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m

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10 mg/mL

2 mL 
(PEDIATRIC)

Single Dose Vial


For IM or IV Use.
NDC63323-173-02

Fonts: Helvetica Neue (A)


20 mg/2 mL

Typesmiths Pi Font
INJECTION, USP

Gentamicin equivalent

Reference ID: 3466754


GENTAMICIN

Must be diluted for IV use.


Rx only
17302

8/14/13hcRIndd4
Sterile, Nonpyrogenic
Preservative Free
Discard unused portion.

Fresenius Kabi USA, LLC


Each mL contains:
Gentamicin sulfate equivalent
to 10 mg gentamicin; Water for

CrossTech72325Proof A2
Injection q.s. Sodium hydroxide
and/or sulfuric acid may have
been added for pH adjustment.
Usual Dosage: See insert.
Warning: Patients treated with
gentamicin sulfate and other
aminoglycosides should be

P.O. 450012196Job No. 42626G


under close clinical observation
18AB

because of the potential toxicity.


See Warnings and Precautions
inthe insert.
Store at 20 to 25C (68 to
77F) [see USPControlled Room
Temperature].
This container closure is not made
with natural rubber latex.

Fresenius Kabi USA, LLC


Lake Zurich, IL 60047
25 Vials

42626G
BLACK 185C 283C

Form M01
Z
18A

NDC63323-010-02 1002

4 018 9 6 F
Fresenius Kabi USA, LLC
GENTAMICIN

Z Z
INJECTION, USP
80 mg/2 mL

FPO
Lake Zurich, IL 60047
40 mg/mL Gentamicin equivalent
For IM or IV Use.

LOT/EXP
Must be diluted for IV use.
2 mL Multiple Dose Vial
Sterile Rx only

Z
BLACK 431C

CrossTech72322Proof A2
Form M01
Fresenius Kabi USA, LLC
P.O. 4500121296Job No. 401896F
8/14/13hcIndd4

Fonts: Helvetica Neue (A)


Helvetica (A)
Typesmiths Pi Font

Reference ID: 3466754


m
Z

Helvetica (A)
40 mg/mL

2 mL 
For IM or IV Use.
NDC63323-010-02

Multiple Dose Vial

Fonts: Helvetica Neue (A)

Typesmiths Pi Font
80 mg/2 mL
INJECTION, USP

Gentamicin equivalent

Reference ID: 3466754


GENTAMICIN

Must be diluted for IV use.

8/14/13hcRIndd4
Rx only
1002

Sterile
Each mL contains: Gentamicin sulfate
equivalent to 40 mg gentamicin;

Fresenius Kabi USA, LLC


1.8 mg methylparaben and 0.2 mg
propylparaben as preservatives;
3.2 mg sodium metabisulfite; 0.1 mg

CrossTech72324Proof A2
disodium edetate; Water for Injection
q.s. Sodium hydroxide and/or sulfuric
acid may have been added for pH
adjustment.
Usual Dosage: See insert.
Warning: Patients treated with

Z
gentamicin sulfate and other amino-

P.O. 4500121296Job No. 42625F


glycosides should be under close
18AB

clinical observation because of the


potential toxicity. See Warnings and
Precautions in the insert.
Store at 20 to 25C (68 to 77F) [see
USPControlled Room Temperature].
This container closure is not made

BLACK 431C
with natural rubber latex.
Fresenius Kabi USA, LLC
Lake Zurich, IL 60047
25 Vials

42625F

Form M01
Z
Z

40 mg/mL

m
For IM or IV Use.
NDC63323-010-20

Form M01
Gentamicin equivalent

Reference ID: 3466754


INJECTION, USP
GENTAMICIN

Must be diluted for IV use.

20 mL Multiple Dose Vial


1020

Rx only
800 mg/20 mL

Helvetica (A)
Sterile

Fonts: Helvetica Neue (A)

Typesmiths Pi Font
Each mL contains: Gentamicin
sulfate equivalent to 40 mg gentamicin;
1.8 mg methylparaben and 0.2 mg

8/14/13hcOIndd4
propylparaben as preservatives; 3.2 mg
sodium metabisulfite; 0.1 mg disodium
edetate; Water for Injection q.s. Sodium
hydroxide and/or sulfuric acid may

Fresenius Kabi USA, LLC


have been added for pH adjustment.
Usual Dosage: See insert.

CrossTech72323Proof A3
Warning: Patients treated with
g entamicin sulfate and other
aminoglycosides should be under
Z
18K

close observation because of the


potential toxicity. See Warnings and
Precautions inthe insert.
Store at 20 to 25C (68 to 77F)
[see USPControlled Room Temperature].
This container closure is not made
with natural rubber latex.
BLACK 270C

Fresenius Kabi USA, LLC

P.O. No. 4500121296Job No. 401897F


Lake Zurich, IL 60047

4 018 9 7 F
LOT/EXP
Z
Z

40 mg/mL

m
For IM or IV Use.
NDC63323-010-20

Form M01
Gentamicin equivalent

Reference ID: 3466754


INJECTION, USP
GENTAMICIN

Must be diluted for IV use.

20 mL Multiple Dose Vial


1020

Rx only
800 mg/20 mL

Helvetica (A)
Sterile

Fonts: Helvetica Neue (A)

Typesmiths Pi Font
Each mL contains: Gentamicin
sulfate equivalent to 40 mg gentamicin;
1.8 mg methylparaben and 0.2 mg

8/14/13hcOIndd4
propylparaben as preservatives; 3.2 mg
sodium metabisulfite; 0.1 mg disodium
edetate; Water for Injection q.s. Sodium
hydroxide and/or sulfuric acid may

Fresenius Kabi USA, LLC


have been added for pH adjustment.
Usual Dosage: See insert.

CrossTech72323Proof A3
Warning: Patients treated with
g entamicin sulfate and other
aminoglycosides should be under
Z
18K

close observation because of the


potential toxicity. See Warnings and
Precautions inthe insert.
Store at 20 to 25C (68 to 77F)
[see USPControlled Room Temperature].
This container closure is not made
with natural rubber latex.
BLACK 270C

