Amikacin (Solution, Powder) Instructions for Use

ATC Code

J01GB06 (Amikacin)

Active Substance

Amikacin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Antibiotic of the aminoglycoside group

Pharmacotherapeutic Group

Systemic antibacterial agents; aminoglycosides; other aminoglycosides

Pharmacological Action

A broad-spectrum semi-synthetic antibiotic from the aminoglycoside group, it acts bactericidally.

By binding to the 30S ribosomal subunit, it prevents the formation of the transfer and messenger RNA complex, blocks protein synthesis, 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 strains resistant to penicillin, some cephalosporins).

Moderately active against Streptococcus spp.

When administered simultaneously with benzylpenicillin, it exhibits a synergistic effect against strains of Enterococcus faecalis.

Anaerobic microorganisms are resistant to the drug.

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

Pharmacokinetics

Absorption

After intramuscular administration, it is absorbed rapidly and completely. C_max in blood plasma after intramuscular administration at a dose of 7.5 mg/kg is 21 µg/ml, after a 30-minute intravenous infusion at a dose of 7.5 mg/kg is 38 µg/ml. After intramuscular administration, T_max is about 1.5 hours.

The average therapeutic concentration after intravenous or intramuscular administration is maintained for 10-12 hours.

Distribution

Plasma protein binding is 4-11%. V_d in adults is 0.26 L/kg, in children is 0.2-0.4 L/kg, in newborns: under 1 week of age and weighing less than 1500 g – up to 0.68 L/kg, under 1 week of age and weighing more than 1500 g – up to 0.58 L/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); found in high concentrations in urine; in low concentrations – in bile, breast milk, aqueous humor of the eye, bronchial secretions, sputum, and cerebrospinal fluid.

It penetrates well into all body tissues, where it accumulates intracellularly; high concentrations are noted in well-perfused organs: lungs, liver, myocardium, spleen, and especially in the kidneys, where it accumulates in the cortical substance; lower concentrations are found in muscles, adipose tissue, and bones.

When prescribed in average therapeutic doses (normally) to adults, Amikacin does not penetrate the blood-brain barrier; with meningitis, permeability increases somewhat. In newborns, higher concentrations in the cerebrospinal fluid are achieved than in adults. It crosses the placental barrier: it is found in the fetal blood and amniotic fluid.

Metabolism

Not metabolized.

Elimination

T_1/2 in adults is 2-4 hours, in newborns is 5-8 hours, in older children is 2.5-4 hours. The terminal T_1/2– is more than 100 hours (release from intracellular depots).

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

Pharmacokinetics in special clinical cases

T_1/2 in adults with impaired renal function 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, T_1/2 may be shorter than average due to increased clearance.

It is removed by hemodialysis (50% over 4-6 hours); peritoneal dialysis is less effective (25% over 48-72 hours).

Indications

Infectious and inflammatory diseases caused by gram-negative microorganisms (resistant to gentamicin, sisomicin, and kanamycin) or associations of gram-positive and gram-negative microorganisms

• Respiratory tract infections (bronchitis, pneumonia, pleural empyema, lung abscess);
• Sepsis;
• Septic endocarditis;
• CNS infections (including meningitis);
• Abdominal infections (including peritonitis);
• Urinary tract infections (pyelonephritis, cystitis, urethritis);
• Purulent skin and soft tissue infections (including infected burns, infected ulcers and bedsores of various origins);
• Biliary tract infections;
• Bone and joint infections (including osteomyelitis);
• Wound infection;
• Postoperative infections.

ICD codes

Dosage Regimen

Powder

The drug is administered intramuscularly, intravenously (bolus over 2 minutes or drip) to adults and children over 6 years – 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours. For bacterial urinary tract infections (uncomplicated) – 250 mg every 12 hours; after a hemodialysis session, an additional dose of 3-5 mg/kg may be prescribed.

Maximum doses for adults – 15 mg/kg/day, but not more than 1.5 g/day for 10 days. The duration of treatment with intravenous administration is 3-7 days, with intramuscular administration – 7-10 days.

For premature newborns, the initial single dose is 10 mg/kg, then 7.5 mg/kg every 18-24 hours; for 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.

For infected burns, a dose of 5-7.5 mg/kg every 4-6 hours may be required due to the shorter T_1/2(1-1.5 hours) in this category of patients.

Amikacin is administered intravenously by drip over 30-60 minutes, or if necessary, by bolus.

For intravenous administration (drip), the drug is preliminarily diluted in 200 ml of a 5% dextrose (glucose) solution or 0.9% sodium chloride solution. The concentration of amikacin in the solution for intravenous administration should not exceed 5 mg/ml.

