Brand name: Tobi
Drug class: Aminoglycosides
CAS number: 49842-07-1

Medically reviewed by Drugs.com on Aug 26, 2024. Written by ASHP.

Introduction

Antibacterial; aminoglycoside antibiotic obtained from cultures of Streptomyces tenebrarius.

Uses for Tobramycin

Bone and Joint Infections

Treatment of serious bone and joint infections caused by susceptible Staphylococcus aureus, Enterobacter, Escherichia coli, Klebsiella, Proteus, or Pseudomonas aeruginosa. Used as an adjunct to other appropriate anti-infectives.

Intra-abdominal Infections

Treatment of serious intra-abdominal infections (including peritonitis) caused by susceptible Enterobacter, E. coli, or Klebsiella. Used as an adjunct to other appropriate anti-infectives.

Meningitis and Other CNS Infections

Treatment of CNS infections (meningitis) caused by susceptible gram-negative bacteria.

Aminoglycosides should not be used alone for treatment of meningitis; usually used as an adjunct to other anti-infectives in initial treatment. Used in conjunction with ampicillin for initial empiric treatment of neonatal Streptococcus agalactiae (group B streptococci) meningitis or for Listeria monocytogenes meningitis.

Respiratory Tract Infections

Treatment of serious respiratory tract infections caused by susceptible S. aureus, Enterobacter, E. coli, Klebsiella, Serratia, or Ps. aeruginosa. Used as an adjunct to an appropriate β-lactam (e.g., ceftriaxone, cefotaxime, cefepime, piperacillin and tazobactam, ticarcillin and clavulanate) or carbapenem (e.g., imipenem, meropenem) for empiric treatment of nosocomial pneumonia.

Administered by oral inhalation via nebulization for management of bronchopulmonary Ps. aeruginosa infections in cystic fibrosis patients ≥6 years of age. Safety and efficacy not established in pediatric patients < 6 years of age, in patients with forced expiratory volume in 1 second (FEV₁) <25% or >75% of the predicted value, or in patients colonized with Burkholderia cepacia (formerly Ps. cepacia).

Septicemia

Treatment of septicemia caused by susceptible E. coli, Klebsiella, or Ps. aeruginosa.

Used as an adjunct to an appropriate β-lactam (e.g., ceftriaxone, cefotaxime, cefepime, piperacillin and tazobactam, ticarcillin and clavulanate) or carbapenem (e.g., imipenem, meropenem) for empiric treatment of life-threatening septicemia.

Skin and Skin Structure Infections

Treatment of serious skin and skin structure infections caused by susceptible S. aureus, Enterobacter, E. coli, Klebsiella, Proteus, or Ps. aeruginosa. Used as an adjunct to other appropriate anti-infectives.

Urinary Tract Infections (UTIs)

Treatment of serious complicated and recurrent UTIs caused by susceptible S. aureus, Citrobacter, Enterobacter, E. coli, Klebsiella, Proteus, Providencia, Serratia, or Ps. aeruginosa. Used as an adjunct to other appropriate anti-infectives.

Not indicated for uncomplicated UTIs unless causative organism is resistant to other less-toxic alternatives.

Empiric Therapy in Febrile Neutropenic Patients

Empiric anti-infective therapy of presumed bacterial infections in febrile neutropenic patients^{† [off-label]}. Used in conjunction with an appropriate antipseudomonal cephalosporin (e.g., ceftazidime, ceftriaxone), extended-spectrum penicillin (e.g., ticarcillin, piperacillin and tazobactam, ticarcillin and clavulanate), or carbapenem (e.g., imipenem, meropenem).

Consult published protocols for the treatment of infections in febrile neutropenic patients for specific recommendations regarding selection of the initial empiric regimen, when to change the initial regimen, possible subsequent regimens, and duration of therapy in these patients. Consultation with an infectious disease expert knowledgeable about infections in immunocompromised patients also is advised.

Tobramycin Dosage and Administration

Administration

Administer by IV infusion or IM injection.

