Amikacin - instructions for use, dose, side effects, contraindications

Semisynthetic antibiotic of broad spectrum of action, possesses bactericidal activity. Communicating with 30S subunit of ribosomes, prevents the formation of a complex of transport and matrix RNA, blocks the synthesis of protein, and also destroys the cytoplasmic membranes of bacteria.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 Streptococcus spp. With simultaneous administration with benzylpenicillin has a synergistic effect on strains Enterococcus faecalis. Does not affect anaerobic 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 (IM injection) absorbed quickly and completely. The maximum concentration (C_m_Oh) with an IM injection of 7.5 mg / kg - 21 μg / ml after 30 minutes of IV infusion of approximately 7.5 mg / kg - 38 μg / ml. The time to reach the maximum concentration (T C_m_Oh) - 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). It penetrates well into all tissues of the body, where it accumulates intracellularly; high concentrations are noted in organs with good blood supply: lungs, liver, myocardium, spleen, and especially in the kidneys, where accumulates in the cortical layer, lower concentrations - in muscles, adipose tissue and bones.

When prescribed in mediotherapeutic doses 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 weighing less than 1.5 kg 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 for IV and IM the administration is maintained for 10-12 hours.

It is not metabolized. The half-life (T_1/2) in adults 2-4 hours, in newborns 5-8 hours, in older children 2.5-4 hours. The final value of T_1/2- more than 100 hours (release from the intracellular depot). It is excreted by the kidneys by glomerular filtration (65-94%), mainly unchanged. Kidney clearance - 79-100 ml / min.

T_1/2 in adults with renal dysfunction varies depending on the degree of impairment - up to 100 h, in patients with cystic fibrosis - 1-2 h, in patients with burns and hyperthermia T_1/2can be shorter compared with the average due to increased clearance.

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

Indications:

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

Contraindications:

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

Carefully:

Myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause a violation of neuromuscular transmission, which leads to further weakening of skeletal muscles), dehydration, renal failure, neonatal period, prematurity of children, advanced age.

Pregnancy and lactation:

Amikacin is contraindicated during pregnancy.

Because the amikacin is excreted in breast milk, it should not be prescribed to nursing mothers. If it is necessary to use amikacin in the mother during breastfeeding, the baby should be stopped before treatment.

Dosing and Administration:

Intramuscularly (in / m), intravenously (iv) (drip for 30-60 minutes). Adults and children over 6 years of age at 5 mg / kg every 8 hours or 7.5 mg / kg every 12 hours; bacterialurinary tract infections (uncomplicated) 250 mg every 12 hours; after the hemodialysis session, an additional dose of 3-5 mg / kg may be prescribed.

Maximum doses for adults up to 15 mg / kg / day, but not more than 1.5 g / day for 10 days. The duration of treatment with iv in the introduction of 3-7 days, with a / m introduction - 7-10 days.

Preterm infants receive an initial dose of 10 mg / kg, then 7.5 mg / kg every 18-24 hours. Newborns and children under 6 years of age receive an initial dose of 10 mg / kg, then 7.5 mg / kg every 12 hours for 7 -10 days.

Patients with burns may need a dose of 5-7.5 mg / kg every 4-6 hours due to a shorter T_1/2 (1-1.5 h) in these patients.

For the / m introduction, use a solution prepared by adding 2-3 ml of water for injection to the contents of the vial (250 mg or 500 mg) and for dosing 1.0 g - 4-5 ml of water for injection.

For IV injection (drip), the contents of the vial are dissolved in 200 ml of a 5% solution of dextrose (glucose) or 0.9% sodium chloride solution. The concentration of amikacin in the solution for intravenous drip administration should not exceed5 mg / ml.

In children, the volume of injected fluid should be reduced depending on the dose of the antibiotic. The duration of IV in the introduction of newborns is 1-2 hours.

Patients with renal failure require a correction of the dosing regimen: a dose reduction or an increase in the interval between administrations is necessary.

