Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/3983
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Tobramycin (Injection, Solution, Concentrate)
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| dailymed-instance:dosage |
Tobramycin Injection, USP may be given intramuscularly or
intravenously. Recommended dosages are the same for both routes. ADD-Vantage
vials are not intravascular administration. The patient's pretreatment
body weight should be obtained for calculation of correct dosage. It is desirable
to measure both peak and trough serum concentrations (see WARNINGS box and PRECAUTIONS). Administration for Patients with Normal Renal Function���Adults with Serious Infections: 3 mg/kg/day in 3 equal doses every 8 hours (see Table 1). Adults with Life-Threatening Infections: Up
to 5 mg/kg/day may be administered in 3 or 4 equal doses (see Table 1).
The dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.
To prevent increased toxicity due to excessive blood levels, dosage should
not exceed 5 mg/kg/day unless serum levels are monitored (see WARNINGS box and PRECAUTIONS). * Applicable to all product forms except Tobramycin Injection,
10 mg/mL (Pediatric). Pediatric
Patients (Greater Than 1 Week of Age): 6 to 7.5 mg/kg/day in 3 or
4 equally divided doses (2 to 2.5 mg/kg every 8 hours or 1.5 to 1.89 mg/kg
every 6 hours). Premature
or Full-Term Neonates 1 Week of Age or Less: Up to 4 mg/kg/day may
be administered in 2 equal doses every 12 hours. It
is desirable to limit treatment to a short term. The usual duration of treatment
is 7 to 10 days. A longer course of therapy may be necessary in difficult
and complicated infections. In such cases, monitoring of renal, auditory,
and vestibular functions is advised, because neurotoxicity is more likely
to occur when treatment is extended longer than 10 days. Dosage in Patients with Cystic Fibrosis���In patients with cystic fibrosis, altered
pharmacokinetics may result in reduced serum concentration of aminoglycosides.
Measurement of tobramycin serum concentration during treatment is especially
important as a basis for determining appropriate dose. In patients with severe
cystic fibrosis, an initial dosing regimen of 10 mg/kg/day in 4 equally divided
doses is recommended. This dosing regimen is suggested only as a guide. The
serum levels of tobramycin should be measured directly during treatment due
to a wide interpatient variability. Administration for Patients With Impaired Renal Function���Whenever possible, serum tobramycin concentrations should
be monitored during therapy. Following a loading dose
of 1 mg/kg, subsequent dosage in these patients must be adjusted, either with
reduced doses administered at 8-hour intervals or with normal doses given
at prolonged intervals. Both of these methods are suggested as guides to be
used when serum levels of tobramycin cannot be measured directly. They are
based on either the creatinine clearance or the serum creatinine of the patient,
because these values correlate with the half-life of tobramycin. The dosage
schedules derived from either method should be used in conjunction with careful
clinical and laboratory observations of the patient and should be modified
as necessary. Neither method should be used when dialysis is being performed. Reduced
dosage at 8-hour intervals: When the creatinine clearance rate is 70 mL or
less per minute or when the serum creatinine value is known, the amount of
the reduced dose can be determined by multiplying the normal dose from Table
1 by the percent of normal dose from the accompanying nomogram. An
alternate rough guide for determining reduced dosage at 8-hour intervals (for
patients whose steady-state serum creatinine values are known) is to divide
the normally recommended dose by the patient's serum creatinine. Normal dosage at prolonged intervals: If the creatinine
clearance rate is not available and the patient's condition is stable,
a dosage frequency in hours for the
dosage given in Table 1 can be determined by multiplying the patient's
serum creatinine by 6. Dosage
in Obese Patients���The appropriate dose may be calculated
by using the patient's estimated lean body weight plus 40% of the excess
