Kanamycin sulfate for intramuscular solution 1 g x1

Pharmacological properties of the drug Kanamycin

Pharmacodynamics . Kanamycin is a broad-spectrum antibiotic. It has a bactericidal effect on most gram-positive and gram-negative microorganisms, as well as acid-fast bacteria. Acts on strains of Mycobacterium tuberculosis, including those resistant to streptomycin, PAS, and isoniazid. By binding to the 30S subunit of the ribosomal membrane, it inhibits protein synthesis in the microbial cell. Effective, as a rule, against microorganisms resistant to tetracycline, erythromycin, and chloramphenicol. Does not affect anaerobic microorganisms, yeast, viruses and most protozoa. Pharmacokinetics. When administered intramuscularly, it quickly enters the blood, the therapeutic concentration is maintained for 8–12 hours. Penetrates into the pleural cavity, synovial fluid, bronchial secretions, bile, and through the placental barrier. Normally, kanamycin does not penetrate the BBB, but with inflammation of the meninges, its concentration in the CSF reaches 30–60% of that in the blood plasma. Excreted by the kidneys within 24–48 hours.

Kanamycin

Stylab / Catalog / Antibacterial drugs / Kanamycin

STYLAB offers test systems for the analysis of kanamycin in animal meat, milk, honey and vaccines by ELISA, as well as pure kanamycin substance and its mixtures with other aminoglycosides to ensure traceability of analyzes in accordance with GOST 32798-2014 and MUK No. 759/5.3.

Kanamycin is a broad-spectrum bactericidal antibiotic belonging to the group of aminoglycosides. It is produced in the form of a complex of three substances - kanamycins A, B and C by the bacteria Streptomyces kanamyceticus. Kanamycin is active against mycobacteria, including the causative agents of tuberculosis. In addition, it destroys many gram-positive and gram-negative bacteria, including E. coli , salmonella , shigella, enterobacter, yersinia, klebsiella, gonococcus, meningococcus, staphylococcus and other bacteria. Kanamycin is effective against microorganisms resistant to tetracycline , chloramphenicol , erythromycin , streptomycin and many other antibiotics. In medicine, kanamycin is prescribed for tuberculosis, diarrhea, infectious gastroenteritis, eye and skin diseases, cystitis, osteomyelitis, as well as pneumonia, peritonitis and endocarditis. In veterinary medicine, it is used for the prevention and treatment of postpartum endometritis in cows and pigs, as well as for other bacterial diseases. As of 2019, 3 kanamycin preparations intended for veterinary use were registered in the Russian Federation.

Like other aminoglycosides, kanamycin irreversibly binds to the 30S ribosomal subunit, which leads to cell death due to impaired protein synthesis. Kanamycin has no effect on streptococci, Pseudomonas aeruginosa , anaerobic bacteria, as well as yeast, protozoa and viruses. Bacteria quickly develop resistance to kanamycin. This resistance may be cross-resistance.

Kanamycin is poorly absorbed from the gastrointestinal tract and is excreted mainly unchanged in feces. This allows it to be used to treat intestinal diseases. However, ulcers and other gastrointestinal injuries or inflammation improve the absorption of this antibiotic. In this case, it is excreted by the kidneys. When used as an aerosol, kanamycin is also poorly absorbed and creates high concentrations in the lungs and respiratory tract. When administered intramuscularly, kanamycin is well and quickly absorbed and distributed throughout the organs and tissues of the body. Particularly high concentrations of kanamycin are created in body fluids, as well as in the liver, lungs and kidneys, and this antibiotic can accumulate in their cortex. Smaller concentrations of kanamycin are present in muscles, fat, bones, sputum, and bile. In healthy adults, kanamycin does not cross the blood-brain barrier. However, with inflammation of the meninges and in children, kanamycin creates noticeable (10–60% of the content in the blood plasma) concentrations in the cerebrospinal fluid. Kanamycin is not metabolized in the body and is excreted unchanged. Its half-life is 2-4 hours in adults and 5-6 hours in newborns. In small quantities, kanamycin can be excreted in both breast milk and animal milk.

