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 tobramycin if renal impairment occurs.
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 tobramycin if renal impairment occurs. Discontinue tobramycin if ototoxicity occurs.
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.
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.
Note: Determination of dosing interval requires consideration of multiple factors including concomitant medications (eg, ibuprofen, indomethacin), history of birth depression, birth hypoxia/asphyxia, and presence of cyanotic congenital heart disease. Dosage should be individualized based upon serum concentration monitoring. Impact of extracorporeal membrane oxygenation (ECMO) on neonatal pharmacokinetic parameters is not fully elucidated; optimal dose and frequency not established in ECMO patients; available data is very limited and based on gentamicin (Buck 2003; Southgate 1989). Patient-specific considerations (eg, reason for ECMO) and variability with ECMO procedure itself make extrapolation of pharmacokinetic data and dosing to all patients receiving ECMO difficult; closely monitor serum concentrations and determine individual dosing needs in these patients.
General dosing; susceptible infection: Limited data available: Dosing strategies may vary by institution as a wide variety of extended-interval dosing regimens have been studied (Bergenwall 2019; de Hoog 2002; El-Chaar 2016; Hartman 2020; Ohler 2000; Valitalo 2015; van Donge 2018; van Maarseveen 2016). Due to maturational processes and developing pharmacokinetics, regimens referred to as "extended-interval" in neonates do not typically achieve concentrations that would be expected with extended-interval dosing in children and adults (Bergenwall 2019; Miller 2014; van Donge 2018). Some dosing is based on gentamicin studies.
Age-directed dosing (Bradley 2021; Red Book [AAP 2021]): IM, IV: Note: Higher doses and different dosing intervals may be required to achieve target concentrations if MIC ≥1 mg/L (Bradley 2021; van Donge 2018).
Gestational Age |
Postnatal Age |
Dose |
---|---|---|
<30 weeks |
≤14 days |
5 mg/kg/dose every 48 hours |
≥15 days |
5 mg/kg/dose every 36 hours | |
30 to 34 weeks |
≤10 days |
5 mg/kg/dose every 36 hours |
11 to 60 days |
5 mg/kg/dose every 24 hours | |
≥35 weeks |
≤7 days |
4 mg/kg/dose every 24 hours |
8 to 60 days |
5 mg/kg/dose every 24 hours |
Dosing adjustment in renal impairment: Consider single-dose administration with serum concentration monitoring rather than scheduled dosing in patients with urine output <1 mL/kg/hour or if SCr significantly increases from baseline.
Note: Initial dosing recommendations presented. 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 (Begg 1999; Jenh 2011; Knoderer 2003; Zobell 2016; manufacturer's labeling). Routes of administration may vary (including IM, IV, intraperitoneal, intrathecal, and intraventricular); use caution. Some dosing is based on gentamicin studies.
Dosing consideration for obesity: In obese pediatric patients, use adjusted body weight (IBW + 0.4 [TBW – IBW]) to calculate initial dosage (Koshida 1989; manufacturer's labeling). Alternatively, adjusted body weight for obese pediatric patients may be calculated using the equation 0.7 x TBW (Bradley 2021), or fat-free mass can be used to calculate the initial dose in pediatric patients ≥2 years regardless of body habitus (Moffett 2018). Dosage should then be individualized based upon serum concentration monitoring.
General dosing, susceptible infection: Note: Optimal dose and frequency not established in patients receiving extracorporeal membrane oxygenation (ECMO); patient-specific considerations (eg, reason for ECMO) and variability with ECMO procedure itself make extrapolation of pharmacokinetic data and dosing to all patients receiving ECMO difficult; closely monitor serum concentrations and determine individual dosing needs in these patients.
Conventional dosing: Infants, Children, and Adolescents: IM, IV: 6 to 7.5 mg/kg/day divided every 6 to 8 hours (Red Book [AAP 2021]; manufacturer's labeling).
Extended-interval dosing: Limited data available:
Weight-directed: Infants, Children, and Adolescents: IV: 5 to 7.5 mg/kg/dose every 24 hours (Bradley 2021; Contopoulos-Ioannidis 2004; Red Book [AAP 2021]).
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; Zobell 2016); maximum reported dose from a survey of 28 Cystic Fibrosis (CF) Foundation-accredited centers ranged from 12 to 20 mg/kg/dose (Zobell 2016). Note: The CF Foundation recommends extended-interval dosing as preferred over conventional dosing.
