GENTAMYCIN SULPHATE
DESCRIPTION:
*************************************************
* *
* WARNINGS *
* Patients treated with aminoglycosides *
* should be under close clinical observation *
* because of the potential toxicity *
* associated with their use. *
* As with other aminoglycosides, GARAMYCIN *
* Injectable is potentially nephrotoxic. The *
* risk of nephrotoxicity is greater in *
* patients with impaired renal function and *
* in those who receive high dosage or *
* prolonged therapy. *
* Neurotoxicity manifested by ototoxicity, *
* both vestibular and auditory, can occur in *
* patients treated with GARAMYCIN Injectable, *
* primarily in those with pre-existing renal *
* damage and in patients with normal renal *
* function treated with higher doses and/or *
* for longer periods than recommended. *
* Aminoglycoside-induced ototoxicity is *
* usually irreversible. Other manifestations *
* of neurotoxicity may include numbness, skin *
* tingling, muscle twitching, and *
* convulsions. *
* Renal and eighth cranial nerve function *
* should be closely monitored, especially in *
* patients with known or suspected reduced *
* renal function at onset of therapy, and *
* also in those whose renal function is *
* initially normal but who develop signs of *
* renal dysfunction during therapy. Urine *
* should be examined for decreased specific *
* gravity, increased excretion of protein, *
* and the presence of cells or casts. Blood *
* urea nitrogen, serum creatinine, or *
* creatinine clearance should be determined *
* periodically. When feasible, it is *
* recommended that serial audiograms be *
* obtained in patients old enough to be *
* tested, particularly high-risk patients. *
* Evidence of ototoxicity (dizziness, *
* vertigo, ataxia, tinnitus, roaring in the *
* ears, or hearing loss) or nephrotoxicity *
* requires dosage adjustment or *
* discontinuance of the drug. As with the *
* other aminoglycosides, on rare occasions *
* changes in renal and eighth cranial nerve *
* function may not become manifest until soon *
* after completion of therapy. *
* Serum concentrations of aminoglycosides *
* should be monitored when feasible to assure *
* adequate levels and to avoid potentially *
* toxic levels. When monitoring gentamicin *
* peak concentrations, dosage should be *
* adjusted so that prolonged levels above 12 *
* mcg/mL are avoided. When monitoring *
* gentamicin trough concentrations, dosage *
* should be adjusted so that levels above 2 *
* mcg/mL are avoided. Excessive peak and/or *
* trough serum concentrations of *
* aminoglycosides may increase the risk of *
* renal and eighth cranial nerve toxicity. In *
* the event of overdose or toxic reactions, *
* hemodialysis may aid in the removal of *
* gentamicin from the blood, especially if *
* renal function is, or becomes, compromised. *
* The rate of removal of gentamicin is *
* considerably less by peritoneal dialysis *
* than by hemodialysis. *
* Concurrent and/or sequential systemic or *
* topical use of other potentially neurotoxic *
* and/or nephrotoxic drugs, such as *
* cisplatin, cephaloridine, kanamycin, *
* amikacin, neomycin, polymyxin B, colistin, *
* paromomycin, streptomycin, tobramycin, *
* vancomycin, and viomycin, should be *
* avoided. Other factors which may increase *
* patient risk of toxicity are advanced age *
* and dehydration. *
* The concurrent use of gentamicin with *
* potent diuretics, such as ethacrynic acid *
* or furosemide, should be avoided, since *
* certain diuretics by themselves may cause *
* ototoxicity. In addition, when administered *
* intravenously, diuretics may enhance *
* aminoglycoside toxicity by altering the *
* antibiotic concentration in serum and *
* tissue. *
* *
*************************************************
DESCRIPTION
Gentamicin sulfate, USP, a water-soluble antibiotic of the aminoglycoside group,
is derived from MICROMONOSPORA PURPUREA, an actinomycete. GARAMYCIN Injectable
is a sterile, aqueous solution for parenteral administration. Each mL contains
gentamicin sulfate, USP equivalent to 40 mg gentamicin base; 1.8 mg
methylparaben and 0.2 mg propylparaben as preservatives; 3.2 mg sodium
bisulfite; and 0.1 mg edetate disodium.