The acute toxicity of kanamycin to humans and other mammals is low. The LD50 of kanamycin for mice when administered orally was 20500 mg/kg body weight, when administered intravenously – 115 mg/kg body weight. LD50 for rats when administered intravenously is 437 mg/kg.

Side effects and consequences of an overdose of kanamycin in humans have been well studied. These include nausea, vomiting, diarrhea, malabsorption of nutrients and minerals, headache, liver and kidney problems, changes in blood composition and allergic skin reactions. Kanamycin has a curare-like effect - it can disrupt signal transmission from nerves to muscles. This leads to sensory disturbances, convulsions and difficulty breathing until it stops. The ability of kanamycin to act on the auditory nerves determines its ototoxicity. It can manifest as tinnitus, hearing loss, or complete deafness. In addition, kanamycin can cause impaired coordination of movements and dizziness. Due to ototoxicity, kanamycin is not prescribed for inflammation of the auditory nerve, and due to hepatotoxicity and nephrotoxicity, it is not prescribed for liver and kidney diseases.

Kanamycin is able to overcome the placental barrier and penetrate both the amniotic fluid and the fetus. In animal studies, this antibiotic caused damage to the auditory nerves in fetal guinea pigs and rats. Therefore, kanamycin is not prescribed during pregnancy. This antibiotic did not show carcinogenic or mutagenic properties in animal studies. It also did not cause skin irritation in either rabbits or human volunteers.

When kanamycin and other aminoglycosides are simultaneously introduced into the body, their medicinal effect is reduced because these substances compete for capture by bacterial cells. The side effects of aminoglycosides are enhanced. Therefore, kanamycin can be used for treatment only 10-12 days after stopping taking other aminoglycosides. Due to its toxic properties and because kanamycin can lead to the emergence of antibiotic-resistant microorganisms, its content in food products must be controlled.

In the Russian Federation and the EAEU, the maximum permissible levels of kanamycin are specified in TR CU 034/2013 “On the safety of meat and meat products.” According to it, meat and raw fat of all types of animals can contain no more than 0.1 mg/kg of kanamycin, in the liver - no more than 0.6 mg/kg, in kidneys - no more than 2.5 mg/kg. Decision No. 28 of the Board of the Eurasian Economic Commission dated February 13, 2021 supplements these MRL restrictions for milk - 0.15 mg/kg. The same restriction for milk applies in European Union countries. In Korea, the maximum permissible content of kanamycin in milk is 0.1 mg/kg.

STYLAB offers Kanamycin ELISA Kit test systems for the analysis of kanamycin in meat and other animal tissues, milk, honey and vaccines. They allow you to quickly screen large numbers of samples and do not require expensive equipment. STYLAB also offers certified standard solutions to ensure traceability of measurements: pure kanamycin substance and its mixtures with other aminoglycosides to ensure traceability of analyzes in accordance with GOST 32798-2014 “Food products, food raw materials. Method for determining the residual content of aminoglycosides using high-performance liquid chromatography with a mass spectrometric detector" and MUK No. 759/5.3.

Literature

1. Kanamycin. Register of medicines in Russia.
2. Kanamicin. Pubchem
3. Na-Reum Ha, In-Pil Jung, Im-Joung La, Ho-Sup Jung, and Moon-Young Yoona. Ultra-sensitive detection of kanamycin for food safety using a reduced graphene oxide-based fluorescent aptasensor. Sci Rep. 2017; 7:40305.
4. Yong Jin, Jin-Wook Jang, Chang-Hoon Han, Mun-Han Lee. Development of immunoassays for the detection of kanamycin in veterinary fields. J Vet Sci. 2006 Jun; 7(2): 111–117.
5. The European Agency for the Evaluation of Medical Products Veterinary Medicines and Inspections. Committee For Veterinary Medicinal Products Kanamycin Summary Report (1). EMEA/MRL/514/98-FINAL January 1999
6. The European Agency for the Evaluation of Medical Products Veterinary Medicines and Inspections. Committee For Veterinary Medicinal Products Kanamycin Summary Report (2). EMEA/MRL/886/03-FINAL October 2003