Endocarditis, treatment: Limited data available:
Synergy dosing (eg, gram-positive bacteria): Children and Adolescents: IV: 3 to 6 mg/kg/day divided every 8 hours; use in combination with other antibiotics dependent upon pathogen and source of infection (ie, valve-type) (AHA [Baltimore 2015]).
Treatment dosing (eg, gram-negative bacteria): Children and Adolescents: IV: 7.5 mg/kg/day divided every 8 hours; use in combination with other antibiotics (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; use in combination with other antibiotics (IDSA [Solomkin 2010]; Surgical Infection Society [Mazuski 2017]).
CNS infection:
Meningitis, including health care-associated meningitis: Limited data available: Infants, Children, and Adolescents: IV: Initial: 7.5 mg/kg/day divided every 8 hours in combination with additional antimicrobials; duration should be individualized based on patient characteristics, infecting organism, and response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
Ventriculitis (including health care-associated ventriculitis and cerebrospinal fluid [CSF] shunt infections): Limited data available: Infants, Children, and Adolescents: Intraventricular, intrathecal: Use a preservative-free preparation: 5 to 20 mg/day (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]). Due to the smaller CSF volume in infants, some guidelines recommend decreasing the infant dose; dosage and administration interval can also be adjusted based on CSF tobramycin concentrations, ventricle size, and daily output from ventricular drain (IDSA [Tunkel 2017]). Duration is individualized according to clinical and microbiological response (IDSA [Tunkel 2004]; IDSA [Tunkel 2017]).
Peritonitis (peritoneal dialysis) (ISPD [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:
Conventional dosing: Infants, Children, and Adolescents: IV: 5 mg/kg/day divided every 8 hours until clinical improvement and able to tolerate oral intake; complete course with oral antibiotics; duration should be individualized based upon age, severity, and degree of urinary tract involvement (eg, patients <24 months or with pyelonephritis: 7 to 14 days; older patients with uncomplicated cystitis: 3 to 7 days) (AAP 2011; Balighian 2018).
Extended-interval dosing: Limited data available: Based on data from 90 patients (ages: 1 month to 12 years) receiving gentamicin, the following age-directed dosing has been suggested (Carapetis 2001): Note: Patients were transitioned to oral therapy once afebrile for 24 hours.
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 11 to 12 years: IV: 4.5 mg/kg/dose every 24 hours.
Single-dose regimen: Limited data available. Note: Recommended for treatment of uncomplicated cystitis caused by antimicrobial resistant gram-negative pathogens (IDSA [Tamma 2020]):
Infants, Children, and Adolescents: IM: 5 mg/kg as a single dose; dosing based on 2 prospective studies evaluating single-dose IM gentamicin in patients 1 month to 15 years and a systematic review evaluating studies of various single-dose aminoglycosides in pediatric and adult patients (Goodlet 2018; Khan 1987; Varese 1980); one study limited doses to 300 mg (Khan 1987). An overall pooled cure rate for single dose IM aminoglycoside for treatment of children and adults with mainly uncomplicated cystitis was reported as 94.5% ± 4.3% (Goodlet 2018). Note: Guidelines do not address pediatric dosing; recommended aminoglycoside doses in adults include IV single doses (IDSA [Tamma 2020]).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Parenteral: Note: Tobramycin serum concentrations should be monitored in patients with kidney impairment; following the initial dose, subsequent doses may be determined based on therapeutic monitoring.
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.
There are no dosage adjustments provided in the manufacturer's labeling; however, dosage adjustment not likely to be necessary (does not undergo hepatic metabolism).
(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), use 40% adjusted body weight ([0.4 × (TBW-IBW)] + IBW) for initial weight-based dosing and for estimating kidney function with Cockcroft-Gault (CrCL) (Bailey 1997; Blackburn 2015; Nicolau 1995; Pai 2014; 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; 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). Note: Published nomograms for dosage adjustment may not apply to patients with altered pharmacokinetics (eg, patients with ascites, burns covering >20% total BSA, end-stage renal disease requiring dialysis, pregnancy) (Bailey 1997; Nicolau 1995).
Indication-specific dosing:
Bloodstream infection: Adjunctive empiric therapy for patients with 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; SSC [Evans 2021]).
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 2022). Duration is usually 10 to 14 days depending on clinical response (Flume 2009; Goss 2021).
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 2022; 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): 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]).
Plague (Yersinia pestis), treatment (alternative agent) (off-label use):
Note: Consult public health officials for event-specific recommendations.
IV, IM: 5 to 7 mg/kg once daily for 7 to 14 days and for at least a few days after clinical resolution (CDC [Nelson 2021]; Stout 2022).
