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

Semisynthetic antibiotic of a wide spectrum of action, acts bactericidal. 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.

When used simultaneously with benzylpenicillin, it 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 injection (in / m) is absorbed quickly and completely. The maximum concentration (Cmах) with an im injection in a dose of 7.5 mg / kg - 21 μg / ml, after 30 min IV infusion 7.5 mg / kg - 38 μg / ml. Time to reach the maximum concentration (TCmah) about 1.5 hours after the / m introduction. 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 it accumulates in the cortex, lower concentrations - in muscles, adipose tissue and bones.

When used in healthy adult volunteers in medicated doses 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 1500 g - up to 0.68 l / kg, in age less than 1 week and body weight over 1500 g - 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. The half-life period (T1 / 2) in adults is 2-4 hours, in newborns 5-8 hours, in older children 2.5-4 hours. The final value of T1 / 2 is more than 100 hours (release from intracellular depot ).

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

T1 / 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 T1 / 2 may 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 gentamycin, 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 infections ) (including meningitis), infections of the abdominal cavity (incl.peritonitis), urinary tract infection (pyelonephritis, cystitis, urethritis, prostatitis), purulent skin and soft tissue infections (including infected burns, infected ulcers and bed sores of various origins), biliary tract infections, bone and joints (including. osteomyelitis), wound infection, postoperative infections.

Contraindications:

Hypersensitivity to amikacin, the drug, other aminoglycosides history, neuritis of the acoustic nerve, severe chronic renal failure with azotemia, and uremia, pregnancy.

Carefully:

Myasthenia gravis, parkinsonism, botulism (aminoglycosides may cause disruption of neuromuscular transmission, resulting in further weakening of skeletal muscle), dehydration, kidney failure, neonatal period, premature babies, elderly.

Pregnancy and lactation:

The use of the drug during pregnancy is contraindicated.

If you need to use the drug during lactation, breastfeeding is discontinued.

Dosing and Administration:

Intramuscular (i / m), intravenous (i / v), dropwise over 30-60 min.

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

With the / m introduction is introduced deep into the areas of the body with a pronounced muscular layer (the supernatulum square of the buttock or the lateral surface of the thigh). It is recommended that an aspiration test be carried out to avoid undesirable introduction of the solution into the blood vessel.

For intravenous drip infusion, the contents of the vial are transferred to 100-200 ml of a compatible infusion fluid - 0.9% sodium chloride solution, 5% dextrose solution. The concentration of amikacin in the solution for intravenous administration should not exceed 5 mg / ml.

In children, the volume of fluid administered should be reduced depending on the dose of the drug. 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 the subsequent doses, it is necessary to separate the creatinine 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, ie:

Side effects:

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

From the nervous system: headache, drowsiness, neurotoxic effect (muscle twitching, numbness, tingling sensations, 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). The incidence of vestibular and auditory disorders Increases in patients with renal insufficiency.

From the urinary system: nephrotoxicity, impaired renal function (oliguria, proteinuria, microhematuria, hypercreatininaemia, azotemia).

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

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

Local reactions: soreness at 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 remove the blockade of the neuromuscular transmission and its consequences - hemodialysis or peritoneal dialysis; anticholinesterase drugs, calcium salts (Ca²⁺), artificial ventilation, other symptomatic and supportive therapy.

Interaction:

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

Exhibits synergistic interaction with Carbenicillin, benzylpenicillin, cephalosporins (in patients with severe chronic renal failure when combined with beta-lactam antibiotics may decrease the effectiveness of aminoglycosides).

Nalidixic acid, polymyxin AT, Cisplatinum and Vancomycin increase the risk of 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 serum, enhancing nephro and neurotoxicity.

Amikacin increases the muscle relaxant effect of curare-like drugs.

When used simultaneously with amikacin methoxyflurane, polymyxins for parenteral administration, capreomycin and other drugs that block neuromuscular transmission (halogenated hydrocarbons - inhalation anesthetics, opioid analgesics), transfusion of large amounts of blood with citrate preservatives increase the risk of respiratory arrest (especially with intraperitoneal administration of amikacin).

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

Amikacin 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 probability of nephrotoxicity was higher in patients with impaired kidney function, and also at high doses and for a long time (in this category of patients may require daily monitoring of renal 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 the increased amount of fluid at 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.

The disulfite contained in the preparation of sodium can cause the development of allergic complications in patients (up to anaphylactic reactions), especially in patients with a history of allergic anamnesis.

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

Care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Solution for intravenous and intramuscular injection, 250 mg.

Packaging:

2 ml or 4 ml into neutral glass ampoules.

5 ampoules of the drug are placed in a contour mesh package made of a polyvinyl chloride film.

5 ampoules of the drug are placed in a contour mesh package made of a polyvinyl chloride film and a flexible packaging based on aluminum foil or a packaging material combined on a paper basis.

1 or 2 contoured cells with ampoules together with the instruction for use are placed in a pack of cardboard.

Packing for hospitals

10, 20, 25, 44, 50, 75, 100, 200, 230, 360, 420 contour cell packs with ampoules together with an equal number of instructions forthe application is placed in a box of cardboard.

Storage conditions:

In 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 the product after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-002111

Date of registration:18.06.2013 / 03.07.2017

Expiration Date:18.06.2018

The owner of the registration certificate:BRYNTSALOV-A, CJSC BRYNTSALOV-A, CJSC Russia

Manufacturer: & nbsp

BRYNTSALOV-A, CJSC Russia

Information update date: & nbsp30.03.2018

Illustrated instructions

Instructions

Amikacin-Ferein® (Amikacin-Ferein®)