Гентамицин®-К

General characteristics. Structure:

Active ingredient: 80,0 mg of Gentamycini sulfas in 2 ml of solution.

Excipients: methylparahydroxybenzoate, propilparagidro-xybenzoate, dinatrium эдетат, sodium hydrosulphite, water for injections.

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

Pharmacological properties:

Pharmacodynamics. The antibiotic 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 a genetic code and formation of nonfunctional proteins.

Drug has bactericidal effect concerning many gram-positive and gram-negative microorganisms, including Pseudomonas aeruginosa, Escherichia coli, Enterobacter spp., Proteus spp., Klebsiella spp., Serratia spp., Citrobacter spp., Providencia spp., Campylobacter pylori, Campylobacter jejuni, Salmonella spp., Shigella spp., Francisella tularensis, Acinetobacter calcoaceticus, Aeromonas spp., etc. Affects Staphylococcus strains зрр., steady against penicillin. Resistance of microorganisms develops slowly, however the strains steady against Neomycinum and Kanamycinum are steady as well against gentamycin (cross stability). Drug does not work on anaerobe bacterias, mushrooms, viruses, the elementary.

Pharmacokinetics. Absorption. Gentamycin is quickly absorbed after intramuscular introduction. The maximum plasma concentration at intramuscular introduction of 80 mg of gentamycin makes 7 mkg/ml in 0,5 - 2 hours. Optimum maximum concentration in plasma makes from 7 to 10 mkg/ml. After an intramuscular injection of drug therapeutic concentration in blood remains within 6-8 hours. Distribution. Communication with proteins of plasma low (25%). In therapeutic concentration at adult patients gentamycin at parenteral administration badly gets through гемато an entsefalichesky barrier; at meningitis its concentration in cerebrospinal fluid increases.

Gentamycin is found in therapeutic concentration in tissue of a liver, kidneys, lungs, in exudates of pleural and peritoneal cavities, ascitic and lymphatic liquids, urine, in separated wounds, pus, granulations. Gets through a placenta. Metabolism and removal. Gentamycin is not exposed to metabolism, in biologically active form is removed preferential by kidneys, in insignificant quantities - with bile. The elimination half-life makes from 1,5 to 5,5 hours, 1 hour - at teenagers. The clearance of gentamycin normal makes 60 ml/min. Removal of gentamycin decreases at a renal failure. 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 infectious and inflammatory diseases caused by sensitive gram-negative aerobic bacteria:

• sepsis, meningitis, peritonitis, an endocarditis (usually in combination with a beta laktamnymi antibiotics);
• abdominal infections: abscesses of abdominal organs, a cholangitis (usually in combination with metronidazole or clindamycin);
• infections of urinary tract;
• consecutive infections at burns, injuries and surgical interventions;
• tularemia;
• infections of a respiratory organs (pneumonia,  pleura empyema, lung abscess);
• prevention of postoperative infections of an abdominal cavity, especially at urinary tract and  intestines operations.

Route of administration and doses:

 The drug is administered intramusculary and intravenously.
Dosing for patients with normal function of kidneys:
Usually daily dose at adults at diseases of moderate severity
makes Zmgkg, frequency rate of introduction - 2 - 3 times a day. At a severe disease a daily dose - 5 mg/kg, frequency rate of introduction 3-4 times a day; after improvement of a state the dose is reduced to 3 mg/kg/days. The maximum daily dose - 5 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. At single intravenous administration of a daily dose of gentamycin time of introduction has to make 30-60 minutes. At 2-Zkh multiple administration of gentamycin: concentration it in serum before the following introduction should not exceed 2 mkg/ml, at single introduction - it is not higher than 1 mkg/ml. The average duration of treatment is 7-10 days.

To children from 1 month to 12 years appoint intramusculary or intravenously in a dose of 6 mg/kg/days in 1-3 receptions.

To children 12 years are more senior: intramusculary or intravenously - 2-5 mg/kg/days in 1-3 receptions. Prevention of postoperative infections of an abdominal cavity: at surgical intervention on intestines the single dose of gentamycin in combination with metronidazole or clindamycin is appointed.