Fresenius Kabi USA, LLC

P.O. No. 4500121296Job No. 401897F


Lake Zurich, IL 60047

4 018 9 7 F
LOT/EXP
Z
5AV

BOXED WARNINGS CLINICAL PHARMACOLOGY: noglycoside may be resistant to one or more other in body sites where the drug is physiologically con- when penicillins or other less potentially toxic
After intramuscular (IM) administration of gentamicin aminoglycosides. The following bacteria are usually centrated. This category also provides a buffer zone drugs are contraindicated and bacterial sus-
Patients treated with aminoglycosides should sulfate, peak serum concentrations usually occur resistant to the aminoglycosides, including gentami- that prevents small uncontrolled technical factors ceptibility tests and clinical judgment indicate its
be under close clinical observation because between 30 and 60 minutes and serum levels are cin: most streptococcal species (including Strepto- from causing major discrepancies in interpretation. use. It may also be considered in mixed infec-
of the potential toxicity associated with their measurable for six to eight hours. When gentamicin coccus pneumoniae and the Group D streptococci), A report of Resistant indicates that the antimicrobial tions caused by susceptible strains of staphylo-
use. is administered by intravenous (IV) infusion over a most enterococcal species (including Enterococcus is not likely to inhibit growth of the pathogen if the cocci and gram-negative organisms.
As with other aminoglycosides, gentamicin two-hour period, the serum concentrations are faecalis, E. faecium, and E. durans), and anaerobic antimicrobial compound reaches the concentrations In the neonate with suspected bacterial sepsis
injection is potentially nephrotoxic. The risk similar to those obtained by IM administration. organisms, such as Bacteroides species and Clos- usually achievable at the infection site; other therapy or staphylococcal pneumonia, a penicillin-type
of nephrotoxicity is greater in patients with In patients with normal renal function, peak serum tridium species. should be selected. drug is also usually indicated as concomitant
impaired renal function and in those who concentrations of gentamicin (mcg/mL) are usu- Aminoglycosides are known to be not effective Quality Control therapy with gentamicin.
receive high dosage of prolonged therapy. ally up to four times the single IM dose (mg/kg); against Salmonella and Shigella species in patients. Standardized susceptibility test procedures require
Neurotoxicity manifested by ototoxicity, both for example, a 1 mg/kg injection in adults may be Therefore, in vitro susceptibility test results should the use of laboratory controls to monitor and ensure CONTRAINDICATIONS:
vestibular and auditory, can occur in patients expected to result in a peak serum concentration not be reported. the accuracy and precision of supplies and Hypersensitivity to gentamicin is a contraindication
treated with gentamicin, primarily in those up to 4 mcg/mL; a 1.5 mg/kg dose may produce reagents used in the assay, and the techniques of to its use. A history of hypersensitivity or serious
with pre-existing renal damage and in patients levels up to 6 mcg/mL. While some variation is to Interactions with Other Antimicrobials toxic reactions to other aminoglycosides may con-
In vitro studies show that an aminoglycoside com- the individuals performing the test.1,2,3 Standard
with normal renal function treated with higher be expected due to a number of variables such as gentamicin powder should provide the following traindicate use of gentamicin because of the known
doses and/or for longer periods than age, body temperature, surface area and physiologic bined with an antibiotic that interferes with cell wall cross-sensitivity of patients to drugs in this class.
synthesis may act synergistically against some range of MIC values provided in Table 2. For the dif-
recommended. Aminoglycoside-induced differences, the individual patient given the same fusion technique using the 10-mcg gentamicin disk
ototoxicity is usually irreversible. Other dose tends to have similar levels in repeated deter- enterococcal strains. The combination of gentamicin WARNINGS:
and penicillin G has a synergistic bactericidal effect the criteria provided in Table 2 should be achieved.
manifestations of neurotoxicity may include minations. Gentamicin administered at 1 mg/kg (See BOXED WARNINGS.)
numbness, skin tingling, muscle twitching every eight hours for the usual 7 to 10 day treat- against strains of Enterococcus faecalis, E. faecium Table 2: Acceptable Quality Control Ranges Contains sodium metabisulfite, a sulfite that may
and convulsions. ment period to patients with normal renal func- and E. durans. An enhanced killing effect against for Susceptibility Testing cause allergic-type reactions including anaphy-
Renal and eighth cranial nerve function tion does not accumulate in the serum. many of these strains has also been shown in vitro lactic symptoms and life-threatening or less severe
should be closely monitored, especially in Gentamicin, like all aminoglycosides, may accu- with combinations of gentamicin and ampicillin, Minimum asthmatic episodes in certain susceptible peo-
carbenicillin, nafcillin or oxacillin. Inhibitory
patients with known or suspected reduced mulate in the serum and tissues of patients treated Concentrations Zone Diameter ple. The overall prevalence of sulfite sensitivity in
renal function at onset of therapy and also in with higher doses and/or for prolonged periods, The combined effect of gentamicin and carbenicil- Quality Control Organism (mcg/mL) (mm) the general population is unknown and probably
those whose renal function is initially normal particularly in the presence of impaired renal func- lin is synergistic for many strains of Pseudomonas low. Sulfite sensitivity is seen more frequently in
but who develop signs of renal dysfunction tion. In adult patients, treatment with gentamicin aeruginosa. In vitro synergism against other Gram- Escherichia coli
asthmatic than in non-asthmatic people.
ATCC 25922 0.25 to 1 19 to 26
during therapy. Urine should be examined for dosages of 4 mg/kg/day or higher for 7 to 10 days negative organisms has been shown with combina- Aminoglycosides can cause fetal harm when
decreased specific gravity, increased excre- may result in a slight, progressive rise in both tions of gentamicin and cephalosporins. Pseudomonas aeruginosa administered to a pregnant woman. Aminoglycoside
tion of protein and the presence of cells or peak and trough concentrations. In patients with Gentamicin may be active against clinical isolates ATCC 27853 0.5 to 2 16 to 21
antibiotics cross the placenta, and there have
casts. Blood urea nitrogen (BUN), serum cre- impaired renal function, gentamicin is cleared from of bacteria resistant to other aminoglycosides. Staphylococcus aureus been several reports of total irreversible bilateral
atinine or creatinine clearance should be deter- the body more slowly than in patients with normal Antibacterial Activity ATCC 25923 Not Applicable 19 to 27 congenital deafness in children whose mothers
mined periodically. When feasible, it is recom- renal function. The more severe the impairment, Gentamicin has been shown to be active against Staphylococcus aureus
received streptomycin during pregnancy. Serious
mended that serial audiograms be obtained the slower the clearance. (Dosage must be adjusted.) most of the following bacteria, both in vitro and in ATCC 29213 0.12 to 1 Not Applicable side effects to mother, fetus or newborn have not
in patients old enough to be tested, particu- Since gentamicin is distributed in extra-cellular clinical infections (see INDICATIONS AND USAGE). been reported in the treatment of pregnant women
larly high-risk patients. Evidence of ototoxicity Enterococcus faecalis with other aminoglycosides. Animal reproduction
fluid, peak serum concentrations may be lower ATCC 29212 4 to 16 Not Applicable
(dizziness, vertigo, tinnitus, roaring in the ears than usual in adult patients who have a large vol- Gram-Positive Bacteria studies conducted on rats and rabbits did not
or hearing loss) or nephrotoxicity requires dos- ume of this fluid. Serum concentrations of genta- Staphylococcus species Note: For control organisms for gentamicin high-level reveal evidence of impaired fertility or harm to
age adjustment or discontinuance of the drug. micin in febrile patients may be lower than those aminoglycoside screen tests for enterococci, see Table the fetus due to gentamicin sulfate.
As with the other aminoglycosides, on rare Gram-Negative Bacteria 2D Supplemental Table 1 in CLSI document M100-S233 It is not known whether gentamicin sulfate can
in afebrile patients given the same dose. When Citrobacter species
occasions changes in renal and eighth cra- body temperature returns to normal, serum con- cause fetal harm when administered to a preg-
nial nerve function may not become manifest Enterobacter species INDICATIONS AND USAGE: nant woman or can affect reproduction capacity.
centrations of the drug may rise. Febrile and ane- Escherichia coli To reduce the development of drug-resistant
until soon after completion of therapy. mic states may be associated with a shorter than If gentamicin is used during pregnancy or if the

