Tobramycin (systemic): Pediatric drug information

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(For additional information see "Tobramycin (systemic): Drug information" and see "Tobramycin
(systemic): Patient drug information")

For abbreviations and symbols that may be used in Lexicomp (show table)

ALERT: US Boxed Warning

Nephrotoxicity:

Tobramycin can result in acute kidney injury, including acute renal failure. Risk
factors that may contribute to nephrotoxicity include tobramycin accumulation
(increasing serum trough levels), high peak concentrations (>12 mcg/mL),
total cumulative dose, advanced age, volume depletion, and concurrent or
sequential use of other nephrotoxic drugs. Avoid concurrent or sequential use
of other potentially nephrotoxic drugs. Monitor serum tobramycin levels and
renal function in all patients during drug treatment. Reduce the dose or
discontinue the drug if renal impairment occurs.

Ototoxicity:

Tobramycin can cause irreversible auditory and vestibular toxicity that may
continue to develop after the drug has been discontinued. Risk factors include
high serum concentrations, prolonged therapy, renal impairment, concurrent
and sequential use of other nephrotoxic or ototoxic drugs (eg,
aminoglycosides), and extremes of age. Avoid concurrent or sequential use
with other potentially ototoxic drugs. Monitor for signs and symptoms of
auditory and vestibular toxicity. Reduce the dose or discontinue the drug if
renal impairment occurs. Discontinue the drug if ototoxicity occurs.
Neuromuscular blockade:

Aminoglycosides have been associated with neuromuscular blockade. During

therapy with tobramycin, monitor for adverse reactions associated with
neuromuscular blockade, particularly in high-risk patients, such as patients
with underlying neuromuscular disorders (including myasthenia gravis) or in
patients concomitantly receiving neuromuscular-blocking agents.

Embryo-fetal toxicity:

Tobramycin and other aminoglycosides can cause fetal harm when

administered to a pregnant woman. If tobramycin is used during pregnancy or
if the patient becomes pregnant while taking tobramycin, apprise the patient of
the potential hazard to the fetus.

Brand Names: Canada

JAMP-Tobramycin

Therapeutic Category
Antibiotic, Aminoglycoside

Dosing: Neonatal
Note: Dosage should be based on actual weight unless the patient has hydrops
fetalis. Dosage should be individualized based upon serum concentration
monitoring.

General dosing; susceptible infection: Limited data available: Extended

interval dosing strategies may vary by institution as a wide variety of dosing
regimens have been studied (de Hoog 2002; DiCenzo 2003; Hagen 2009;
Hansen 2003; Ohler 2000; Serane 2009). Note: Consider prolongation of
dosing interval when coadministered with ibuprofen or indomethacin or in
neonates with history of the following: Birth depression, birth
hypoxia/asphyxia, or cyanotic congenital heart disease. Some dosing based on
gentamicin studies.

Age-directed dosing (Bradley 2016): IM, IV:

GA <30 weeks:

PNA ≤14 days: 5 mg/kg/dose every 48 hours

PNA ≥15 days: 5 mg/kg/dose every 36 hours

GA 30 to 34 weeks:

PNA ≤10 days: 4.5 mg/kg/dose every 36 hours

PNA ≥11 days: 5 mg/kg/dose every 36 hours

GA ≥35 weeks:

PNA ≤7 days: 4 mg/kg/dose every 24 hours

PNA ≥8 days: 5 mg/kg/dose every 24 hours

Weight-directed dosing (Red Book [AAP 2015]): IM, IV:

Body weight <1 kg:

PNA ≤14 days: 5 mg/kg/dose every 48 hours

PNA 15 to 28 days: 5 mg/kg/dose every 36 hours

Body weight 1 to 2 kg:

PNA ≤7 days: 5 mg/kg/dose every 48 hours

PNA 8 to 28 days: 5 mg/kg/dose every 36 hours

Body weight >2 kg:

PNA ≤7 days: 4 mg/kg/dose every 24 hours

 PNA 8 to 28 days: 4 to 5 mg/kg/dose every 24 hours

Dosing adjustment in renal impairment: Consider single-dose administration

with serum concentration monitoring in patients with urine output <1
mL/kg/hour or serum creatinine >1.3 mg/dL rather than scheduled dosing.

Dosing: Pediatric
Note: Dosage should be based on an estimate of ideal body weight. In
morbidly obese children, adolescents, and adults, dosage requirement may
best be estimated using a dosing weight of IBW + 0.4 (TBW - IBW). Dosage
should be individualized based upon serum concentration monitoring. Initial
and periodic plasma drug concentrations (eg, peak and trough with
conventional dosing, post dose level at a prespecified time with extended-
interval dosing) should be determined, particularly in critically ill patients with
serious infections or in disease states known to significantly alter
aminoglycoside pharmacokinetics (eg, cystic fibrosis, burns, or major surgery).
Some dosing based on gentamicin studies:

General dosing, susceptible infection:

Conventional dosing: Infants, Children, and Adolescents: IM, IV: 6 to 7.5

mg/kg/day divided every 6 to 8 hours; individualize dosing based on
patient-specific clinical parameters (Red Book [AAP 2015]).

Extended-interval dosing: Limited data available:

Weight-directed: Infants, Children, and Adolescents: IV: 4.5 to 7.5

mg/kg/dose every 24 hours (Contopoulos-Ioannidis 2004; Red Book
[AAP 2015]).