ACTIONS/CLINICAL PHARMACOLOGY:
After intramuscular administration of GARAMYCIN Injectable, peak serum
concentrations usually occur between 30 and 60 minutes and serum levels are
measurable for 6 to 8 hours. When gentamicin is administered by intravenous
infusion over a 2-hour period, the serum concentrations are similar to those
obtained by intramuscular administration.
In patients with normal renal function, peak serum concentrations of gentamicin
(mcg/mL) are usually up to four times the single intramuscular dose (mg/kg); for
example, a 1.0 mg/kg injection in adults may be expected to result in a peak
serum concentration up to 4 mcg/mL; a 1.5 mg/kg dose may produce levels up to 6
mcg/mL. While some variation is to be expected due to a number of variables such
as age, body temperature, surface area, and physiologic differences, the
individual patient given the same dose tends to have similar levels in repeated
determinations. Gentamicin administered at 1.0 mg/kg every 8 hours for the usual
7- to 10-day treatment period to patients with normal renal function does not
accumulate in the serum.
Gentamicin, like all aminoglycosides, may accumulate in the serum and tissues of
patients treated with higher doses and/or for prolonged periods, particularly in
the presence of impaired renal function. In adult patients, treatment with
gentamicin dosages of 4 mg/kg/day or higher for 7 to 10 days may result in a
slight, progressive rise in both peak and trough concentrations. In patients
with impaired renal function, gentamicin is cleared from the body more slowly
than in patients with normal renal function. The more severe the impairment, the
slower the clearance. (Dosage must be adjusted.)
Since gentamicin is distributed in extracellular fluid, peak serum
concentrations may be lower than usual in adult patients who have a large volume
of this fluid. Serum concentrations of gentamicin in febrile patients may be
lower than those in afebrile patients given the same dose. When body temperature
returns to normal, serum concentrations of the drug may rise. Febrile and anemic
states may be associated with a shorter than usual serum half-life. (Dosage
adjustment is usually not necessary.) In severely burned patients, the half-life
may be significantly decreased and resulting serum concentrations may be lower
than anticipated from the mg/kg dose.
Protein-binding studies have indicated that the degree of gentamicin binding is
low; depending upon the methods used for testing, this may be between 0% and
30%.
After initial administration to patients with normal renal function, generally
70% or more of the gentamicin dose is recoverable in the urine in 24 hours;
concentrations in urine above 100 mcg/mL may be achieved. Little, if any,
metabolic transformation occurs; the drug is excreted principally by glomerular
filtration. After several days of treatment, the amount of gentamicin excreted
in the urine approaches the daily dose administered. As with other
aminoglycosides, a small amount of the gentamicin dose may be retained in the
tissues, especially in the kidneys. Minute quantities of aminoglycosides have
been detected in the urine weeks after drug administration was discontinued.
Renal clearance of gentamicin is similar to that of endogenous creatinine.
In patients with marked impairment of renal function, there is a decrease in the
concentration of aminoglycosides in urine and in their penetration into
defective renal parenchyma. This decreased drug excretion, together with the
potential nephrotoxicity of aminoglycosides, should be considered when treating
such patients who have urinary tract infections.
Probenecid does not affect renal tubular transport of gentamicin.
The endogenous creatinine clearance rate and the serum creatinine level have a
high correlation with the half-life of gentamicin in serum. Results of these
tests may serve as guides for adjusting dosage in patients with renal impairment
(see DOSAGE AND ADMINISTRATION).
Following parenteral administration, gentamicin can be detected in serum, lymph,
tissues, sputum, and in pleural, synovial, and peritoneal fluids. Concentrations
in renal cortex sometimes may be eight times higher than the usual serum levels.
Concentrations in bile, in general, have been low and have suggested minimal
biliary excretion. Gentamicin crosses the peritoneal as well as the placental
membranes. Since aminoglycosides diffuse poorly into the subarachnoid space
after parenteral administration, concentrations of gentamicin in cerebrospinal
fluid are often low and dependent upon dose, rate of penetration, and degree of
meningeal inflammation. There is minimal penetration of gentamicin into ocular
tissues following intramuscular or intravenous administration.