In case of impaired renal excretory function, a dose reduction or an increase in the intervals between administrations is necessary. If the interval between administrations is increased (if the creatinine clearance value is unknown and the patient’s condition is stable), the interval between drug administrations is set according to the following formula:

Interval (hours) = serum creatinine concentration × 9.

If the serum creatinine concentration is 2 mg/dl, then 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 case of a reduction in the single dose with an unchanged dosing regimen, the first dose for patients with renal failure is 7.5 mg/kg. Subsequent doses are calculated using the following formula:

Subsequent dose (mg), administered every 12 hours = patient’s CC (ml/min) × initial dose (mg)/normal CC (ml/min).

Solution

Set individually, taking into account the severity and location of the infection, and the sensitivity of the pathogen. Administered intramuscularly, intravenous administration (bolus over 2 minutes or drip) is also possible.

Intramuscularly or intravenously for adults and adolescents – 5 mg/kg every 8 hours or 7.5 mg/kg every 12 hours for 7-10 days. For children, the initial dose is 10 mg/kg, then 7.5 mg/kg every 12 hours.

Maximum doses for adults: daily dose – 1.5 g.

Adverse Reactions

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

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

From the central and peripheral nervous system headache, drowsiness, neurotoxic effect (muscle twitching, numbness, tingling sensation, epileptic seizures), impaired neuromuscular transmission (respiratory arrest).

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

From the urinary system nephrotoxicity – impaired renal function (oliguria, proteinuria, microhematuria).

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

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

Contraindications

• Acoustic neuritis;
• Severe chronic renal failure with azotemia and uremia;
• Pregnancy;
• Hypersensitivity to the components of the drug;
• History of hypersensitivity to other aminoglycosides.

Use with caution in myasthenia gravis, parkinsonism, botulism (aminoglycosides can cause impaired neuromuscular transmission, leading to further weakening of skeletal muscles), dehydration, renal failure, in the neonatal period, in premature infants, in elderly patients, during lactation.

Use in Pregnancy and Lactation

The drug is contraindicated during pregnancy.

If there are vital indications, the drug can be used in nursing women. It should be borne in mind that aminoglycosides are excreted in breast milk in small amounts. They are poorly absorbed from the gastrointestinal tract, and no associated complications have been reported in breastfed infants.

Use in Renal Impairment

Contraindicated in severe chronic renal failure with azotemia and uremia.

In case of impaired renal excretory function, adjustment of the dosing regimen is required.

Pediatric Use

For premature newborns, the initial single dose is 10 mg/kg, then 7.5 mg/kg every 18-24 hours; for 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.

Geriatric Use

Use with caution in elderly patients.

Special Precautions

Before use, determine the sensitivity of the isolated pathogens using discs containing 30 mcg of amikacin. If the diameter of the growth-free zone is 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 µg/ml (the therapeutic concentration is 15-25 µg/ml).

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

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

If audiometric tests are unsatisfactory, the drug dose should be reduced or treatment discontinued.

Patients with infectious and inflammatory diseases of the urinary tract are recommended to take increased amounts of fluid with adequate diuresis.

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

The sodium disulfite contained in the drug may cause the development of allergic complications (up to anaphylactic reactions) in patients, especially in patients with an allergic history.

Overdose

Symptoms toxic reactions – hearing loss, ataxia, dizziness, urination disorders, thirst, decreased appetite, nausea, vomiting, ringing or feeling of stuffiness in the ears, respiratory distress.

Treatment to relieve neuromuscular blockade and its consequences – hemodialysis or peritoneal dialysis; anticholinesterase agents, calcium salts, artificial ventilation, other symptomatic and supportive therapy.

Drug Interactions

Exhibits synergism when interacting with carbenicillin, benzylpenicillin, cephalosporins (in patients with severe chronic renal failure, when used concomitantly with beta-lactam antibiotics, a decrease in the effectiveness of aminoglycosides is possible).

Nalidixic acid, polymyxin B, cisplatin, 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 the blood serum, enhancing nephro- and neurotoxicity.

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

With simultaneous use of amikacin with methoxyflurane, polymyxins for parenteral administration, capreomycin, and other drugs that block neuromuscular transmission (halogenated hydrocarbons – agents for inhalation anesthesia, opioid analgesics), transfusion of large amounts of blood with citrate preservatives increases the risk of respiratory arrest.

Parenteral administration of indomethacin increases the risk of toxic effects of aminoglycosides (increased T_1/2 and decreased clearance).

Amikacin reduces the effectiveness of antimyasthenic drugs.

Pharmaceutical interaction

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

Storage Conditions

List B. The drug should be stored out of the reach of children, in a dry, light-protected place at a temperature from 5°C (41°F) to 25°C (77°F).

Shelf Life

The shelf life is 2 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.