m
Serum concentrations of aminoglycosides Klebsiella species bacteria and maintain the effectiveness of patient becomes pregnant while taking genta-
usual serum half-life. (Dosage adjustment is usu- Proteus species Gentamicin Injection, USP and other antibacterial
should be monitored when feasible to assure ally not necessary.) In severely burned patients, micin, she should be apprised of the potential
adequate levels and to avoid potentially toxic Serratia species drugs, Gentamicin Injection, USP should be used hazard to the fetus.
the half-life may be significantly decreased and Pseudomonas aeruginosa only to treat or prevent infections that are proven
levels. When monitoring gentamicin peak con- resulting serum concentrations may be lower than
centrations, dosage should be adjusted so that or strongly suspected to be caused by susceptible PRECAUTIONS:
anticipated from the mg/kg dose. Susceptibility Test Methods bacteria. When culture and susceptibility infor-
prolonged levels above 12 mcg/mL are avoided. Protein binding studies have indicated that the When available, the clinical microbiology labora- General
When monitoring gentamicin trough concen- mation are available, they should be considered Prescribing Gentamicin Injection, USP in the
degree of gentamicin binding is low; depending tory should provide cumulative results of the in vitro in selecting or modifying antibacterial therapy. In
trations, dosage should be adjusted so that upon the methods used for testing, this may be susceptibility tests for antimicrobial drugs used in absence of a proven or strongly suspected
levels above 2 mcg/mL are avoided. Exces- the absence of such data, local epidemiology and bacterial infection or a prophylactic indication
between 0 and 30%. local hospitals and practice areas to the physician susceptibility patterns may contribute to the
sive peak and/or trough serum concentra- After initial administration to patients with nor- as periodic reports that describe the susceptibility is unlikely to provide benefit to the patient and
tions of aminoglycosides may increase the empiric selection of therapy. increases the risk of the development of drug-
mal renal function, generally 70% or more of the profile of nosocomial and community-acquired Gentamicin Injection, USP is indicated in the
risk of renal and eighth cranial nerve toxicity. gentamicin dose is recoverable in the urine in 24 pathogens. These reports should aid the physician resistant bacteria.
In the event of overdosage or toxic reac- treatment of serious infections caused by sus- Neurotoxic and nephrotoxic antibiotics may be
hours; concentrations in urine above 100 mcg/mL in selecting the most effective antimicrobial. ceptible strains of the following microorganisms:
tions, hemodialysis may aid in the removal of may be achieved. Little, if any, metabolic transfor- almost completely absorbed from body surfaces
gentamicin from the blood, especially if renal Dilution Technique Pseudomonas aeruginosa, Proteus species (indole- (except urinary bladder) after local irrigation and
mation occurs; the drug is excreted principally by Quantitative methods are used to determine anti- positive and indole-negative), Escherichia coli,
function is, or becomes, compromised. The glomerular filtration. After several days of treat- after topical application during surgical procedures.
rate of removal of gentamicin is considerably microbial minimal inhibitory concentrations (MICs). Klebsiella-Enterobacter-Serratia species, Citrobacter The potential toxic effects of antibiotics administered
ment, the amount of gentamicin excreted in the These MICs provide estimates of the susceptibility species and Staphylococcus species (coagulase-
lower by peritoneal dialysis than it is by urine approaches the daily dose administered. in this fashion (neuromuscular blockage, respiratory
hemodialysis. of bacteria to antimicrobial compounds. The MICs positive and coagulase-negative). paralysis, oto- and nephrotoxicity) should be con-
As with other aminoglycosides, a small amount of should be determined using a standardized test Clinical studies have shown gentamicin
In the newborn infant, exchange transfu- the gentamicin dose may be retained in the tis- sidered (see BOXED WARNINGS).
sions may also be considered. method.1,3 Standardized procedures are based injection to be effective in bacterial neonatal sep- Increased nephrotoxicity has been reported fol-
sues, especially in the kidneys. Minute quantities sis; bacterial septicemia and serious bacterial
Concurrent and/or sequential systemic or of aminoglycosides have been detected in the on a dilution method (broth or agar) or equivalent lowing concomitant administration of aminogly-
topical use of other potentially neurotoxic and/or with standardized inoculum concentrations and infections of the central nervous system (menin- coside antibiotics and cephalosporins.
urine weeks after drug administration was discon- gitis), urinary tract, respiratory tract, gastrointesti-
nephrotoxic drugs, such as cisplatin, cepha- tinued. Renal clearance of gentamicin is similar standardized concentrations of gentamicin powder. Neuromuscular blockade and respiratory paral-
loridine, kanamycin, amikacin, neomycin, poly- The MIC values should be interpreted according to nal tract (including peritonitis), skin, bone and soft ysis have been reported in the cat receiving high
to that of endogenous creatinine. the criteria provided in Table 1. tissue (including burns). Aminoglycosides, includ-
myxin B, colistin, paromomycin, streptomycin, In patients with marked impairment of renal func- doses (40 mg/kg) of gentamicin. The possibility
tobramycin, vancomycin and viomycin, should ing gentamicin, are not indicated in uncomplicated of these phenomena occurring in man should be
4 5 8 5 5 H /Revised: October 2013 tion, there is a decrease in the concentration of Diffusion Technique initial episodes of urinary tract infections unless
be avoided. Other factors which may increase aminoglycosides in urine and in their penetration Quantitative methods that require measurement of considered if aminoglycosides are administered
patient risk of toxicity are advanced age and the causative organisms are susceptible to these by any route to patients receiving anesthetics,
into defective renal parenchyma. This decreased zone diameters also provide reproducible estimates antibiotics and are not susceptible to antibiotics
GENTAMICIN
dehydration. drug excretion, together with the potential nephro- of the susceptibility of bacteria to antimicrobial or to patients receiving neuromuscular blocking
The concurrent use of gentamicin with potent having less potential for toxicity. agents, such as succinylcholine, tubocurarine
toxicity of aminoglycosides, should be considered compounds. One such standardized procedure Specimens for bacterial culture should be
diuretics, such as ethacrynic acid or furosemide, when treating such patients who have urinary tract requires the use of standardized inoculum concen- or decamethonium, or in patients receiving
obtained to isolate and identify causative organ-
INJECTION, USP should be avoided, since certain diuretics by
themselves may cause ototoxicity. In addition,
infections.
Probenecid does not affect renal tubular trans-
trations and paper disks impregnated with 10 mcg
of gentamicin.2,3 The disk diffusion values should
isms and to determine their susceptibility to
gentamicin.
massive transfusions of citrate-anticoagulated
blood. If neuromuscular blockade occurs, calcium
when administered intravenously, diuretics may be interpreted according to the criteria provided salts may reverse it.
enhance aminoglycoside toxicity by altering the port of gentamicin. Gentamicin injection may be considered as initial
The endogenous creatinine clearance rate and in Table 1. Aminoglycosides should be used with caution
antibiotic concentration in serum and tissue. therapy in suspected or confirmed gram-negative in patients with neuromuscular disorders, such
Aminoglycosides can cause fetal harm when the serum creatinine level have a high correla- infections, and therapy may be instituted before
tion with the half-life of gentamicin in serum. Results Table 1: Susceptibility Interpretive Criteria as myasthenia gravis or parkinsonism, since these
administered to a pregnant woman (see WARN- for Gentamicin obtaining results of susceptibility testing. The drugs may aggravate muscle weakness because
INGS section). of these tests may serve as guides for adjusting decision to continue therapy with this drug should
dosage in patients with renal impairment (see of their potential curare-like effects on the neuro-
DOSAGEANDADMINISTRATION).
Susceptibility Interpretive Criteria be based on the results of susceptibility tests, muscular junction. During or following gentamicin
Minimal Inhibitory the severity of the infection and the important therapy, paresthesias, tetany, positive Chvostek
DESCRIPTION: Following parenteral administration, gentamicin Concentration Zone Diameter additional concepts contained in the BOXED
Gentamicin sulfate, a water-soluble antibiotic of can be detected in serum, lymph, tissues, spu- Pathogen (mcg/mL) (mm) and Trousseau signs and mental confusion have
WARNINGS. If the causative organisms are resist- been described in patients with hypomagnesemia,
the aminoglycoside group, is derived by the growth

P.O. No. 4500121296Job No. 45855H


tum and in pleural, synovial and peritoneal fluids. (S) (I) (R) (S) (I) (R) ant to gentamicin, other appropriate therapy should
of Micromonospora purpurea, an actinomycete. Concentrations in renal cortex sometimes may hypocalcemia and hypokalemia. When this has
be instituted. occurred in infants, tetany and muscle weakness
It has the following structural formula. be eight times higher than the usual serum lev- Enterobacteriaceaea 4 8 16 15 13 to 14 12 In serious infections when the causative organ-
els. Concentrations in bile, in general, have been has been described. Both adults and infants
Pseudomonas isms are unknown, gentamicin injection may be required corrective electrolyte therapy.
low and have suggested minimal biliary excre- aeruginosa 4 8 16 15 13 to 14 12 administered as initial therapy in conjunction
To reduce the development of drug-resistant tion. Gentamicin crosses the peritoneal as well as with a penicillin-type or cephalosporin-type drug Elderly patients may have reduced renal func-
Staphylococcus
bacteria and maintain the effectiveness of the placental membranes. Since aminoglycosides speciesb 4 8 16 15 13 to 14 12 before obtaining results of susceptibility testing. tion which may not be evident in the results of
Gentamicin Injection, USPand other antibacterial diffuse poorly into the subarachnoid space after If anaerobic organisms are suspected as etiologic routine screening tests such as BUN or serum

CrossTech72869Proof A1
drugs, Gentamicin Injection, USP should be used S = Susceptible, I = Intermediate, R = Resistant creatinine. A creatinine clearance determination
parenteral administration, concentrations of a For Salmonella and Shigella spp., aminoglycosides agents, consideration should be given to using
only to treat or prevent infections that are proven gentamicin in cerebrospinal fluid are often low may be more useful. Monitoring of renal function

Fresenius Kabi USA, LLC


may appear active in vitro but are not effective clini- other suitable antimicrobial therapy in conjunc
or strongly suspected to be caused by bacteria. and dependent upon dose, rate of penetration tion with gentamicin. Following identification of during treatment with gentamicin, as with other
cally; the results should not be reported as susceptible aminoglycosides, is particularly important in such
and degree of meningeal inflammation. There is bFor staphylococci that test susceptible, aminoglyco- the organism and its susceptibility, appropriate

10/8/13bwOIndd4
minimal penetration of gentamicin into ocular antibiotic therapy should then be continued. patients. A Fanconi-like syndrome, with amino-
sides are used only in combination with other active aciduria and metabolic acidosis has been reported
tissuesfollowingIMorIVadministration. agents that test susceptible Gentamicin injection has been used effectively
in combination with carbenicillin for the treat in some adults and infants being given gentamicin

Typesmiths Pi Font
Gentamicin injection is a sterile, nonpyrogenic Microbiology A report of Susceptible indicates that the antimi- injections.
Mechanism of Action ment of life-threatening infections caused by
aqueous solution for parenteral administration. crobial is likely to inhibit growth of the pathogen if the Pseudomonas aeruginosa. It has also been Cross-allergenicity among aminoglycosides has
Each mL contains: Gentamicin sulfate equiva- Gentamicin, an aminoglycoside, binds to the pro- antimicrobial compound reaches the concentration found effective when used in conjunction with a been demonstrated.

Fonts: Helvetica (A)


lent to 40 mg gentamicin, methylparaben 1.8 mg karyotic ribosome, inhibiting protein synthesis in at the infection site necessary to inhibit growth of the penicillin-type drug for treatment of endocarditis Patients should be well hydrated during treatment.
and propylparaben 0.2 mg as preservatives, sodium susceptible bacteria. It is bactericidal in vitro against pathogen. A report of Intermediate indicates that caused by group D streptococci. Although the in vitro mixing of gentamicin and

Form M01
metabisulfite 3.2 mg and edetate disodium Gram-positive and Gram-negative bacteria. the result should be considered equivocal, and if the Gentamicin injection has also been shown to carbenicillin results in a rapid and significant inac-
0.1 mg, Water for Injection q.s. Sodium hydroxide Drug Resistance microorganism is not fully susceptible to alternative be effective in the treatment of serious staphy- tivation of gentamicin, this interaction has not been
and/or sulfuric acid may have been added for pH Bacterial resistance to gentamicin is generally clinically feasible drugs, the test should be repeated. lococcal infections. While not the antibiotic of first demonstrated in patients with normal renal func-
adjustment. developed slowly. Bacteria resistant to one ami- This category implies possible clinical applicability choice, gentamicin injection may be considered tion who received both drugs by different routes

