2010/09/20

Amikacin

Composition, structure and packing

Solution for in / and / m the introduction of transparent, colorless or slightly colored.

1 ml of 1 amp. - Amikacin (in the form of sulfate) 250 mg 500 mg

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

Solution for in / and / m the introduction of transparent, colorless or slightly colored.

1 ml of 1 amp. - Amikacin (in the form of sulfate) 250 mg 1 g

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

Powder for solution for in / and / m the introduction of white or almost white, hygroscopic.

1 vial. - Amikacin (in the form of sulfate) 1 g

Clinico-pharmacological group

Aminoglycoside antibiotic.

Pharmacological action

Semisynthetic broad-spectrum antibiotic of the aminoglycoside, bactericidal effect. Communicating with the 30S subunit of ribosomes, prevents the formation of the complex transport and messenger RNA, blocking protein synthesis, but also destroys the cytoplasmic membrane 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 penicillin-resistant, some cephalosporins).

Moderately active against Streptococcus spp.

At the same time the appointment shows synergy with benzylpenicillin acts against strains of Enterococcus faecalis.

No effect on anaerobic microorganisms.

Amicacin not lose activity under the action of enzymes, inactivating other aminoglycosides, and may remain active against strains of Pseudomonas aeruginosa, resistant to tobramitsinu, gentamicin and netilmitsinu.

Pharmacokinetics

Absorption

After i / m administration is absorbed quickly and completely. Cmax in blood plasma in v / m a dose 7.5 mg / kg - 21 mg / ml after 30 min i / v infusion at a dose of 7.5 mg / kg - 38 mg / ml. After a / m administration Tmax - about 1.5 hours

The average therapeutic concentration at in / or / m administration persists for 10-12 hours

Distribution

Plasma protein binding is 4-11%. Vd in adults - 0.26 L / kg in children - 0.2-0.4 L / kg, in infants: age less than 1 week and weighing less than 1500 grams - up to 0.68 L / kg, at the age of less than 1 weeks and weighing more than 1500 g - up to 0.58 liter / kg, in patients with cystic fibrosis - 0.3-0.39 L / kg.

It is well distributed in the extracellular fluid (abscess contents, pleural effusion, ascitic, pericardial, synovial, lymphatic, and peritoneal fluid) in high concentrations found in urine in low - in the bile, breast milk, aqueous eyes, bronchial secretion, sputum, and cerebrospinal fluid. Good penetrates all body tissues where they can accumulate intracellularly; high concentrations are found in organs with a good blood supply: the lungs, liver, myocardium, spleen, and especially in the kidneys, which accumulates in the cortical substance, the lower concentrations - in muscle, fat and bones .

In the appointment in medium doses (normal) adult amikacin does not penetrate the BBB, the inflammation of the meninges permeability increases slightly. Babies are achieved with higher concentrations in the cerebrospinal fluid than in adults. Penetrates the placental barrier: is found in fetal blood and amniotic fluid.

Metabolism

Not metabolized.

Withdrawal

T1 / 2 in adults - 2-4 hours, newborn - 5-8 hours, in children older - 2.5-4 hours on end T1 / 2 - more than 100 hours (release from intracellular stores).

We derive the kidneys by glomerular filtration (65-94%) mainly unchanged. Renal clearance - 79-100 ml / min.

Pharmacokinetics in special clinical situations

T1 / 2 of adults in violation of renal function varies depending on the degree of violation - up to 100 h, in patients with cystic fibrosis - 1-2 hours in patients with burns and hyperthermia T1 / 2 may be shorter than average due to increased clearance .

We derive in hemodialysis patients (50% for 4-6 h), peritoneal dialysis is less efficient (25% for 48-72 h).

Indications for use of the drug

Infectious-inflammatory diseases caused by Gram-negative microorganisms (resistant to gentamicin, kanamycin and sizomitsinu) or associations of gram-positive and Gram-negative microorganisms:
respiratory tract infections (bronchitis, pneumonia, empyema, lung abscess);
sepsis
bacterial endocarditis;
CNS infection (including meningitis);
abdominal infections (including peritonitis);
urinary tract infection (pyelonephritis, cystitis, urethritis);
suppurative infection of skin and soft tissue (including infected burns, infected ulcers and pressure sores of various origins);
biliary tract infection;
infections of bones and joints (including osteomyelitis);
wound infection;
postoperative infection.

Dosage regimen

The drug is introduced into / m / v (jet, within 2 minutes, or drip) in adults and children over 6 years - 5 mg / kg every 8 hours or 7.5 mg / kg every 12 h. The bacterial urinary tract infections ( uncomplicated) - 250 mg every 12 h after hemodialysis may be assigned additional dose - 3-5 mg / kg.

The maximum dose for adults - 15 mg / kg but not more than 1,5 g / in 10 days. Duration of treatment with a / in the introduction - 3-7 days, with a / m - 7-10 days.

For premature infants the initial single dose of 10 mg / kg followed by 7.5 mg / kg every 18-24 h for infants and children under 6 years of the initial dose - 10 mg / kg followed by 7.5 mg / kg every 12 h for 7-10 days.

When infected burns may require dose 5-7.5 mg / kg every 4-6 hours in connection with a shorter T1 / 2 (1-1.5 h) in this category of patients.

In / in amikacin infusion over 30-60 minutes, if necessary - the jet.

For iv administration (infusion) product previously diluted with 200 ml of 5% dextrose (glucose) or 0.9% sodium chloride solution. The concentration of amikacin in the solution for i / in the introduction should not exceed 5 mg / ml.