as the basic weight on which to figure mg/kg. Intramuscular Administration���Tobramycin
Injection may be administered by withdrawing the appropriate dose directly
from a vial. Tobramycin sulfate in 0.9% Sodium Chloride is not intended for
intramuscular administration. Intravenous
Administration���For intravenous administration, the usual
volume of diluent (0.9% Sodium Chloride Injection or 5% Dextrose Injection)
is 50 to 100 mL for adult doses. For pediatric patients, the volume of diluent
should be proportionately less than for adults. The diluted solution usually
should be infused over a period of 20 to 60 minutes. Infusion periods of less
than 20 minutes are not recommended because peak serum levels may exceed
12 mcg/mL (see WARNINGS box). Use of ADD-Vantage Vials���ADD-Vantage Tobramycin
Injection vials are not intended for multiple use and should not be used with
a syringe in the conventional way. These products are intended for use only
with 50 mL or 100 mL ADD-Vantage Flexible Diluent Containers and in those
instances in which the physician's order specified 80 mg doses. Use
within 24 hours after activation. Tobramycin Injection
should not be physically premixed with other drugs but should be administered
separately according to the recommended dose and route. Parenteral
drug products should be inspected visually for particulate matter and discoloration
prior to administration, whenever solution and container permit. INSTRUCTIONS FOR USE To Open Diluent Container: Peel
overwrap from the corner and remove container. Some opacity of the plastic
due to moisture absorption during the sterilization process may be observed.
This is normal and does not affect the solution quality or safety. The opacity
will diminish gradually. To
Assemble Vial and Flexible Diluent Container: (Use Aseptic Technique) To Prepare Admixture: Preparation for Administration (Use Aseptic Technique) WARNING: Do not use flexible container
in series connections.
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| dailymed-instance:descripti... |
Tobramycin sulfate, a water-soluble antibiotic of the aminoglycoside
group, is derived from the actinomycete Streptomyces
tenebrarius. Tobramycin Injection, USP is a clear and colorless
sterile aqueous solution for parenteral administration. Each
mL contains tobramycin sulfate equivalent to 10 mg tobramycin; sodium metabisulfite
added as an antioxidant, 1.5 mg; and edetate disodium added as a stabilizer,
0.1 mg. Contains sulfuric acid and may contain sodium hydroxide for pH adjustment.
pH 4.5 (3.0 to 6.5). Tobramycin sulfate is O-3-amino-3-deoxy-��-D-glucopyranosyl-(1���4)-O-[2,6-diamino-2,3,6-trideoxy-��-D-ribo-hexopyranosyl-(1���6)]-2-deoxy-,L-streptamine
sulfate (2:5)(salt) and has the chemical formula (CHNO)���5HSO. The molecular weight is 1,425.45. The structural
formula for tobramycin is as follows:
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Tobramycin is rapidly absorbed following intramuscular administration.
Peak serum concentrations of tobramycin occur between 30 and 90 minutes after
intramuscular administration. Following an intramuscular
dose of 1 mg/kg of body weight, maximum serum concentrations reach about 4
mcg/mL, and measurable levels persist for as long as 8 hours. Therapeutic
serum levels are generally considered to range from 4 to 6 mcg/mL. When tobramycin
is administered by intravenous infusion over a 1-hour period, the serum concentrations
are similar to those obtained by intramuscular administration. Tobramycin
is poorly absorbed from the gastrointestinal tract. In
patients with normal renal function, except neonates, tobramycin administered
every 8 hours does not accumulate in the serum. However, in those patients
with reduced renal function and in neonates, the serum concentration of the
antibiotic is usually higher and can be measured for longer periods of time
than in normal adults. Dosage for such patients must, therefore, be adjusted
accordingly (see DOSAGE AND ADMINISTRATION). Following
parenteral administration, little, if any, metabolic transformation occurs,
and tobramycin is eliminated almost exclusively by glomerular filtration.