Reference ID: 3466754


5AV

of administration. A reduction in gentamicin serum PATIENTS WITH NORMAL recommended route of administration and dos- REFERENCES:
half-life has been reported in patients with severe RENAL FUNCTION age schedule. 1. Clinical and Laboratory Standards Institute (CLSI).
renal impairment receiving carbenicillin concom- Adults Methods for Dilution Antimicrobial Susceptibility
itantly with gentamicin. The recommended dosage of gentamicin injection PATIENTS WITH IMPAIRED Tests for Bacteria that Grow Aerobically; Approved
Treatment with gentamicin may result in over- for patients with serious infections and normal RENAL FUNCTION Standard Ninth Edition. CLSI document M07-A9,
growth of nonsusceptible organisms. If this occurs, renal function is 3 mg/kg/day, administered in three Dosage must be adjusted in patients with impaired Clinical and Laboratory Standards Institute, 950
appropriate therapy is indicated. equal doses every eight hours (Table 3). renal function to assure therapeutically adequate, West Valley Road, Suite 2500, Wayne, Pennsyl-
See BOXED WARNINGS regarding concurrent For patients with life-threatening infections, dos- but not excessive blood levels. Whenever possible vania 19087, USA, 2012.
use of potent diuretics and regarding concurrent ages up to 5 mg/kg/day may be administered in serum concentration of gentamicin should be 2. Clinical and Laboratory Standards Institute (CLSI).
and/or sequential use of other neurotoxic and/or three or four equal doses. This dosage should be monitored. One method of dosage adjustment is Performance Standards for Antimicrobial Disk
for other essential information. reduced to 3 mg/kg/day as soon as clinically indi- to increase the interval between administration of Diffusion Susceptibility Tests; Approved Standard
cated (Table 3). the usual doses. Since the serum creatinine con- Eleventh Edition. CLSI document M02-A11, Clini-
Information for Patients It is desirable to measure both peak and trough centration has a high correlation with the serum cal and Laboratory Standards Institute, 950 West
Patients should be counseled that antibacterial serum concentrations of gentamicin to determine half-life of gentamicin, this laboratory test may Valley Road, Suite 2500, Wayne, Pennsylvania
drugs including Gentamicin Injection, USP should the adequacy and safety of the dosage. When provide guidance for adjustment of the interval 19087, USA, 2012.
only be used to treat bacterial infections. They do such measurements are feasible, they should be between doses. The interval between doses (in 3. Clinical and Laboratory Standards Institute (CLSI).
not treat viral infections (e.g., the common cold). carried out periodically during therapy to assure hours) may be approximated by multiplying the Performance Standards for Antimicrobial Suscep-
When Gentamicin Injection, USP is prescribed to adequate but not excessive drug levels. For exam- serum creatinine level (mg/100 mL) by 8. For tibility Testing; Twenty-third Informational Supple-
treat a bacterial infection, patients should be told ple, the peak concentration (at 30 to 60 minutes example, a patient weighing 60 kg with a serum ment. CLSI document M100-S23, Clinical and
that although it is common to feel better early in after IM injection) is expected to be in the range creatinine level of 2 mg/100 mL could be given Laboratory Standards Institute, 950 West Valley
the course of therapy, the medication should of 4 to 6 mcg/mL. When monitoring peak con- 60 mg (1 mg/kg) every 16 hours (2 x 8). Road, Suite 2500, Wayne, Pennsylvania 19087,
be taken exactly as directed. Skipping doses or centrations after IM or IV administration, dosage In patients with serious systemic infections and USA, 2013.
not completing the full course of therapy may should be adjusted so that prolonged levels above renal impairment, it may be desirable to adminis-
(1) decrease the effectiveness of the immediate 12 mcg/mL are avoided. When monitoring trough ter the antibiotic more frequently but in reduced
treatment and (2) increase the likelihood that concentrations (just prior to the next dose), dos- dosage. In such patients, serum concentrations
bacteria will develop resistance and will not be age should be adjusted so that levels above of gentamicin should be measured so that ade-
treatable by Gentamicin Injection, USP or other 2 mcg/mL are avoided. Determination of the ade- quate but not excessive levels result. A peak and
antibacterial drugs in the future. quacy of a serum level for a particular patient trough concentration measured intermittently dur-
must take into consideration the susceptibility of ing therapy will provide optimal guidance for
Pregnancy Category D the causative organism, the severity of the infec- adjusting dosage. After the usual initial dose, a
See WARNINGS section. tion and the status of the patients host-defense rough guide for determining reduced dosage at
mechanisms. eight-hour intervals is to divide the normally
ADVERSE REACTIONS: In patients with extensive burns, altered phar- recommended dose by the serum creatinine level
Nephrotoxicity macokinetics may result in reduced serum con- (Table 4). For example, after an initial dose of
Adverse renal effects, as demonstrated by the centrations of aminoglycosides. In such patients 60 mg (1 mg/kg), a patient weighing 60 kg with a
presence of casts, cells or protein in the urine or treated with gentamicin, measurement of serum serum creatinine level of 2 mg/100 mL could be
by rising BUN, NPN, serum creatinine or oliguria, concentrations is recommended as a basis for given 30 mg every eight hours (6042). It should
have been reported. They occur more frequently dosage adjustment. be noted that the status of renal function may be
changing over the course of the infectious process.
in patients with a history of renal impairment
(especially if dialysis is required) and in patients TABLE 3 It is important to recognize that deteriorating
treated for longer periods or with larger doses DOSAGE SCHEDULE GUIDE renal function may require a greater reduction in
than recommended. FOR ADULTS WITH NORMAL dosage than that specified in the above guide-
RENAL FUNCTION lines for patients with stable renal impairment.
Neurotoxicity (Dosage at Eight-Hour Intervals)
Serious adverse effects on both vestibular and 40 mg per mL TABLE 4

m
auditory branches of the eighth nerve have been Dose for DOSAGE ADJUSTMENT GUIDE
reported, primarily in patients with renal impair- Life-Threatening FOR PATIENTS WITH RENAL IMPAIRMENT
ment (especially if hemodialysis is required) Usual Dose for Infections (Reduce (Dosage at Eight-Hour Intervals
and in patients on high doses and/or prolonged Serious As Soon As After the Usual Initial Dose)
therapy. Symptoms include dizziness, vertigo, tin- Patients Infections Clinically Indicated)
nitus, roaring in the ears and also hearing loss, Weight* 1 mg/kg q8h 1.7 mg/kg q8h** Approximate
which, as with the other aminoglycosides, may kg (lb) (3 mg/kg/day) (5 mg/kg/day) Serum Creatinine Percent of
Creatinine Clearance Rate Usual Doses
be irreversible. Hearing loss is usually manifested mg/dose mL/dose mg/dose mL/dose (mg %) (mL/min/1.73m2) Shown Above
initially by diminution of high-tone acuity. Other q8h q8h
factors which may increase the risk of toxicity 140 (188) 140 1.11 166 1.61 1.0-1.1 >100 -111 100
include excessive dosage, dehydration and pre- 145 (199) 145 1.11 175 1.91 1.1 to 1.3 170 to 100 180
vious exposure to other ototoxic drugs. 150 (110) 150 1.25 183 2.11 1.4 to 1.6 155 to 701 165
Peripheral neuropathy or encephalopathy, includ- 155 (121) 155 1.41 191 2.25 1.7 to 1.9 1 45 to 551 155
160 (132) 160 1.51 100 2.51 2 to 2.2 1 40 to 451 150
ing numbness, skin tingling, muscle twitching, 2.3 to 2.5 1 35 to 401 140
convulsions and a myasthenia gravis-like syn- 165 (143) 165 1.61 108 2.71
170 (154) 170 1.75 116 2.91 2.6 to 3.0 130 to 351 135
drome have been reported. 3.1 to 3.5 1 25 to 301 130
NOTE: The risk of toxic reactions is low in patients 175 (165) 175 1.91 125 3.11
180 (176) 180 2.11 133 3.31 3.6 to 4.0 1 20 to 251 125
with normal renal function who did not receive 185 (187) 185 2.11 141 3.51 4.1 to 5.1 1 15 to 201 120
gentamicin sulfate at higher doses or for longer 190 (198) 190 2.25 150 3.75 5.2 to 6.6 110 to 151 115
periods of time than recommended. 195 (209) 195 2.41 158 4.11 6.7 to 8.0 <10-111 110
Other reported adverse reactions possibly related 100 (220) 100 2.51 166 4.21
to gentamicin include: respiratory depression, leth- In adults with renal failure undergoing hemodial-
**The dosage of aminoglycosides in obese patients should ysis, the amount of gentamicin removed from the
argy, confusion, depression, visual disturbances, be based on an estimate of the lean body mass.
decreased appetite, weight loss and hypotension **for q6h schedules, dosage should be recalculated. blood may vary depending upon several factors
and hypertension; rash, itching, urticaria, gener- including the dialysis method used. An eight-hour
alized burning, laryngeal edema, anaphylactoid Children hemodialysis may reduce serum concentrations
reactions, fever and headache; nausea, vomiting, 6 to 7.5 mg/kg/day (2 to 2.5 mg/kg administered of gentamicin by approximately 50%. The recom-
increased salivation and stomatitis; purpura, every eight hours). mended dosage at the end of each dialysis period
pseudotumor cerebri, acute organic brain syn- is 1 to 1.7 mg/kg depending upon the severity of
Infants and Neonates the infection. In children, a dose of 2 mg/kg may
drome, pulmonary fibrosis, alopecia, joint pain, 7.5 mg/kg/day (2.5 mg/kg administered every eight
transient hepatomegaly and splenomegaly. be administered.
hours). The above dosage schedules are not intended
Laboratory abnormalities possibly related to Premature or Full-Term Neonates One Week of
gentamicin include: increased levels of serum trans- as rigid recommendations but are provided as
Age or Less guides to dosage when measurement of gentamicin
aminase (SGOT, SGPT), serum LDH and biliru- 5 mg/kg/day (2.5 mg/kg administered every
bin; decreased serum calcium, magnesium, sodium serum level is not feasible.
12 hours). A variety of methods are available to measure
and potassium; anemia, leukopenia, granulocy- For further information concerning the use of
topenia, transient agranulocytosis, eosinophilia, gentamicin concentrations in body fluids; these
gentamicin in infants and children, see gentamicin include microbiologic, enzymatic and radioim-
increased and decreased reticulocyte counts and injection (pediatric) product information.
thrombocytopenia. While clinical laboratory test munoassay techniques.
The usual duration of treatment for all patients Parenteral drug products should be inspected
abnormalities may be isolated findings, they may is 7 to 10 days. In difficult and complicated infec-
also be associated with clinically related signs visually for particulate matter and discoloration
tions, a longer course of therapy may be neces- prior to administration, whenever solution and
and symptoms. For example, tetany and muscle sary. In such cases monitoring of renal, auditory
weakness may be associated with hypomagnese- container permit.
and vestibular functions is recommended, since

