Amikacin Sulfate

Amikacin Sulfate

100mg/2ml

250mg/2ml

500mg/2ml

Description: Amikacin Sulfate is a semisynthetic aminoglycoside antibiotic derived from kanamycin. It is C₂₂H₄₃N₅O₁₃.2H₂SO₄. D-Streptamine, 0-3-amino-3deoxy-a-D-glycopyranosyl-(1→6)-)(6-aamino-6deoxy-a-d-glucopyranosyl-(1→ 4)-N1-(4-amino-2-hydroxyl-oxobuty)2-deoxy-, (S)-, sulfate (1:2) (salt).

Clinical Pharmacology:

Intramuscular Administration – Amikacin is rapidly absorbed after intramuscular administration. In normal adult volunteers, average peak serum concentration about 12, 16 and locally, following repeated intramuscular dosing, and when given at maximally recommended doses, no ototoxicity or nephrotoxicity has been reported. There is no evidence of drug accumulation with repeated dosing for 10 days when administered according to recommended doses.

With normal function, 91.9% of the intramuscular dose is excreted unchanged in the urine in the first 8 hours, and 98.2% within 24 hours. Mean urine concentrations for 6 hours are 563 mcg/ml following a 250mg dose. 697 mcg/ml following a 375 mg dose, and 832mcg/ml, following a 500mg dose.

Preliminary intramuscular studies in newborns of different weights (less than 1.5kg, 1.5 to 2.0 kg) at dose of 7.5mg/kg revealed that like other aminoglycosides, serum half-life values were correlated inversely with postnatal age and renal clearances of amikacin. The volume of distribution that amikacin, like other aminoglycosides remains primarily in the extracellular fluid space in neonates. Repeated dosing every 12 hours in all the above groups not demonstrate accumulation after 5 days.

Intravenous Administration – Single doses of 500mg (7.5mg/kg0 administered to normal adults as an infusion over a period of 30 minutes produced a peak serum concentration of 38mcg/ml at the end of the infusion, and levels of 24mcg/ml, 18mcg/ml and 0.75mcg/ml at 30 minutes. 1 hour an 10 hours, post infusion, respectively. Eighty four percent of the administered dose was excreted in the urine in 9 hours and about 94% within 24 hours. Repeated infusions of 7.5mg/kg every 12hours in normal adults were tolerated and caused no drug accumulation.

General – Pharmacokinetics studies in normal adult subjects reveal the mean serum half-life to be slightly over 2 hours with a mean total apparent volume of distribution of 24 liters (28% of the body weight). By the ultrafiltration technique, reports of protein binding range from 0 to 11%. The Mean serum clearance rate is about 100ml/min and the renal clearance rate is 94ml/min in subjects with normal renal function.

Indication and dosage:

Amikacin is indicated in short-treatment of serious infection due to susceptible strains of Gram negative bacteria, including Pseudomonas species, Escherichia coli, species of indole positive and indole-negative, Proteus, Providencia species, Klebsiella – Enterobacter – Seratia species and Acinobacter (mima-Herella) species.

Amikacin is effective in bacteria septecemia (including neonatal sepsis); serious infection of the respiratory tract, bones, joints, central nervous system (including meningitis) and skin and soft tissue intra-abdominal infections (including peritonitis); and in burns and post-operative infections (including postvascular surgery). Aminoglycosides are not indicated in the uncomplicated initial episodes of urinary tract infection, unless the causative organisms are not susceptible to antibiotics having less potential toxicity.

Amikacin is also effective in staphylococcal disease such as, severe infections, where the causative organisms may either Gram negative (-) bacterium or a staphylococcus, infections due to susceptible strains of staphylococci in patients allergic to other antibiotics, and in mixed staphylococcal/Gram negative (-) infections.

Contraindications:

A history of hypersensitivity to amikacin is contraindicated for its use. A history of hypersensitivity of serious toxic reactions to aminoglycosides may containdicate the use of any other aminoglycosides, because of the known cross-sensitivities of patients to drugs in this class.

Dosage and Adminstration:

The patient's pre-treatment body weight should be obtained for calculation of correct dosage. Amikacin may be given intramuscularly or intravenously.

Intramuscular Administration For Patients With Normal Renal Function:

Recommended dosage for adults, children and other infant – 15mg/kg/day divided into 2 to 3 equal doses administered at equally divided intervals i.e., 7.5mg/kg every 12 hours or 5 mg/kg every 8 hours. Treatment of patients in the heavier weight classes should not exceed 1.5g/day. When amikacin is indicated in newborns, it is recommended that a loading dose of 10mg/kg be administered initially to be followed with 7.5mg/kg every 12 hours.

The usual duration of treatment is 7 to 10 days. It is desirable to limit the duration of treatment to short term whenever feasible.

Intramuscular Administration For Patients with Impaired Renal Function:

Whenever possible, serum amikacin concentration should be monitored by appropriate assay procedures. Doses may be adjusted in patients with impaired renal function either by administering normal doses at prolonged intervals or by administering reduced doses at a fixed intervals.

Intravenous Administration:

The individual dose, the total daily dose, and the total cumulative dose of amikacin are identical to the dose recommended for intramuscular administration. The solution of intravenous use is prepared by adding the contents of 500mg vial to 100 or 200 ml of sterile diluent such as Normal Saline or 5% Dextrose in Water or any of the compatible solutions listed below.

The solution is administered to adults over 30 to 60 minutes period. The total daily dose should not exceed 15mg/kg/day and may be divided into, either 2 to 3 equally – divided doses at equally divided intervals.

Stability in IV Fluid : Aminkacin is stable for 24 hours at room temperature at concentrations of 0.25 and 5.0mg/ml in the following solutions:

5% Dextrose Injection

5% Dextrose Solution and 0.2% Sodium Chloride Injection

5% Dextrose Solution and 0.45% Sodium Chloride Injection

0.9% Sodium Chloride Injection

Lactated Ringer's Injection

Normosol R in 5% Dextrose Injection

In the above solutions with amikacin concentrations of 0.25 and 5.0mg/ml, solutions aged for 60 days at 4^oC and then stored at 25^oC had utility time of 24 hours.

At the same concentrations, solutions frozen and aged for 30 days at -15^oC and stored at 25^oC had utility time of 24 hours.

Warnings:

Patients treated with parenteral Aminoglycosides should be under close clinical observation because of the potential ototoxicity and nephrotoxicity associated with their use.

Neurotoxicity manifested as vestibular and permanent bilateral auditory ototoxicity can occur in patients with preexisting renal damage and in patients with normal renal function treated higher doses and for those longer than recommended.

Aminoglycosides are potentially nephortoxic. The risk of nephrotoxicity is greated in patients with impaired renal function and in those who receive higher doses or prolonged the therapy.

Most amikacin contains Sodium Metabisulfite, which may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in certain susceptible persons.

Storage Condition: Store at temperature not exceeding 30^oC.