MICROBIOLOGY: In Vitro tests have demonstrated that gentamicin is a
bactericidal antibiotic which acts by inhibiting normal protein synthesis in
susceptible microorganisms. It is active against a wide variety of pathogenic
bacteria including ESCHERICHIA COLI, PROTEUS species (indole-positive and
indole-negative), PSEUDOMONAS AERUGINOSA, species of the KLEBSIELLA-
ENTEROBACTER-SERRATIA group. CITROBACTER species, and STAPHYLOCOCCUS species
(including penicillin- and methicillin-resistant strains). Gentamicin is also
active In Vitro against species of SALMONELLA and SHIGELLA. The following
bacteria are usually resistant to aminoglycosides: STREPTOCOCCUS PNEUMONIAE,
most species of streptococci, particularly group D and anaerobic organisms, such
as BACTEROIDES species or CLOSTRIDIUM species.
In Vitro studies have shown that an aminoglycoside combined with an antibiotic
that interferes with cell wall synthesis may act synergistically against some
group D streptococcal strains. The combination of gentamicin and penicillin G
has a synergistic bactericidal effect against virtually all strains of
STREPTOCOCCUS FAECALIS and its varieties (S. FAECALIS var. LIQUIFACIENS, S.
FAECALIS var. ZYMOGENES), S. FAECIUM and S. DURANS. An enhanced killing effect
against many of these strains has also been shown In Vitro with combinations of
gentamicin and ampicillin, carbenicillin, nafcillin, or oxacillin.
The combined effect of gentamicin and carbenicillin is synergistic for many
strains of PSEUDOMONAS AERUGINOSA. In Vitro synergism against other gram-
negative organisms has been shown with combinations of gentamicin and
cephalosporins.
Gentamicin may be active against clinical isolates of bacteria resistant to
other aminoglycosides. Bacteria resistant to one aminoglycoside may be resistant
to one or more other aminoglycosides. Bacterial resistance to gentamicin is
generally developed slowly.
SUSCEPTIBILITY TESTING: If the disc method of susceptibility testing used is
that described by Bauer ET AL. (AM J CLIN PATH 45:493, 1966; FEDERAL REGISTER
37:20525-20529, 1972), a disc containing 10 mcg of gentamicin should give a zone
of inhibition of 15 mm or more to indicate susceptibility of the infecting
organism. A zone of 12 mm or less indicates that the infecting organism is
likely to be resistant. Zones greater than 12 mm and less than 15 mm indicate
intermediate susceptibility. In certain conditions it may be desirable to do
additional susceptibility testing by the tube or agar dilution method;
gentamicin substance is available for this purpose.
INDICATIONS AND USAGE:
GARAMYCIN Injectable 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 GARAMYCIN Injectable 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.
GARAMYCIN Injectable 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, GARAMYCIN
Injectable 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.
GARAMYCIN Injectable 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.
GARAMYCIN Injectable has also been shown to be effective in the treatment of
serious staphylococcal infections. While not the antibiotic of first choice,
GARAMYCIN Injectable 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.
CONTRAINDICATIONS:
Hypersensitivity to gentamicin is a contraindication to its use. A history of
hypersensitivity or serious toxic reactions to other aminoglycosides may
contraindicate use of gentamicin because of the known cross-sensitivity of
patients to drugs in this class.
WARNINGS:
Patients treated with aminoglycosides should be under close clinical observation
because of the potential toxicity associated with their use.
As with other aminoglycosides, GARAMYCIN Injectable is potentially nephrotoxic.
The risk of nephrotoxicity is greater in patients with impaired renal function
and in those who receive high dosage or prolonged therapy.
Neurotoxicity manifested by ototoxicity, both vestibular and auditory, can occur
in patients treated with GARAMYCIN Injectable, primarily in those with pre-
existing renal damage and in patients with normal renal function treated with
higher doses and/or for longer periods than recommended. Aminoglycoside-induced
ototoxicity is usually irreversible. Other manifestations of neurotoxicity may
include numbness, skin tingling, muscle twitching, and convulsions.