P.O. No. 4500121296Job No. 45855H


mia, hypocalcemia and hypokalemia. toxicity is more apt to occur with treatment extended HOW SUPPLIED:
While the local tolerance of gentamicin sulfate for more than 10 days. Dosage should be reduced Gentamicin Injection, USP, containing gentamicin
is generally excellent, there has been an occa- if clinically indicated. 40 mg/mL is supplied as follows:
sional report of pain at the injection site. Subcu-
taneous atrophy or fat necrosis suggesting local FOR INTRAVENOUS ADMINISTRATION Product NDC
irritation has been reported rarely. The IV administration of gentamicin may be par- No. No. Strength
ticularly useful for treating patients with bacterial 1002 63323-010-02 80 mg/2 mL 2 mL fill in a
OVERDOSAGE: septicemia or those in shock. It may also be the (40 mg/mL) 2 mL flip-top
In the event of overdosage or toxic reactions, preferred route of administration for some patients vial, in pack-

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ages of 25.

Fresenius Kabi USA, LLC


hemodialysis may aid in the removal of gentamicin with congestive heart failure, hematologic disor-
from the blood, especially if renal function is, or ders, severe burns or those with reduced muscle 1020 63323-010-20 800 mg/20 mL 20 mL fill in a
becomes, compromised. The rate of removal of mass. For intermittent IV administration in adults, (40 mg/mL) 20 mL flip-top
vial, in pack-

10/7/13hcOIndd4
gentamicin is considerably lower by peritoneal a single dose of gentamicin injection may be
dialysis than it is by hemodialysis. diluted in 50 to 200 mL of sterile isotonic saline ages of 25.

Typesmiths Pi Font
solution or in a sterile solution of dextrose 5% in Also available, Gentamicin Injection (Pediatric),
DOSAGE AND ADMINISTRATION: water; in infants and children, the volume of dilu- 10 mg/mL, supplied in 2 mL (20 mg) vials in pack-
Gentamicin injection may be given IM or IV. The ent should be less. The solution may be infused ages of 25.

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patients pretreatment body weight should be over a period of one-half to two hours.
obtained for calculation of correct dosage. The The recommended dosage for IM and IV admin- Store at 20 to 25C (68 to 77F) [see USP Fresenius Kabi USA, LLC

Form M02
dosage of aminoglycosides in obese patients should istration is identical. Controlled Room Temperature]. Lake Zurich, IL 60047
be based on an estimate of the lean body mass. It Gentamicin injection should not be physically
is desirable to limit the duration of treatment with premixed with other drugs, but should be This container closure is not made with natural 45855H
aminoglycosides to short term. administered separately in accordance with the rubber latex. Revised: October 2013

Reference ID: 3466754


5AV

CLINICAL PHARMACOLOGY: tissues following intramuscular or intravenous A report of Susceptible indicates that the antimi- aeruginosa. It has also been found effective when
BOXED WARNINGS After intramuscular administration of gentamicin administration. crobial is likely to inhibit growth of the pathogen if the used in conjunction with a penicillin-type drug
Patients treated with aminoglycosides should sulfate, peak serum concentrations usually occur Microbiology antimicrobial compound reaches the concentration for the treatment of endocarditis caused by group
be under close clinical observation because of between 30 and 60 minutes and serum levels are Mechanism of Action at the infection site necessary to inhibit growth of the D streptococci.
the potential toxicity associated with their use. measurable for 6 to 8 hours. In infants, a single Gentamicin, an aminoglycoside, binds to the pro- pathogen. A report of Intermediate indicates that Gentamicin Injection has also been shown to
As with other aminoglycosides, Gentamicin dose of 2.5 mg/kg usually provides a peak serum karyotic ribosome, inhibiting protein synthesis in the result should be considered equivocal, and if the be effective in the treatment of serious staphylo-
Injection is potentially nephrotoxic. The risk level in the range of 3 to 5 mcg/mL. When genta- susceptible bacteria. It is bactericidal in vitro against microorganism is not fully susceptible to alternative coccal infections. While not the antibiotic of first
of nephrotoxicity is greater in patients with micin is administered by intravenous infusion over Gram-positive and Gram-negative bacteria. clinically feasible drugs, the test should be repeated. choice, gentamicin may be considered when
impaired renal function and in those who a two-hour period, the serum concentrations This category implies possible clinical applicability penicillins or other less potentially toxic drugs are
receive high dosage or prolonged therapy. are similar to those obtained by intramuscular Drug Resistance in body sites where the drug is physiologically con- contraindicated and bacterial susceptibility tests
Neurotoxicity manifested by ototoxicity, both administration. Age markedly affects the peak Bacterial resistance to gentamicin is generally centrated. This category also provides a buffer zone and clinical judgment indicate its use. It may also
vestibular and auditory, can occur in patients concentrations: in one report, a 1 mg/kg dose pro- developed slowly. Bacteria resistant to one ami- that prevents small uncontrolled technical factors be considered in mixed infections caused by
treated with gentamicin, primarily in those duced mean peak concentrations of 1.58, 2.03, and noglycoside may be resistant to one or more other from causing major discrepancies in interpretation. A susceptible strains of staphylococci and gram-
with pre-existing renal damage and in patients 2.81 mcg/mL in patients six months to five years old, aminoglycosides. The following bacteria are usu- report of Resistant indicates that the antimicrobial negative organisms.
with normal renal function treated with higher 5 to 10 years old, and over 10 years old, respectively. ally resistant to the aminoglycosides, including is not likely to inhibit growth of the pathogen if the In the neonate with suspected bacterial sepsis or
doses and/or for longer periods than recom- In infants one week to six months of age, the gentamicin: most streptococcal species (includ- antimicrobial compound reaches the concentrations staphylococcal pneumonia, a penicillin-type drug
mended. Aminoglycoside-induced ototoxicity half-life is 3 to 312 hours. In full-term and large ing Streptococcus pneumoniae and the Group D usually achievable at the infection site; other therapy is also usually indicated as concomitant therapy
is usually irreversible. Other manifestations premature infants less than one week old, the streptococci), most enterococcal species (including should be selected. with gentamicin.
of neurotoxicity may include numbness, skin approximate serum half-life of gentamicin is 512 Enterococcus faecalis, E. faecium, and E. durans),
and anaerobic organisms, such as Bacteroides Quality Control CONTRAINDICATIONS:
tingling, muscle twitching and convulsions. hours. In small premature infants, the half-life is Standardized susceptibility test procedures require
Renal and eighth cranial nerve function inversely related to birth weight. In premature species and Clostridium species. Hypersensitivity to gentamicin is a contraindication
Aminoglycosides are known to be not effective the use of laboratory controls to monitor and ensure to its use. A history of hypersensitivity or serious
should be closely monitored, especially in infants weighing less than 1,500 grams, the half- the accuracy and precision of supplies and
patients with known or suspected reduced life is 1112 hours; in those weighing 1,500 to 2,000 against Salmonella and Shigella species in patients. toxic reactions to other aminoglycosides may con
Therefore, in vitro susceptibility test results should reagents used in the assay, and the techniques of traindicate use of gentamicin because of the
renal function at onset of therapy, and also in grams, the half-life is eight hours; in those weigh- the individuals performing the test.1,2,3 Standard
those whose renal function is initially normal ing over 2,000 grams, the half-life is approximately not be reported. known cross-sensitivity of patients to drugs in this
gentamicin powder should provide the following class.
but who develop signs of renal dysfunction five hours. While some variation is to be expected Interactions with Other Antimicrobials range of MIC values provided in Table 2. For the dif-
during therapy. Urine should be examined for due to a number of variables such as age, body In vitro studies show that an aminoglycoside com- fusion technique using the 10-mcg gentamicin disk WARNINGS:
decreased specific gravity, increased excre- temperature, surface area and physiologic differ- bined with an antibiotic that interferes with cell wall the criteria provided in Table 2 should be achieved. (See BOXED WARNINGS.)
tion of protein, and the presence of cells or ences, the individual patient given the same dose synthesis may act synergistically against some Aminoglycosides can cause fetal harm when
casts. Blood urea nitrogen (BUN), serum cre tends to have similar levels in repeated determi- enterococcal strains. The combination of gentamicin Table 2: Acceptable Quality Control Ranges administered to a pregnant woman. Aminoglyco-
atinine, or creatinine clearance should be nations. and penicillin G has a synergistic bactericidal effect for Susceptibility Testing side antibiotics cross the placenta, and there have
determined periodically. When feasible, it is Gentamicin, like all aminoglycosides, may accu- against strains of Enterococcus faecalis, E. faecium been several reports of total irreversible bilateral
recommended that serial audiograms be ob- mulate in the serum and tissues of patients treated and E. durans. An enhanced killing effect against Minimum congenital deafness in children whose mothers
Inhibitory
tained in patients old enough to be tested, with higher doses and/or for prolonged periods, many of these strains has also been shown in vitro Concentrations Zone Diameter received streptomycin during pregnancy. Serious
particularly high-risk patients. Evidence of particularly in the presence of impaired or imma- with combinations of gentamicin and ampicillin, Quality Control Organism (mcg/mL) (mm) side effects to mother, fetus, or newborn have not
ototoxicity (dizziness, vertigo, tinnitus, roar- ture renal function. In patients with immature or carbenicillin, nafcillin or oxacillin. been reported in the treatment of pregnant women
ing in the ears or hearing loss) or nephrotox- The combined effect of gentamicin and carbenicil- Escherichia coli
impaired renal function, gentamicin is cleared ATCC 25922 0.25 to 1 19 to 26 with other aminoglycosides. Animal reproduction
icity requires dosage adjustment or discon- from the body more slowly than in patients with lin is synergistic for many strains of Pseudomonas studies conducted on rats and rabbits did not
tinuance of the drug. As with the other amino- normal renal function. The more severe the impair aeruginosa. In vitro synergism against other Gram- Pseudomonas aeruginosa reveal evidence of impaired fertility or harm to the
glycosides, on rare occasions changes in renal negative organisms has been shown with combina- ATCC 27853 0.5 to 2 16 to 21
ment, the slower the clearance. (Dosage must be fetus due to gentamicin sulfate.
and eighth cranial nerve function may not adjusted.) tions of gentamicin and cephalosporins. Staphylococcus aureus It is not known whether gentamicin sulfate can
become manifest until soon after completion Since gentamicin is distributed in extracellular Gentamicin may be active against clinical isolates ATCC 25923 Not Applicable 19 to 27 cause fetal harm when administered to a preg-
of therapy. fluid, peak serum concentrations may be lower of bacteria resistant to other aminoglycosides. nant woman or can affect reproduction capacity.
Staphylococcus aureus
Serum concentrations of aminoglycosides than usual in patients who have a large volume Antibacterial Activity If gentamicin is used during pregnancy or if the