Renal clearance is similar to that of endogenous creatinine. Ultrafiltration
studies demonstrate that practically no serum protein binding occurs. In patients
with normal renal function, up to 84% of the dose is recoverable from the
urine in 8 hours and up to 93% in 24 hours. Peak urine
concentrations ranging from 75 to 100 mcg/mL have been observed following
the intramuscular injection of a single dose of 1 mg/kg. After several days
of treatment, the amount of tobramycin excreted in the urine approaches the
daily dose administered. When renal function is impaired, excretion of tobramycin
is slowed, and accumulation of the drug may cause toxic blood levels. The
serum half-life in normal individuals is 2 hours. An inverse relationship
exists between serum half-life and creatinine clearance, and the dosage schedule
should be adjusted according to the degree of renal impairment (see DOSAGE AND ADMINISTRATION). In patients undergoing
dialysis, 25% to 70% of the administered dose may be removed, depending on
the durationand type of dialysis. Tobramycin can be
detected in tissues and body fluids after parenteral administration. Concentrations
in bile and stools ordinarily have been low, which suggests minimum biliary
excretion. Tobramycin has appeared in low concentration in the cerebrospinal
fluid following parenteral administration, and concentrations are dependent
on dose, rate of penetration, and degree of meningeal inflammation. It has
also been found in sputum, peritoneal fluid, synovial fluid, and abscess fluids,
and it crosses the placental membranes. Concentrations in the renal cortex
are several times higher than the usual serum levels. Probenecid
does not affect the renal tubular transport of tobramycin. Microbiology���Tobramycin acts by
inhibiting synthesis of protein in bacterial cells. In
vitro tests demonstrate that tobramycin is bactericidal. Tobramycin
has been shown to be active against most strains of the following organisms
both in vitro and in clinical infections:
(see INDICATIONS AND USAGE) Gram-positive aerobes Staphylococcus aureus Gram-negative aerobes Citrobacter sp Enterobacter sp Escherichia coli Klebsiella sp Morganella morganii Pseudomonas aeruginosa Proteus mirabilis Proteus vulgaris Providencia sp Serratia sp Aminoglycosides
have a low order of activity against most gram-positive organisms, including Streptococcus pyogenes, Streptococcus pneumoniae,
and enterococci. Although most strains of enterococci
demonstrate in vitro resistance, some
strains in this group are susceptible. In vitro studies have shown that an aminoglycoside combined with an antibiotic
that interferes with cell-wall synthesis affects some enterococcal strains
synergistically. The combination of penicillin G and tobramycin results in
a synergistic bactericidal effect in vitro against
certain strains of Enterococcus faecalis.
However, this combination is not synergistic against other closely related
organisms, e.g., Enterococcus faecium.
Speciation of enterococci alone cannot be used to predict susceptibility.
Susceptibility testing and tests for antibiotic synergism are emphasized. Cross-resistance
between aminoglycosides may occur. Susceptibility
Tests: Diffusion Techniques: Quantitative
methods that require measurement of zone diameters give the most precise estimate
of the susceptibility of bacteria to antimicrobial agents. One such procedure
is the National Committee for Clinical Laboratory Standards (NCCLS) approved
procedure. This method has been recommended for use with disks
to test susceptibility to tobramycin. Interpretation involves correlation
of the diameters obtained in the disk test with the minimum inhibitory concentration
(MIC) for tobramycin. Reports from the laboratory giving
results of the standard single-disk susceptibility test with a 10-mcg tobramycin
disk should be interpreted according to the following criteria: A report of���Susceptible���indicates that
the pathogen is likely to be inhibited by generally achievable blood levels.
A report of���Intermediate���suggests that the organism would
be susceptible if high dosage is used or if the infection is confined to tissues
and fluids in which high antimicrobial levels are attained. A report of���Resistant���indicates that achievable concentrations are unlikely to be inhibitory, and
other therapy should be selected. Standardized procedures
require the use of laboratory control organisms. The 10-mcg tobramycin disk
should give the following zone diameters: Dilution Techniques: Broth
and agar dilution methods, such as those recommended by the NCCLS,
may be used to determine the minimum inhibitory concentration (MIC) of tobramycin.
