 h, to 2 kg - 8 h.

It is removed generally by kidneys in not changed look: in insignificant quantities - with bile. At patients with normal function of kidneys for the first days 70-95% are removed, at the same time in urine concentration more than 100 mkg/ml are created. At patients with reduced glomerular filtering removal considerably decreases.

It is removed at a hemodialysis - in each 4-6 h concentration decreases by 50%. Peritoneal dialysis is less effective - for 48-72 h 25% of a dose are removed.

At repeated introductions kumulirut, mainly in lymphatic space of an inner ear and in proximal departments of renal tubules

Indications to use:

The bacterial infections caused by sensitive microflora: infections of upper and lower respiratory tracts (including bronchitis, pneumonia, a pleura empyema), the complicated urogenital infections (including pyelonephritis, cystitis, an urethritis, prostatitis, gonorrhea, an endometritis), infections of bones and joints (including osteomyelitis), infections of skin and soft tissues, abdominal infections (peritonitis, a pelviperitonitis), TsNS infections (meningitis, etc.), sepsis, a wound fever, a burn infection, otitis.

Route of administration and doses:

Parenterally. The daily dose for in/in and introductions in oil at moderately severe diseases is identical to adults with normal function of kidneys - 3 mg/kg/days. Frequency rate of introduction - 2-3 times a day. In/in kapelno, during 1.5-2 h in 0.9% NaCl solution or 5% dextrose solution, the entered volume - 50-300 ml; children have to have a smaller volume of the entered liquid (concentration should not exceed 1 mg/ml of-0.1%).

At the heavy course of diseases a daily dose - 5 mg/kg, frequency rate - 3-4 times a day; after improvement of a state the dose is reduced to 3 mg/kg.

To patients with infectious and inflammatory diseases of urinary tract and normal function of kidneys appoint 1 time a day in a dose of 120-160 mg within 7-10 days; at gonorrhea - 240-280 mg once.

To children 2 years are more senior appoint 3-5 mg/kg/days; frequency rate of introduction - 3 times; premature and newborn (age less than 1 week) appoint 6 mg/kg in a daily dose; frequency rate - 2 times; to children up to 2 years - 6 mg/kg with a frequency of introduction of 3 times a day.

Patients with disturbance of secretory function of kidneys and to elderly patients, and also at a serious burn disease for the adequate choice of the mode of dosing need definition of concentration of gentamycin in plasma.

The interval between introduction of average doses of gentamycin (in hours) is determined by a formula: interval (ch) = concentration of creatinine (mg / 100 ml) x 8.

At the heavy course of infections purpose of smaller single doses with bigger frequency rate is recommended; decrease in size of a single dose has to be multiple to the relation calculated by the stated above interval formula to the size of a normal interval between introductions (8 h). The dose has to be picked up so that Cmax did not exceed 12 mkg/ml (decrease in risk of development nefro-, from - and a neurotoxicity).

At hypostases, ascites, obesity the dose is calculated on "ideal" or Sukhoi to body weight. At a renal failure and carrying out a hemodialysis the recommended doses after the session adult - 1-1.7 mg/kg (depending on weight of an infection), to children - 2-2.5 mg/kg

Features of use:

In the presence "vital" indications it can be used at pregnant women and the feeding women.
Aminoglycosides get into breast milk in small amounts. However they are poorly soaked up from digestive tract, and the related complications at babies was not registered.

The bisulphite which is contained in sodium ampoules can cause development in sick allergic complications, especially at patients with the allergological anamnesis.

Patients with infectious and inflammatory diseases of urinary tract are recommended to accept the increased amount of liquid.

During treatment it is necessary to determine by aminoglycosides concentration of drug in blood serum (for the prevention of purpose of low inefficient doses or, on the contrary, drug overdose), and also to carry out control of the clearance of creatinine (CC), especially at elderly people.

The probability of development of nephrotoxicity is higher at patients with an impaired renal function, and also at purpose of high doses or for a long time therefore regularly (1 or 2 times a week, and at the patients receiving high doses or being on treatment more than 10 days - daily) it is necessary to control function of kidneys.

In order to avoid development of a hearing disorder it is recommended regularly (1 or 2 times a week) to conduct a research of vestibular function for definition of a hearing loss at high frequencies (at unsatisfactory audiometric tests the dose of drug is reduced or stop treatment).