m
ATCC 29213 0.12 to 1 Not Applicable
should be monitored when feasible to assure of this fluid. Serum concentrations of genta- Gentamicin has been shown to be active against patient becomes pregnant while taking genta-
adequate levels and to avoid potentially toxic micin in febrile patients may be lower than those most of the following bacteria, both in vitro and
Enterococcus faecalis micin, she should be apprised of the potential
ATCC 29212 4 to 16 Not Applicable
levels. When monitoring gentamicin peak con- in afebrile patients given the same dose. When body in clinical infections (see INDICATIONS AND hazard to the fetus.
centrations, dosage should be adjusted so that temperature returns to normal, serum con- USAGE). Note: For control organisms for gentamicin high-level Preserved Gentamicin Injection contains
prolonged levels above 12 mcg/mL are avoided. centrations of the drug may rise. Febrile and ane aminoglycoside screen tests for enterococci, see Table sodium metabisulfite, a sulfite that may cause
When monitoring gentamicin trough con- Gram-Positive Bacteria 2D Supplemental Table 1 in CLSI document M100-S233
mic states may be associated with a shorter than Staphylococcus species allergic-type reactions including anaphylactic
centrations, dosage should be adjusted so that usual serum half-life. (Dosage adjustment is usu- INDICATIONS AND USAGE: symptoms and life-threatening or less severe asth
levels above 2 mcg/mL are avoided. Exces- ally not necessary.) In severely burned patients, Gram-Negative Bacteria To reduce the development of drug-resistant matic episodes in certain susceptible people. The
sive peak and/or trough serum concentra- the half-life may be significantly decreased and Citrobacter species bacteria and maintain the effectiveness of Gentamicin overall prevalence of sulfite sensitivity in the gen-
tions of aminoglycosides may increase the resulting serum concentrations may be lower than Enterobacter species Injection, USP and other antibacterial drugs, eral population is unknown and probably low. Sul-
risk of renal and eighth cranial nerve toxicity. anticipated from the mg/kg dose. Escherichia coli Gentamicin Injection, USP should be used only fite sensitivity is seen more frequently in asthmatic
In the event of overdose or toxic reactions, Protein-binding studies have indicated that the Klebsiella species to treat or prevent infections that are proven or than in nonasthmatic people.
hemodialysis may aid in the removal of gen- degree of gentamicin binding is low, depending Proteus species strongly suspected to be caused by susceptible
tamicin from the blood, especially if renal func- Serratia species PRECAUTIONS:
upon the methods used for testing, this may be bacteria. When culture and susceptibility infor General
tion is, or becomes, compromised. The rate between 0 and 30%. Pseudomonas aeruginosa mation are available, they should be considered
of removal of gentamicin is considerably less Prescribing Gentamicin Injection in the absence
In neonates less than three days old, approx- Susceptibility Test Methods in selecting or modifying antibacterial therapy. In of a proven or strongly suspected bacterial infec-
by peritoneal dialysis than by hemodialysis. imately 10% of the administered dose is excreted When available, the clinical microbiology labora- the absence of such data, local epidemiology
In the newborn infant, exchange transfu- tion or a prophylactic indication is unlikely to pro-
in 12 hours; in infants 5 to 40 days old, approxi- tory should provide cumulative results of the in vitro and susceptibility patterns may contribute to the vide benefit to the patient and increases the risk of
sions may also be considered. mately 40% is excreted over the same period. susceptibility tests for antimicrobial drugs used in empiric selection of therapy.
Concurrent and/or sequential systemic or the development of drug-resistant bacteria.
Excretion of gentamicin correlates with postnatal local hospitals and practice areas to the physician Gentamicin Injection is indicated in the treat- Neurotoxic and nephrotoxic antibiotics may be
topical use of other potentially neurotoxic age and creatinine clearance. Thus, with increas as periodic reports that describe the susceptibility ment of serious infections caused by susceptible
and/or nephrotoxic drugs, such as cisplatin, almost completely absorbed from body surfaces
ing postnatal age and concomitant increase in profile of nosocomial and community-acquired strains of the following microorganisms: (except the urinary bladder) after local irrigation
cephaloridine, kanamycin, amikacin, neomy renal maturity, gentamicin is excreted more rap- pathogens. These reports should aid the physician Pseudomonas aeruginosa, Proteus species
cin, polymyxin B, colistin, paromomycin, strep- and after topical application during surgical pro-
idly. Little, if any, metabolic transformation occurs; in selecting the most effective antimicrobial. (indole-positive and indole-negative), Escherichia cedures. The potential toxic effects of antibiotics
tomycin, tobramycin, vancomycin, and vio- the drug is excreted principally by glomerular coli, Klebsiella-Enterobacter-Serratia species,
mycin, should be avoided. Other factors Dilution Technique administered in this fashion (neuromuscular block-
filtration. After several days of treatment, the Quantitative methods are used to determine anti- Citrobacter species, and Staphylococcus species ade, respiratory paralysis, oto- and nephrotoxicity)
which may increase patient risk of toxicity are amount of gentamicin excreted in the urine (coagulase-positive and coagulase-negative).
45814J/Revised: October 2013 advanced age and dehydration. microbial minimal inhibitory concentrations (MICs). should be considered (see BOXED WARNINGS).
approaches, but does not equal, the daily dose These MICs provide estimates of the susceptibility Clinical studies have shown Gentamicin Injec- Increased nephrotoxicity has been reported fol
The concurrent use of gentamicin with administered. As with other aminoglycosides, a tion to be effective in bacterial neonatal sepsis;
of bacteria to antimicrobial compounds. The MICs lowing concomitant administration of aminogly-

