Active substanceAmikacinAmikacin
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  • Dosage form: & nbsppowder for solution for intravenous and intramuscular administration
    Composition:

    Active substance: Amicacin sulfate 500 mg (in terms of amikacin)

    Description:

    The powder is white or almost white.

    Pharmacotherapeutic group:Antibiotic-aminoglycoside
    ATX: & nbsp

    J.01.G.B.06   Amikacin

    Pharmacodynamics:

    Semisynthetic broad-spectrum antibiotic from the group of aminoglycosides of the third generation, acts bactericidal. Communicating with 30S a subunit of ribosomes, prevents the formation of a complex of transport and matrix RNA, blocks the synthesis of protein, and also destroys the bacterial cell membranes.

    Highly active against aerobic gram-negative microorganisms - Pseudomonas aeruginosa, Escherichia coli, Klebsiella spp., Serratia spp., Providencia spp., Enterobacter spp., Salmonella spp., Shigella spp.; some Gram-positive microorganisms - Staphylococcus spp. (including those resistant to penicillin, some cephalosporins); moderately active against Sreptococcus spp.

    When administered concomitantly with benzylpenicillin, it has a synergistic effect on strains Enterococcus faecalis. Does not affect aerobic microorganisms.

    Amicacin does not lose activity under the action of enzymes that inactivate other aminoglycosides, and can remain active against strains Pseudomonas aeruginosa, resistant to tobramycin, gentamycin and netilmicin.

    Pharmacokinetics:

    After intramuscular injection (in / m) is absorbed quickly and completely. The maximum concentration of the drug in the blood (CmOh) with an im injection in a dose of 7.5 mg / kg - 21 mcg / ml, after 30 min IV infusion at a dose of 7.5 mg / kg - 38 mcg / ml. Time to reach the maximum concentration of the drug in the blood (TfrommOh) - about 1.5 hours after the / m administration.Connection with plasma proteins - 4-11%.

    It is well distributed in the extracellular fluid (the contents of abscesses, pleural effusion, ascitic, pericardial, synovial, lymphatic and peritoneal fluid); in high concentrations is found in the urine; in low - in bile, breast milk, watery eye moisture, bronchial secretion, sputum and cerebrospinal fluid (CSF). Well penetrates into all tissues of the body, where accumulates intracellularly; high concentrations are noted in organs with good blood supply: lungs, liver, myocardium, spleen, and especially in the kidneys where it accumulates in the cortex, lower concentrations - in muscles, adipose tissue and bones.

    At appointment in sredneverapepticheskih doses (in norm or rate) to adults amikacin does not penetrate the blood-brain barrier (BBB), with inflammation of the meninges, the permeability slightly increases. In newborns, higher concentrations are achieved in CSF than in adults; passes through the placenta - is found in the fetal blood and amniotic fluid. The volume of distribution in adults is 0.26 l / kg, in children 0.2-0.4 l / kg, in newborns less than 1 week old. and body weight less than 1.5 kg up to 0,68 l / kg, at the age of less than 1 week. and a body weight of more than 1.5 kg - up to 0.58 l / kg, in patients with cystic fibrosis - 0.3-0.39 l / kg. The average therapeutic concentration with IV or IM injection is maintained for 10-12 hours.

    It is not metabolized. Half-life of blood (T1/2) in adults - 2-4 hours, in newborns - 5-8 hours, in older children - 2.5-4 hours. The final value T1/2 more than 100 hours (release from the intracellular depot).

    It is excreted by the kidneys through glomerular filtration (65-94%), mostly unchanged. Kidney clearance - 79-100 ml / min.

    T1/2 in adults with renal dysfunction varies depending on the degree of impairment - up to 100 hours, in patients with cystic fibrosis - 1-2 hours, in patients with burns and hyperthermia T1/2 can be shorter compared with the average due to increased clearance.

    It is excreted during hemodialysis (50% for 4-6 hours), peritoneal dialysis is less effective (25% for 48-72 hours).

