Gentamicin Injection (Gentamicin Injection) - Indications and Dosage

INDICATIONS AND USAGE

To reduce the development of drug-resistant bacteria and maintain the effectiveness of gentamicin and other antibacterial drugs, gentamicin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Gentamicin Sulfate in 0.9% Sodium Chloride Injection is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella - Enterobacter-Serratia species, Citrobacter species, and Staphylococcus species (coagulase-positive and coagulase-negative).

Clinical studies have shown gentamicin sulfate to be effective in bacterial neonatal sepsis; bacterial septicemia; and serious bacterial infections of the central nervous system (meningitis), urinary tract, respiratory tract, gastrointestinal tract (including peritonitis), skin, bone and soft tissue (including burns).

Aminoglycosides, including gentamicin, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are susceptible to these antibiotics and are not susceptible to antibiotics having less potential for toxicity.

Specimens for bacterial culture should be obtained to isolate and identify causative organisms and to determine their susceptibility to gentamicin.

Gentamicin may be considered as initial therapy in suspected or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing. The decision to continue therapy with this drug should be based on the results of susceptibility tests, the severity of the infection, and the important additional concepts contained in the “WARNINGS box”. If the causative organisms are resistant to gentamicin, other appropriate therapy should be instituted.

In serious infections when the causative organisms are unknown, gentamicin may be administered as initial therapy in conjunction with a penicillin-type or cephalosporin-type drug before obtaining results of susceptibility testing. If anaerobic organisms are suspected as etiologic agents, consideration should be given to using other suitable antimicrobial therapy in conjunction with gentamicin. Following identification of the organism and its susceptibility, appropriate antibiotic therapy should then be continued.

Gentamicin has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa. It has also been found effective when used in conjunction with a penicillin-type drug for the treatment of endocarditis caused by group D streptococci.

Gentamicin has also been shown to be effective in the treatment of serious staphylococcal infections. While not the antibiotic of first choice, gentamicin may be considered when penicillins or other less potentially toxic drugs are contraindicated and bacterial susceptibility tests and clinical judgment indicate its use. It may also be considered in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms.

In the neonate with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug is also usually indicated as concomitant therapy with gentamicin.

DOSAGE AND ADMINISTRATION

Gentamicin Sulfate in 0.9% Sodium Chloride Injection is administered by intravenous infusion only. The patient’s pretreatment body weight should be obtained for calculation of correct dosage. The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass. It is desirable to limit the duration of treatment with aminoglycosides to short term.

Patients with Normal Renal Function

Adults: The recommended dosage of gentamicin sulfate for patients with serious infections and normal renal function is 3 mg/kg/day, administered in three equal doses every eight hours (Table 1).

For patients with life-threatening infections, dosages up to 5 mg/kg/day may be administered in three or four equal doses. The dosage should be reduced to 3 mg/kg/day as soon as clinically indicated (Table 1).

It is desirable to measure both peak and trough serum concentrations of gentamicin to determine the adequacy and safety of the dosage. When such measurements are feasible, they should be carried out periodically during therapy to assure adequate but not excessive drug levels. For example, the peak concentration (at 30 to 60 minutes following cessation of infusion) is expected to be in the range of 4 to 6 mcg/mL. When monitoring peak concentrations, dosage should be adjusted so that prolonged levels above 12 mcg/mL are avoided. When monitoring trough concentrations (just prior to the next dose), dosage should be adjusted so that levels above 2 mcg/mL are avoided. Determination of the adequacy of a serum level for a particular patient must take into consideration the susceptibility of the causative organism, the severity of the infection, and the status of the patient’s host-defense mechanisms. In patients with extensive burns, altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides. In such patients treated with gentamicin, measurement of serum concentrations is recommended as a basis for dosage adjustment.

Table 1 Dosage Schedule Guide For Adults With Normal Renal Function (Dosage at Eight-Hour Intervals)
		Usual Dose			Dose for Life-Threatening
Patient’s		for Serious			Infections (Reduce as Soon
Weight*		Infections			as Clinically Indicated)
		1 mg/kg q8h			1.7 mg/kg q8h**
kg	(lb)	(3 mg/kg/day)			(5 mg/kg/day)
		mg/dose			mg/dose
		q8h			q8h
40	(88)		40			66
45	(99)	45			75
50	(110)	50			83
55	(121)	55			91
60	(132)	60			100
65	(143)	65			108
70	(154)	70			116
75	(165)	75			125
80	(176)	80			133
85	(187)	85			141
90	(198)	90			150
95	(209)	95			158
100	(220)	100			166
* The dosage of aminoglycosides in obese patients should be based on an estimate of the lean body mass.
** For q6h schedules, dosage should be recalculated.

NOTE: For information concerning the use of gentamicin in infants and children, see Pediatric Gentamicin Sulfate Injection product information.

The usual duration of treatment for all patients is seven to ten days. In difficult and complicated infections, a longer course of therapy may be necessary. In such cases monitoring of renal, auditory, and vestibular functions is recommended, since toxicity is more apt to occur with treatment extended for more than ten days. Dosage should be reduced if clinically indicated.