Age-directed: Based on data from 114 pediatric patients receiving

extended-interval dosing of gentamicin, the following has been
suggested for tobramycin (McDade 2010):
 Infants ≥3 months and Children <2 years: IV: 9.5 mg/kg/dose
every 24 hours.

Children 2 to <8 years: IV: 8.5 mg/kg/dose every 24 hours.

Children ≥8 years and Adolescents: IV: 7 mg/kg/dose every 24

hours.

Cystic fibrosis, pulmonary infection: Infants, Children, and Adolescents:

Conventional dosing: IM, IV: 3.3 mg/kg/dose every 8 hours (Flume

2009).

Extended-interval dosing: IV: Initial: 10 to 12 mg/kg/dose every 24

hours (Flume 2009; Smyth 2005; Van Meter 2009); Note: The CF
Foundation recommends extended-interval dosing as preferred over
conventional dosing.

Endocarditis, treatment: Children and Adolescents: IV: 3 to 6 mg/kg/day

divided every 8 hours; use in combination with other antibiotics dependent
upon organism and source of infection (ie, valve-type) (AHA [Baltimore
2015]).

Intra-abdominal infection, complicated: Infants, Children, and Adolescents:

IV: 3 to 7.5 mg/kg/day divided every 8 to 24 hours (Solomkin 2010).

CNS infection:

Meningitis (Tunkel 2004):

Infants and Children: IV: 7.5 mg/kg/day divided every 8 hours.

Adolescents: IV: 5 mg/kg/day divided every 8 hours.

VP-shunt infection, ventriculitis: Limited data available: Infants,

Children, and Adolescents: Intraventricular/intrathecal (use a
preservative-free preparation): 5 to 20 mg/day.
 Peritonitis (CAPD) (Warady 2012): Limited data available: Infants, Children,
and Adolescents: Intraperitoneal: Continuous: Loading dose: 8 mg per liter
of dialysate; maintenance dose: 4 mg per liter.

Urinary tract infection:

Traditional dosing: Infants and Children 2 to 24 months: IV: 5

mg/kg/day divided every 8 hours (AAP 2011).

Extended-interval dosing: Limited data available: Based on data from

179 patients, the following age-directed dosing has been suggested
(Carapetis 2001):

Infants and Children <5 years: IV: 7.5 mg/kg/dose every 24 hours.

Children 5 to 10 years: IV: 6 mg/kg/dose every 24 hours.

Children >10 years and Adolescents: IV: 4.5 mg/kg/dose every 24

hours.

Dosing: Renal Impairment: Pediatric

Parenteral:

Infants, Children, and Adolescents: IM, IV:

The following adjustments have been recommended (Aronoff 2007):

Note: Renally adjusted dose recommendations are based on doses of
2.5 mg/kg/dose every 8 hours.

GFR >50 mL/minute/1.73 m2: No adjustment required

GFR 30 to 50 mL/minute/1.73 m2: Administer every 12 to 18 hours

GFR 10 to 29 mL/minute/1.73 m2: Administer every 18 to 24 hours

GFR <10 mL/minute/1.73 m2: Administer every 48 to 72 hours

 Intermittent hemodialysis: Dialyzable (25% to 70%): 2 mg/kg/dose;
redose as indicated by serum concentrations

Peritoneal dialysis (PD): 2 mg/kg/dose; redose as indicated by serum

concentrations

Continuous renal replacement therapy (CRRT): 2 to 2.5 mg/kg/dose

every 12 to 24 hours, monitor serum concentrations

Dosing: Hepatic Impairment: Pediatric

No dosage adjustment necessary; does not undergo hepatic metabolism.

Dosing: Adult
(For additional information see "Tobramycin (systemic): Drug information")
Note: Aminoglycoside dosing weight: For underweight patients (ie, total body
weight [TBW] < ideal body weight [IBW]), calculate the dose based on TBW. For
nonobese patients (ie, TBW 1 to 1.25 × IBW), calculate the dose based on TBW or
IBW. TBW may be preferred in nonobese patients who may have increased Vd (eg,
critically ill). For obese patients (ie, TBW > 1.25 × IBW), calculate the dose based
on 40% adjusted body weight (IBW + [0.4 × (TBW-IBW)]) (Bailey 1997; Blackburn
2015; Nicolau 1995; Rea 2008; Traynor 1995). Therapeutic drug monitoring:
Monitoring of serum concentrations is recommended to ensure efficacy and avoid
toxicity, particularly in critically ill patients with serious infection or in disease
states known to significantly alter aminoglycoside pharmacokinetics (eg, cystic
fibrosis, burns, major surgery). Timing and frequency of concentration monitoring
is individualized based on dosing and monitoring strategy (Buijk 2002; Drew 2020;
Nezic 2014).

Usual dosage range:

Gram negative infections:

 Conventional/traditional dosing: IV, IM: 3 to 5 mg/kg/day in divided
doses every 8 hours (manufacturer’s labeling). Some experts favor an
initial loading dose of 2.5 to 3 mg/kg (Drew 2020). Target peak
concentration depends on indication and site of infection; in general,
adjust dose to achieve peak of 4 to 6 mg/L for urinary tract infections
and 7 to 10 mg/L for serious infections (including life-threatening
infections). Target trough concentrations should be <2 mg/L; ideal
target <1 mg/L (Bertino 1994; Drew 2020; Matzke 1983).