In violation of renal excretory function should reduce the dose or increasing the intervals between infusions. In the case of increasing the interval between infusions (if the value of CC is unknown, but the patient is stable), the interval between the introduction of the drug set as follows:

interval (h) = serum creatinine × 9.

If serum creatinine is 2 mg / dl, the recommended single dose (7.5 mg / kg) must be entered every 18 h. In the interval a single dose not change.

In the case of reducing the single dose in unmodified batch mode the first dose for patients with renal failure is 7.5 mg / kg. The calculation of subsequent doses is as follows:

Follow-up dose (mg), entered every 12 h = QC (ml / min) in a patient × initial dose (mg) / QC standard (ml / min).

Side effect
On the part of the digestive system: nausea, vomiting, abnormal liver function (increased activity of "liver" transaminases, hyperbilirubinemia).
On the part of the hemopoietic system: anemia, leukopenia, granulocytopenia, thrombocytopenia.
From the central nervous system and peripheral nervous system: headache, drowsiness, neurotoxicity (muscle twitching, feeling of numbness, tingling, seizures), violation of neuromuscular transmission (respiratory arrest).
From the senses: ototoxicity (hearing loss, vestibular and labyrinthine disorders, irreversible deafness), the toxic effect on the vestibular apparatus (discoordination movements, dizziness, nausea, vomiting).
On the part of the urinary system: renal toxicity - renal dysfunction (oliguria, proteinuria, microhematuria).

Allergic reactions: skin rash, itching, skin flushing, fever, edema Quincke.

Local reactions: pain at the injection site, dermatitis, phlebitis and periflebit (with a / in the introduction).

Contraindications to the use of the drug
neuritis of the auditory nerve;
severe chronic renal insufficiency with azotemia and uremia;
Pregnancy
Hypersensitivity to the drug's components;
hypersensitivity to other aminoglycosides in history.

With care use in patients with myasthenia gravis, Parkinson's disease, botulism (aminoglycosides may result in violation of neuromuscular transmission, which leads to further weakening of the skeletal muscles), dehydration, kidney failure, in the neonatal period, preterm infants, elderly patients, in the period lactation.

Pregnancy and lactation

The drug is contraindicated in pregnancy.

In the presence of vital evidence the drug can be used by lactating women. It should be borne in mind that aminoglycosides are excreted with breast milk in small amounts. They are poorly absorbed from the gastrointestinal tract, and associated complications in infants has been reported.

Application for violations of renal function

Do not use this in chronic renal failure with severe azotemia and uremia.

In violation of renal excretory function requires correction dosing regimen.

Cautions

Before use, determine the sensitivity of isolated pathogens, using disks containing 30 micrograms amikacin. If the diameter of the growth of free zones of 17 mm and a microorganism is considered sensitive, from 15 to 16 mm - moderately susceptible, less than 14 mm - sustainable.

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

During the period of treatment must be at least 1 time per week to monitor kidney function, auditory nerve and the vestibular apparatus.

The likelihood of nephrotoxicity was higher in patients with impaired renal function, as well as the appointment of high doses or for long periods (such patients may require daily monitoring of kidney function).

When poor audiometric test dose reduce or stop treatment.

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

In the absence of positive clinical dynamics should be mindful of the possibility of development of resistant microorganisms. In such cases, you must cancel the treatment and initiate appropriate therapy.

Contained in the preparation of sodium disulfit may cause the development of patients with allergic complications (up to anaphylactic reactions), especially in patients with a history of allergenic.

Overdose

Symptoms: Toxic reaction - hearing loss, ataxia, dizziness, disorders of urination, thirst, loss of appetite, nausea, vomiting, ringing or a sense of laying in ears, impaired breathing.

Treatment: removal of the blockade of neuromuscular transmission and its consequences - hemodialysis or peritoneal dialysis; anticholinesterase funds, calcium salts, mechanical ventilation, the other symptomatic and supportive therapy.

Drug Interactions

Shows synergy in the interaction with Carbenicillin, benzylpenicillin, cephalosporins (in patients with severe chronic renal insufficiency or combined with beta-lactam antibiotics may decrease the effectiveness of aminoglycosides).

Nalidixic acid, polymyxin B, vancomycin and cisplatin increases the risk of Oto-and nephrotoxicity.

Diuretics (especially furosemide), cephalosporins, penicillins, sulfonamides, and NSAIDs, competing for the active secretion in the tubules of the nephron, blocking the elimination of aminoglycosides, increase their concentration in the serum, increasing nefro-and neurotoxicity.

Amicacin enhances miorelaksiruyuschee action curariform drugs.

When applied simultaneously with amikacin Methoxyflurane, Polymyxin for parenteral administration, capreomycin and other drugs that block neuromuscular transmission (halogenated hydrocarbons - tools for inhalation anesthesia, opioid analgesics), transfusion of large amounts of blood with citrate preservative increase the risk of stopping breathing.

Parenteral administration of indomethacin increases the risk of toxic effects of aminoglycosides (increased T1 / 2 and decrease in clearance).

Amicacin antimiastenicheskih reduces the effectiveness of medicines.

Pharmaceutical interactions

Pharmaceutical incompatible with penicillins, heparin, cephalosporins, capreomycin, amphotericin B, hydrochlorothiazide, erythromycin, Nitrofurantoin, vitamins B and C, potassium chloride.

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Drug prescription.

Terms and Conditions of storage

List B. The drug should be stored out of reach of children, dry, dark place at temperatures from 5 ° to 25 ° C. Shelf life - 2 years.