Against the background of treatment resistance of microorganisms can develop. In similar cases it is necessary to cancel drug and to appoint treatment on the basis of data of an antibiotikogramma.

Side effects:

From the alimentary system: nausea, vomiting, increase in activity of "hepatic" transaminases, hyperbilirubinemia.

From bodies of a hemopoiesis: anemia, leukopenia, granulocytopenia, thrombocytopenia.

From a nervous system: twitching of muscles, paresthesias, feeling of numbness, epileptic seizures, a headache, drowsiness, children have a psychosis.

From an urinary system: nephrotoxicity - a renal failure (an oliguria, a proteinuria, a microhematuria), in rare instances - a renal tubular necrosis.

From sense bodys: ototoxicity - a sonitus, decrease in hearing, vestibular and labyrinth disturbances, irreversible deafness.

Allergic reactions: skin rash, itch, fever, Quincke's edema, eosinophilia.

Laboratory indicators: children have a hypocalcemia, a hypopotassemia, a hypomagnesiemia.

Other fever, development of superinfection.

Interaction with other medicines:

Pharmaceutical it is incompatible (it is impossible to mix in one syringe) with other medicines (M) (including with other aminoglycosides, Amphotericinum In, heparin, ampicillin, a benzylpenalty fee-tsillinom, kloksatsilliny, karbenitsilliny, kapreomitsiny).

Increases myorelaxation action of kurarepodobny HP.

Reduces effect of anti-myasthenic HP.

Metoksifluran, polymyxins for parenteral administration, etc. The hp blocking neuromuscular transmission (halogenated hydrocarbons as HP for inhalation anesthesia, narcotic analgetics, transfusion of large amounts of blood with citrate preservatives), increase risk of emergence of nefroksichesky action and an apnoea (as a result of strengthening of neuromuscular blockade). "Loopback" diuretics strengthen from - and nephrotoxicity (decrease in canalicular secretion of gentamycin). Toxicity amplifies at joint appointment with Cisplatinum both др from - and нефротоксичнымн HP.

Antibiotics of a penicillinic row (ampicillin, карбенициллин) strengthen antimicrobic action due to expansion of a range of activity.

Parenteral administration of indometacin increases risk of development of toxic effects of aminoglycosides (increase Т½ and decrease in clearance).

Contraindications:

Hypersensitivity (including to other aminoglycosides in the anamnesis), neuritis of an acoustical nerve, the heavy chronic renal failure (CRF) with an azotemia and uraemia, pregnancy.

With care. A myasthenia, parkinsonism, botulism (aminoglycosides can cause neuromuscular transmission disturbance that leads to further weakening of skeletal muscles), dehydration, a renal failure, advanced age. Pregnancy and period of a lactation, newborn and premature children.

Due to the high risk of development of ototoksichesky and nephrotoxic action, drug has to be appointed only according to "vital" indications, in the absence of alternative antibacterial therapy.

Overdose:

Symptoms: decrease in neuromuscular conductivity (apnoea).

Treatment: the adult in/in enter antikholinesterazny medicines (прозерин), and also calcium drugs (Calcii chloridum of 10% 5-10 ml, calcium a gluconate of 10% 5-10 ml). Before introduction of a prozerin previously in/in enter atropine in a dose of 0.5-0.7 mg, expect increase of pulse and in 1.5-2 min. enter into 1.5 mg (3 ml of 0,05% of solution) of a prozerin. If the effect of this dose was insufficient, enter repeatedly the same dose of a prozerin (at emergence of bradycardia do an additional injection of atropine).

In hard cases of respiratory depression artificial ventilation of the lungs is necessary. It can be removed by means of a hemodialysis (is more effective) also peritoneal dialysis.

Storage conditions:

List B. In the dry, protected from light place at a temperature not above 25 °C. In the place, unavailable to children. Period of validity 2 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous and intramuscular administration of 40 mg/ml. On 2 ml in ampoules of neutral glass. On 10 ampoules place in a pack from a cardboard for a retail container with partitions or lattices, or a separator from a cardboard or paper bag.

On 10 ampoules place in a box from a cardboard. Put the application instruction, a knife in each pack or a box ampoule or the scarificator ampoule.

When using ampoules with notches, rings or points the knife ampoule or the scarificator ampoule is not put.