Pneumonia, hospital-acquired or ventilator-associated (alternative agent):
Note: Some experts reserve for patients with risk for multidrug-resistant pathogens (Klompas 2022).
IV: 5 to 7 mg/kg once daily in combination with a second gram-negative agent; once culture and susceptibility results are available, can generally discontinue tobramycin and use a single agent with documented activity (IDSA/ATS [Kalil 2016]; Klompas 2022). Note: Avoid use of tobramycin monotherapy (IDSA/ATS [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; SSC [Evans 2021]).
IV: 5 to 7 mg/kg once daily in combination with a second gram-negative agent (Schmidt 2020; SSC [Evans 2021]); 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; Schmidt 2020; SSC [Evans 2021]).
Urinary tract infection, complicated (pyelonephritis or urinary tract infection with systemic signs/symptoms) (alternative agent): Note: Some experts reserve for use when other long-acting parenteral antimicrobials (eg, ceftriaxone) or fluoroquinolones cannot be used due to allergy, intolerance, unmodifiable drug interactions, or resistance (Hooton 2021).
Inpatients: IV, IM: 5 mg/kg once daily. Switch to an appropriate oral regimen once symptoms improve, if culture and susceptibility results allow. Total duration of therapy ranges from 5 to 14 days and depends on clinical response and the antimicrobial chosen to complete the regimen (Hooton 2021; IDSA/ESCMID [Gupta 2011]).
Outpatients: IV, IM: 5 mg/kg once, followed by 5 to 14 days of appropriate oral therapy (Hooton 2021; IDSA/ESCMID [Gupta 2011]). Note: For patients who are systemically ill or at risk for more severe illness, some experts continue daily parenteral therapy pending culture and susceptibility results (Hooton 2021).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
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.
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]).
No dosage adjustment necessary; does not undergo hepatic metabolism.
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)
Yes
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Injection:
Generic: 10 mg/mL (2 mL)
Solution, Injection, as sulfate:
Generic: 40 mg/mL (2 mL, 30 mL)
Solution Reconstituted, Injection:
Generic: 1.2 g (1 ea)
Parenteral:
IM: May be administered undiluted.
IV: Administer by intermittent infusion over 20 to 60 minutes; shorter infusion times (≤5 minutes) have been reported in pediatric patients, including preterm and term neonates, receiving ≤4 mg/kg/dose (Bergenwall 2019; König 2015; Robinson 2001). Avoid infusing concomitantly with penicillins or cephalosporins if feasible; consult drug interactions database for more information.
Intrathecal/Intraventricular: Use preservative-free preparations only; must be diluted prior to administration. No specific administration information available; it has been suggested that instillation of small volumes (<3 mL) over 1 to 2 minutes is safe (Cook 2009). When administered through a ventricular drain, clamp drain for 15 to 60 minutes to allow tobramycin solution to equilibrate in the cerebrospinal fluid (CSF) (IDSA [Tunkel 2017]).
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]).
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.
Treatment of bloodstream infections caused by susceptible Escherichia coli, Klebsiella spp., and Pseudomonas aeruginosa; treatment of lower respiratory tract infections caused by susceptible E. coli, Enterobacter spp., Klebsiella spp., P. aeruginosa, Serratia spp., and Staphylococcus aureus; treatment of meningitis caused by susceptible bacteria; treatment of intra-abdominal infections, including peritonitis, caused by susceptible E. coli, Enterobacter spp., and Klebsiella spp.; treatment of skin and skin structure infections caused by susceptible E. coli, Enterobacter spp., Klebsiella spp., P. aeruginosa, Proteus spp., and S. aureus; treatment of bone infections caused by susceptible E. coli, Enterobacter spp., Klebsiella spp., P. aeruginosa, Proteus spp., and S. aureus; treatment of complicated urinary tract infections caused by susceptible Citrobacter spp., E. coli, Enterobacter spp., Klebsiella spp., P. aeruginosa, Proteus spp., Providencia spp., and S. aureus (All indications: FDA approved in all ages); has also been used for treatment of endocarditis, treatment of pulmonary infection in cystic fibrosis, and intra-peritoneally for treatment of peritonitis.
Tobramycin may be confused with Trobicin, vancomycin
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]
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.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
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 difficile-associated diarrhea, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis
Hypersensitivity to tobramycin, other aminoglycosides, or any component of the formulation
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.
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.