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Use of the drug Kanamycin

Kanamycin is prescribed only intramuscularly. Before prescribing the drug, in the absence of contraindications, it is necessary to conduct a skin test for tolerability. For children under 1 year of age with infections of non-tuberculous etiology (in exceptional cases), the drug is prescribed in an average daily dose of 0.1 g; at the age of 1–5 years – 0.1–0.3 g; over 5 years - 0.3–0.5 g; maximum daily dose - 15 mg/kg; frequency of administration - 2-3 times a day. The duration of treatment is 5–7 days. For adults, a single dose for the treatment of infections of non-tuberculous etiology is 0.5 g every 8–12 hours, the daily dose is 1–1.5 g; maximum single dose - 1 g with an interval between administrations of 12 hours; the maximum daily dose is 2 g. Duration of treatment is 5–7 days. For the treatment of tuberculosis, adults are prescribed 1 g 1 time per day, children - 15 mg/kg 1 time per day. Treatment lasts ≥1 month (the drug is administered in cycles: daily for 6 days, on the 7th day - a break). A solution for intramuscular administration is prepared ex tempore by adding 4 ml of sterile water for injection or 0.25–0.5% procaine solution to the contents of the bottle (1 g), injected deep into the upper outer quadrant of the buttock 2–3 once a day.

Kanamycin sulfate for intramuscular solution 1 g x1

Trade name: Kanamycin International name: Kanamycin

Release forms: powder for the preparation of solution for intramuscular administration 0.5 g, 1 g (bottles)

Composition: kanamycin monosulfate 500/1000 mg [in terms of kanamycin]

Pharmacological group: antibiotic-aminoglycoside

Pharmacological group according to ATK: J01GB04 (Kanamycin)

Pharmacological action: aminoglycoside, antibacterial, antituberculosis,

Indications: Infectious diseases caused by susceptible pathogens. Parenteral administration - infections of the biliary tract, bones and joints, central nervous system, abdominal cavity, respiratory organs (including tuberculosis, pneumonia, pleural empyema, lung abscess), skin and soft tissues (including infected burns), urinary pathways (including pyelonephritis, pyelitis, cystitis), sepsis, postoperative infections. Orally - intestinal infections (dysentery, dysentery bacteria carriage, bacterial colitis, enterocolitis), preparation for operations on the gastrointestinal tract, hepatic coma (as an auxiliary drug).

Dosage regimen: IV drip, IM, in the cavity and orally (for local action). IV drip, a single dose (0.5 g) is dissolved in 200 ml of 5% dextrose solution and administered at a rate of 60-80 drops/min. For infections of non-tuberculosis etiology, a single dose for adults is 0.5 g, a daily dose is 1-1.5 g (0.5 g every 8-12 hours). The highest daily dose is 2 g. The course of treatment is 5-7 days. Children (IM only) - 50 mg/kg/day, premature infants and children in the first month of life - only for “vital” indications. For tuberculosis - intramuscularly, adults - 1 g once a day or 0.5 g 2 times a day, children - 15-20 mg/kg/day, but not more than 0.5-0.75 g. Every 7th day - break . Orally, for intestinal infections, in equal doses, 4-6 times a day (regardless of the form and severity of the disease). Single dose for adults - 0.5-0.75 g, daily dose - 3 g. The highest daily dose - 4 g. For intestinal sanitation in the preoperative period, adults are prescribed tablets orally: during the day before surgery, 0.75 g every 4-6 hours (per day - no more than 4 g) together with other antibacterial drugs, for 3 days: on the first day - 0.5 g every 4 hours (daily dose - 3 g), in the next 2 days - 1 g 4 times (daily dose - 4 G). For hepatic encephalopathy (as an auxiliary drug) - orally, 2-3 g every 6 hours. 10-50 ml of a 0.25% aqueous solution is injected into the cavity (pleural, abdominal, articular) for washing. When performing peritoneal dialysis, dissolve 1-2 g in 500 ml of dialysate fluid. The injection solution can also be used in the form of aerosol inhalations of 250 mg 2-4 times a day. Intraperitoneal - 500 mg (in the form of a 2.5% solution).

Contraindications: Hypersensitivity (including a history of other aminoglycosides). Parenteral administration - severe chronic renal failure with azotemia and uremia, neuritis of the VIII pair of cranial nerves, pregnancy.