Renal and eighth cranial nerve function should be closely monitored, especially
in patients with known or suspected reduced renal function at onset of therapy,
and also in those whose renal function is initially normal but who develop signs
of renal dysfunction during therapy. Urine should be examined for decreased
specific gravity, increased excretion of protein, and the presence of cells or
casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be
determined periodically. When feasible, it is recommended that serial audiograms
be obtained in patients old enough to be tested, particularly high-risk
patients. Evidence of ototoxicity (dizziness, vertigo, ataxia, tinnitus, roaring
in the ears, or hearing loss) or nephrotoxicity requires dosage adjustment or
discontinuance of the drug. As with the other aminoglycosides, on rare occasions
changes in renal and eighth cranial nerve function may not become manifest until
soon after completion of therapy.
Serum concentrations of aminoglycosides should be monitored when feasible to
assure adequate levels and to avoid potentially toxic levels. When monitoring
gentamicin peak concentrations, dosage should be adjusted so that prolonged
levels above 12 mcg/mL are avoided. When monitoring gentamicin trough
concentrations, dosage should be adjusted so that levels above 2 mcg/mL are
avoided. Excessive peak and/or trough serum concentrations of aminoglycosides
may increase the risk of renal and eighth cranial nerve toxicity. In the event
of overdose or toxic reactions, hemodialysis may aid in the removal of
gentamicin from the blood, especially if renal function is, or becomes,
compromised. The rate of removal of gentamicin is considerably less by
peritoneal dialysis than by hemodialysis.
Concurrent and/or sequential systemic or topical use of other potentially
neurotoxic and/or nephrotoxic drugs, such as cisplatin, cephaloridine,
kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin,
tobramycin, vancomycin, and viomycin, should be avoided. Other factors which may
increase patient risk of toxicity are advanced age and dehydration.
The concurrent use of gentamicin with potent diuretics, such as ethacrynic acid
or furosemide, should be avoided, since certain diuretics by themselves may
cause ototoxicity. In addition, when administered intravenously, diuretics may
enhance aminoglycoside toxicity by altering the antibiotic concentration in
serum and tissue.
WARNINGS(See boxed WARNINGS.) Aminoglycosides can cause fetal harm when
administered to a pregnant woman. Aminoglycoside antibiotics cross the placenta,
and there have been several reports of total irreversible bilateral congenital
deafness in children whose mothers received streptomycin during pregnancy.
Serious side effects to mother, fetus, or newborn have not been reported in the
treatment of pregnant women with other aminoglycosides. Animal reproduction
studies conducted on rats and rabbits did not reveal evidence of impaired
fertility or harm to the fetus due to gentamicin sulfate.
It is not known whether gentamicin sulfate can cause fetal harm when
administered to a pregnant woman or can affect reproduction capacity. If
gentamicin is used during pregnancy or if the patient becomes pregnant while
taking gentamicin, she should be apprised of the potential hazard to the fetus.
GARAMYCIN Injectable contains sodium bisulfite, a sulfite that may cause
allergic-type reactions including anaphylactic symptoms and life- threatening or
less severe asthmatic episodes in certain susceptible people. The overall
prevalence of sulfite sensitivity in the general population is unknown and
probably low. Sulfite sensitivity is seen more frequently in asthmatic than in
nonasthmatic people.
PRECAUTIONS:
Neurotoxic and nephrotoxic antibiotics may be absorbed in significant quantities
from body surfaces after local irrigation or application. The potential toxic
effect of antibiotics administered in this fashion should be considered.
Increased nephrotoxicity has been reported following concomitant administration
of aminoglycoside antibiotics and cephalosporins.
Neuromuscular blockade and respiratory paralysis have been reported in the cat
receiving high doses (40 mg/kg) of gentamicin. The possibility of these
phenomena occurring in man should be considered if aminoglycosides are
administered by any route to patients receiving anesthetics, or to patients
receiving neuromuscular blocking agents, such as succinylcholine, tubocurarine,
or decamethonium, or in patients receiving massive transfusions of citrate-
anticoagulated blood. If neuromuscular blockade occurs, calcium salts may
reverse it.
