AMIKACIN

Active material: Amikacin
When ATH: J01GB06
CCF: Antibiotics aminoglycoside
ICD-10 codes (testimony): A39, A40, A41, G00, i33, J15, J20, J42, J85, J86, K65.0, K81.0, K81.1, K83.0, L01, L02, L03, L08.0, L89, M00, M86, N10, N11, N30, N34, N41, T79.3, Z29.2
When CSF: 06.05.01
Manufacturer: Synthesis of {Russia}

Pharmaceutical form, composition and packaging

Solution for in / and the / m clear, colorless or slightly colored.

Excipients: sodium bisulfite (sodium metabisulfite), sodium citrate d/and (sodium citrate pentaseskvigidrat), sulfuric acid divorced, water d / and.

2 ml – glass ampoule (5) – contour cell package (1) – packs cardboard.
2 ml – glass ampoule (5) – contour cell package (2) – packs cardboard.
2 ml – glass ampoule (10) – contour cell package (1) – packs cardboard.
2 ml – glass ampoule (10) – cardboard boxes.

Solution for in / and the / m clear, colorless or slightly colored.

Excipients: sodium bisulfite (sodium metabisulfite), sodium citrate d/and (sodium citrate pentaseskvigidrat), sulfuric acid divorced, water d / and.

4 ml – glass ampoule (5) – contour cell package (1) – packs cardboard.
4 ml – glass ampoule (5) – contour cell package (2) – packs cardboard.
4 ml – glass ampoule (10) – contour cell package (1) – packs cardboard.
4 ml – glass ampoule (10) – cardboard boxes.

Powder for solution for I / O, and the / m white or nearly white, hygroscopic.

Vials 10 ml (1) – packs cardboard.
Vials 10 ml (5) – packs cardboard.
Vials 10 ml (10) – packs cardboard.

Pharmacological action

Polusinteticeski antibiotic broad-spectrum from aminoglycoside, bactericidal effect. Communicating with the 30S subjedinica ribosom, prevents the formation of complex transport and messenger RNA, blocking protein synthesis, as well as destroying zitoplazmaticalkie membranes of bacteria.

Vsokoakteven 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. (incl. resistant to penicillin, some zefalosporynam).

Moderately active against Streptococcus spp.

Together with the appointment of benzilpenitsillinom shows synergies action against strains of Enterococcus faecalis.

No effect on anaerobic microorganisms.

Amikacin does not lose activity under the action of enzymes, inaktiviruûŝih other aminoglycosides, and may remain active against strains of Pseudomonas aeruginosa, resistant to tobramicinu, gentamicin and netilmicinu.

Pharmacokinetics

Absorption

After the/m of rapidly and completely absorbed. C_max in plasma with the/m in a dose of 7.5 mg / kg – 21 ug / ml, after 30 min on/in infusions in the dose 7.5 mg / kg – 38 ug / ml. After the/m of t_max – about 1.5 no.

The average therapeutic concentration in/in or/m introduction maintained for a period of 10-12 no.

Distribution

Plasma protein binding is 4-11%. V_d adult – 0.26 l / kg, children – 0.2-0.4 l / kg, in newborn: at the age of less than 1 weeks and weighing less than 1500 g – to 0.68 l / kg, at the age of less than 1 weeks and weighing more than 1500 g – to 0.58 l / kg, in cystic fibrosis patients – 0.3-0.39 l / kg.

It is distributed in the extracellular fluid (contents of abscesses, pleural effusion, ascite, pericardial, synovial, lymphatic and peritoneal fluid); in high concentrations detected in the urine; in low – in bile, breast milk, the aqueous humor of the eye, bronchial secretions, sputum and cerebrospinal fluid. It penetrates into all body tissues, where accumulated intracellularly; high concentrations are observed in organs with a good blood supply: lungs, liver, myocardial, spleen, and particularly in the kidneys, where is accumulated in the cortical substance, lower concentrations – muscle, adipose tissue and bones.

When you assign in sredneterapevtičeskih doses (normal) adults not to cross the Geb amikacin, When brain nerve membrane permeability increases slightly. The newborn is achieved higher concentrations in cerebrospinal fluid, than in adults. It penetrates through the placental barrier: detected in the blood of the fetus and amniotic fluid.