The intravenous administration of gentamicin may be particularly useful for treating patients with bacterial septicemia or those in shock. It may also be the preferred route of administration for some patients with congestive heart failure, hematologic disorders, severe burns, or those with reduced muscle mass. For multiple intravenous administration in adults, a single dose of Gentamicin Sulfate in 0.9% Sodium Chloride Injection may be administered according to individual patient requirements from a premixed flexible bag. The solution may be infused over a period of one-half to two hours.

Gentamicin sulfate should not be physically premixed with other drugs, but should be administered separately in accordance with the recommended route of administration and dosage schedule.

Patients with Impaired Renal Function

Dosage must be adjusted in patients with impaired renal function to assure therapeutically adequate, but not excessive blood levels. Whenever possible, serum concentrations of gentamicin should be monitored. One method of dosage adjustment is to increase the interval between administration of the usual doses. Since the serum creatinine concentration has a high correlation with the serum half-life of gentamicin, this laboratory test may provide guidance for adjustment of the interval between doses. The interval between doses (in hours) may be approximated by multiplying the serum creatinine level (mg/100 mL) by 8. For example, a patient weighing 60 kg with a serum creatinine level of 2 mg/100 mL could be given 60 mg (1 mg/kg) every 16 hours (2 x 8).

In patients with serious systemic infections and renal impairment, it may be desirable to administer the antibiotic more frequently but in reduced dosage. In such patients, serum concentrations of gentamicin should be measured so that adequate, but not excessive levels result. A peak and trough concentration measured intermittently during therapy will provide optimal guidance for adjusting dosage. After the usual initial dose, a rough guide for determining reduced dosage at eight-hour intervals is to divide the normally recommended dose by the serum creatinine level (Table 2). For example, after an initial dose of 60 mg (1 mg/kg), a patient weighing 60 kg with a serum creatinine level of 2 mg/100 mL could be given 30 mg every eight hours (60 ÷ 2). It should be noted that the status of renal function may be changing over the course of the infectious process.

It is important to recognize that deteriorating renal function may require a greater reduction in dosage than that specified in the above guidelines for patients with stable renal impairment.

Table 2 Dosage Adjustment Guide for Patients with Renal Impairment (Dosage at Eight-Hour Intervals After the Usual Initial Dose)
	Approximate	Percent of
Serum	Creatinine	Usual Doses
Creatinine	Clearance	Shown in
(mg %)	(mL/min/1.73M 2 )	Table 1
≤1.0	>100	100
1.1 - 1.3	70 - 100	80
1.4 - 1.6	55 - 70	65
1.7 - 1.9	45 - 55	55
2.0 - 2.2	40 - 45	50
2.3 - 2.5	35 - 40	40
2.6 - 3.0	30 - 35	35
3.1 - 3.5	25 - 30	30
3.6 - 4.0	20 - 25	25
4.1 - 5.1	15 - 20	20
5.2 - 6.6	10 - 15	15
6.7 - 8.0	<10	10

In adults with renal failure undergoing hemodialysis, the amount of gentamicin removed from the blood may vary depending upon several factors including the dialysis method used. An eight-hour hemodialysis may reduce serum concentrations of gentamicin by approximately 50%. The recommended dose at the end of each dialysis period is 1 to 1.7 mg/kg depending upon the severity of infection.

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

A variety of methods are available to measure gentamicin concentrations in body fluids; these include microbiologic, enzymatic and radioimmunoassay techniques.

Gentamicin Sulfate Injection is a ready-to-use isotonic solution. NO DILUTION OR BUFFERING IS REQUIRED.

If the prescribed dose is exactly 60, 70, 80, 90 or 100 mg, use the appropriate container. If the prescribed dose is higher or lower than that of the supplied container, adjustments can be made in either container. If the dose is higher than the contents of the 100 mg container, the additional amount should be removed from a container of gentamicin sulfate (40 mg/mL) and added to the 100 mg container. If the prescribed dose is less, decrements can be made by removing and discarding the appropriate amount from either unit.

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

INSTRUCTIONS FOR USE

To Open

Tear outer wrap at notch and remove solution container. If supplemental medication is desired, follow directions below before preparing for administration. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.

Preparation for Administration

(Use aseptic technique)

1. Close flow control clamp of administration set.

2. Remove cover from outlet port at bottom of container.

3. Insert piercing pin of administration set into port with a twisting motion until the set is firmly seated. NOTE: See full directions on administration set carton.

4. Suspend container from hanger.

5. Squeeze and release drip chamber to establish proper fluid level in chamber.

6. Open flow control clamp and clear air from set. Close clamp.

7. Attach set to venipuncture device. If device is not indwelling, prime and make venipuncture.

8. Regulate rate of administration with flow control clamp.

WARNING: DO NOT USE FLEXIBLE CONTAINER IN SERIES CONNECTIONS.

HOW SUPPLIED

Gentamicin Sulfate in 0.9% Sodium Chloride Injection is supplied in a single-dose flexible container as follows:

List No.	Vol. (size)	Total Gentamicin Content
7879	50 mL	60 mg
7881	50 mL	70 mg
7883	50 mL	80 mg
7884	100 mL	80 mg
7886	100 mL	90 mg
7889	100 mL	100 mg

Exposure of pharmaceutical products to heat should be minimized. Avoid excessive heat. Protect from freezing. Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]

October, 2004

©Hospira 2004 EN-0581 (10/04) Printed in USA

HOSPIRA, INC., LAKE FOREST, IL 60045 USA