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Intravenous Dilution Guidelines

AMIKACIN

The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.

Usual Diluents

NS, D5W

Standard Dilutions   [Amount of drug] [Infusion volume] [Infusion rate]

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amikacin and other antibacterial drugs, amikacin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

Admixture:
[0-1000 mg] [100 ml] [30 minutes]
Infusion rate range: 30 to 60 minutes.

Stability / Miscellaneous

Label: Refrigerate.

---- Storage/Stability ----
Amikacin sulfate is stable for 24 hours at room temperature and 2 days at refrigeration at concentrations of 0.25 and 5.0 mg/mL in the following solutions:
5% Dextrose Injection, USP
5% Dextrose and 0.2% Sodium Chloride Injection, USP
5% Dextrose and 0.45% Sodium Chloride Injection, USP
0.9% Sodium Chloride Injection, USP
Lactated Ringer’s Injection, USP
Normosol®-M in 5% Dextrose Injection
Normosol®-R in 5% Dextrose Injection

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit.

Aminoglycosides administered by any of the above routes should not be physically premixed with other drugs but should be administered separately.

Because of the potential toxicity of aminoglycosides, “fixed dosage” recommendations which are not based upon body weight are not advised. Rather, it is essential to calculate the dosage to fit the needs of each patient.


Therapeutic levels:
Peak:
Life-threatening infections: 25-30 mcg/mL
Serious infections: 20-25 mcg/mL
Urinary tract infections: 15-20 mcg/mL

Trough:
Serious infections: 1-4 mcg/mL
Life-threatening infections: 4-8 mcg/mL
Toxic concentration: Peak: >35 mcg/mL; Trough: >10 mcg/mL

Timing of serum samples: Draw peak 30 minutes after completion of 30-minute infusion or at 1 hour following initiation of infusion or I.M. injection; draw trough within 30 minutes prior to next dose

WARNINGS

Patients treated with parenteral aminoglycosides should be under close clinical observation because of the potential ototoxicity and nephrotoxicity associated with their use. Safety for treatment periods which are longer than 14 days has not been established.

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 at higher doses and/or for periods longer than those recommended. The risk of aminoglycoside-induced ototoxicity is greater in patients with renal damage. High frequency deafness usually occurs first and can be detected only by audiometric testing. Vertigo may occur and may be evidence of vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions. The risk of hearing loss due to aminoglycosides increases with the degree of exposure to either high peak or high trough serum concentrations. Patients developing cochlear damage may not have symptoms during therapy to warn them of developing eighth-nerve toxicity, and total or partial irreversible bilateral deafness may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.

Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy.

Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and following oral use of aminoglycosides. The possibility of these phenomena should be considered if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular blocking agents such as tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood. If blockage occurs, calcium salts may reverse these phenomena, but mechanical respiratory assistance may be necessary.

Renal and eighth-nerve function should be closely monitored especially in patients with known or suspected renal impairment at the onset of therapy and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels and prolonged peak concentrations above 35 micrograms per mL. Urine should be examined for decreased specific gravity, increased excretion of proteins, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained where feasible in patients old enough to be tested, particularly high risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.

Concurrent and/or sequential systemic, oral, or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration.

The concurrent use of amikacin with potent diuretics (ethacrynic acid, or furosemide) should be avoided since diuretics by themselves may cause ototoxicity. In addition, when administered, intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Dosing interval in renal impairment: Some patients may require larger or more frequent doses if serum levels document the need (ie, cystic fibrosis or febrile granulocytopenic patients)

Clcr >/=60 mL/minute: Administer every 8 hours
Clcr 40-60 mL/minute: Administer every 12 hours
Clcr 20-40 mL/minute: Administer every 24 hours
Clcr<20 mL/minute: Loading dose, then monitor levels

Hemodialysis: Dialyzable (50% to 100%); administer dose postdialysis or administer 2 /3 normal dose as a supplemental dose postdialysis and follow levels

Peritoneal dialysis: Dose as Clcr<20 mL/minute: Follow levels

Continuous arteriovenous or venovenous hemodiafiltration effects: Dose as for Clcr 10-40 mL/minute and follow levels

OVERDOSAGE
In the event of overdosage or toxic reaction, peritoneal dialysis or hemodialysis will aid in the removal of amikacin from the blood. In the newborn infant, exchange transfusion may also be considered.