High-dose extended-interval dosing (once-daily dosing): IV: 5 to 7

mg/kg once daily; method is generally not recommended in patients
with ascites, burns covering >20% of the total BSA, end-stage renal
disease (eg, requiring hemodialysis), or pregnancy (except for
intrapartum therapy for intra-amniotic infection) due to altered
pharmacokinetics. Use with caution in patients with CrCl <40
mL/minute (Bailey 1997; Buijk 2002; Drew 2020; Nicolau 1995). Adjust
tobramycin dose and interval to achieve an extrapolated peak
concentration of ~15 to 20 mg/L and trough concentration ≤1 mg/L;
ideal target <0.5 mg/L (Buijk 2002; Drew 2020; Leggett 2014; Nicolau
1995; Pagkalis 2011).

Indication-specific dosing:

Bloodstream infection: Adjunctive empiric therapy for patients with

sepsis/septic shock and concern for resistant gram-negative bacteria (eg,
immunosuppression, prevalent local resistance, recent antibiotic exposure):
IV: 5 to 7 mg/kg once daily in combination with a second gram-negative
active agent; once culture and susceptibility results are available, can
generally discontinue and use a single agent with documented activity.
Tobramycin should not be used as monotherapy (Bailey 1997; Kanj 2020;
Moehring 2020; Nicolau 1995; SCCM [Rhodes 2017]).
Cerebrospinal fluid shunt infection (adjunct to systemic therapy): Note:
Reserve for infections due to multidrug-resistant organisms, infections
refractory to appropriate parenteral therapy, or when infected shunts
cannot be removed (Baddour 2020; Friedman 2020).

Intraventricular (use a preservative-free preparation): 5 to 20 mg/day;

some experts recommend adjusting dosage and administration interval
based on cerebrospinal fluid (CSF) tobramycin concentrations (goal: 10
to 20 times minimum inhibitory concentration of causative organism),
ventricle size, and daily output from ventricular drain (IDSA [Tunkel
2017]). When intraventricular tobramycin is administered via a
ventricular drain, clamp drain for 15 to 60 minutes after administration
(allows solution to equilibrate in CSF). Duration is individualized
according to clinical and microbiological response (IDSA [Tunkel 2004];
IDSA [Tunkel 2017]; LeBras 2016).

Cystic fibrosis, acute pulmonary exacerbation: For empiric or targeted

therapy of P. aeruginosa or other gram-negative bacilli:

IV: 10 mg/kg once daily as part of an appropriate combination regimen

(Flume 2009; Prescott 2010; Simon 2020). Duration is usually 10 days
to 3 weeks or longer based on clinical response (Flume 2009; Simon
2020).

Meningitis, bacterial: P. aeruginosa: IV: 5 mg/kg/day in divided doses every

8 hours as part of an appropriate combination regimen (IDSA [Tunkel
2004]; IDSA [Tunkel 2017]).

Peritonitis, treatment (peritoneal dialysis patients) (off-label use): As a

component of empiric therapy or for pathogen-directed therapy.

Note: Intraperitoneal administration is preferred to IV administration.

Once culture results are available, switch to another active antibiotic
 class, if possible, to decrease the risk of toxicity; otherwise, duration of
therapy is ≥3 weeks for patients with adequate clinical response
(Burkart 2020; ISPD [Li 2016]). Consider a 25% dose increase in
patients with significant residual renal function (urine output >100
mL/day) (ISPD [Li 2010]; ISPD [Li 2016]; Mancini 2018; Szeto 2018).

Intermittent (strongly preferred): Intraperitoneal: 0.6 mg/kg added to

one exchange of dialysis solution once daily (allow to dwell ≥6 hours)
(ISPD [Li 2016]).

Continuous (with every exchange) (dose is per liter of dialysate):

Intraperitoneal: Loading dose: 3 mg/kg with first exchange of dialysate;
maintenance dose: 0.3 mg/kg with each subsequent exchange of
dialysate (ISPD [Li 2016]).

Pneumonia, hospital-acquired or ventilator-associated: IV: 5 to 7

mg/kg/day once daily for 7 days; may consider shorter or longer duration
depending on rate of clinical improvement. When used as empiric therapy,
use in combination with an agent active against S. aureus and an additional
antipseudomonal agent. Note: Aminoglycosides are not recommended as
monotherapy in patients with hospital-acquired or ventilator-associated
pneumonia due to P. aeruginosa (ATS/IDSA [Kalil 2016]).

Sepsis or septic shock, adjunctive empiric gram-negative coverage (eg, in

the setting of intra-abdominal infection, pneumonia, gram-negative
bacteremia, or severe burn): Note: Some experts reserve for patients with
immunocompromising conditions or risk for resistant gram-negative
pathogens, in particular P. aeruginosa (Kanj 2020; Moehring 2020; Schmidt
2020).

IV: 5 to 7 mg/kg once daily in combination with a second gram-negative

agent (SCCM [Rhodes 2017]; Schmidt 2020); once culture and
susceptibility tests are available, can generally discontinue and use a
 single agent with documented activity. Tobramycin should not be used
as monotherapy for severe infections outside of the urinary tract (Kanj
2020; Nicolau 1995; SCCM [Rhodes 2017]; Schmidt 2020).