GENTAMICIN
potent diuretics, such as ethacrynic acid or small amount of the gentamicin dose may be bacterial septicemia; and serious bacterial infec-
furosemide, should be avoided, since certain should be determined using a standardized test coside antibiotics and cephalosporins.
retained in the tissues, especially in the kidneys. method.1,3 Standardized procedures are based tions of the central nervous system (meningitis), Neuromuscular blockade and respiratory paral-
diuretics by themselves may cause ototoxicity. Minute quantities of aminoglycosides have been urinary tract, respiratory tract, gastrointestinal
on a dilution method (broth or agar) or equivalent ysis have been reported in the cat receiving high
INJECTION, USP (Pediatric)
In addition, when administered intravenously,
diuretics may enhance aminoglycoside tox-
detected in the urine of some patients weeks after
drug administration was discontinued. Renal clear-
with standardized inoculum concentrations and
standardized concentrations of gentamicin powder.
tract (including peritonitis), skin, bone and soft
tissue (including burns). Aminoglycosides, includ-
doses (40 mg/kg) of gentamicin. The possibility
of these phenomena occurring in man should be
icity by altering the antibiotic concentration in ance of gentamicin is similar to that of endogenous ing gentamicin, are not indicated in uncompli-
serum and tissue. The MIC values should be interpreted according to considered if aminoglycosides are administered
creatinine. the criteria provided in Table 1. cated initial episodes of urinary tract infections by any route to patients receiving anesthetics, or
Aminoglycosides can cause fetal harm In patients with marked impairment of renal func unless the causative organisms are susceptible
when administered to a pregnant woman Diffusion Technique to patients receiving neuromuscular blocking
tion, there is a decrease in the concentration of to these antibiotics and are not susceptible to agents, such as succinylcholine, tubocurarine or
(see WARNINGS section). aminoglycosides in urine and in their penetration Quantitative methods that require measurement of antibiotics having less potential for toxicity.
zone diameters also provide reproducible estimates decamethonium, or in patients receiving massive
into defective renal parenchyma. This decreased Specimens for bacterial culture should be ob- transfusions of citrate-anticoagulated blood. If neu-
drug excretion, together with the potential nephro- of the susceptibility of bacteria to antimicrobial tained to isolate and identify causative organisms
DESCRIPTION: compounds. One such standardized procedure romuscular blockade occurs, calcium salts may
Gentamicin sulfate, a water-soluble antibiotic of toxicity of aminoglycosides, should be considered and to determine their susceptibility to gentamicin. reverse it.
when treating such patients who have urinary tract requires the use of standardized inoculum concen- Gentamicin may be considered as initial ther-
the aminoglycoside group, is derived from trations and paper disks impregnated with 10 mcg Aminoglycosides should be used with caution
Micromonospora purpurea, an actinomycete. infections. apy in suspected or confirmed gram-negative in patients with neuromuscular disorders, such
Probenecid does not affect renal tubular trans- of gentamicin.2,3 The disk diffusion values should infections, and therapy may be instituted before
It has the following structural formula: as myasthenia gravis, since these drugs may aggra
port of gentamicin. be interpreted according to the criteria provided obtaining results of susceptibility testing. The deci- vate muscle weakness because of their potential
The endogenous creatinine clearance rate and in Table 1. sion to continue therapy with this drug should be curare-like effects on the neuromuscular junction.

P.O. 4500121296Job No. 45814J


the serum creatinine level have a high correla- Table 1: Susceptibility Interpretive Criteria based on the results of susceptibility tests, the During or following gentamicin therapy, paresthe-
To reduce the development of drug-resistant bac- tion with the half-life of gentamicin in serum. for Gentamicin severity of the infection, and the important addi- sias, tetany, positive Chvostek and Trousseau signs,
teria and maintain the effectiveness of Gentamicin Results of these tests may serve as guides for Susceptibility Interpretive Criteria tional concepts contained in the BOXED WARN- and mental confusion have been described in
Injection, USP and other antibacterial drugs, adjusting dosage in patients with renal impairment Minimal Inhibitory INGS above. If the causative organisms are resis- patients with hypomagnesemia, hypocalcemia,

CrossTech72868Proof A1
Gentamicin Injection, USP should be used only to (see DOSAGE AND ADMINISTRATION). Concentration Zone Diameter tant to gentamicin, other appropriate therapy and hypokalemia. When this has occurred in
treat or prevent infections that are proven or strongly Following parenteral administration, gentamicin Pathogen (mcg/mL) (mm) should be instituted. infants, tetany and muscle weakness have been

Fresenius Kabi USA, LLC


suspected to be caused by bacteria. can be detected in serum, lymph, tissues, spu- (S) (I) (R) (S) (I) (R) In serious infections when the causative organ described. Both adults and infants required appro
tum, and in pleural, synovial, and peritoneal fluids. isms are unknown, gentamicin may be adminis- priate corrective electrolyte therapy.

10/8/13bwOIndd4
Concentrations in renal cortex sometimes may Enterobacteriaceaea 4 8 16 15 13 to 14 12 tered as initial therapy in conjunction with a A Fanconi-like syndrome, with amino-aciduria
be eight times higher than the usual serum lev- Pseudomonas penicillin-type or cephalosporin type drug before and metabolic acidosis, has been reported in some
els. Concentrations in bile, in general, have been obtaining results of susceptibility testing. If anaer- adults and infants being given gentamicin

Typesmiths Pi Font
aeruginosa 4 8 16 15 13 to 14 12
Gentamicin Injection is a sterile, nonpyro- low and have suggested minimal biliary excre- Staphylococcus obic organisms are suspected as etiologic agents, injections.
genic, aqueous solution for parenteral admin- tion. Gentamicin crosses the peritoneal as well as speciesb 4 8 16 15 13 to 14 12 consideration should be given to using other suit- Cross-allergenicity among aminoglycosides has
istration and is available both with and without the placental membranes. Since aminoglycosides able antimicrobial therapy in conjunction with been demonstrated.

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S = Susceptible, I = Intermediate, R = Resistant
preservatives. diffuse poorly into the subarachnoid space after a For Salmonella and Shigella spp., aminoglycosides gentamicin. Following identification of the organ- Patients should be well hydrated during treat-
Each mL of the preservative free product con- p arenteral administration, concentrations of ism and its susceptibility, appropriate antibiotic ment.

Form M01
may appear active in vitro but are not effective clini-
tains: Gentamicin sulfate, equivalent to gentamicin gentamicin in cerebrospinal fluid are often low cally; the results should not be reported as susceptible therapy should then be continued. Although the in vitro mixing of gentamicin and
10 mg; Water for Injection q.s. Sulfuric acid and/or and dependent upon dose, rate of penetration, bFor staphylococci that test susceptible, aminoglyco- Gentamicin has been used effectively in com- carbenicillin results in a rapid and significant inac-
sodium hydroxide may have been added for pH and degree of meningeal inflammation. There is sides are used only in combination with other active bination with carbenicillin for the treatment of life- tivation of gentamicin, this interaction has not been
adjustment (3 to 5.5). minimal penetration of gentamicin into ocular agents that test susceptible threatening infections caused by Pseudomonas demonstrated in patients with normal renal func-

Reference ID: 3466754


5AV

tion who received both drugs by different routes mate of the lean body mass. It is desirable to TABLE 3
of administration. A reduction in gentamicin serum limit the duration of treatment with aminogly- DOSAGE ADJUSTMENT GUIDE
half-life has been reported in patients with severe cosides to short term. FOR PATIENTS WITH RENAL IMPAIRMENT
renal impairment receiving carbenicillin con- (Dosage at Eight-Hour Intervals
comitantly with gentamicin. DOSAGE FOR PATIENTS
WITH NORMAL RENAL FUNCTION After the Usual Initial Dose)
Treatment with gentamicin may result in over-
growth of nonsusceptible organisms. If this occurs, Children: 6 to 7.5 mg/kg/day. (2 to 2.5 mg/kg
Approximate
appropriate therapy is indicated. administered every 8 hours.) Serum Creatinine Percent of
Do not administer unless solution is clear and Infants and Neonates: 7.5 mg/kg/day. (2.5 mg/kg Creatinine Clearance Rate Usual Doses
package undamaged. administered every 8 hours.) (mg %) (mL/min/1.73m2) Shown Above
See BOXED WARNINGS regarding concur- 1.0-1.1 >100-111 100
rent use of potent diuretics and regarding con- Premature or Full-term Neonates One Week of 1.1 to 1.3 170 to 100 180
current and/or sequential use of other neurotoxic Age or Less: 5 mg/kg/day. (2.5 mg/kg administered 1.4 to 1.6 155 to 701 165
and/or nephrotoxic antibiotics and for other every 12 hours.) 1.7 to 1.9 1 45 to 551 155
essential information. It is desirable to measure periodically both peak 2 to 2.2 1 40 to 451 150
Information for Patients and trough serum concentrations of gentamicin 2.3 to 2.5 1 35 to 401 140
Patients should be counseled that antibacterial when feasible during therapy to assure adequate 2.6 to 3.0 130 to 351 135
drugs including Gentamicin Injection should but not excessive drug levels. For example, the 3.1 to 3.5 1 25 to 301 130
peak concentration (at 30 to 60 minutes after intra- 3.6 to 4.0 1 20 to 251 125
only be used to treat bacterial infections. They 4.1 to 5.1 1 15 to 201 120
do not treat viral infections (e.g., the common muscular injection) is expected to be in the range
of 3 to 5 mcg/mL. When monitoring peak con- 5.2 to 6.6 110 to 151 115
cold). When Gentamicin Injection is prescribed 6.7 to 8.0 <10-111 110
to treat a bacterial infection, patients should be centrations after intramuscular or intravenous
told that although it is common to feel better administration, dosage should be adjusted so that
prolonged levels above 12 mcg/mL are avoided. In patients with renal failure undergoing hemo-
early in the course of therapy, the medication dialysis, the amount of gentamicin removed from
should be taken exactly as directed. Skipping When monitoring trough concentrations (just prior
to the next dose), dosage should be adjusted so the blood may vary depending upon several fac-
doses or not completing the full course of ther- tors including the dialysis method used. An eight-
apy may (1) decrease the effectiveness of the that levels above 2 mcg/mL are avoided. Deter-
mination of the adequacy of a serum level for a hour hemodialysis may reduce serum concen-
immediate treatment and (2) increase the likeli- trations of gentamicin by approximately 50%. In
hood that bacteria will develop resistance and particular patient must take into consideration the
susceptibility of the causative organism, the sever- children, the recommended dose at the end of
will not be treatable by Gentamicin Injection or each dialysis period is 2 to 2.5 mg/kg depending
other antibacterial drugs in the future. ity of the infection, and the status of the patients
host-defense mechanisms. upon the severity of the infection.
Pregnancy Category D In patients with extensive burns, altered The above dosage schedules are not intended
See WARNINGS section. pharmacokinetics may result in reduced serum as rigid recommendations but are provided as
ADVERSE REACTIONS: concentrations of aminoglycosides. In such guides to dosage when the measurement of
Nephrotoxicity patients treated with gentamicin, measurement gentamicin serum levels is not feasible.
Adverse renal effects, as demonstrated by the of serum concentrations is recommended as a A variety of methods are available to measure
presence of casts, cells, or protein in the urine or basis for dosage adjustment. gentamicin concentrations in body fluids; these
by rising BUN, NPN, serum creatinine or oliguria, The usual duration of treatment is 7 to 10 days. include microbiologic, enzymatic and radio-
have been reported. They occur more frequently In difficult and complicated infections, a longer immunoassay techniques.
in patients treated for longer periods or with larger course of therapy may be necessary. In such cases Parenteral drug products should be inspected
dosages than recommended. monitoring of renal, auditory, and vestibular func- visually for particulate matter and discoloration
tions is recommended, since toxicity is more apt prior to administration, whenever solution and con-
Neurotoxicity tainer permit.
Serious adverse effects on both vestibular and to occur with treatment extended for more than
auditory branches of the eighth nerve have been 10 days. Dosage should be reduced if clinically HOW SUPPLIED:

m
reported, primarily in patients with renal impair- indicated. Gentamicin Injection, USP (Preservative Free) is
ment (especially if dialysis is required), and in For Intravenous Administration supplied as:
patients on high doses and/or prolonged therapy. The intravenous administration of gentamicin may Product NDC
Symptoms include dizziness, vertigo, tinnitus, roar- be particularly useful for treating patients with No. No. Strength
ing in the ears and hearing loss, which, as with bacterial septicemia or those in shock. It may also 17302 63323-173-02 20 mg/2 mL 2 mL fill in a
other aminoglycosides, may be irreversible. Hearing be the preferred route of administration for some (10 mg/mL) 2 mL single
loss is usually manifested initially by diminu- patients with congestive heart failure, hemato- dose vial,
tion of high-tone acuity. Other factors which may logic disorders, severe burns, or those with packaged
increase the risk of toxicity include excessive reduced muscle mass. in 25.
dosage, dehydration and previous exposure to For intermittent intravenous administration, a
other ototoxic drugs. single dose of Gentamicin Injection may be Store at 20 to 25C (68 to 77F) [see USP Controlled
Peripheral neuropathy or encephalopathy, diluted in 0.9% Sodium Chloride Injection or in Room Temperature].
including numbness, skin tingling, muscle twitch- 5% Dextrose Injection. The solution may be
ing, convulsions and a myasthenia gravis-like This container closure is not made with natural
infused over a period of one-half to two hours. rubber latex.
syndrome, have been reported. The recommended dosage for intravenous and
Note: The risk of toxic reactions is low in neo- intramuscular administration is identical.
nates, infants and children with normal renal func- REFERENCES:
Gentamicin Injection should not be physically 1. Clinical and Laboratory Standards Institute (CLSI).
tion who do not receive Gentamicin Injection at premixed with other drugs, but should be admin-
higher doses or for longer periods of time than Methods for Dilution Antimicrobial Susceptibility
istered separately in accordance with the recom- Tests for Bacteria that Grow Aerobically; Approved
recommended. mended route of administration and dosa ge
Other reported adverse reactions possibly Standard Ninth Edition. CLSI document M07-A9,
schedule. Clinical and Laboratory Standards Institute, 950
related to gentamicin include: respiratory depres
sion, lethargy, confusion, depression, visual dis- DOSAGE FOR PATIENTS West Valley Road, Suite 2500, Wayne, Pennsyl-
turbances, decreased appetite, weight loss, hypo- WITH IMPAIRED RENAL FUNCTION vania 19087, USA, 2012.
tension and hypertension; rash, itching, urticaria, Dosage must be adjusted in patients with impaired 2. Clinical and Laboratory Standards Institute (CLSI).
generalized burning, laryngeal edema, anaphylac- renal function to assure therapeutically adequate Performance Standards for Antimicrobial Disk
toid reactions, fever and headache; nausea, vomit- but not excessive, blood levels. Whenever possi- Diffusion Susceptibility Tests; Approved Standard
ing, increased salivation and stomatitis; purpura, ble, serum concentrations of gentamicin should Eleventh Edition. CLSI document M02-A11, Clini-
pseudotumor cerebri, acute organic brain syn- be monitored. One method of dosage adjustment cal and Laboratory Standards Institute, 950 West
drome, pulmonary fibrosis, alopecia, joint pain, is to increase the interval between administration Valley Road, Suite 2500, Wayne, Pennsylvania
transient hepatomegaly and splenomegaly. of the usual doses. Since the serum creatinine 19087, USA, 2012.
Laboratory abnormalities possibly related to concentration has a high correlation with the 3. Clinical and Laboratory Standards Institute (CLSI).
gentamicin include: increased levels of serum serum half-life of gentamicin, this laboratory test Performance Standards for Antimicrobial Suscep-
transaminase (SGOT, SGPT), serum LDH and bili may provide guidance for adjustment of the inter tibility Testing; Twenty-third Informational Supple-
rubin, decreased serum calcium, magnesium, val between doses. In adults, the interval between ment. CLSI document M100-S23, Clinical and
sodium and potassium; anemia, leukopenia, doses (in hours) may be approximated by multi- Laboratory Standards Institute, 950 West Valley
granulocytopenia, transient agranulocytosis, eosin plying the serum creatinine level (mg/100 mL) by Road, Suite 2500, Wayne, Pennsylvania 19087,
ophilia, increased and decreased reticulocyte 8. For example, a patient weighing 60 kg with a USA, 2013.
counts and thrombocytopenia. While clinical lab- serum creatinine level of 2 mg/100 mL could be
oratory test abnormalities may be isolated find- given 60 mg (1 mg/kg) every 16 hours (2 x 8).
ings, they may also be associated with clinically These guidelines may be considered when
related signs and symptoms. For example, tetany treating infants and children with serious renal
and muscle weakness may be associated with impairment.
hypomagnesemia, hypocalcemia, and hypoka- In patients with serious systemic infections and
lemia. renal impairment, it may be desirable to adminis-
While local tolerance of Gentamicin Injection ter the antibiotic more frequently but in reduced
is generally excellent, there has been an occa- dosage. In such patients, serum concentrations

P.O. 4500121296Job No. 45814J


sional report of pain at the injection site. Subcu of gentamicin should be measured so that ade-
taneous atrophy or fat necrosis suggesting local quate but not excessive levels result.
irritation has been reported rarely. A peak and trough concentration measured
intermittently during therapy will provide optimal

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OVERDOSAGE:
In the event of overdose or toxic reactions, hemo- guidance for adjusting dosage. After the usual

Fresenius Kabi USA, LLC


dialysis may aid in the removal of gentamicin from initial dose, a rough guide for determining reduced
the blood, and is especially important if renal func- dosage at eight-hour intervals is to divide the nor

10/15/13bwOIndd4
tion is, or becomes, compromised. The rate of mally recommended dose by the serum creati-
removal of gentamicin is considerably less by peri nine level (Table 3). For example, after an initial
toneal dialysis than it is by hemodialysis. In the dose of 20 mg (2 mg/kg), a child weighing 10 kg

Typesmiths Pi Font
newborn infant, exchange transfusions may also with a serum creatinine level of 2 mg/100 mL
be considered. could be given 10 mg every eight hours (20 4 2). It
should be noted that the status of renal function

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DOSAGE AND ADMINISTRATION:
Gentamicin Injection may be given intramuscu-
may be changing over the course of the infec-
tious process. It is important to recognize that
Fresenius Kabi USA, LLC
Lake Zurich, IL 60047

Form M02
larly or intravenously. The patients pretreatment deteriorating renal function may require a greater
body weight should be obtained for calculation of reduction in dosage than that specified in the
correct dosage. The dosage of aminoglycosides above guidelines for patients with stable renal 4 5 8 14 J
in obese patients should be based on an esti- impairment. Revised: October 2013

Reference ID: 3466754