DOSAGE AND ADMINISTRATION
The patient’s pretreatment body weight should be obtained for calculation of correct dosage. Amikacin Sulfate Injection, USP may be given intramuscularly or intravenously.

The status of renal function should be estimated by measurement of the serum creatinine concentration or calculation of the endogenous creatinine clearance rate. The blood urea nitrogen (BUN) is much less reliable for this purpose. Reassessment of renal function should be made periodically during therapy.

Whenever possible, amikacin concentrations in serum should be measured to assure adequate but not excessive levels. It is desirable to measure both peak and trough serum concentrations intermittently during therapy. Peak concentrations (30-90 minutes after injection) above 35 micrograms per mL and trough concentrations (just prior to the next dose) above 10 micrograms per mL should be avoided. Dosage should be adjusted as indicated.

Intramuscular Administration for Patients with Normal Renal Function-The recommended dosage for adults, children and older infants (see “WARNINGS” box) with normal renal function is 15 mg/kg/day divided into 2 or 3 equal doses administered at equally-divided intervals, i.e., 7.5 mg/kg q.12h or 5 mg/kg q.8h. Treatment of patients in the heavier weight classes should not exceed 1.5 gram/day.

When amikacin is indicated in newborns (see “WARNINGS” box), it is recommended that a loading dose of 10 mg/kg be administered initially to be followed with 7.5 mg/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. The total daily dose by all routes of administration should not exceed 15 mg/kg/day. In difficult and complicated infections where treatment beyond 10 days is considered, the use of amikacin should be re-evaluated. If continued, amikacin serum levels and renal, auditory, and vestibular functions should be monitored. At the recommended dosage level, uncomplicated infections due to amikacin-sensitive organisms should respond in 24 to 48 hours. If definite clinical response does not occur within 3 to 5 days, therapy should be stopped and the antibiotic susceptibility pattern of the invading organism should be rechecked. Failure of the infection to respond may be due to resistance of the organism or to the presence of septic foci requiring surgical drainage.

When amikacin is indicated in uncomplicated urinary tract infections, a dose of 250 mg twice daily may be used.

DOSAGE GUIDELINES

ADULTS AND CHILDREN WITH NORMAL RENAL FUNCTION

Patient Weight

Dosage

7.5 mg/kg

5 mg/kg

lbs.

kg

q12h

OR

q8h

99

45

337.5 mg

225 mg

110

50

375 mg

250 mg

121

55

412.5 mg

275 mg

132

60

450 mg

300 mg

143

65

487.5 mg

325 mg

154

70

525 mg

350 mg

165

75

562.5 mg

375 mg

176

80

600 mg

400 mg

187

85

637.5 mg

425 mg

198

90

675 mg

450 mg

209

95

712.5 mg

475 mg

220

100

750 mg

500 mg


Intramuscular Administration for Patients with Impaired Renal Function-Whenever possible, serum amikacin concentrations 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 interval.

Both methods are based on the patient’s creatinine clearance or serum creatinine values since these have been found to correlate with aminoglycoside half-lives in patients with diminished renal function. These dosage schedules must be used in conjunction with careful clinical and laboratory observations of the patient and should be modified as necessary. Neither method should be used when dialysis is being performed.

Normal Dosage at Prolonged Intervals-If the creatinine clearance rate is not available and the patient’s condition is stable, a dosage interval in hours for the normal dose can be calculated by multiplying the patient’s serum creatinine by 9, e.g., if the serum creatinine concentration is 2 mg/100 mL, the recommended single dose (7.5 mg/kg) should be administered every 18 hours.

