Kanamycin

Pharmacological properties

kanamycin is a broad-spectrum antibiotic. It has a bactericidal effect on most gram-positive and gram-negative microorganisms, as well as acid-resistant bacteria. acts on strains of mycobacterium tuberculosis, including those resistant to streptomycin, pask, isoniazid. binding to the 30s subunit of the ribosomal membrane disrupts protein synthesis in the microbial cell.

Effective, as a rule, against microorganisms resistant to tetracycline, erythromycin, chloramphenicol.

Does not affect anaerobic microorganisms, yeast, viruses and most protozoa.

Pharmacokinetics When injected intramuscularly, it quickly enters the bloodstream, the therapeutic concentration is retained for 8-12 hours. It penetrates the pleural cavity, synovial fluid, bronchial secretion, bile, 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.

It is excreted by the kidneys in 24–48 hours.

Indications

• Severe purulent-septic diseases (sepsis, meningitis, peritonitis, septic endocarditis); infectious and inflammatory diseases of the respiratory system (pneumonia, pleural empyema, lung abscess); kidney and urinary tract infections; purulent complications in the postoperative period; infected burns; pulmonary tuberculosis and tuberculosis lesions of other organs caused by microorganisms that are resistant to anti-TB drugs of the first and second series, sensitive to kanamycin.

Application

Kanamycin is used in oil. Before prescribing the drug in the absence of contraindications, it is necessary to conduct a skin test for tolerance.

A solution for i / m administration is prepared ex tempore, adding 4 ml of sterile water for injection or 0.25–0.5% procaine solution to the contents of the vial (1 g), not more often than deep into the upper outer quadrant of the buttock 2 –3 times a day. For children, only water for injection is used as a solvent.

For adults, a single dose in the treatment of infections of non-tuberculous etiology is 0.5 g every 8-12 hours, the daily dose is 1-1.5 g; the maximum single dose is 1 g with an interval between administrations of 12 hours; the maximum daily dose is 2 g. The duration of treatment is 5-7 days. Depending on the severity of the disease, the effectiveness of treatment and the course of the disease, the duration of treatment can be changed.

For children under the age of 1 year 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 year – 5 years - 0.1–0.3 g; over 5 years old - 0.3-0.5 g; maximum daily dose - 15 mg / kg body weight; the frequency of administration is 2-3 times a day. The duration of treatment is 5-7 days.

For the treatment of tuberculosis, kanamycin is administered to adults 1 time per day at a dose of 1 g, for children - 15 mg / kg 6 days a week with a break on the 7th day. The number of cycles and the total duration of treatment are determined by the stage and characteristics of the course of the disease.

In renal failure, the regimen of administration of kanamycin is corrected by reducing doses or increasing the intervals between administrations.

To calculate the intervals between injections, taking into account the degree of impaired renal function, the following formula can be recommended:

interval between administrations (in h) = plasma creatinine content (in mg / 100 ml) • 9.

For example: if the concentration of creatinine in the blood plasma is 2 mg, the recommended dose for patients should be taken every 18 hours.

The initial dose of the drug is calculated taking into account body weight according to the formula:

dose (in mg) = body weight (in kg) • 7.

Subsequent doses (in mg) = initial dose (in mg) / plasma creatinine content (in mg / 100 ml) with a frequency of administration of 2-3 times a day.

In the days of hemodialysis after it is additionally administered a single dose of the drug.

Contraindications

A history of hypersensitivity to kanamycin and other aminoglycosides; auditory nerve neuritis; myasthenia gravis; parkinsonism; botulism; bowel obstruction; severe renal impairment (creatinine clearance 10 ml / min) (see application).

Side effects

Disorders from the nervous system: ototoxicity (damage to a pair of 8 cranial nerves). with prolonged use, it is possible to develop neuritis of the auditory nerve, which is manifested by noise, ringing or a feeling of stuffiness in the ears, a decrease in hearing acuity. these symptoms may be irreversible. Initially, the perception of high frequencies (detected by audiometry) is impaired; an irreversible violation of speech recognition, noticeable to the patient, is added later.