Tobramycin solution for oral inhalation is administered via nebulization; the oral inhalation solution should not be administered IV, IM, sub-Q, or intrathecally.

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution and Dilution

Prepare IV solutions from the pharmacy bulk package according to the manufacturer's directions.

ADD-Vantage vials should be diluted according to the manufacturer’s directions prior to IV infusion.

IV infusions are prepared by diluting the calculated dose of tobramycin with 50–100 mL of a compatible IV infusion solution. In pediatric patients, the volume of infusion solution depends on the patient’s needs, but should be sufficient to allow an infusion period of 20–60 minutes.

Rate of Administration

IV infusions should be given over 20–60 minutes. Infusion periods of <20 minutes should not be used because they may result in peak serum concentrations >12 mcg/mL.

IM Injection

For IM injection, the appropriate dose should be withdrawn from a vial or should be injected directly using a commercially available prefilled syringe.

Solutions prepared from or commercially available in pharmacy bulk packages, those available in ADD-Vantage vials, or the commercially available injections in 0.9% sodium chloride should not be used for IM administration.

Oral Inhalation

Administer tobramycin solution for oral inhalation using a PARI LC PLUS nebulizer (a hand-held, reusable nebulizer) connected to a DeVilbiss Pulmo-Aide compressor.

Review manufacturers’ information to ensure thorough familiarity with the use and maintenance of the nebulizer and compressor.

Administer the solution for oral inhalation while the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebulizer; breathing through the mouth may be aided by using nose clips.

A nebulizer treatment period of about 15 minutes usually required to completely administer the usual tobramycin dose.

Tobramycin solution for oral inhalation should not be diluted prior to administration and should not be admixed with other drugs (e.g., dornase alfa) in the nebulizer.

Tobramycin solution for oral inhalation usually is used in conjunction with various other standard therapies recommended for patients with cystic fibrosis. Patients should receive such therapies prior to doses of tobramycin solution for oral inhalation.

Based on protocols used in clinical studies evaluating tobramycin solution for oral inhalation, patients should receive doses of inhaled bronchodilators first, then dornase alfa administered by oral inhalation, then chest physiotherapy, then tobramycin solution administered by oral inhalation.

If orally inhaled corticosteroids, cromolyn sodium, or nedocromil sodium also are indicated in the patient, administer these following the tobramycin dose.

Dosage

Available as tobramycin sulfate or tobramycin; dosage expressed in terms of tobramycin.

Dosage is identical for either IV or IM administration.

Parenteral dosage should be based on patient's pretreatment body weight and renal status.

Many clinicians recommend that parenteral dosage be determined using appropriate pharmacokinetic methods for calculating dosage requirements and patient-specific pharmacokinetic parameters (e.g., elimination rate constant, volume of distribution) derived from serum concentration-time data; susceptibility of the causative organism; severity of infection; and the patient’s immune and clinical status.

Determine peak and trough serum tobramycin concentrations periodically during parenteral therapy. Adjust dosage to maintain desired serum concentrations whenever possible, especially in patients with life-threatening infections, suspected toxicity or nonresponse to treatment, decreased or varying renal function, and/or when increased aminoglycoside clearance (e.g., patients with cystic fibrosis, burns) or prolonged therapy is likely.

In general, desirable peak serum tobramycin concentrations during parenteral therapy are 4–12 mcg/mL and trough concentrations should not be >1–2 mcg/mL. Some evidence suggests that an increased risk of toxicity may be associated with prolonged peak tobramycin serum concentrations >10–12 mcg/mL and/or trough concentrations >2 mcg/mL.

Once-daily administration^{† [off-label]} of parenteral aminoglycosides is at least as effective as, and may be less toxic than, conventional parenteral dosage regimens employing multiple daily doses.

Usual duration of parenteral treatment is 7–10 days. In difficult and complicated infections, reevaluate use of tobramycin if >10 days of treatment is being considered.

If the drug is continued, monitor serum tobramycin concentrations and renal, auditory, and vestibular functions closely.