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.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program
Aminoglycosides: May enhance the nephrotoxic effect of other Aminoglycosides. Aminoglycosides may enhance the neurotoxic effect of other Aminoglycosides. Risk X: Avoid combination
Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Amphotericin B may enhance the neurotoxic 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
Bacillus clausii: Antibiotics may diminish the therapeutic effect of Bacillus clausii. Management: Bacillus clausii should be taken in between antibiotic doses during concomitant therapy. Risk D: Consider therapy modification
Bacitracin (Systemic): May enhance the nephrotoxic effect of Aminoglycosides. Bacitracin (Systemic) may enhance the neurotoxic effect of 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: May enhance the nephrotoxic effect of Aminoglycosides. 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. CISplatin may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
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
Cyclizine: May enhance the ototoxic effect of Aminoglycosides. Risk C: Monitor therapy
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
Immune Checkpoint Inhibitors: Antibiotics may diminish the therapeutic effect of Immune Checkpoint Inhibitors. Risk C: Monitor therapy
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
Netilmicin (Ophthalmic): Aminoglycosides may enhance the nephrotoxic effect of Netilmicin (Ophthalmic). 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
Polymyxin B: May enhance the nephrotoxic effect of Aminoglycosides. Polymyxin B may enhance the neurotoxic effect of Aminoglycosides. Risk X: Avoid combination
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
Tacrolimus (Systemic): Aminoglycosides may enhance the nephrotoxic effect of Tacrolimus (Systemic). Risk C: Monitor therapy
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: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Vancomycin may enhance the neurotoxic effect of Aminoglycosides. Management: Consider avoiding coadministration of aminoglycosides and vancomycin unless clinically indicated. If coadministered, monitor closely for signs of nephrotoxicity and neurotoxicity. Risk D: Consider therapy modification
May require supplementation of calcium, magnesium, potassium.
Tobramycin crosses the placenta.
Tobramycin and other aminoglycosides can cause fetal harm when administered to a pregnant patient. 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).
Tobramycin is used in the management of plague (Yersinia pestis). Untreated infections in pregnant patients may result in hemorrhage (including postpartum hemorrhage), maternal and fetal death, preterm birth, and stillbirth. Limited data suggest maternal-fetal transmission of Y. pestis can occur if not treated. Pregnant patients should be treated for Y. pestis; parenteral antibiotics are preferred for initial treatment when otherwise appropriate. Tobramycin is an alternative aminoglycoside recommended for use (in combination with a fluroquinolone) for treating pregnant patients with bubonic, pharyngeal, pneumonic, or septicemic plague (CDC [Nelson 2021]).
Urinalysis, urine output, BUN, SCr, hearing test (especially for those at risk of ototoxicity or who will be receiving prolonged therapy [>2 weeks]).
Serum tobramycin concentrations: Note: Avoid fingerstick blood samples for monitoring serum tobramycin concentrations in patients concurrently receiving inhaled tobramycin; results may be falsely elevated (Redmann 2005).
Conventional dosing: Initial serum concentrations typically obtained after the third dose; may consider obtaining serum concentrations sooner in neonates or patients with rapidly changing renal function.
Extended-interval dosing: Initial serum concentrations may be obtained following the first or second dose (Begg 1999; Knoderer 2003).
Patients receiving outpatient therapy: Serum tobramycin concentrations (at least weekly); CBC with differential (weekly); basic metabolic panel including potassium, creatinine, and BUN (twice weekly) (Norris 2019).
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.
Some beta-lactam agents (penicillins and cephalosporins) may accelerate the degradation of aminoglycosides in vitro; this may be clinically significant in patients with significant renal impairment. Close monitoring of aminoglycoside concentrations and clinical response is warranted.
Note: Sampling times and target concentrations provided reflect general practices; patient-specific factors, including type and site of infection, goals of therapy, severity of illness, clinical status, fluid status, and kidney function should be considered when determining patient-specific therapeutic monitoring plans and targets. Outcomes are predicted by serum concentrations and the minimum inhibitory concentration (MIC) of the infecting organism. Efficacy has been associated with peak:MIC ratios of ≥8 to 10 and AUC24:MIC ratios of 30 to 100 depending on severity of infection (Bland 2018; Craig 2011; Knoderer 2003). Nephrotoxicity is associated with elevated trough concentrations (Bertino 1993; Rybak 1999).
Neonates:
Timing of serum samples (El-Chaar 2016; Touw 2009; van Donge 2018; van Maarseveen 2016; manufacturer's labeling):
Peak: 30 minutes after end of 30-minute infusion, or 1 hour following start of infusion or IM injection.
Trough: End of dosing interval, just prior to the next dose.