MIC tests results should be interpreted according to the following criteria: As with standard diffusion methods, dilution procedures
require the use of laboratory control organisms. Standard tobramycin powder
should give the following MIC values:
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A hypersensitivity to any aminoglycoside is a contraindication
to the use of tobramycin. A history of hypersensitivity or serious toxic reactions
to aminoglycosides may also contraindicate the use of any other aminoglycoside
because of the known cross-sensitivity of patients to drugs in this class.
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Tobramycin Injection is supplied in single-dose ADD-Vantage
Vials as follows: Store at 20 to 25��C (68 to 77��F). [See USP Controlled
Room Temperature.] Covered by one or more of the following
U.S. patents: 4,614,515 and 4,614,267.
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| dailymed-instance:boxedWarn... |
WARNINGS: Patients treated with Tobramycin Injection and other aminoglycosides
should be under close clinical observation, because these drugs have an inherent
potential for causing ototoxicity and nephrotoxicity. Neurotoxicity,
manifested as both auditory and vestibular ototoxicity, can occur. The auditory
changes are irreversible, are usually bilateral, and may be partial or total.
Eighth-nerve impairment and nephrotoxicity may develop, primarily in patients
having pre-existing renal damage and in those with normal renal function to
whom aminoglycosides are administered for longer periods or in higher doses
than those recommended. Other manifestations of neurotoxicity may include
numbness, skin tingling, muscle twitching, and convulsions. The risk of aminoglycoside-induced
hearing loss increases with the degree of exposure to either high peak or
high trough serum concentrations. Patients who develop cochlear damage may
not have symptoms during therapy to warn them of eighth-nerve toxicity, and
partial or total irreversible bilateral deafness may continue to develop after
the drug has been discontinued. Rarely, nephrotoxicity may not become apparent
until the first few days after cessation of therapy. Aminoglycoside-induced
nephrotoxicity usually is reversible. Renal and eighth-nerve
function should be closely monitored in patients with known or suspected renal
impairment and also in those whose renal function is initially normal but
who develop signs of renal dysfunction during therapy. Peak and trough serum
concentrations of aminoglycosides should be monitored periodically during
therapy to assure adequate levels and to avoid potentially toxic levels. Prolonged
serum concentrations above 12 mcg/mL should be avoided. Rising trough levels
(above 2 mcg/mL) may indicate tissue accumulation. Such accumulation, excessive
peak concentrations, advanced age, and cumulative dose may contribute to ototoxicity
and nephrotoxicity (see PRECAUTIONS).
Urine should be examined for decreased specific gravity and increased excretion
of protein, cells, and casts. Blood urea nitrogen, serum creatinine, and creatinine
clearance should be measured periodically. When feasible, it is recommended
that serial audiograms be obtained in patients old enough to be tested, particularly
high-risk patients. Evidence of impairment of renal, vestibular, or auditory
function requires discontinuation of the drug or dosage adjustment. Tobramycin
should be used with caution in premature and neonatal infants because of their
renal immaturity and the resulting prolongation of serum half-life of the
drug. Concurrent and sequential use of other neurotoxic
and/or nephrotoxic antibiotics, particularly other aminoglycosides (e.g.,
amikacin, streptomycin, neomycin, kanamycin, gentamicin, and paromomycin),
cephaloridine, viomycin, polymyxin B, colistin, cisplatin, and vancomycin,
should be avoided. Other factors that may increase patient risk are advanced
age and dehydration. Aminoglycosides should not be given
concurrently with potent diuretics, such as ethacrynic acid and furosemide.
Some diuretics themselves cause ototoxicity, and intravenously administered
diuretics enhance aminoglycoside toxicity by altering antibiotic concentrations
in serum and tissue. Aminoglycosides can cause fetal
harm when administered to a pregnant woman (see PRECAUTIONS).
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Serum and urine specimens for examination should be collected
during therapy, as recommended in the WARNINGS box.