Pediatric Patients

General Dosage for Neonates

IV or IM

Manufacturer recommends ≤4 mg/kg daily given in 2 divided doses every 12 hours in premature or full-term neonates ≤1 week of age.

Neonates <1 week of age: AAP recommends 2.5 mg/kg every 18–24 hours for those weighing <1.2 kg and 2.5 mg/kg every 12 hours for those weighing ≥1.2 kg.

Neonates 1–4 weeks of age: AAP recommends 2.5 mg/kg every 18–24 hours for those weighing <1.2 kg, 2.5 mg/kg every 8 or 12 hours for those weighing 1.2–2 kg, and 2.5 mg/kg every 8 hours for those weighing >2 kg.

General Dosage for Infants and Children

IV or IM

Older infants and children: Manufacturer recommends 6–7.5 mg/kg daily given in 3 or 4 equally divided doses (2–2.5 mg/kg every 8 hours or 1.5–1.89 mg/kg every 6 hours).

Children ≥1 month of age: AAP recommends 3–7.5 mg/kg daily given in 3 divided doses for treatment of severe infections. Inappropriate for mild to moderate infections according to AAP.

Ps. aeruginosa Infections in Cystic Fibrosis Patients

Inhalation

Children ≥6 years of age: 300 mg twice daily for 28 days. Doses should be administered using the recommended nebulizer system every 12 hours (or at intervals as close to every 12 hours as possible); doses should not be administered at intervals <6 hours. Each 28-day regimen should be followed by a 28-day period when the drug is not administered.

Adults

General Adult Dosage

Treatment of Serious Infections

IV or IM

3 mg/kg daily given in 3 equally divided doses every 8 hours.

Treatment of Life-threatening Infections

IV or IM

≤5 mg/kg daily given in 3 or 4 equally divided doses. Dosage may be reduced to 3 mg/kg daily when clinically indicated.

Ps. aeruginosa Infections in Cystic Fibrosis Patients

Inhalation

300 mg twice daily for 28 days. Doses should be administered using the recommended nebulizer system every 12 hours (or at intervals as close to every 12 hours as possible); doses should not be administered at intervals <6 hours. Each 28-day regimen should be followed by a 28-day period when the drug is not administered.

Prescribing Limits

Pediatric Patients

Treatment of Infections

IV or IM

Maximum of 4 mg/kg daily in neonates ≤1 week of age.

Adults

Treatment of Life-threatening Infections

IV or IM

Maximum 5 mg/kg daily unless serum concentrations are monitored.

Special Populations

Renal Impairment

Dosage adjustments necessary in patients with renal impairment. Whenever possible, monitor serum tobramycin concentrations.

Various methods have been used to determine aminoglycoside dosage for patients with renal impairment and there is wide variation in dosage recommendations for these patients.

Manufacturer recommends an initial loading dose of 1 mg/kg followed by subsequent dosage that involves 1-mg/kg doses given at intervals (in hours) calculated by multiplying the patient’s steady-state serum creatinine (in mg/dL) by 6.

The dosing method of Sarubbi and Hull (based on corrected Cl_cr) also has been recommended. Specialized references should be consulted for specific information on dosage for patients with renal impairment.

Dosage calculation methods should not be used in patients undergoing hemodialysis or peritoneal dialysis.

In adults with renal failure undergoing hemodialysis, some clinicians recommend supplemental doses of 50–75% of the initial loading dose at the end of each dialysis period.

Serum tobramycin concentrations should be monitored in dialysis patients and dosage adjusted to maintain desired concentrations.

Geriatric Patients

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.

No dosage adjustments except those related to renal impairment. (See Renal Impairment under Dosage and Administration.)

Cautions for Tobramycin

Contraindications

• History of hypersensitivity or serious toxic reactions to tobramycin or other aminoglycosides.

Warnings/Precautions

Warnings

Ototoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible ototoxicity.

Vestibular and permanent bilateral auditory ototoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other ototoxic drugs, and those who receive high dosage or prolonged treatment.

Serial audiograms should be obtained, if feasible, in patients old enough to be tested, particularly in high-risk patients.