Aminoglycosides should be used with caution in patients with neuromuscular
disorders, such as myasthenia gravis, since these drugs may aggravate muscle
weakness because of their potential curare-like effects on the neuromuscular
junction. During or following gentamicin therapy, paresthesias, tetany, positive
Chvostek and Trousseau signs, and mental confusion have been described in
patients with hypomagnesemia, hypocalcemia, and hypokalemia. When this has
occurred in infants, tetany and muscle weakness has been described. Both adults
and infants required appropriate corrective electrolyte therapy.
Elderly patients may have reduced renal function which may not be evident in the
results of routine screening tests, such as BUN or serum creatinine. A
creatinine clearance determination may be more useful. Monitoring of renal
function during treatment with gentamicin, as with other aminoglycosides, is
particularly important in such patients. A Fanconi-like syndrome, with
aminoaciduria and metabolic acidosis, has been reported in some adults and
infants being given gentamicin injections.
Cross-allergenicity among aminoglycosides has been demonstrated.
Patients should be well hydrated during treatment.
Although the In Vitro mixing of gentamicin and carbenicillin results in a rapid
and significant inactivation of gentamicin, this interaction has not been
demonstrated in patients with normal renal function who received both drugs by
different routes of administration. A reduction in gentamicin serum half-life
has been reported in patients with severe renal impairment receiving
carbenicillin concomitantly with gentamicin.
Treatment with gentamicin may result in overgrowth of nonsusceptible organisms.
If this occurs, appropriate therapy is indicated.
See "WARNINGS" Box regarding concurrent use of potent diuretics and regarding
concurrent and/or sequential use of other neurotoxic and/or nephrotoxic
antibiotics and for other essential information.
USAGE IN PREGNANCY--Safety for use in pregnancy has not been established.
ADVERSE REACTIONS:
NEPHROTOXICITY Adverse renal effects, as demonstrated by the presence of casts,
cells, or protein in the urine or by rising BUN, NPN, serum creatinine or
oliguria, have been reported. They occur more frequently in patients with a
history of renal impairment and in patients treated for longer periods or with
larger dosage than recommended.
NEUROTOXICITY Serious adverse effects on both vestibular and auditory branches
of the eighth cranial nerve have been reported, primarily in patients with renal
impairment (especially if dialysis is required) and in patients on high doses
and/or prolonged therapy. Symptoms include dizziness, vertigo, ataxia, tinnitus,
roaring in the ears and hearing loss, which, as with the other aminoglycosides,
may be irreversible. Hearing loss is usually manifested initially by diminution
of high-tone acuity. Other factors which may increase the risk of toxicity
include excessive dosage, dehydration, and previous exposure to other ototoxic
drugs.
Peripheral neuropathy or encephalopathy, including numbness, skin tingling,
muscle twitching, convulsions, and a myasthenia gravis- like syndrome, have been
reported.
NOTE: The risk of toxic reactions is low in patients with normal renal function
who do not receive GARAMYCIN Injectable at higher doses or for longer periods of
time than recommended.
Other reported adverse reactions possibly related to gentamicin include:
respiratory depression, lethargy, confusion, depression, visual disturbances,
decreased appetite, weight loss, and hypotension and hypertension; rash,
itching, urticaria, generalized burning, laryngeal edema, anaphylactoid
reactions, fever, and headache; nausea, vomiting, increased salivation, and
stomatitis; purpura, pseudotumor cerebri, acute organic brain syndrome,
pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly, and
splenomegaly.
Laboratory abnormalities possibly related to gentamicin include: increased
levels of serum transaminase (SGOT, SGPT), serum LDH, and bilirubin; decreased
serum calcium, magnesium, sodium, and potassium; anemia, leukopenia,
granulocytopenia, transient agranulocytosis, eosinophilia, increased and
decreased reticulocyte counts, and thrombocytopenia. While clinical laboratory
test abnormalities may be isolated findings, they may also be associated with
clinically related signs and symptoms. For example, tetany and muscle weakness
may be associated with hypomagnesemia, hypocalcemia, and hypokalemia.
While local tolerance of GARAMYCIN Injectable is generally excellent, there has
been an occasional report of pain at the injection site. Subcutaneous atrophy or
fat necrosis suggesting local irritation has been reported rarely.