Side effects: From the digestive system: nausea, vomiting, diarrhea, liver dysfunction (increased activity of “liver” transaminases, hyperbilirubinemia), with prolonged oral administration - malabsorption syndrome (diarrhea, flatulence, light, foamy, oily feces). From the hematopoietic organs: anemia, leukopenia, granulocytopenia, thrombocytopenia. From the nervous system: headache, drowsiness, weakness, neurotoxic effect (muscle twitching, numbness, tingling, paresthesia, epileptic seizures), impaired neuromuscular transmission (respiratory arrest). From the senses: ototoxicity (ringing or a feeling of congestion in the ears, hearing loss, up to irreversible deafness), toxic effects on the vestibular apparatus (discoordination of movements, dizziness, nausea, vomiting). From the urinary system: nephrotoxicity - impaired renal function (increase or decrease in frequency of urination, thirst, cylindruria, microhematuria, albuminuria). Allergic reactions: skin rash, itching and redness of the skin, fever, angioedema. Overdose. Symptoms: toxic reactions (hearing loss, ataxia, dizziness, urination disorders, thirst, loss of appetite, nausea, vomiting, ringing or fullness in the ears, breathing problems). Treatment: to relieve the blockade of neuromuscular transmission and its consequences - hemodialysis or peritoneal dialysis, anticholinesterase drugs, Ca2+ salts, mechanical ventilation, other symptomatic and supportive therapy.

Pharmacodynamics: A broad-spectrum antibiotic from the group of aminoglycosides, penetrates the microbial cell, binds to specific receptor proteins on the 30S ribosomal subunit. It disrupts the formation of the transport and messenger RNA complex (30S ribosomal subunit) and blocks protein synthesis, damaging microbial cell membranes. Effective against most gram-positive and gram-negative microorganisms, as well as acid-fast bacteria: Mycobacterium tuberculosis (including those resistant to streptomycin, PAS, isoniazid and other anti-tuberculosis drugs, except viomycin), Escherichia coli, Shigella spp., Salmonella spp., Proteus spp., Enterobacter spp., Klebsiella pneumoniae, Neisseria gonorrhoeae et meningitidis, Staphylococcus spp. Strains of these microorganisms that are resistant to tetracycline, erythromycin, chloramphenicol, benzylpenicillin, streptomycin, chloramphenicol, etc., in most cases remain sensitive to kanamycin. Does not affect Pseudomonas aeruginosa, Streptococcus spp., Bacteroides and other anaerobic bacteria, yeasts, viruses and protozoa. Weakly active against Streptococcus spp.

Pharmacokinetics: When taken orally, it is practically not absorbed (only about 1% is absorbed through the intact intestinal mucosa; large quantities can be absorbed through the damaged or ulcerated mucous membrane of the gastrointestinal tract), has a local effect. TCmax with intramuscular injection - 0.5-1.5 hours, after 30 minutes of intravenous infusion - 30 minutes, after 60 minutes of intravenous infusion - 15 minutes. Cmax after intravenous or intramuscular administration of 7.5 mg/kg - 22 mcg/ml. Penetrates into the pleural cavity, lymphatic, synovial and peritoneal fluids, blood serum, bronchial secretions and bile. TCmax in bile - 6 hours. High concentrations are found in urine, low concentrations are found in bile, breast milk, aqueous humor, bronchial secretions, sputum and CSF. It penetrates well into all tissues of the body, where it accumulates intracellularly; high concentrations are observed in organs with good blood supply: lungs, liver, myocardium, spleen and especially in the kidneys, where it accumulates in the cortical layers; lower concentrations are found in muscles, adipose tissue and bones. Normally, kanamycin does not penetrate the BBB, but with inflammation of the meninges, the concentration of the drug in the CSF reaches 30-60% of that in the plasma. In newborns, higher concentrations are created in the CSF than in adults; it passes through the placenta and is found in the fetal blood and amniotic fluid. Volume of distribution in adults - 0.26 l/kg, in children - 0.2-0.4 l/kg, in newborns less than 1 week old and weighing less than 1.5 kg - up to 0.68 l/kg, less than 1 week old and weighing more than 1.5 kg - up to 0.58 l/kg, in patients with cystic fibrosis - 0.3-0.39 l/kg. Not metabolized. T1/2 in adults - 2-4 hours, in newborns - 5-8 hours, in older children - 2.5-4 hours. Final T1/2 - more than 100 hours (release from intracellular depots). After parenteral administration, it is excreted by the kidneys by glomerular filtration, mainly unchanged (70-95% is found in urine after 24 hours), and when taken orally, in feces. T1/2 in adults with impaired renal function varies depending on the degree of dysfunction up to 100 hours, in patients with cystic fibrosis - 1-2 hours, in patients with burns and hyperthermia T1/2 may be shorter than the average due to increased clearance . It is eliminated by hemodialysis (50% in 4-6 hours), peritoneal dialysis is less effective (25% in 48-72 hours).