Discontinue tobramycin or adjust dosage if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss) or nephrotoxicity.

Some aminoglycosides have caused fetal ototoxicity when administered to pregnant women. (See Pregnancy under Cautions.)

Nephrotoxicity

Patients receiving aminoglycosides should be under close clinical observation because of possible nephrotoxicity. Renal function should be assessed prior to and periodically during therapy.

Nephrotoxicity occurs most frequently in those with past or present history of renal impairment, those receiving other nephrotoxic drugs, and those who receive high dosage or prolonged treatment.

Dosage reduction may be desirable if other evidence of renal dysfunction occurs (e.g., decreased Cl_cr, decreased urine specific gravity, increased BUN or serum creatinine, oliguria).

If azotemia increases or if a progressive decrease in urinary output occurs, discontinue tobramycin.

Neuromuscular Blockade

Neuromuscular blockade and respiratory paralysis reported with high tobramycin dosage (40 mg/kg). Possibility of prolonged or secondary apnea should be considered.

Possibility of neuromuscular blockade should be considered, especially in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium) or in those receiving massive transfusions of citrate-anticoagulated blood.

Calcium salts may reverse neuromuscular blockade, but mechanical respiratory assistance may be necessary.

Sensitivity Reactions

Cross-sensitivity

Cross-sensitivity occurs among the aminoglycosides.

Sulfite Sensitivity

Tobramycin injection contains sodium metabisulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

General Precautions

Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi. Discontinue drug and institute appropriate therapy if superinfection occurs.

Interactions

Because of possible additive toxicity, avoid concurrent and/or sequential use of other neurotoxic or nephrotoxic drugs (systemic, oral, or topical), particularly bacitracin, cisplatin, amphotericin B, cephaloridine (no longer available in US), paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides.

Do not administer concurrently with potent diuretics (e.g., ethacrynic acid, furosemide). (See Specific Drugs under Interactions.)

Consider possibility of neuromuscular blockade and respiratory paralysis in patients receiving anesthetics or neuromuscular blocking agents (e.g., tubocurarine, succinylcholine, decamethonium). (See Specific Drugs under Interactions.)

Use with caution in patients with muscular disorders such as myasthenia gravis or parkinsonism since drugs used in these patients may aggravate muscle weakness because of their potential curare-like effect on the neuromuscular junction.

Topical Instillation

Aminoglycoside may be absorbed in significant quantities from body surfaces after topical instillation^{† [off-label]} and may cause neurotoxicity and nephrotoxicity.

Specific Populations

Pregnancy

Category D.

Possibility of fetal harm if administered to a pregnant woman. Complete, irreversible, bilateral congenital deafness reported when another aminoglycoside (i.e., streptomycin) was used during pregnancy.

If used during pregnancy or if patient becomes pregnant while receiving tobramycin, patient should be apprised of the potential hazard to the fetus.

Lactation

Low concentrations of aminoglycosides may be distributed into milk. Use with caution.

Pediatric Use

Use with caution in neonates and premature infants because renal immaturity in these patients may result in prolonged serum half-life.

Safety and efficacy of tobramycin for oral inhalation not established in children <6 years of age.

Geriatric Use

Select dosage with caution and closely monitor renal function because of age-related decreases in renal function.

Monitoring renal function during aminoglycoside therapy is particularly important in geriatric patients. Cl_cr may be more useful than determining BUN or serum creatinine.

Renal Impairment

Risk of neurotoxicity (manifested as vestibular and permanent bilateral auditory ototoxicity) is greater in patients with renal damage than in other patients.

Renal function should be assessed prior to and during therapy.

Eighth-cranial nerve function should be monitored closely, especially in patients who have known or suspected renal impairment at the start of treatment and also in those whose renal function is initially normal but who develop signs of renal dysfunction during treatment.

Common Adverse Effects

Ototoxicity or nephrotoxicity.