Serum calcium, magnesium, and sodium should be monitored. Peak
and trough serum levels should be measured periodically during therapy. Prolonged
concentrations above 12 mcg/mL should be avoided. Rising trough levels (above
2 mcg/mL) may indicate tissue accumulation. Such accumulation, advanced age,
and cumulative dosage may contribute to ototoxicity and nephrotoxicity. It
is particularly important to monitor serum levels closely in patients with
known renal impairment. A useful guideline would be
to perform serum level assays after 2 or 3 doses, so that the dosage could
be adjusted if necessary, and also at 3-to 4-day intervals during therapy.
In the event of changing renal function, more frequent serum levels should
be obtained and the dosage or dosage interval adjusted according to the guidelines
provided in the DOSAGE AND ADMINISTRATION section. In
order to measure the peak level, a serum sample should be drawn about 30 minutes
following intravenous infusion or 1 hour after an intramuscular injection.
Trough levels are measured by obtaining serum samples at 8 hours or just prior
to the next dose of tobramycin. These suggested time intervals are intended
only as guidelines and may vary according to institutional practices. It is
important, however, that there be consistency within the individual patient
program unless computerized pharmacokinetic dosing programs are available
in the institution. These serum-level assays may be especially useful for
monitoring the treatment of severely ill patients with changing renal function
or of those infected with less sensitive organisms or those receiving maximum
dosage. Neuromuscular blockade and respiratory paralysis
have been reported in cats receiving very high doses of tobramycin (40 mg/kg).
The possibility of prolonged or secondary apnea should be considered if tobramycin
is administered to anesthetized patients who are also receiving neuromuscular
blocking agents, such as succinylcholine, tubocurarine, or decamethonium,
or to patients receiving massive transfusions of citrated blood. If neuromuscular
blockade occurs, it may be reversed by the administration of calcium salts. Cross-allergenicity
among aminoglycosides has been demonstrated. In patients
with extensive burns or cystic fibrosis, altered pharmacokinetics may result
in reduced serum concentrations of aminoglycosides. In such patients treated
with tobramycin, measurement of serum concentration is especially important
as a basis for determination of appropriate dosage. Elderly
patients may have reduced renal function that 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 aminoglycosides is particularly important in such patients. An
increased incidence of nephrotoxicity has been reported following concomitant
administration of aminoglycoside antibiotics and cephalosporins. Aminoglycosides
should be used with caution in patients with muscular disorders, such as myasthenia
gravis or parkinsonism, since these drugs may aggravate muscle weakness because
of their potential curare-like effect on neuromuscular function. Aminoglycosides
may be absorbed in significant quantities from body surfaces after local irrigation
or application and may cause neurotoxicity and nephrotoxicity. Aminoglycosides
have not been approved for intraocular and/or subconjunctival use. Physicians
are advised that macular necrosis has been reported following administration
of aminoglycosides, including tobramycin, by these routes. See WARNINGS box regarding concurrent use of potent
diuretics and concurrent and sequential use of other neurotoxic or nephrotoxic
drugs. The inactivation of tobramycin and other aminoglycosides
by��-lactam-type antibiotics (penicillins or cephalosporins) has been
demonstrated in vitro and in patients
with severe renal impairment. Such inactivation has not been found in patients
with normal renal function who have been given the drugs by separate routes
of administration. Therapy with tobramycin may result
in overgrowth of nonsusceptible organisms. If overgrowth of nonsusceptible
organisms occurs, appropriate therapy should be initiated.<br/>Pregnancy Category D: 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. If tobramycin is used during
pregnancy or if the patient becomes pregnant while taking tobramycin, she
should be apprised of the potential hazard to the fetus.<br/>Pediatric Use: See INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION.<br/>Geriatric Use: Elderly patients may be at a higher risk of developing nephrotoxicity
and ototoxicity while receiving tobramycin (see WARNINGS, PRECAUTIONS and OVERDOSAGE ). Other factors that may contribute
to nephrotoxicity and ototoxicity are rising trough levels, excessive peak
concentrations, dehydration, concomitant use of other neurotoxic or nephrotoxic
drugs, and cumulative dose. Peak and trough serum levels should be measured
periodically during therapy to assure adequate levels and to avoid potentially
toxic levels (see WARNINGS and PRECAUTIONS). Tobramycin
is known to be substantially excreted by the kidney, and the risk of toxic
reactions to this drug may be greater in patients with impaired renal function.