Special instructions: During treatment, it is necessary to monitor the function of the kidneys, auditory nerve and vestibular apparatus at least once a week. The likelihood of developing nephrotoxicity is higher in patients with impaired renal function, as well as when prescribed in high doses or for a long time (in these patients, daily monitoring of renal function may be required). If audiometric tests are unsatisfactory, the dose of the drug is reduced or treatment is stopped. Aminoglycosides pass into breast milk in small quantities (since they are poorly absorbed from the gastrointestinal tract, no complications associated with them have been reported in infants). Patients with infectious and inflammatory diseases of the urinary tract are recommended to take increased amounts of fluid. In the absence of positive clinical dynamics, one should remember the possibility of the development of resistant microorganisms. In such cases, it is necessary to discontinue treatment and begin appropriate therapy. Due to the possibility of developing neuromuscular blockade, intravenous administration of undiluted kanamycin is not recommended. In case of hepatic coma, it is used for the purpose of long-term inhibition of bacteria in the intestinal flora to reduce ammonia intoxication. Carefully. Myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause disruption of neuromuscular transmission, which leads to further weakening of skeletal muscles), renal failure, old age, premature babies, neonatal period (up to 1 month), lactation period.

Interaction: Reduces the effect of antimyasthenic drugs. Enhances the muscle relaxant effect of curare-like drugs, general anesthetics and polymyxins. Pharmaceutically incompatible with streptomycin, gentamicin, monomycin, penicillins, heparin, cephalosporins, capreomycin, amphotericin B, erythromycin, nitrofurantoin, viomycin. Beta-lactam antibiotics (cephalosporins, penicillins) in patients with severe chronic renal failure reduce the effect of aminoglycosides. Nalidixic acid, polymyxin, cisplatin and vancomycin increase the risk of developing oto- and nephrotoxicity. Diuretics (especially furosemide), cephalosporins, penicillins, sulfonamides and NSAIDs, competing for active secretion in the nephron tubules, block the elimination of aminoglycosides, increase their concentration in the blood serum, increasing nephro- and neurotoxicity. Cyclopropane increases the risk of apnea with intraperitoneal administration of kanamycin. Parenteral administration of indomethacin increases the risk of developing toxic effects of aminoglycosides (prolongation of T1/2 and decreased clearance). Methoxyflurane, polymyxins for parenteral administration and other drugs that block neuromuscular transmission (halogenated hydrocarbons as drugs for inhalation anesthesia, narcotic analgesics, transfusion of large amounts of blood with citrate preservatives) increase the risk of nephrotoxicity and respiratory arrest (as a result of increased neuromuscular blockade).

Drug registration number: LS-001536

Date of registration (re-registration) of the drug: 04/28/2006

Special instructions for the use of Kanamycin

Before using the drug, it is necessary to determine the state of kidney function and the sensitivity of microflora to kanamycin. During treatment, audiometric monitoring and monitoring of renal function should be periodically performed. During pregnancy and breastfeeding, as well as in children of the first year of life, the use of the drug is allowed only for health reasons. In elderly patients, Kanamycin should be prescribed only if it is impossible to use less toxic antibiotics. When using the drug, do not exceed the recommended dose. During treatment, renal function must be carefully monitored.