Gentamycin dosage at patients with an impaired renal function. At a renal failure the scheme of administration of gentamycin is adjusted by reduction of a dose or lengthening of intervals between introductions. In this case the single dose of drug for patients with body weight higher than 60 kg makes 1 mg/kg, it is less than 60 kg - 0,8 mg/kg.

For calculation of intervals between administrations of drug by the patient with disturbance of secretory function of kidneys the following formula can be recommended: an interval between introductions (in hours) = concentration of creatinine in blood serum (mg / 100мл) h8.

Urea		Clearance of creatinine		Serumal creatinine		Doses and intervals between doses
mg / 100 ml	mmol/l	ml/min.	ml / with	mg / 100 ml	µ¼«½ý/l
<40	<6.8	> 70	> 1.16	<1.4	<124	80 mg*kazhdy 8 hours
40-100>	6.8-17>	30-70	0.5-1.16	1.4-1.9	124-168	80 mg*kazhdy 12 hours
				1.9-2.8	168-248	80 mg*kazhdy 18 hours
100-200	17-34	10-30	0.16-0.5	2.8-3.7	248-327	80 mg * each 24 hours
				3.7-5.3	327-169	80 mg*kazhdy 36 hours
> 200	> 34	5-10	0.08-0.16	5.3-7.2	469-636	80 mg*kazhdy 48 hours

* 60 mg, gentamycin if body weight makes less than 60 kg.
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. 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 thus 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 defined 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. At intravenous administration of gentamycin: ampoule contents (1 or 2 ml of solution for injections) should be dissolved in 100 ml or 200 ml of sterile normal saline solution or sterile 5% of solution of glucose. Concentration of gentamycin in solution should not exceed 1 mg/ml. To enter intravenously kapelno within 30-60 minutes.

Urea		Clearance of creatinine		Serumal creatinine		Doses and intervals between doses
mg / 100 ml	mmol/l	ml/min.	ml / with	mg / 100 ml	µ¼«½ý/l
<40	<6.8	> 70	> 1.16	<1.4	<124	80 mg*kazhdy 8 hours
40-100	6.8-17	30-70	0.5-1.16	1.4-1.9	124-168	80 mg*kazhdy 12 hours
				1.9-2.8	168-248	80 mg*kazhdy 18 hours
100-200	17-34	10-30	0.16-0.5	2.8-3.7	248-327	80 mg * each 24 hours
				3.7-5.3	327-169	80 mg*kazhdy 36 hours
> 200	> 34	5-10	0.08-0.16	5.3-7.2	469-636	80 mg*kazhdy 48 hours

Features of use:

 With care: a myasthenic syndrome, Parkinson's disease, botulism (can cause disturbance of neuromuscular conductivity), a hypopotassemia, a renal failure, dehydration, advanced age, existence in the anamnesis of an allergy or bronchial asthma.

Gentamitsin-K contains parahydroxybenzoate, sodium bisulphite which, especially in the presence in the anamnesis of an allergy or bronchial asthma, can cause reactions of the delayed type (contact dermatitis, etc.), in rare instances - urticaria, an anaphylaxis, a bronchospasm. At their emergence drug is cancelled. Patients with an infectious vospalitelnvsh diseases of urinary tract are recommended to accept the increased amount of liquid at an adequate diuresis. During treatment it is necessary to determine by aminoglycosides concentration of drug in blood serum, and also to carry out control of clearance of creatinine, especially at elderly people.

The probability of development of nephrotoxicity is higher at patients with the broken renal function, and also at appointment a long time of high doses of drug therefore it is regularly necessary to control function of kidneys (1 or 2 times a week), and at patients more than 10 days which were on treatment - daily. In order to avoid development of a hearing disorder it is recommended regularly (1 or 2 times a week) to conduct researches of vestibular function and hearing, to control function of kidneys, and also to define concentration of gentamycin in blood. In case of identification of symptoms of decrease in hearing - the dose of drug is reduced or stop treatment.

Against the background of long therapy resistance of microorganisms can develop, in this case it is necessary to cancel drug.