Urinary tract infection, complicated (pyelonephritis or cystitis symptoms

with signs/symptoms of systemic infection) (alternative agent): Note:
Reserve for use when other long-acting parenteral antimicrobials or
fluoroquinolones cannot be used due to allergy, intolerance, unmodifiable
drug interactions, or resistance (Hooton 2020).

IM, IV: 5 mg/kg once at the initiation of therapy or once daily pending
culture and susceptibility results. Duration of therapy depends on
antimicrobial chosen to complete the regimen and ranges from 5 to 14
days (Hooton 2020; IDSA/ESCMID [Gupta 2011]).

Dosing: Renal Impairment: Adult

IM, IV:

Conventional dosing:

CrCl >60 mL/minute: Administer every 8 hours.

CrCl 40 to 60 mL/minute: Administer every 12 hours.

CrCl 20 to 39 mL/minute: Administer every 24 hours.

CrCl <20 mL/minute: Loading dose, then monitor levels.

IV:

High-dose extended-interval dosing (Bailey 1997; Nicolau 1995): Interval may

be extended (eg, every 36 to 48 hours) in patients with renal impairment and/or
adjusted based on therapeutic drug monitoring.

CrCl ≥60 mL/minute: Administer every 24 hours.

 CrCl 40 to 59 mL/minute: Administer every 36 hours.

CrCl 20 to 39 mL/minute: Administer every 48 hours.

CrCl <20 mL/minute: Monitor serum levels and redose when tobramycin
level is <1 mg/L or use conventional dosing.

Note: In patients with sepsis/septic shock and severe renal impairment,

the Society of Critical Care Medicine guidelines do not recommend the use
of once-daily dosing. Patients with mild renal impairment should still
receive once-daily dosing with an extended interval (ie, up to 3 days)
(SCCM [Rhodes 2017]).

Intermittent hemodialysis (IHD) (administer after hemodialysis on dialysis

days) (Heintz 2009): Dialyzable (25% to 70%; variable; dependent on filter,
duration, and type of HD): IV:

Loading dose of 2 to 3 mg/kg, followed by:

Mild UTI: 1 mg/kg/dose every 48 to 72 hours; consider redosing for pre-

HD or post-HD serum concentrations <1 mg/L.

Moderate to severe UTI: 1 to 1.5 mg/kg/dose every 48 to 72 hours;

consider redosing for pre-HD serum concentrations <1.5 to 2 mg/L or
post-HD concentrations <1 mg/L.

Systemic gram-negative infection: 1.5 to 2 mg/kg/dose every 48 to 72

hours; consider redosing for pre-HD serum concentrations <3 to 5 mg/L
or post-HD serum concentrations <2 mg/L.

Note: Dosing dependent on the assumption of 3 times/week, complete IHD

sessions.

CRRT (Heintz 2009; Trotman 2005): Drug clearance is highly dependent on the
method of renal replacement, filter type, and flow rate. Appropriate dosing
requires close monitoring of pharmacologic response, signs of adverse
 reactions due to drug accumulation, as well as target drug concentrations (if
appropriate). Note: The following are general recommendations only (based
on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual
renal function) and should not supersede clinical judgment; therapeutic drug
monitoring is recommended:

CVVH/CVVHD/CVVHDF: IV:

Mild UTI: Loading dose of 2 to 3 mg/kg, followed by 1 mg/kg/dose

every 24 to 36 hours (redose when serum concentration <1 mg/L
[Heintz 2009]).

Moderate-severe UTI: Loading dose of 2 to 3 mg/kg, followed by 1 to

1.5 mg/kg/dose every 24 to 36 hours (redose when serum
concentration <1.5 to 2 mg/L [Heintz 2009]).

Systemic gram-negative infection: Loading dose of 2 to 3 mg/kg,

followed by 1.5 to 2.5 mg/kg/dose every 24 to 48 hours (generally
accepted to redose when serum concentration <2 mg/L; one reference
suggests redosing when <3 mg/L [Heintz 2009]).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary; does not undergo hepatic metabolism.

Dosage Forms: US
Excipient information presented when available (limited, particularly for generics);
consult specific product labeling.

Solution, Injection:

Generic: 10 mg/mL (2 mL); 80 mg/2 mL (2 mL); 1.2 g/30 mL (30 mL)

Solution, Injection [preservative free]:

Generic: 80 mg/2 mL (2 mL); 2 g/50 mL (50 mL)

 Solution Reconstituted, Injection:

Generic: 1.2 g (1 ea)

Solution Reconstituted, Injection [preservative free]:

Generic: 1.2 g (1 ea)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics);
consult specific product labeling.

Solution, Injection:

Generic: 10 mg/mL (2 mL); 40 mg/mL (2 mL, 30 mL)

Solution Reconstituted, Injection:

Generic: 1.2 g (1 ea)

Administration: Pediatric
Parenteral:

IM: Administer undiluted by deep IM route if possible. Slower absorption and

lower peak concentrations, probably due to poor circulation in the atrophic
muscle, may occur following IM injection in paralyzed patients, suggest IV
route.