    Indications:

    Infectious-inflammatory diseases caused by gram-negative microorganisms (resistant to gentamicin, sizomycin and kanamycin) or associations of gram-positive and gram-negative microorganisms: respiratory tract infections (bronchitis,pneumonia, pleural empyema, lung abscess), sepsis, septic endocarditis, central nervous system (CNS) infections (including meningitis), abdominal infections (including peritonitis), urinary tract infections (pyelonephritis, cystitis, urethritis, prostatitis, gonorrhea), purulent infections of the skin and soft tissues (including infected burns, infected ulcers and bedsores of various genesis), biliary tract infections, bones and joints (including osteomyelitis), wound infection, postoperative infections.

    Contraindications:

    Hypersensitivity (including to other aminoglycosides in the anamnesis), neuritis of the auditory nerve, chronic renal failure (CRF) with azotemia and uremia, pregnancy.

    Carefully:Myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause a violation of neuromuscular transmission, which leads to further weakening of skeletal muscles), dehydration, renal insufficiency, the period of newborns, prematurity of children, advanced age, lactation.
    Pregnancy and lactation:

    In the presence of "vital" indications can be used in the lactation period (aminoglycosides penetrate into breast milk in small amounts,but they are poorly absorbed from the gastrointestinal tract, and complications associated with them in infants were not recorded).

    Dosing and Administration:

    Intramuscularly or intravenously (struyno, for 2 min or drip). Adults and children over 6 years of age - 5 mg / kg every 8 hours or 7.5 mg / kg every 12 hours; bacterial urinary tract infections (uncomplicated) - 250 mg every 12 hours; after the hemodialysis session, an additional dose of 3-5 mg / kg may be prescribed. The maximum dose for adults is up to 15 mg / kg / day, but not more than 1.5 g / day for 10 days.

    The duration of treatment with iv introduction is 3-7 days, with a / m - 7-10 days.

    Preterm neonates with an initial dose of 10 mg / kg, then 7.5 mg / kg every 18-24 hours; newborns and children under 6 years of age, the initial dose is 10 mg / kg, then 7.5 mg / kg every 12 hours for 7-10 days.

    Patients with renal failure require a correction of the dosing regimen: a dose reduction or an increase in the interval between administrations is necessary. Treatment should be carried out under the control of the content of the drug in the plasma (the therapeutic concentration is 15-25 μg / ml).

    Patients with burns may need a dose of 5-7.5 mg / kg every 4 to 6 hours due to shorter T1/2 (1-1.5 h) in these patients.

    For the / m introduction use a solution prepared ex tempore from the powder with the addition of 2-3 ml of water for injections to the contents of the vial. For IV infusion, 4-5 ml of water for injection, 0.9% of sodium chloride solution or 5% of dextrose solution are added to the contents of the vial. For IV injection apply the same solutions as for IM, previously diluted with 200 ml of a 5% solution of dextrose or 0.9% solution of sodium chloride. The concentration of amikacin in the solution for intravenous administration should not exceed 5 mg / ml.

    In violation of excretory function of the kidneys it is necessary to reduce doses or increase the intervals between administrations.

    In the case of an increase in the interval between administrations (if the level of creatinine clearance is not known and the patient's condition is stable), the interval between drug intake is established as follows:

    Interval (hours) = serum creatinine concentration * 9.

    If the serum creatinine concentration is 2 mg / 100 ml, the recommended single dose (7.5 mg / kg) should be administered every 18 hours. When the interval is increased, the single dose is not changed.

    In the case of a single dose reduction with an unchanged dosing regimen, the first dose for patients with renal insufficiency is 7.5 mg / kg.To calculate the subsequent doses, it is necessary to separate the clearance value (ml / min) in patients for creatinine clearance in norm, then multiply the obtained figure by the amount of the initial dose in mg:

    the subsequent dose (mg) = the creatinine clearance found in the patient (ml / min) / creatinine clearance in norm (ml / min) x initial dose (mg).

    Side effects:

    From the digestive system: nausea, vomiting, impaired liver function (increased activity of "liver" transaminases, hyperbilirubinemia).

    On the part of the organs of hematopoiesis: anemia, leukopenia, granulocytopenia, thrombocytopenia.

    From the nervous system: headache, drowsiness, neurotoxic effect (muscle twitching, numbness, tingling, epileptic seizures), violation of neuromuscular transmission (respiratory arrest).