Dose reduction is required for patients with impaired renal function (see DOSAGE AND ADMINISTRATION). Elderly patients may
have reduced renal function that 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 aminoglycosides
is particularly important in the elderly (see PRECAUTIONS). Tobramycin 80 mg/8 mL vial contains 2.9
mg (0.13 mEq) of sodium.<br/>General: Prescribing tobramycin in the absence of a proven or strongly
suspected bacterial infection or a prophylactic indication is unlikely to
provide benefit to the patient and increases the risk of the development of
drug-resistant bacteria.<br/>Information for Patients: Patients should be counseled that antibacterial drugs including
tobramycin should only be used to treat bacterial infections. They do not
treat viral infections (e.g., the common cold). When tobramycin is prescribed
to treat a bacterial infection, the patient should be told that although it
is common to feel better earlyin the course of therapy, the medication should
be taken exactly as directed. Skipping doses or not completing the full course
of therapy may (1) decrease the effectiveness of the immediate treatment and
(2) increase the likelihood that bacteria will develop resistance and will
not be treatable by tobramycin or other antibacterial drugs in the future.
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| dailymed-instance:overdosag... |
Signs and Symptoms���The severity of the signs and symptoms
following a tobramycin overdose are dependent on the dose administered, the
patient's renal function, state of hydration, and age and whether or
not other medications with similar toxicities are being administered concurrently.
Toxicity may occur in patients treated more than 10 days, in adults given
more than 5 mg/kg/day, pediatric patients given more than 7.5 mg/kg/day, or
patients with reduced renal function whose dose has not been appropriately
adjusted. Nephrotoxicity following the parenteral administration
of an aminoglycoside is most closely related to the area under the curve of
the serum concentration versus time graph. Nephrotoxicity is more likely if
trough blood concentrations fail to fall below 2 mcg/mL and is also proportional
to the average blood concentration. Patients who are elderly, have abnormal
renal function, are receiving other nephrotoxic drugs, or are volume depleted
are at greater risk for developing acute tubular necrosis. Auditory and vestibular
toxicity has been associated with aminoglycoside overdose; these toxicities
occur in patients treated longer than 10 days, in patients with abnormal renal
function, in dehydrated patients, or in patients receiving medications with
additive auditory toxicities. These patients may not have signs or symptoms
or may experience dizziness, tinnitus, vertigo, and a loss of high-tone acuity,
as ototoxicity progresses. Ototoxicity signs and symptoms may not begin to
occur until long after the drug has been discontinued. Neuromuscular
blockade or respiratory paralysis may occur following administration of many
aminoglycosides. Neuromuscular blockade, respiratory failure, and prolonged
respiratory paralysis may occur more commonly in patients with myasthenia
gravis or Parkinson's disease. Prolonged respiratory paralysis may
also occur in patients receiving decamethonium, tubocurarine, or succinylcholine.
If neuromuscular blockade occurs, it may be reversed by the administration
of calcium salts but mechanical assistance may be necessary. If
tobramycin were ingested, toxicity would be less likely because aminoglycosides
are poorly absorbed from an intact gastrointestinal tract. Treatment���In all cases of suspected overdosage, call your Regional Poison
Control Center to obtain the most up-to-date information about the treatment
of overdose. This recommendation is made because, in general, information
regarding the treatment of overdose may change more rapidly than the package
insert. In managing overdosage, consider the possibility of multiple drug
overdoses, interaction among drugs, and unusual drug kinetics in your patient. The
initial intervention in a tobramycin overdose is to establish an airway and
ensure oxygenation and ventilation. Resuscitative measures should be initiated
promptly if respiratory paralysis occurs. Patients that
have received an overdose of tobramycin and have normal renal function should
be adequately hydrated to maintain a urine output of 3 to 5 mL/kg/hr. Fluid
balance, creatinine clearance, and tobramycin plasma levels should be carefully
monitored until the serum tobramycin level falls below 2 mcg/mL. Patients
in whom the elimination half-life is greater than 2 hours or whose renal function
is abnormal may require more aggressive therapy. In such patients, hemodialysis
may be beneficial.