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 doses is set as follows:

Interval (hours) = serum creatinine concentration x 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 unchanged dosing regimen, the first dose for patients with renal insufficiency is 7.5 mg / kg.

To calculate subsequent doses necessary to divide the value of the clearance of creatinine (ml / min) in patients with a creatinine clearance rate, then the resulting number is multiplied by the amount of the initial dose in mg, i.e .:

Side effects:

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

From the hematopoiesis: anemia, leukopenia, granulocytopenia, thrombocytopenia, eosinophilia.

From the nervous system: headache, drowsiness, neurotoxic action (twitching of muscles, numbness, tingling, epileptic seizures), violation of neuromuscular transmission (respiratory arrest), often the occurrence of vestibular and auditory disorders, increases in patients with renal insufficiency.

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 - renal dysfunction (oliguria, proteinuria, microhematuria, hypercreatininaemia, azotemia).

Allergic reactions: skin rash, itching and hyperemia of the skin, fever, angioedema, arthralgia.

Local reactions: pain in the injection site, dermatitis, phlebitis and periphlebitis (with intravenous administration).

Overdose:

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

Treatment: to relieve the blockade of the neuromuscular transmission and its consequences - hemodialysis orperitoneal dialysis; cholinesterase inhibitors, calcium salts, artificial ventilation (IVL), and other symptomatic and supportive therapies.

Interaction:

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

It shows a synergy with carbenicillin, benzylpenicillin, cephalosporins (in patients with severe CRF, beta-lactam antibiotics can 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-steroidal anti-inflammatory drugs (indomethacin), competing for active secretion in the tubules of the nephron, block the elimination of aminoglycosides, increase their concentration in the serum, enhancing nephro- and neurotoxicity.

Strengthens the muscle relaxant effect of nondepolarizing muscle relaxants.

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

Amikacin reduces the effect 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.

It is recommended that simultaneous use of oto- and nephrotoxic drugs should be avoided.

The probability of developing nephrotoxicity is higher in patients with impaired kidney 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-inflammatory diseases of the urinary tract are advised to take an increased amount of fluid with adequate diuresis. 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.

Effect on the ability to drive transp. cf. and fur:

With caution apply to drivers of vehicles and people whose activities require increased concentration and speed of psychomotor reactions.

Form release / dosage:Powder for solution for intravenous and intramuscular injection 250 mg, 500 mg, 1.0 g. By 250 mg, 500 mg, 1.0 g.

Packaging:

Powder for solution for intravenous and intramuscular injection 250 mg, 500 mg, 1.0 g.250 mg, 500 mg, 1.0 g of active ingredient in bottles of a glass tube for medicines with a capacity of 10 ml, hermetically sealed with rubber stoppers, crimped with aluminum caps.

1; 5; 10 bottles together with the instruction for use are placed in an individual pack.

50 bottles with the application of an equal number of instructions are placed in a box of cardboard (for hospitals).

Packaging complete with a solvent - water for injection. The kit includes:

a) 1 bottle with the drug and 1 ampoule with water for injection for 5 ml;

b) 5 bottles of the drug and 5 ampoules of water for injection for 5 ml;

at) 10 vials of the drug and 10 ampoules of water for injection for 5 ml.

The kit is placed in an individual pack of cardboard together with instructions for medical use, ampoule scarifier. When using ampoules with an incision, a ring of fracture or a break point, the ampoule scaper is not inserted.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Keep out of the reach of children.

Shelf life:

3 years. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004398

Date of registration:01.08.2017

Expiration Date:01.08.2022

The owner of the registration certificate:Promomed Rus, Open CompanyPromomed Rus, Open Company Russia

Manufacturer: & nbsp

BIOCHEMIST, OJSC Russia

Information update date: & nbsp12.09.2017

Illustrated instructions

Instructions

Amikacin (Amikacin)