IV: Administer by slow intermittent infusion over 30 to 60 minutes (administer

higher doses over 60 minutes) or by direct injection over 15 minutes

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to
inactivate aminoglycosides in vitro. This has been observed to a greater extent
with tobramycin and gentamicin, while amikacin has shown greater stability
against inactivation. Concurrent use of these agents may pose a risk of reduced
antibacterial efficacy in vivo, particularly in the setting of profound renal
impairment; however, definitive clinical evidence is lacking. If combination
penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction,
separation of doses (if feasible), and routine monitoring of aminoglycoside levels,
CBC, and clinical response should be considered.

Administration: Adult
IM: May be administered IM by withdrawing the appropriate dose directly from
a vial or by using a prefilled syringe. The pharmacy bulk package and
tobramycin in sodium chloride 0.9% is not intended for IM administration.

IV: Administer by intermittent infusion over 20 to 60 minutes; higher doses are

generally administered over 60 minutes (Aminimanizani 2002; Demczar 1997).
Flush line with saline before and after administration.

Intraventricular (off-label route): Use preservative-free preparations only. When

administered through a ventricular drain, clamp drain for 15 to 60 minutes
before opening the drain to allow tobramycin solution to equilibrate in the CSF
(IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).

Storage/Stability
Store intact vials at 20ºC to 25ºC (68ºF to 77ºF). Reconstituted solutions remain
stable for 24 hours at room temperature and 96 hours when refrigerated.

Use
Parenteral: Treatment of documented or suspected infections caused by
susceptible gram-negative bacilli, including Pseudomonas aeruginosa;
nonpseudomonal enteric bacillus infection which is more susceptible to
tobramycin than gentamicin based on microbiology testing; susceptible
organisms in lower respiratory tract infections (FDA approved in adults); serious
central nervous system infection caused by susceptible organisms (FDA approved
in adults); septicemia (FDA approved in all ages); intra-abdominal, skin, bone, soft
tissue, and urinary tract infections (FDA approved in adults); has also been used
for empiric therapy in cystic fibrosis and immunocompromised patients

Medication Safety Issues

Sound-alike/look-alike issues:

Tobramycin may be confused with Trobicin, vancomycin

International issues:

Nebcin [Multiple international markets] may be confused with Naprosyn

brand name for naproxen [US, Canada, and multiple international markets];
Nubain brand name for nalbuphine [Multiple international markets]

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this

medication (intrathecal administration) among its list of drug classes
which have a heightened risk of causing significant patient harm when
used in error.

Adverse Reactions
Frequency not defined.

Central nervous system: Confusion, disorientation, dizziness, headache,

lethargy, vertigo

Dermatologic: Exfoliative dermatitis, pruritus, skin rash, urticaria

Endocrine & metabolic: Decreased serum calcium, decreased serum

magnesium, decreased serum potassium, decreased serum sodium, increased
lactate dehydrogenase, increased nonprotein nitrogen
 Gastrointestinal: Diarrhea, nausea, vomiting

Genitourinary: Casts in urine, oliguria, proteinuria

Hematologic & oncologic: Anemia, eosinophilia, granulocytopenia,

leukocytosis, leukopenia, thrombocytopenia

Hepatic: Increased serum ALT, increased serum AST, increased serum bilirubin

Local: Pain at injection site

Otic: Auditory ototoxicity, hearing loss, tinnitus, vestibular ototoxicity

Renal: Increased blood urea nitrogen, increased serum creatinine

Miscellaneous: Fever

<1%, postmarketing, and/or case reports: Anaphylaxis, Clostridioides (formerly

Clostridium) difficile-associated diarrhea, erythema multiforme, Stevens-
Johnson syndrome, toxic epidermal necrolysis

Contraindications
Hypersensitivity to tobramycin, other aminoglycosides, or any component of the
formulation

Warnings/Precautions
Concerns related to adverse effects:

• Hypersensitivity: Severe allergic reactions (some fatal), including

anaphylaxis, and dermatologic reactions (eg, exfoliative dermatitis, toxic
epidermal necrolysis, erythema multiforme, Stevens-Johnson syndrome)
have been reported; discontinue therapy and initiate appropriate treatment
if allergic reaction occurs.

• Nephrotoxicity: [US Boxed Warning]: May cause acute kidney injury,

including acute renal failure. Risk factors include tobramycin
accumulation (increasing serum trough levels), high peak concentrations
(>12 mcg/mL), total cumulative dose, advanced age, volume depletion,
and concurrent or sequential use of other nephrotoxic drugs. Avoid
concurrent or sequential use of other potentially nephrotoxic drugs.
Monitor serum tobramycin levels and renal function in all patients during
drug treatment. Reduce the dose or discontinue the drug if renal
impairment occurs. Kidney injury is usually reversible.

• Neuromuscular blockade: [US Boxed Warning]: Aminoglycosides have

been associated with neuromuscular blockade. Monitor for adverse
reactions associated with neuromuscular blockade during therapy,
particularly in high-risk patients, such as patients with underlying
neuromuscular disorders (including myasthenia gravis) or in patients
concomitantly receiving neuromuscular-blocking agents. Neuromuscular
blockade may lead to respiratory failure and prolonged respiratory
paralysis; additional signs of neurotoxicity may include numbness, skin
tingling, muscle twitching, and convulsions. Neuromuscular blockade is
reversible but may require treatment (eg, administration of calcium salts).