Reduced Dosage at Fixed Time Intervals-When renal function is impaired and it is desirable to administer amikacin at a fixed time interval, dosage must be reduced. In these patients serum amikacin concentrations should be measured to assure accurate administration of amikacin and to avoid concentrations above 35 mcg/mL. If serum assay determinations are not available and the patient’s condition is stable, serum creatinine and creatinine clearance values are the most readily available indicators of the degree of renal impairment to use as a guide for dosage.

First, initiate therapy by administering a normal dose, 7.5 mg/kg, as a loading dose. This loading dose is the same as the normally recommended dose which would be calculated for a patient with a normal renal function as described above.

To determine the size of maintenance doses administered every 12 hours, the loading dose should be reduced in proportion to the reduction in the patient’s creatinine clearance rate

Maintenance Dose

=

observed CC in mL/min

x

calculated loading

Every 12 Hours

normal CC in mL/min

dose in mg

(CC-creatinine clearance rate)


An alternate rough guide for determining reduced dosage at 12 hour intervals (for patients whose steady state serum creatinine values are known) is to divide the normally recommended dose by the patient’s serum creatinine.

The above dosage schedules are not intended to be rigid recommendations but are provided as guides to dosage when the measurement of amikacin serum levels is not feasible.

Intravenous Administration-The individual dose, the total daily dose, and the total cumulative dose of amikacin sulfate are identical to the dose recommended for intramuscular administration. The solution for intravenous use is prepared by adding the contents of a 500 mg vial to 100-200 mL of sterile diluent such as 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP or any of the compatible solutions listed below.

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

In pediatric patients the amount of fluid used will depend on the amount ordered for the patient. It should be a sufficient amount to infuse the amikacin over a 30 to 60 minute period. Infants should receive a 1 to 2 hour infusion.

Stability in I.V. Fluids-Amikacin sulfate is stable for 24 hours at room temperature at concentrations of 0.25 and 5.0 mg/mL in the following solutions:

5% Dextrose Injection, USP

5% Dextrose and 0.2% Sodium Chloride Injection, USP

5% Dextrose and 0.45% Sodium Chloride Injection, USP

0.9% Sodium Chloride Injection, USP

Lactated Ringer’s Injection, USP

Normosol®-M in 5% Dextrose Injection

Normosol®-R in 5% Dextrose Injection

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever the solution and container permit.

Aminoglycosides administered by any of the above routes should not be physically premixed with other drugs but should be administered separately.

Because of the potential toxicity of aminoglycosides, “fixed dosage”recommendations which are not based upon body weight are not advised. Rather, it is essential to calculate the dosage to fit the needs of each patient.

To prevent needle-stick injuries, needles should not be recapped, purposely bent, or broken by hand.


HOW SUPPLIED
Amikacin Sulfate Injection, USP is supplied as a colorless solution which requires no refrigeration. At times the solution may become a light straw yellow; this does not indicate a decrease in potency.

List No.
Package/Volume
Amikacin Content

1955
Fliptop Vial/2 mL
100 mg ( 50 mg/mL)

1956
Fliptop Vial/2 mL
500 mg (250 mg/mL)

1957
Fliptop Vial/4 mL
1 g (250 mg/mL)


Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature]

*Bauer, A.W., Kirby, W.M.M., Sherris, J.C., and Turck, M.: Antibiotic Testing by a Standardized Single Disc Method. Am.J.Clin.Pathol., 45:493, 1966; Standardized Disc Susceptibility Test, FEDERAL REGISTER, 37:20527-29, 1972

Source: package insert
Disclaimer
The authors make no claims of the accuracy of the information contained herein; and these suggested doses are not a substitute for clinical judgment. Neither GlobalRPh Inc. nor any other party involved in the preparation of this program shall be liable for any special, consequential, or exemplary damages resulting in whole or part from any user's use of or reliance upon this material.  PLEASE READ THE DISCLAIMER CAREFULLY BEFORE ACCESSING OR USING THIS SITE. BY ACCESSING OR USING THIS SITE, YOU AGREE TO BE BOUND BY THE TERMS AND CONDITIONS SET FORTH IN THE DISCLAIMER.   Read the disclaimer
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