    From the sense organs: ototoxicity (hearing loss, vestibular and labyrinthine disorders, irreversible deafness), toxic effect on the vestibular apparatus (discoordination of movements, dizziness, nausea, vomiting).

    From the urinary system: nephrotoxicity - a violation of kidney function (oliguria, proteinuria, microhematuria).

    Allergic reactions: skin rash, itching, skin hyperemia, fever, angioedema.

    Local: soreness at the injection site, dermatitis, phlebitis and periphlebitis (with intravenous administration).

    Overdose:

    Symptoms: toxic reactions (hearing loss, ataxia, dizziness, urination disorders, thirst, decreased appetite, nausea, vomiting, ringing or feeling in the ears, respiratory failure).

    Treatment: to remove the blockade of the neuromuscular transmission and its consequences - hemodialysis or peritoneal dialysis; anticholinesterase drugs, calcium salts, artificial lung ventilation, and other symptomatic and supportive therapies.

    Interaction:

    Pharmaceutically incompatible with penicillins, heparin, cephalosporins, capreomycin, amphotericin B, hydrochlorothiazide, erythromycin, nitrofurantoin, vitamins of group B and C, potassium chloride.

    It exhibits synergism in interaction with carbenicillin, benzylpenicillin, cephalosporins (in patients with severe chronic renal failure (CRF), beta-lactam antibiotics may reduce the effect of aminoglycosides).

    Nalidixic acid, polymyxin AT, cisplatin and vancomycin increase the risk of oto and nephrotoxicity.

    Diuretics (especially furosemide), cephalosporins, penicillins, sulfonamides and non-specific anti-inflammatory drugs, compete for active secretion in the nephron tubules, block the elimination of aminoglycosides, increase their serum concentration, enhancing nephro- and neurotoxicity.

    Strengthens the muscle relaxant effect of curare like medicines.

    Methoxyflurane, polymyxins for parenteral administration, capreomycin and other drugs that block neuromuscular transmission (halogenated hydrocarbons as drugs for inhalation anesthesia, narcotic analgesics), transfusion of large amounts of blood with citrated preservatives increase the risk of stopping breathing.

    Parenteral administration of indomethacin increases the risk of toxic effects of aminoglycosides (an increase T1/2 and reduced clearance).

    Reduces the effectiveness of antimiasthenic drugs.

    Special instructions:

    Before use, the sensitivity of the isolated pathogens is determined using discs containing 30 μg of amikacin.With a diameter of a growth free zone of 17 mm or more, the microorganism is considered sensitive, from 15 to 16 mm - moderately sensitive, less than 14 mm - resistant.

    The concentration of amikacin in plasma should not exceed 25 mcg / ml (the therapeutic concentration is 15-25 mcg / ml).

    During the treatment period, it is necessary to monitor the function of the kidneys, the auditory nerve and the vestibular apparatus at least once a week.

    The likelihood of developing nephrotoxicity is higher in patients with impaired renal function, as well as when administered at high doses or for a long time (this category of patients may require daily monitoring of kidney function).

    When unsatisfactory audiometric tests, the dose of the drug is reduced or discontinued.

    Patients with infectious and inflammatory diseases of the urinary tract is recommended to take an increased amount of liquid.

    In the absence of positive clinical dynamics should be remembered the possibility of developing resistant microorganisms. In such cases, it is necessary to cancel treatment and begin appropriate therapy.

    Form release / dosage:Powder for the preparation of solution for intravenous and intramuscular injection.
    Packaging:

    In bottles of 500 mg. The bottle with instructions for use is placed in a cardboard box.

    10 vials of the preparation together with instructions for use are placed in a pack.

    50 bottles of the drug along with instructions for use are placed in a box of cardboard (for hospitals).

    Storage conditions:

    In a dry, the dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:2 years. Do not use after the expiry date printed on the package.
    Terms of leave from pharmacies:On prescription
    Registration number:LSR-008632/08
    Date of registration:30.10.2008
    Expiration Date:Unlimited
    The owner of the registration certificate: Mapichem AG Mapichem AG Switzerland
    Manufacturer: & nbsp
    Representation: & nbspMapichem AGMapichem AG
    Information update date: & nbsp05.08.2017
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