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Tobramycin
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Tobramycin (Injection, Solution, Concentrate)
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| dailymed-instance:adverseRe... |
Neurotoxicity���Adverse effects on both the vestibular
and auditory branches of the eighth nerve have been noted, especially in patients
receiving high doses or prolonged therapy, in those given previous courses
of therapy with an ototoxin, and in cases of dehydration. Symptoms include
dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss. Hearing
loss is usually irreversible and is manifested initially by diminution of
high-tone acuity. Tobramycin and gentamicin closely parallel each other in
regard to ototoxic potential. Nephrotoxicity���Renal function
changes, as shown by rising BUN, NPN, and serum creatinine and by oliguria,
cylindruria, and increased proteinuria, have been reported, especially in
patients with a history of renal impairment who are treated for longer periods
or with higher doses than those recommended. Adverse renal effects can occur
in patients with initially normal renal function. Clinical
studies and studies in experimental animals have been conducted to compare
the nephrotoxic potential of tobramycin and gentamicin. In some of the clinical
studies and in the animal studies, tobramycin caused nephrotoxicity significantly
less frequently than gentamicin. In some other clinical studies, no significant
difference in the incidence of nephrotoxicity between tobramycin and gentamicin
was found. Other reported adverse reactions possibly
related to tobramycin include anemia, granulocytopenia, and thrombocytopenia;
and fever, rash, itching, urticaria, nausea, vomiting, diarrhea, headache,
lethargy, pain at the injection site, mental confusion, and disorientation.
Laboratory abnormalities possibly related to tobramycin include increased
serum transaminases (AST, ALT); increased serum LDH and bilirubin; decreased
serum calcium, magnesium, sodium, and potassium; and leukopenia, leukocytosis,
and eosinophilia.
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| dailymed-instance:warning |
Patients treated with Tobramycin Injection and other aminoglycosides
should be under close clinical observation, because these drugs have an inherent
potential for causing ototoxicity and nephrotoxicity. Neurotoxicity,
manifested as both auditory and vestibular ototoxicity, can occur. The auditory
changes are irreversible, are usually bilateral, and may be partial or total.
Eighth-nerve impairment and nephrotoxicity may develop, primarily in patients
having pre-existing renal damage and in those with normal renal function to
whom aminoglycosides are administered for longer periods or in higher doses
than those recommended. Other manifestations of neurotoxicity may include
numbness, skin tingling, muscle twitching, and convulsions. The risk of aminoglycoside-induced
hearing loss increases with the degree of exposure to either high peak or
high trough serum concentrations. Patients who develop cochlear damage may
not have symptoms during therapy to warn them of eighth-nerve toxicity, and
partial or total irreversible bilateral deafness may continue to develop after
the drug has been discontinued. Rarely, nephrotoxicity may not become apparent
until the first few days after cessation of therapy. Aminoglycoside-induced
nephrotoxicity usually is reversible. Renal and eighth-nerve
function should be closely monitored in patients with known or suspected renal
impairment and also in those whose renal function is initially normal but
who develop signs of renal dysfunction during therapy. Peak and trough serum
concentrations of aminoglycosides should be monitored periodically during
therapy to assure adequate levels and to avoid potentially toxic levels. Prolonged
serum concentrations above 12 mcg/mL should be avoided. Rising trough levels
(above 2 mcg/mL) may indicate tissue accumulation. Such accumulation, excessive
peak concentrations, advanced age, and cumulative dose may contribute to ototoxicity
and nephrotoxicity (see PRECAUTIONS).