OVERDOSAGE:
In the event of overdose or toxic reactions, hemodialysis may aid in the removal
of gentamicin from the blood, and is especially important if renal function is,
or becomes, compromised. The rate of removal of gentamicin is considerably less
by peritoneal dialysis than it is by hemodialysis.
DOSAGE AND ADMINISTRATION:
GARAMYCIN Injectable may be given intramuscularly or intravenously. 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.
DOSAGE FOR PATIENTS WITH NORMAL RENAL FUNCTION
ADULTS: The recommended dosage of GARAMYCIN Injectable for patients with
serious infections and normal renal function is 3 mg/kg/day, administered in
three equal doses every 8 hours (Table I).
For patients with life-threatening infections, dosages up to 5 mg/kg/day may be
administered in three or four equal doses. This dosage should be reduced to 3
mg/kg/day as soon as clinically indicated (Table I).
It is desirable to measure periodically both peak and trough serum
concentrations of gentamicin when feasible during therapy to assure adequate but
not excessive drug levels. For example, the peak concentration (at 30 to 60
minutes after intramuscular injection) is expected to be in the range of 4 to 6
mcg/mL. When monitoring peak concentrations after intramuscular or intravenous
administration, 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 I
DOSAGE SCHEDULE GUIDE FOR ADULTS
WITH NORMAL RENAL FUNCTION
(Dosage at 8-Hour Intervals)
40 mg per mL
Usual Dose for Dose For Life-Threatening
Patient's 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 ML/DOSE MG/DOSE ML/DOSE
Q8H Q8H
40 ( 88) 40 1.0 66 1.6
45 ( 99) 45 1.1 75 1.9
50 (110) 50 1.25 83 2.1
55 (121) 55 1.4 91 2.25
60 (132) 60 1.5 100 2.5
65 (143) 65 1.6 108 2.7
70 (154) 70 1.75 116 2.9
75 (165) 75 1.9 125 3.1
80 (176) 80 2.0 133 3.3
85 (187) 85 2.1 141 3.5
90 (198) 90 2.25 150 3.75
95 (209) 95 2.4 158 4.0
100 (220) 100 2.5 166 4.2
* 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.
CHILDREN: 6 to 7.5 mg/kg/day. (2.0 to 2.5 mg/kg administered every 8 hours.)
INFANTS AND NEONATES: 7.5 mg/kg/day. (2.5 mg/kg administered every 8 hours.)
PREMATURE OR FULL-TERM NEONATES ONE WEEK OF AGE OR LESS: 5 mg/kg/day. (2.5
mg/kg administered every 12 hours.)
The usual duration of treatment for all patients is 7 to 10 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 10
days. Dosage should be reduced if clinically indicated.
For Intravenous Administration
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 intermittent intravenous administration in adults, a single dose of
GARAMYCIN Injectable may be diluted in 50 to 200 mL of sterile isotonic saline
solution or in a sterile solution of dextrose 5% in water; in infants and
children, the volume of diluent should be less. The solution may be infused over
a period of 1/2 to 2 hours.
The recommended dosage for intravenous and intramuscular administration is
identical.
GARAMYCIN Injectable should not be physically premixed with other drugs, but
should be administered separately in accordance with the recommended route of
administration and dosage schedule.
DOSAGE FOR 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 2.0
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 8-hour intervals is to divide the normally recommended dose by
the serum creatinine level (Table II). For example, after an initial dose of 60
mg (1.0 mg/kg), a patient weighing 60 kg with a serum creatinine level of 2.0
mg/100 mL could be given 30 mg every 8 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 II
DOSAGE ADJUSTMENT GUIDE FOR PATIENTS
WITH RENAL IMPAIRMENT
(Dosage at 8-Hour Intervals After the Usual Initial Dose)
Approximate Percent of
Serum Creatinine Clearance Rate Usual Doses
(mg %) (mL/min/1.73M(squared)) Shown in Table I
(=) 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 8-hour hemodialysis may reduce serum concentrations of
gentamicin by approximately 50%. The recommended dosage at the end of each
dialysis period is 1 to 1.7 mg/kg depending upon the severity of infection. In
children, a dose of 2 mg/kg may be administered.
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 is available to measure gentamicin concentrations in body
fluids; these include microbiologic, enzymatic, and radioimmunoassay techniques.
************************************************************************