• Ototoxicity: [US Boxed Warning]: May cause irreversible auditory and

vestibular toxicity that may continue to develop after discontinuation. Risk
factors include high serum concentrations, prolonged therapy, renal
impairment, concurrent and sequential use of other nephrotoxic or
ototoxic drugs (eg, aminoglycosides), and extremes of age. Avoid
concurrent or sequential use with other potentially ototoxic drugs.
Monitor for signs and symptoms of auditory and vestibular toxicity.
Reduce the dose or discontinue therapy if renal impairment occurs.
Discontinue use if ototoxicity occurs. Auditory changes are usually
bilateral and may be partial or total. Ototoxicity symptoms may include
dizziness, vertigo, tinnitus, roaring in the ears and hearing loss; consider
serial audiograms in high-risk patients.
 • Superinfection: Prolonged use may result in fungal or bacterial
superinfection, including C. difficile-associated diarrhea (CDAD) and
pseudomembranous colitis; CDAD has been observed >2 months
postantibiotic treatment.

Disease-related concerns:

• Hearing impairment: Use with caution in patients with pre-existing vertigo,

tinnitus, or hearing loss.

• Hypocalcemia: Use with caution in patients with hypocalcemia.

• Neuromuscular disorders: Use with caution in patients with

neuromuscular disorders, including myasthenia gravis and Parkinson
disease.

• Renal impairment: Use with caution in patients with preexisting renal

insufficiency; dosage modification required during systemic therapy.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist,

requiring dose or frequency adjustment, additional monitoring, and/or
selection of alternative therapy. Consult drug interactions database for
more detailed information.

Special populations:

• Pregnancy: [US Boxed Warnings]: Tobramycin and other aminoglycosides

can cause fetal harm when administered to a pregnant woman. If
tobramycin is used during pregnancy or if the patient becomes pregnant
while taking tobramycin, apprise the patient of the potential hazard to the
fetus.

Dosage form specific issues:

 • Sulfite: Solution for injection may contain sodium metabisulfate; use
caution in patients with sulfite allergy.

Other warnings/precautions:

• Appropriate use: Not for intraocular and/or subconjunctival

administration; macular necrosis has been reported following
administration of aminoglycosides by these routes.

• Long-term use: Systemic therapy is not intended for long-term therapy

due to toxic hazards associated with extended administration.

Warnings: Additional Pediatric Considerations

Use with caution in premature infants and neonates; immature renal function may
increase risk of accumulation and related toxicity. Use with caution in pediatric
patients on extracorporeal membrane oxygenation (ECMO); pharmacokinetics of
aminoglycosides may be altered; dosage adjustment and close monitoring
necessary.

Metabolism/Transport Effects
None known.

Drug Interactions
(For additional information: Launch drug interactions program)

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Risk

C: Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin

may enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy

Ataluren: May enhance the adverse/toxic effect of Aminoglycosides.

Specifically, an increased risk of nephrotoxicity may occur with the
concomitant use of ataluren and aminoglycosides. Risk X: Avoid combination
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG
(Intravesical). Risk X: Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect

of BCG Vaccine (Immunization). Risk C: Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic

effect of Bisphosphonate Derivatives. Risk C: Monitor therapy

Botulinum Toxin-Containing Products: Aminoglycosides may enhance the

neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Risk C:
Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of

Aminoglycosides. Risk C: Monitor therapy

CARBOplatin: Aminoglycosides may enhance the ototoxic effect of

CARBOplatin. Especially with higher doses of carboplatin. Risk C: Monitor
therapy

Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides.

Cephalosporins may decrease the serum concentration of Aminoglycosides.
Risk C: Monitor therapy

Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera

Vaccine. Management: Avoid cholera vaccine in patients receiving systemic
antibiotics, and within 14 days following the use of oral or parenteral
antibiotics. Risk X: Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C:

Monitor therapy

Colistimethate: Aminoglycosides may enhance the nephrotoxic effect of

Colistimethate. Aminoglycosides may enhance the neuromuscular-blocking
effect of Colistimethate. Management: Avoid coadministration of
colistimethate and aminoglycosides whenever possible due to the risk of
nephrotoxicity and neuromuscular blockade. If coadministration cannot be
avoided, monitor renal and neuromuscular function. Risk D: Consider therapy
modification

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic

effect of CycloSPORINE (Systemic). Risk C: Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of

Distigmine. Risk C: Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Risk X:

Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of

Lactobacillus and Estriol. Risk C: Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides.

Specifically, nephrotoxicity and ototoxicity. Risk C: Monitor therapy

Mannitol (Systemic): May enhance the nephrotoxic effect of Aminoglycosides.

Risk X: Avoid combination

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking

effect of Mecamylamine. Risk X: Avoid combination

Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of

Methoxyflurane. Risk X: Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the

therapeutic effect of Neuromuscular-Blocking Agents. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of

Aminoglycosides. Data only in premature infants. Risk C: Monitor therapy
 Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Risk C:
Monitor therapy

Penicillins: May decrease the serum concentration of Aminoglycosides.