Metabolism

Do not metabolized.

Deduction

T_1/2 adult – 2-4 no, in newborn – 5-8 no, older children have – 2.5-4 no. The final T_1/2 – more 100 no (release from intracellular depots).

Report kidneys by clubockova filtering (65-94 %) mainly unchanged. Renal clearance – 79-100 ml / min.

Pharmacokinetics in special clinical situations

T_1/2 in adults with violation of kidney function varies depending on the extent of the violation – to 100 no, in patients with cystic fibrosis – 1-2 no, patients with burns and hyperthermia T_1/2 may be shorter than average due to increased ground clearance.

Displayed in hemodialysis (50% for 4-6 no), peritoneal dialysis is less effective (25% for 48-72 no).

Testimony

Infectious-inflammatory diseases, caused by Gram-negative microorganisms (resistant to gentamicin, sizomicinu and kanamycin) or associations of grampolaugitionah and gramotricationah microorganisms:

- Respiratory tract infections (bronchitis, pneumonia, empyema, lung abscess);

- Sepsis;

- Bacterial endocarditis;

-CNS infections (including meningitis);

- Infections of the abdominal cavity (incl. peritonitis);

-urinary tract infection (pyelonephritis, cystitis, uretrit);

-fatigue infections of the skin and soft tissues (incl. infected burns, infected sores and decubitus different Genesis);

- Infection of the biliary tract;

- Bone and joint infections (incl. osteomyelitis);

-wound infection;

- Postoperative infections.

Dosage regimen

The drug is introduced into / m, I / (spray, during 2 minutes or drip) adults and children over 6 years – by 5 mg / kg every 8 or h 7.5 mg / kg every 12 no. At bacterial infections of the urinary tract (uncomplicated) – by 250 mg every 12 no; After the hemodialysis session can be assigned additional dose – 3-5 mg / kg.

The maximum dose for Adult – 15 mg / kg / day, but not more 1,5 g / day for 10 days. The duration of treatment with on/in the introduction – 3-7 days, with the / m – 7-10 days.

To preterm infants initial single dose of 10 mg / kg, then 7.5 mg / kg every 18-24 no; to infants and children up to 6 years the initial dose – 10 mg / kg, then 7.5 mg / kg every 12 h for 7-10 days.

At infected Burns may require dose 5-7.5 mg / kg every 4-6 h in connection with shorter T_1/2 (1-1.5 no) This category of patients.

In/in drip for misleading amikacin 30-60 m, in case of need – spray.

For i / v administration (drop) the drug previously diluted 200 ml 5% dextrose (Glucose) or 0.9% sodium chloride solution. Amikaczina concentration in the solution for the on/in the introduction should not exceed 5 mg / ml.

At violation excretory functions of the kidneys It is necessary to reduce the dose or increase the interval between wvedeniami. In the event of an increase the interval between wvedeniami (If the value CC is unknown, and the patient's condition stable) the interval between the introduction of the preparation set according to the following formula:

interval (no) = concentration of whey creatinine × 9.

If the concentration of serum creatinine is 2 mg / dL, the recommended single dose (7.5 mg / kg) You must enter every 18 no. When you increase the single dose interval does not change.

If a single dose with an unmodified first dose dispensing mode for patients with renal insufficiency is 7.5 mg / kg. Calculation of subsequent doses is as follows:

Subsequent dose (mg), you enter every 12 h = QC (ml / min) patient × initial dose (mg)/QA OK (ml / min).

Side effect

From the digestive system: nausea, vomiting, abnormal liver function (activity increase “Hepatic” transaminases, giperʙiliruʙinemija).

From the hematopoietic system: anemia, leukopenia, granulocytopenia, thrombocytopenia.

From the central and peripheral nervous system: headache, drowsiness, neurotoxic effects (clonus, benumbed sensation, tingling, seizures), violation of neuromuscular transmission (respiratory arrest).

From the senses: ototoxicity (hearing loss, vestibular and labyrinth disorders, irreversible deafness), a toxic effect on the vestibular system (discoordination movements, dizziness, nausea, vomiting).