Urine should be examined for decreased specific gravity and increased excretion
of protein, cells, and casts. Blood urea nitrogen, serum creatinine, and creatinine
clearance should be measured periodically. When feasible, it is recommended
that serial audiograms be obtained in patients old enough to be tested, particularly
high-risk patients. Evidence of impairment of renal, vestibular, or auditory
function requires discontinuation of the drug or dosage adjustment. Tobramycin
should be used with caution in premature and neonatal infants because of their
renal immaturity and the resulting prolongation of serum half-life of the
drug. Concurrent and sequential use of other neurotoxic
and/or nephrotoxic antibiotics, particularly other aminoglycosides (e.g.,
amikacin, streptomycin, neomycin, kanamycin, gentamicin, and paromomycin),
cephaloridine, viomycin, polymyxin B, colistin, cisplatin, and vancomycin,
should be avoided. Other factors that may increase patient risk are advanced
age and dehydration. Aminoglycosides should not be given
concurrently with potent diuretics, such as ethacrynic acid and furosemide.
Some diuretics themselves cause ototoxicity, and intravenously administered
diuretics enhance aminoglycoside toxicity by altering antibiotic concentrations
in serum and tissue. Aminoglycosides can cause fetal
harm when administered to a pregnant woman (see PRECAUTIONS).
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| dailymed-instance:indicatio... |
To reduce the development of drug-resistant bacteria and
maintain the effectiveness of tobramycin and other antibacterial drugs, tobramycin
should be used only to treat or prevent infections that are proven or strongly
suspected to be caused by susceptible bacteria. When culture and susceptibility
information are available, they should be considered in selecting or modifying
antibacterial therapy. In the absence of such data, local epidemiology and
susceptibility patterns may contribute to the empiric selection of therapy. Tobramycin
is indicated for the treatment of serious bacterial infections caused by susceptible
strains of the designated microorganisms in the diseases listed below: Septicemia
in the pediatric patient and adult caused by P
aeruginosa, E coli, and Klebsiella sp Lower respiratory
tract infections caused by P aeruginosa, Klebsiella sp, Enterobacter sp, Serratia sp, E coli, and S aureus (penicillinase and non-penicillinase-producing strains) Serious
central-nervous-system infections (meningitis) caused by susceptible organisms Intra-abdominal
infections, including peritonitis, caused by E
coli, Klebsiella sp, and Enterobacter sp Skin,
bone, and skin-structure infections caused by P
aeruginosa, Proteus sp, E coli, Klebsiella sp, Enterobacter sp, and S aureus Complicated and
recurrent urinary tract infections caused by P
aeruginosa, Proteus sp (indole-positive
and indole-negative), E coli, Klebsiella sp, Enterobacter sp, Serratia sp, S aureus, Providencia sp, and Citrobacter sp Aminoglycosides,
including tobramycin, are not indicated in uncomplicated initial episodes
of urinary tract infections unless the causative organisms are not susceptible
to antibiotics having less potential toxicity. Tobramycin may be considered
in serious staphylococcal infections when penicillin or other potentially
less toxic drugs are contraindicated and when bacterial susceptibility testing
and clinical judgment indicate its use. Bacterial cultures
should be obtained prior to and during treatment to isolate and identify etiologic
organisms and to test their susceptibility to tobramycin. If susceptibility
tests show that the causative organisms are resistant to tobramycin, other
appropriate therapy should be instituted. In patients in whom a serious life-threatening
gram-negative infection is suspected, including those in whom concurrent therapy
with a penicillin or cephalosporin and an aminoglycoside may be indicated,
treatment with tobramycin may be initiated before the results of susceptibility
studies are obtained. The decision to continue therapy with tobramycin should
be based on the results of susceptibility studies, the severity of the infection,
and the important additional concepts discussed in the WARNINGS box above.
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Tobramycin
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