The defeat of the vestibular apparatus is manifested by dizziness or vertigo, impaired coordination of movements. With a symmetric lesion of the vestibular apparatus, these disorders in the first stages may be invisible. Cases of ototoxicity of an irreversible nature have been noted.

Neurotoxicity (encephalopathy, confusion, lethargy, hallucinations, depression). Peripheral neuropathy.

Neuromuscular blockade is also possible, manifested by respiratory depression due to respiratory muscle paralysis, headache, general weakness, drowsiness, muscle twitching, paresthesia, cramps.

From the urinary system: nephrotoxicity. Renal failure, manifested by reversible renal failure, usually of mild degree, rarely with acute tubular necrosis, interstitial nephritis, decreased glomerular filtration rate (observed after several days of treatment or after discontinuation of therapy), increased plasma creatinine, microhematuria, albuminuria, cylindruria.

In addition to a high concentration of the drug in blood plasma, which especially increases the risk of developing ototoxicity and nephrotoxicity, there are many other risk factors (see SPECIAL INSTRUCTIONS).

Electrolyte imbalance: hypomagnesemia, hypocalcemia, hypokalemia.

Disorders of the digestive tract: nausea, vomiting, diarrhea, dysbiosis.

From the cardiovascular system: arterial hypotension.

On the part of the skin and mucous membrane: stomatitis.

Allergic reactions: rarely - rash, itching, swelling, flushing of the skin. In isolated cases, anaphylactoid reactions may occur.

Changes at the injection site: possible irritation and pain at the injection site. Also possible: hyperemia, bruising, hematoma, induration, atrophy or necrosis of the subcutaneous tissue.

From the side of the blood coagulation system: purple.

On the part of laboratory indicators: increased levels of aminotransferases in blood plasma, increased levels of bilirubin. Changes in the blood (anemia, leukopenia, granulocytopenia, thrombocytopenia).

special instructions

The basis for the use of kanamycin is the ineffectiveness of other antibiotics. when the pathogen is insensitive to drugs of the neomycin group (gentamicin, neomycin), cross resistance to kanamycin is usually observed.

Risk factors for the development of ototoxicity and / or nephrotoxicity of the drug are: genetically determined susceptibility to ototoxic effects (the presence of cases of manifestations of ototoxicity of aminoglycosides in relatives should be ascertained); elderly age; initial hearing impairment (otitis media, meningitis, birth injury, hypoxia in childbirth); high doses, a long course of treatment; simultaneous use of other ototoxic and nephrotoxic drugs (see INTERACTIONS); diseases of the kidneys and cardiovascular system, leading to cumulation of the drug; dehydration; diabetes; HIV infection; renal failure.

In this regard, before starting therapy, as well as during treatment with the drug, it is necessary to carry out:

• careful monitoring of renal function (repeated urine tests, determination of blood plasma creatinine and calculation of glomerular filtration every 3 days, if this indicator decreases by 50%, the drug should be discontinued);
• study of auditory function (conducting audiometry at least 2 times a week);
• monitoring the concentration of kanamycin in the blood. At the first sign of an ototoxic effect (even slight tinnitus) or a nephrotoxic effect, kanamycin is canceled.

In case of imbalance, the interval between injections must be increased.

The possibility of neuromuscular blockade should be taken into account (an injection must be carried out if all the necessary conditions for the implementation of mechanical ventilation are available). The risk of developing severe neuromuscular blockade with the use of the drug increases in patients with parkinsonism, myasthenia, botulism, with the simultaneous use of kanamycin with muscle relaxants. To stop the manifestations of neuromuscular blockade, calcium chloride IV or anticholinesterase drugs are used.

When signs of respiratory depression appear, it is necessary to stop the administration of kanamycin and urgently inject iv calcium chloride solution and sc proserinum solution with atropine. If necessary, the patient is transferred to controlled breathing.

With a decrease in potassium levels, it is necessary to control the content of magnesium and calcium in blood plasma.

The elderly, kanamycin should be prescribed only if it is impossible to use less toxic antibiotics.

A slower metabolism of the drug in elderly patients leads to a longer circulation in the blood even with normal renal function, which leads to an increased risk of ototoxic manifestations in this category of patients.

In the case of the use of the drug should not exceed the recommended dose.