From the urinary system: nephrotoxicity – impairment of renal function (oligurija, proteinuria, mikrogematuriâ).

Allergic reactions: skin rash, itch, dermahemia, fever, angioedema.

Local reactions: soreness at the injection site, dermatitis, phlebitis and periphlebitis (at / in the introduction).

Contraindications

-Neuritis of the auditory nerve;

-severe chronic renal insufficiency with azotemia and uremyei;

- Pregnancy;

- Hypersensitivity to the drug;

-hypersensitivity to other aminoglikozidam history.

FROM caution the drug should be used when myasthenia, parkinsonizme, botulizme (aminoglycosides can cause a violation of neuromuscular transmission, which leads to a further weakening of the skeletal muscles), degidratacii, renal failure, in the newborn, in preterm infants, in elderly patients, lactation.

Pregnancy and lactation

The drug is contraindicated in pregnancy.

In the presence of the living testimony of the drug can be used in lactating women. It will be appreciated, that aminoglikozida stand out with breast milk in small amounts. They are poorly absorbed from the digestive tract, and related complications in infants is not registered.

Cautions

Before using the define sensitivity of selected pathogens, using disks, containing 30 micrograms amikaczina. In diameter growth-free zone 17 mm or more is considered a sensitive organism, from 15 to 16 mm – moderately sensitive, less 14 mm – sustainable.

Amikaczina concentration in the plasma should not exceed 25 ug / ml (therapeutic concentration is 15-25 ug / ml).

During the period of treatment should be not less than 1 times per week to monitor kidney function, the auditory nerve and the vestibular apparatus.

The likelihood of higher Nephrotoxicity in patients with impairment of renal function, as well as in the appointment of high doses or for a long time (This category of patients may require daily monitoring of renal function).

When poor audiometric test dose reduce or stop treatment.

Patients with infectious and inflammatory diseases of the urinary tract are advised to take an increased amount of fluid with adequate diureze.

In the absence of positive clinical Dynamics should be mindful of the possible development of resistant microorganisms. In such cases, it is necessary to cancel treatment and initiate appropriate therapy.

Contained in the composition of sodium disul′fit may lead to the development of patients with allergic complications (until the anaphylactic reactions), especially in patients with allergological history.

Overdose

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

Treatment: for the lifting of the embargo neuromuscular transmission and its consequences – hemodialysis or peritoneal dialysis; anticholinesterase agents, calcium salt, IVL, other symptomatic and supportive therapy.

Drug Interactions

Shows high synergy with karbenicillinom, benzilpenicillinom, cephalosporins (in patients with severe chronic renal insufficiency when coupled with the use of beta-lactam antibiotics may decrease the effectiveness of aminoglycosides).

Nalidixic acid, polymyxin b, cisplatin, Vancomycin increases the risk of development of OTO- and nephrotoxicity.

Diuretic (especially furosemide), cephalosporins, penicillins, sulfonamides and NSAIDS, competing for the active secretion in bone nefrona, block eliminatiu aminoglycosides, increase their concentration in the serum, reinforcing nefro- and neurotoxicity.

Amikacin enhances miorelaksirutee kurarepodobnykh drugs.

Together with amikacin methoxyflurane, Parenteral polymyxin, capreomycin and other medicines, blocking neuromuscular transmission (halogenated hydrocarbons – means for inhalation anesthesia, opioid analgesics), a large number of blood transfusions citratnymi preservatives to increase the risk of breathing stops.

Injecting a indometacin increases the risk of toxic effects aminoglikozidov (the increase in T_1/2 and reduced ground clearance).

Amikacin reduces the effectiveness antimiasteniceskih drugs.

Pharmaceutical interaction

Farmatsevticeski incompatible with penitsillinami, geparinom, cephalosporins, capreomycin, amphotericin B, hydrochlorothiazide, Erythromycin, nitrofurantoinom, vitamins b and c, potassium chloride.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

List B. The drug should be stored out of reach of children, dry, the dark place at a temperature between 5° c to 25° c. Shelf life – 2 year.