Use of once daily dose is not recommended to patients: with a neutropenia, with severe damages of kidneys, with cystous fibrosis, with abscesses, an infectious endocarditis, massive burns (more than 20% of a surface of skin).

During pregnancy drug is contraindicated. In need of use in the period of a lactation it is necessary to stop breastfeeding.

Influence on psychophysical activity was not noted. In some cases passing disturbance of balance can develop. This state can proceed also after drug withdrawal what it is necessary to warn the patient about.

Side effects:

From an urinary system: nephrotoxic action (a proteinuria, a microhematuria, an azotemia less often - an oliguria). The specified effect of drug is noted more often at patients with an impaired renal function. In rare instances - a renal tubular necrosis.

From sense bodys: ototoksichesky effect: vestibular and labyrinth disturbances, decrease in hearing, sonitus, irreversible deafness. Vision disorders are in rare instances possible.

From a nervous system: headache, paresthesias, twitching of muscles, feeling of numbness, epileptic seizures, drowsiness; a rare complication is blockade of neuromuscular conductivity and respiratory depression; at children psychoses.

From the alimentary system: nausea, vomiting, hyperbilirubinemia, increase  in activity of "hepatic" transaminases of blood, diarrhea (pseudomembranous colitis).

From cardiovascular system: heartbeat.

From system of a hemopoiesis: granulocytopenia, neutropenia, leukopenia, thrombocytopenia, anemia.

Other laboratory indicators: hypopotassemia, hypocalcemia, hypomagnesiemia, proteinuria, increase in levels of urea, creatinine.
Allergic reactions: skin rashes, itch, Quincke's disease, eosinophilia, bronchospasm, anaphylactic reaction.

Others: fervescence, weakness, development of superinfection, in isolated cases can develop passing disturbance of balance.

Interaction with other medicines:

Pharmaceutical it is incompatible (it is impossible to mix in one syringe) with other medicines (including with other aminoglycosides, Amphotericinum In, heparin, ampicillin, benzylpenicillin, kloksatsilliny, karbenitsilliny, kapreomiotsiny).

Due to the broad spectrum of activity gentamycin is often appointed at multi-infection, and also in cases if the activator is not installed (usually in combination with semi-synthetic penicillin - ampicillin, karbenitsilliny, etc.). At simultaneous or consecutive use with others from - and nephrotoxic drugs (with other aminoglycosides), "loopback diuretics" and indometacin, cyclosporine, Cisplatinum, clindamycin, piperatsilliny, metoksiflurany, foskarnety and intravenous forms of X-ray contrast substances the risk of development of damage of kidneys, hearing and a vestibular mechanism increases.

Polymyxins for parenteral administration and other medicines blocking neuromuscular transmission (halogenated hydrocarbons as medicine for inhalation anesthesia, narcotic analgetik, transfusion of a large amount of blood with citrate preservatives), increase risk of emergence of nefrotoksicheky action and an apnoea (as a result of strengthening of neuromuscular blockade). The effect of anti-myasthenic means decreases.

Contraindications:

• Hypersensitivity to drug, components of drug and to other antibiotics from group of aminoglycosides;
• neuritis of an acoustical nerve;
• myasthenia гравис;
• a heavy renal failure with uraemia and an azotemia;
• the period of a neonatality and prematurity of children (in connection with high risk of development of ototoksichesky and nephrotoxic action);
• pregnancy and period of a lactation.

Overdose:

Symptoms: decrease in neuromuscular conductivity (apnoea). Treatment: the adult in/in enter antikholinesterazny medicines (прозерин), and also calcium drugs (10% solution of calcium chloride of 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 repeated the same dose of a prozerin (at emergence of bradycardia do an additional injection of atropine).

To children administer the calcium drugs. 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:

To store at a temperature no more than 25 °C. To store in    the place, unavailable to children

Issue conditions:

According to the recipe

Packaging:

Solution for intravenous and intramuscular administration, 40 mg / 1 ml and 80 mg / 2 ml. Ampoules on 1 ml or on 2 ml from neutral glass. On an ampoule are put a color point on site of a break and a color quoted ring. 5 ampoules in the blister. 10 ampoules together with the application instruction in a cardboard pack.