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Tobramycin (Systemic)

Medically reviewed by Drugs.com. Last updated on Jun 6, 2020.

Pronunciation

(toe bra MYE sin)

Index Terms

  • Tobramycin Sulfate

Dosage Forms

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)

Pharmacologic Category

  • Antibiotic, Aminoglycoside

Pharmacology

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: 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).

Excretion

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

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

Protein Binding

<30%

Special Populations: Renal Function Impairment

Clearance is decreased in renal impairment.

Special Populations Note

Antiinfective 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).

Use: Labeled Indications

Bloodstream infection: Treatment of bloodstream infection caused by Pseudomonas aeruginosa, Escherichia coli, and Klebsiella spp., in adult and pediatric patients.

Bone infections: Treatment of bone infections caused by P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., and Staphylococcus aureus in adult and pediatric patients.

Intra-abdominal infections: Treatment of intra-abdominal infections, including peritonitis, caused by E. coli, Klebsiella spp., and Enterobacter spp. in adult and pediatric patients.

Meningitis, bacterial: Treatment of bacterial meningitis caused by susceptible bacteria in adult and pediatric patients.

Pneumonia: Treatment of pneumonia caused by P. aeruginosa, Klebsiella spp., Enterobacter spp., Serratia spp., E. coli, and Staphylococcus aureus in adult and pediatric patients.

Skin and skin structure infections: Treatment of skin and skin structure infections caused by P. aeruginosa, Proteus spp., E. coli, Klebsiella spp., Enterobacter spp., and S. aureus in adult and pediatric patients.

Urinary tract infections: Treatment of complicated urinary tract infections caused by P. aeruginosa, Proteus spp., (indole-positive and indole-negative), E. coli, Klebsiella spp., Enterobacter spp., Serratia spp., S. aureus, Providencia spp., and Citrobacter spp. in adult and pediatric patients.

Off Label Uses

Peritonitis, treatment (peritoneal dialysis patients)

Based on the International Society for Peritoneal Dialysis guidelines for prevention and treatment of peritonitis, intraperitoneal tobramycin, in combination with other antibiotics, is effective and recommended for empiric treatment of peritoneal dialysis-associated peritonitis; for gram-negative organisms including P. aeruginosa [ISPD [Li 2016]].

Contraindications

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

Dosing: Adult

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: Geriatric

Refer to adult 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: Obesity

In moderate obesity (TBW/IBW ≥1.25) or greater, (eg, morbid obesity [TBW/IBW >2]), initial dosage requirement may be estimated using a dosing weight of IBW + 0.4 (TBW - IBW) (Traynor 1995).

Reconstitution

Solution for injection: Dilute in 50-100 mL NS or D5W for IV infusion.

Administration

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]).

Dietary Considerations

May require supplementation of calcium, magnesium, potassium.

Storage

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.

Drug Interactions

Amphotericin B: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Arbekacin: May enhance the nephrotoxic effect of Aminoglycosides. Arbekacin may enhance the ototoxic effect of Aminoglycosides. 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. Avoid combination

BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Monitor therapy

Bisphosphonate Derivatives: Aminoglycosides may enhance the hypocalcemic effect of Bisphosphonate Derivatives. Monitor therapy

Botulinum Toxin-Containing Products: Aminoglycosides may enhance the neuromuscular-blocking effect of Botulinum Toxin-Containing Products. Monitor therapy

Capreomycin: May enhance the neuromuscular-blocking effect of Aminoglycosides. Monitor therapy

CARBOplatin: Aminoglycosides may enhance the ototoxic effect of CARBOplatin. Especially with higher doses of carboplatin. Monitor therapy

Cephalosporins: May enhance the nephrotoxic effect of Aminoglycosides. Cephalosporins may decrease the serum concentration of Aminoglycosides. 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. Avoid combination

CISplatin: May enhance the nephrotoxic effect of Aminoglycosides. 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. Consider therapy modification

CycloSPORINE (Systemic): Aminoglycosides may enhance the nephrotoxic effect of CycloSPORINE (Systemic). Monitor therapy

Distigmine: Aminoglycosides may diminish the therapeutic effect of Distigmine. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Aminoglycosides. Avoid combination

Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Monitor therapy

Loop Diuretics: May enhance the adverse/toxic effect of Aminoglycosides. Specifically, nephrotoxicity and ototoxicity. Monitor therapy

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

Mecamylamine: Aminoglycosides may enhance the neuromuscular-blocking effect of Mecamylamine. Avoid combination

Methoxyflurane: Aminoglycosides may enhance the nephrotoxic effect of Methoxyflurane. Avoid combination

Neuromuscular-Blocking Agents: Aminoglycosides may enhance the therapeutic effect of Neuromuscular-Blocking Agents. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May decrease the excretion of Aminoglycosides. Data only in premature infants. Monitor therapy

Oxatomide: May enhance the ototoxic effect of Aminoglycosides. Monitor therapy

Penicillins: May decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. 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. Consider therapy modification

Tenofovir Products: Aminoglycosides may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. 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. Consider therapy modification

Vancomycin: May enhance the nephrotoxic effect of Aminoglycosides. Monitor therapy

Test Interactions

Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro, leading to a potential underestimation of aminoglycoside serum concentration.

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

ALERT: U.S. 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.

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.

Monitoring Parameters

Urinalysis, urine output, BUN, serum creatinine, peak and trough plasma tobramycin levels. Levels are typically obtained after the third dose in conventional dosing. Be alert to ototoxicity; hearing should be tested before and during treatment

Some penicillin derivatives may accelerate the degradation of aminoglycosides in vitro. This may be clinically-significant for certain penicillin (ticarcillin, piperacillin, carbenicillin) and aminoglycoside (gentamicin, tobramycin) combination therapy in patients with significant renal impairment. Close monitoring of aminoglycoside levels is warranted.

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).

Patient Education

What is this drug used for?

• It is used to treat bacterial infections.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Diarrhea

• Nausea

• Vomiting

• Injection site pain

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• Electrolyte problems like mood changes, confusion, muscle pain or weakness, abnormal heartbeat, seizures, lack of appetite, or severe nausea or vomiting.

• Dizziness

• Passing out

• Chills

• Sore throat

• Muscle weakness

• Burning or numbness feeling

• Twitching

• Noise or ringing in the ears

• Trouble hearing

• Hearing loss

• Seizures

• Bruising

• Bleeding

• Severe loss of strength and energy

• Confusion

Clostridioides (formerly Clostridium) difficile-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.