Primarily associated with extended spectrum penicillins, and patients with
renal dysfunction. Risk C: Monitor therapy

Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium

Picosulfate. Management: Consider using an alternative product for bowel
cleansing prior to a colonoscopy in patients who have recently used or are
concurrently using an antibiotic. Risk D: Consider therapy modification

Tenofovir Products: Aminoglycosides may increase the serum concentration

of Tenofovir Products. Tenofovir Products may increase the serum
concentration of Aminoglycosides. Risk C: Monitor therapy

Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid

Vaccine. Only the live attenuated Ty21a strain is affected. Management:
Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in
patients being treated with systemic antibacterial agents. Use of this vaccine
should be postponed until at least 3 days after cessation of antibacterial
agents. Risk D: Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Risk C:

Monitor therapy

Dietary Considerations
May require supplementation of calcium, magnesium, potassium.

Pregnancy Considerations
Tobramycin crosses the placenta.
[US Boxed Warning]: Tobramycin and other aminoglycosides can cause fetal
harm when administered to a pregnant woman. If tobramycin is used during
pregnancy or if the patient becomes pregnant while taking tobramycin, apprise
the patient of the potential hazard to the fetus.

There are several reports of total irreversible bilateral congenital deafness in

children whose mothers received another aminoglycoside (streptomycin) during
pregnancy. Although serious side effects to the fetus/infant have not been
reported following maternal use of all aminoglycosides, a potential for harm
exists.

Due to pregnancy-induced physiologic changes, some pharmacokinetic

parameters of tobramycin may be altered (Bourget 1991). Tobramycin injection
may be used for the management of cystic fibrosis in pregnant patients with P.
aeruginosa (inhalation is preferred unless risk of infection is great) (Edenborough
2008) and as an alternative antibiotic for prophylactic use prior to cesarean
delivery (Bratzler 2013).

Monitoring Parameters
Urinalysis, urine output, BUN, serum creatinine, peak and trough serum tobramycin
concentrations; Note: Do not use fingerstick for obtaining blood sample in patients
concurrently receiving inhaled tobramycin as it may result in falsely elevated drug
concentrations); be alert to ototoxicity, audiograms

With conventional dosing, typically obtain serum concentration after the third
dose; exceptions for earlier monitoring may include neonates, patients with rapidly
changing renal function, or patients receiving extended-interval dosing. Not all
pediatric patients who receive aminoglycosides require monitoring of serum
aminoglycoside concentrations. Indications for use of aminoglycoside serum
concentration monitoring include:
 Treatment course >5 days

Patients with decreased or changing renal function

Patients with a poor therapeutic response

Neonates and Infants <3 months of age

Atypical body constituency (obesity, expanded extracellular fluid volume)

Clinical need for higher doses or shorter intervals (cystic fibrosis, burns,
endocarditis, meningitis, relatively resistant organism)

Patients on hemodialysis or chronic ambulatory peritoneal dialysis

Signs of nephrotoxicity or ototoxicity

Concomitant use of other nephrotoxic agents

Reference Range
Traditional dosing: Timing of serum samples: Draw peak 30 minutes after 30-
minute infusion has been completed or 1 hour following IM injection or
beginning of infusion; draw trough immediately before next dose

Therapeutic concentrations:

Peak:

Serious infections: 6 to 8 mcg/mL (12 to 17 micromole/L)

Life-threatening infections: 8 to 10 mcg/mL (17 to 21 micromole/L)

Urinary tract infections: 4 to 6 mcg/mL

Synergy against gram-positive organisms: 3 to 5 mcg/mL

Trough:

Serious infections: 0.5 to 1 mcg/mL

 Life-threatening infections: 1 to 2 mcg/mL

The American Thoracic Society (ATS) recommends trough levels of <1

mcg/mL for adult patients with hospital-acquired pneumonia.

Timing of serum samples: Draw peak 30 minutes after completion of 30-

minute infusion or at 1 hour following initiation of infusion or IM injection; draw
trough within 30 minutes prior to next dose; aminoglycoside levels measured
from blood taken from Silastic central catheters can sometimes give falsely
elevated readings

Extended-interval: Note: Pediatric therapeutic monitoring protocols have not

been standardized; peak values are 2 to 3 times greater with extended-interval
dosing regimens compared to traditional dosing

Noncystic fibrosis patients: Consider monitoring tobramycin serum

concentration 18 to 20 hours after the start of the infusion to ensure the
drug-free interval does not exceed typical postantibiotic effect (PAE)
duration.

Cystic fibrosis patients: Clinically two methods are utilized. Peak: 25 to 35

mcg/mL (some centers use 20 to 30 mcg/mL); 18- to 20-hour value:
Detectable but <1 mcg/mL; trough: Nondetectable

Method A: Obtain two serum concentrations at least 1 half-life apart

after distribution is complete (eg, obtain a serum concentration 2 hours
and 10 hours after the start of the infusion), calculate elimination rate
and extrapolate a Cmax and Cmin

Method B: Obtain a peak serum concentration 60 minutes after a 60-

minute infusion and a serum concentration 18 to 20 hours after the
start of the infusion to ensure the drug-free interval does not exceed
typical postantibiotic effect (PAE) duration (4 to 6 hours)
Mechanism of Action
Interferes with bacterial protein synthesis by binding to 30S ribosomal subunit,
resulting in a defective bacterial cell membrane

Pharmacodynamics and Pharmacokinetics (Adult data unless

noted)
Absorption:

Oral: Poorly absorbed.

IM: Rapid and complete.

Distribution: Distributes to extracellular fluid, including serum, abscesses,

ascitic, pericardial, pleural, synovial, lymphatic, and peritoneal fluids; poor
penetration into CSF, eye, bone, prostate.