Drug Interactions

Neurotoxic, Ototoxic, or Nephrotoxic Drugs

Concomitant or sequential use with other drugs that have neurotoxic, ototoxic, or nephrotoxic effects (e.g., aminoglycosides, acyclovir, amphotericin B, bacitracin, capreomycin, cephalosporins, colistin, cephaloridine, viomycin, polymyxin B, colistin, cisplatin, vancomycin) may result in additive toxicity and should be avoided, if possible.

Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, aminoglycosides should not be given concurrently with potent diuretics (e.g., ethacrynic acid, furosemide).

Specific Drugs

Tobramycin Pharmacokinetics

Absorption

Bioavailability

Not absorbed orally; must be given parenterally.

Rapidly absorbed following IM injection; peak serum concentrations attained within 30–90 minutes.

Following oral inhalation via nebulization, tobramycin remains concentrated principally in the airways; the drug does not readily cross epithelial membranes.

Distribution

Extent

Distributed into bone, heart, gallbladder, lung tissue, bile, sputum, bronchial secretions, and interstitial, pleural, and synovial fluids.

Only low concentrations distributed into CSF following IM or IV administration.

Crosses placenta.

Aminoglycosides may be distributed into milk in low concentrations.

Plasma Protein Binding

Only minimally bound to plasma proteins

Elimination

Metabolism

Not metabolized.

Elimination Route

Up to 84% of a single IM dose is excreted unchanged by glomerular filtration within 8 hours and up to 93% is excreted unchanged within 24 hours.

When administered by oral inhalation using a nebulizer, any drug that is not absorbed systemically probably is eliminated principally in expectorated sputum.

Half-life

2–3 hours in adults with normal renal function.

4.6 hours in full-term infants and 8.7 hours in low birth-weight infants.

Special Populations

Half-life is 5–70 hours in adults with impaired renal function.

Stability

Storage

Parenteral

Injection for IV Infusion or IM Injection

15–30°C.

Oral Inhalation

Solution for Nebulization

2–8°C. If refrigeration not available, intact or opened foil pouches containing ampuls of the solution for oral inhalation may be stored at room temperature ≤25°C for ≤28 days.

Do not expose ampuls to intense light.

Solution may darken if stored at room temperature; this does not indicate a change in quality.

Discard any solution for oral inhalation that is cloudy or has visible particles.

Discard any solution for oral inhalation that has been stored at 2–8°C beyond the expiration date stamped on the ampul or stored for >28 days at room temperature.

Compatibility

Parenteral

Solution CompatibilityHID

Drug Compatibility

Actions and Spectrum

• Usually bactericidal.

• Inhibits protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits.

• In vitro spectrum of activity includes many gram-negative aerobic bacteria (including most Enterobacteriaceae and Pseudomonas aeruginosa) and some aerobic gram-positive bacteria. Inactive against fungi, viruses, and most anaerobic bacteria.

• Gram-positive aerobes: Active in vitro against penicillinase-producing and nonpenicillinase-producing Staphylococcus aureus and S. epidermidis. May be active against some strains of oxacillin-resistant (methicillin-resistant) staphylococci. Streptococcus pyogenes (group A β-hemolytic streptococci), S. pneumoniae, and Enterococcus faecalis usually are resistant.

• Gram-negative aerobes: Active in vitro and in clinical infections against Acinetobacter, Citrobacter, Enterobacter, Escherichia coli, Haemophilus influenzae, Klebsiella, Morganella, Proteus, Providencia, Pseudomonas, Salmonella, Shigella, and Serratia. Burkholderia and Stenotrophomonas usually are resistant.

• Partial cross-resistance occurs between tobramycin and other aminoglycosides.

Advice to Patients

• For patients using tobramycin for oral inhalation, advise patients on proper use of the solution and nebulizer. If patient also is taking other medications, importance of not mixing the tobramycin solution with any other medications in the nebulizer and importance of using bronchodilators first, followed by chest physiotherapy, then other inhaled medications, and then tobramycin.

• Importance of informing clinician if there is evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, hearing loss), other neurotoxicity (numbness, skin tingling, muscle twitching, seizures), or nephrotoxicity (e.g., decreased urine output).

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, and any concomitant illnesses.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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