Target concentrations: Note: Studies evaluating extended-interval dosing in neonates typically target concentrations more often associated with conventional dosing (Miller 2014).
Peak: ≥8 to 12 mg/L; 10 x MIC (El-Chaar 2016; Touw 2009; van Maarseveen 2016).
Trough: <0.5 to 1 mg/L (Touw 2009; van Maarseveen 2016).
Infants, Children, and Adolescents:
Conventional dosing:
Timing of serum samples:
Peak: 30 minutes after 30-minute infusion, or 1 hour following start of infusion or IM injection.
Trough: End of dosing interval, immediately before next dose.
Target concentrations:
Peak:
General: 6 to 12 mg/L or 10 x MIC (Red Book [AAP 2021]). Note: Peak concentrations on the lower end of the range would only achieve efficacy target (10 x MIC) for MICs ≤0.5 mg/L.
Urinary tract infections: 4 to 6 mg/L (Matzke 1983).
Synergy against gram-positive organisms (based on gentamicin): 3 to 4 mg/L (AHA [Baltimore 2015]).
Trough:
General: <1 to 2 mg/L (Hammett-Stabler 1998; Red Book [AAP 2021]); others suggest a target of <0.5 to 1 mg/L (Bland 2018; Touw 2009).
Synergy against gram-positive organisms (based on gentamicin): <1 mg/L (AHA [Baltimore 2015]).
Extended-interval dosing: Note: Monitoring protocols are not standardized; various approaches exist. In addition to the strategies discussed, AUC monitoring has also been described (Begg 1999; Bland 2018; Roy 2016).
Timing of serum samples:
Peak: 30 minutes after the end of a 30-minute infusion (Jenh 2011; Knoderer 2003). Some suggest waiting ≥60 minutes after the end of the infusion to allow time for distribution of higher doses, and using patient-specific pharmacokinetic parameters to back-extrapolate true peak concentration (Prescott 2010; Safi 2016). It is not always necessary to monitor peak concentration depending on clinical situation (Begg 1999; Jenh 2011).
Trough: Obtain at the end of a dosing interval, just prior to the next dose (Begg 1999; Knoderer 2003). May also obtain 4 hours prior to the next dose to ensure that drug has cleared (McDade 2010).
Patient-specific calculations: Two concentrations at least one half-life apart can be obtained (eg, a peak and a mid-interval concentration 8 to 12 hours after the dose, or 2 postdistribution concentrations while drug is still detectable) to calculate patient-specific pharmacokinetic parameters and extrapolate peak, trough, AUC, and/or drug-free interval (Jenh 2011; Knoderer 2003). For patients with cystic fibrosis, the 2 random samples postinfusion is the most common strategy used to monitor aminoglycosides (eg, obtain a serum concentration 2 hours and 8 to 10 hours after the start of the infusion, calculate elimination rate, and extrapolate peak and trough) (Zobell 2016).
Target concentrations:
Patients without cystic fibrosis:
Peak: 8 to 10 x MIC of the pathogen (~15 to 35 mg/L) (Jenh 2011; Knoderer 2003; Roy 2016).
Trough: <0.5 to 1 mg/L; ideally undetectable; a drug-free period is desired (Jenh 2011; Knoderer 2003; McDade 2010).
Patients with cystic fibrosis:
Peak: 20 to 30 mg/L (Safi 2016; Smyth 2005); target range variable; higher target concentrations up to 40 mg/L have been reported (Flume 2009; Zobell 2016). May be necessary to modify target based on MIC to achieve targets associated with efficacy (Burkhardt 2006).
Trough: <0.5 to 1 mg/L; undetectable (Flume 2009; Safi 2016; Wassil 2008; Zobell 2016). A drug-free period is desired; some centers adjust dose to provide a drug-free interval of ≤8 to 12 hours (Zobell 2016).
AUC: 75 to 125 mg•hr/L; most centers target 80 to 120 mg•hr/L (Zobell 2016).
Interferes with bacterial protein synthesis by binding to 30S ribosomal subunit, resulting in a defective bacterial cell membrane
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: Varies with age; increased in patients with edema, ascites, fluid overload; decreased in patients with dehydration:
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.
Altered kidney function: 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: Cmax (peak)/MIC ≥10, AUC/MIC ≥50 (Burkhardt 2006).
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).
Solution (Tobramycin Sulfate Injection)
1.2 g/30 mL (per mL): $0.86 - $0.88
2 gm/50 mL (per mL): $1.26
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): $92.40 - $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.