Vd: Higher in neonates than older pediatric and adult patients; also
increased in patients with edema, ascites, fluid overload; decreased in
patients with dehydration; Systemic:

Neonates: 0.45 ± 0.1 L/kg.

Infants: 0.4 ± 0.1 L/kg.

Children: 0.35 ± 0.15 L/kg.

Adolescents: 0.3 ± 0.1 L/kg.

Adults: 0.2 to 0.3 L/kg.

CSF:blood level ratio: Normal meninges: <10%; Inflamed meninges: ≤25%

(MacDougall 2011).

Lung: Epithelial lining fluid Cmax (peak):serum Cmax (peak) ratio: ~12% to
30%, varies with time (Boselli 2007; Carcas 1999; Heffernan 2019; Rodvold
2011).
 Protein binding: <30%.

Half-life elimination:

Neonates: ≤1,200 g: 11 hours; >1,200 g: 2 to 9 hours.

Infants: 4 ± 1 hour.

Children: 2 ± 1 hour.

Adolescents: 1.5 ± 1 hour.

Adults: IV: 2 to 3 hours; directly dependent upon glomerular filtration rate.

Adults with impaired renal function: 5 to 70 hours.

Time to peak, serum: IM: 30 to 60 minutes; IV: ~30 minutes.

Note: Distribution is prolonged after larger doses (≥60 minutes after 60-
minute infusion of 10 mg/kg [Aminimanizani 2002]; ≥90 minutes after 60-
minute infusion of a high-dose aminoglycoside [gentamicin 7 mg/kg]
[Demczar 1997]).

Excretion: Normal renal function: Urine (~90% to 95%) within 24 hours.

Pharmacodynamics and Pharmacokinetics: Additional

Considerations
Renal function impairment: Clearance is decreased in renal impairment.

Anti-infective considerations:

Parameters associated with efficacy:

Gram-negative bacilli: Concentration-dependent, associated with Cmax

(peak)/minimum inhibitory concentration (MIC), goal: ≥8 to 10 (Craig
2011; Kashuba 1999; Moore 1987; Zelenitsky 2003) or AUC24/MIC,
 goal: 30 to 50 (mild/moderate infection) or 80 to 100 (severe infection)
(Bland 2018; Craig 2011; Drusano 2007; Smith 2001).

P. aeruginosa in patients with cystic fibrosis: fCmax (peak)/MIC ≥5,

fAUC/MIC ≥50 (Mouton 2005).

Expected drug exposure in adults with normal renal function:

Cmax (peak), postdistributional: 7 mg/kg: ~20 to 22 mg/mL (Craig 2011;

Finnell 1998).

AUC24:

Cystic fibrosis:

10 mg/kg: ~108 mg•hour/L (Aminimanizani 2002).

7 mg/kg: 70 to 110 mg•hour/L (Barclay 1995; Craig 2011; Finnell

1998).

Critically ill: 5 mg/kg: ~86 mg•hour/L (Conil 2011).

Parameters associated with toxicity: Nephrotoxicity is associated with more

frequent administration and elevated Cmin (trough) concentrations leading
to renal accumulation (Bertino 1993; Rybak 1999).

Postantibiotic effect: Bacterial killing continues after tobramycin

concentration drops below the MIC of targeted pathogen; generally 0.5 to
7.5 hours, though the actual time of postantibiotic effect varies based on
multiple factors including organism, tobramycin Cmax (peak), and
concomitant antimicrobial therapy (Craig 2011; Gudmundsson 1993; Lacy
1998).

Pricing: US
Solution (Tobramycin Sulfate Injection)
 1.2 g/30 mL (per mL): $0.86 - $0.88

2 gm/50 mL (per mL): $1.15

10 mg/mL (per mL): $3.17

80 mg/2 mL (per mL): $0.93 - $2.03

Solution (reconstituted) (Tobramycin Sulfate Injection)

1.2 g (per each): $93.24 - $218.75

Disclaimer: A representative AWP (Average Wholesale Price) price or price range

is provided as reference price only. A range is provided when more than one
manufacturer's AWP price is available and uses the low and high price reported by
the manufacturers to determine the range. The pricing data should be used for
benchmarking purposes only, and as such should not be used alone to set or
adjudicate any prices for reimbursement or purchasing functions or considered to
be an exact price for a single product and/or manufacturer. Medi-Span expressly
disclaims all warranties of any kind or nature, whether express or implied, and
assumes no liability with respect to accuracy of price or price range data
published in its solutions. In no event shall Medi-Span be liable for special, indirect,
incidental, or consequential damages arising from use of price or price range data.
Pricing data is updated monthly.

Brand Names: International

Bactob (IN); Brulamicina (RO); Brulamycin (HU); Intolacin (VN); Jiu Tai (CN);
Nebcin (AE, PK, VN); Nebcina (DK, NO); Nebcine (FR); Obracin (BE, CH); Rui Nuo
Sai (CN); Tobra (KR); Tobra-Day (AU, NZ); Tobra-gobens (ES); Tobracin (EG, JO);
Tobrasik (AT); Tobrin (EG, QA); Tocin (PK); Tofib (AR); Tomycin (FI)

For country abbreviations used in Lexicomp (show table)

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