Patients with impaired liver function. In patients with liver pathology, the level of the drug in the blood does not change (except for severe alcoholic cirrhosis with ascites, which leads to a larger volume of the distribution of the drug).

Prescribing kanamycin to patients with serious liver disease is considered safe, but special caution is recommended, since some patients may rapidly progress hepatorenal syndrome.

Use during pregnancy or lactation. Kanamycin passes into breast milk in small amounts (up to 18 μg / ml) and is poorly absorbed in the digestive tract, therefore, no complications associated with it in children have been reported. Nevertheless, during the treatment should stop breastfeeding.

Kanamycin is contraindicated during pregnancy. With the use of kanamycin during pregnancy, cases of congenital deafness have been noted. The use of the drug is allowed in some cases only for health reasons, when antibiotics of other groups were ineffective or cannot be used.

Children. Premature infants and newborns due to insufficiently developed renal function have a longer T_½ , which can lead to the accumulation of the drug and its toxic effect. Therefore, the use of kanamycin in this category of patients and children under the age of 1 year is allowed only for health reasons.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. There is no data on the effect on the ability to drive vehicles or work with mechanisms. However, one should consider the possibility of developing vestibular disorders (dizziness, impaired coordination of movements) and refrain from potentially dangerous work.

Interactions

The simultaneous use with loop diuretics (furosemide, ethacrylic acid) should be avoided, since the latter can enhance the ototoxic and nephrotoxic effect of kanamycin.

Possible respiratory dysfunction (oppression and respiratory arrest) due to neuromuscular blockade in patients who are simultaneously prescribed non-depolarizing muscle relaxants (succinylcholine, tubocurarine, decamethonium), anesthetics, narcotic analgesics, magnesium sulfate, as well as in the case of large amounts of blood transfusion with citrate preservatives. Their simultaneous administration should be avoided, and if necessary, adjust the doses of muscle relaxants and tightly monitor neuromuscular function.

The simultaneous and / or sequential systemic or topical use of kanamycin with other neurotoxic and / or nephrotoxic agents (such as cisplatin, other aminoglycoside antibiotics, polymyxin B, acyclovir, ganciclovir, amphotericin B, platinum and gold preparations, dextrans - polyglucin, reopoliglukin, should be avoided, cyclosporin, cephalosporins of the first generation, capreomycin, vancomycin).

When taking streptomycin, monomycin, florimycin, treatment with kanamycin can begin no earlier than 10 days after the end of treatment with the indicated antibiotics.

Mixing kanamycin with penicillins or cephalosporins leads to inactivation of kanamycin, and when they are administered separately, synergism is observed.

Indomethacin, phenylbutazone and other NSAIDs that interfere with renal blood flow can slow the elimination of aminoglycosides from the body.

The simultaneous use of kanamycin with iv solution of indomethacin in premature infants leads to an increase in plasma concentration, prolonged action and an increase in the toxic effect of aminoglycoside.

With tuberculosis, kanamycin can be used simultaneously with all the main and reserve anti-TB drugs (with the exception of streptomycin, florimycin and capreomycin), and with infections of non-tuberculous etiology with penicillins.

Incompatibility. Do not use with solvents other than those indicated (water for injection or 0.25–0.5% procaine solution for i / m administration, isotonic sodium chloride solution or 5% glucose solution for i / v administration) . Kanamycin is pharmaceutically incompatible with streptomycin, gentamicin, monomycin, penicillins, heparin, cephalosporins, capreomycin, amphotericin B, erythromycin, nitrofurantoin, and viomycin. Their mixing in one volume is not allowed.

Overdose

Symptoms of an overdose - increased manifestations of adverse reactions. with parenteral administration, neuromuscular blockade may occur (curariform effect).

Treatment: there is no specific antidote. With symptoms of an overdose, it is urgent to stop taking the drug and prescribe symptomatic therapy. In the event of a blockade or respiratory depression, proserin with atropine is administered; if necessary, mechanical ventilation is indicated. When toxic reactions occur - peritoneal dialysis or hemodialysis. Newborns undergo an exchange blood transfusion.

Storage conditions

In the original packaging at a temperature not exceeding 20 ° C.

Translation of the brain instruction