Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

Extended-interval dosing: 4 to 7 mg/kg IV every 24 hours

-A loading dose of 1.5 to 2 mg/kg has been recommended.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

Extended-interval dosing: 4 to 7 mg/kg IV every 24 hours

-A loading dose of 1.5 to 2 mg/kg has been recommended.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

Extended-interval dosing: 4 to 7 mg/kg IV every 24 hours

-A loading dose of 1.5 to 2 mg/kg has been recommended.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

Extended-interval dosing: 4 to 7 mg/kg IV every 24 hours

-A loading dose of 1.5 to 2 mg/kg has been recommended.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

Extended-interval dosing: 4 to 7 mg/kg IV every 24 hours

-A loading dose of 1.5 to 2 mg/kg has been recommended.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

Extended-interval dosing: 4 to 7 mg/kg IV every 24 hours

-A loading dose of 1.5 to 2 mg/kg has been recommended.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

Extended-interval dosing: 4 to 7 mg/kg IV every 24 hours

-A loading dose of 1.5 to 2 mg/kg has been recommended.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

Extended-interval dosing: 4 to 7 mg/kg IV every 24 hours

-A loading dose of 1.5 to 2 mg/kg has been recommended.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

-In patients with extensive burns, altered pharmacokinetics may result in reduced serum levels of aminoglycosides; measurement of tobramycin serum levels is recommended as basis for dose adjustment.

Some experts recommend: 2 to 2.5 mg/kg loading dose, followed by 1.7 to 2 mg/kg IV every 8 hours

IV: 5 to 10 mg/kg/day IV in 2 to 4 divided doses or 10 to 15 mg/kg/day IV in 3 to 4 divided doses; alternatively, 7 to 15 mg/kg IV every 24 hours has been used

-In patients with cystic fibrosis, altered pharmacokinetics may result in reduced serum levels of aminoglycosides; measurement of tobramycin serum levels is recommended as basis for dose adjustment.

-In patients with severe cystic fibrosis, an initial dosing regimen of 10 mg/kg/day in 4 equally divided doses is suggested only as a guide by the manufacturer.

-The serum levels of tobramycin should be measured directly during therapy due to wide interpatient variability.

Inhalation Solution: 300 mg via nebulizer over approximately 15 minutes twice a day

Inhalation Powder: Using the Podhaler(TM) device, inhale the contents of four 28 mg capsules twice a day

Duration of therapy: 28 days

-Doses should be inhaled as close to 12 hours apart as possible and not less than 6 hours apart.

-Administer in alternating cycles of 28 days on and 28 days off.

-If patient is on multiple therapies, the following order of administration has been recommended: bronchodilator, chest physiotherapy, other inhaled medications, and lastly, inhaled tobramycin.

-Safety and efficacy have not been established in patients colonized with Burkholderia cepacia.

-Bethkis(R): Safety and efficacy have not been established in patients with forced expiratory volume in 1 second (FEV1) less than 40% or greater than 80% predicted.

-TOBI(R): Safety and efficacy have not been established in patients with FEV1 less than 25% or greater than 75% predicted.

-TOBI(R) Podhaler(TM): Safety and efficacy have not been established in patients with FEV1 less than 25% or greater than 80% predicted.

Approved indication: The management of cystic fibrosis patients with Pseudomonas aeruginosa

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Some experts recommend a loading dose of 1.5 to 2 mg/kg.

Preferred regimen for infective endocarditis due to Pseudomonas aeruginosa: 8 mg/kg IV or IM once a day

-Maintenance of peak levels of 15 to 20 mcg/mL and trough levels of 2 mcg/mL or less is recommended.

-Tobramycin should be administered in combination with either an extended-spectrum penicillin (e.g., ticarcillin, piperacillin) or ceftazidime or cefepime in full doses.

-The toxicity associated with this regimen has been reported as low; combination therapy should be given for at least 6 weeks.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Some experts recommend a loading dose of 2 mg/kg.

-Parenteral therapy should be continued for at least 1 week after the patient becomes afebrile and cerebrospinal fluid (CSF) normalizes.

Parenteral: 5 mg/kg/day IV or IM in 3 divided doses

Intraventricular: 5 to 20 mg intraventricularly (preservative-free formulation) per day; subsequent doses should be based on the CSF concentration

Neisseria meningitidis: 7 days

Haemophilus influenzae: 7 days

Streptococcus pneumoniae: 10 to 14 days

Streptococcus agalactiae: 14 to 21 days

Aerobic gram-negative bacilli: 21 days

Listeria monocytogenes: 21 days or longer

-These guidelines are not standardized and the duration of therapy should be individualized based on the patient's clinical response.

-IV antimicrobial therapy is recommended for the duration of therapy to ensure that adequate CSF levels are attained.

Serious infections: 1 mg/kg IV or IM every 8 hours

Life-threatening infections: Up to 5 mg/kg/day may be administered IV or IM in 3 or 4 equal doses; however, the dosage should be reduced to 3 mg/kg/day as soon as clinically indicated.

-To prevent increased toxicity due to excessive blood levels, dosage should not exceed 5 mg/kg/day unless serum levels are monitored.

-Limiting the duration of tobramycin therapy may help limit toxicity; once patient is stable for at least 48 hours, less toxic IV or oral antibiotic therapy may be considered according to microbiology sensitivity data.

IV: 2 mg/kg loading dose, followed by 1.7 mg/kg IV every 8 hours or 5 mg/kg IV every 24 hours

Intraperitoneal in CAPD patients: 0.6 to 0.75 mg/kg intraperitoneally once a day or 16 to 20 mg per every 2 L dialysate

(Not approved by FDA)

IDSA recommendations: 5 to 20 mg intraventricularly (preservative-free formulation) up to every 24 hours, in addition to parenteral antibiotic therapy

-Subsequent doses should be based on the CSF concentration.

-Shunt removal is usually necessary to achieve a cure.

Premature or full-term neonates 1 week of age or less: Up to 4 mg/kg/day may be administered IV or IM in 2 equal doses every 12 hours.

Greater than 1 week of age: 6 to 7.5 mg/kg/day IV or IM in 3 or 4 equally divided doses (2 to 2.5 mg/kg IV or IM every 8 hours or 1.5 to 1.89 mg/kg IV or IM every 6 hours)

7 days or less, 2000 g or less: 5 mg/kg IV or IM every 48 hours

7 days or less, greater than 2000 g: 4 mg/kg IV or IM every 24 hours

8 to 28 days, 2000 g or less: 4 to 5 mg/kg IV or IM every 24 to 48 hours

8 to 28 days, greater than 2000 g: 4 mg/kg IV or IM every 12 to 24 hours

1 month or older: 1 to 2.5 mg/kg IV or IM every 8 hours for severe infections

-The longer dosing interval may be used in extremely low birth weight (less than 1000 g) neonates until 2 weeks of life.

-Tobramycin is not appropriate for the treatment of mild to moderate infections in patients 1 month or older.

-Measurement of serum levels is recommended in order to individualize and optimize dosing.

IV or IM: 2.5 mg/kg IV or IM every 6 hours or 3.3 mg/kg IV or IM every 8 hours

-In patients with severe cystic fibrosis, an initial dosing regimen of 10 mg/kg/day in 4 equally divided doses is suggested only as a guide by the manufacturer.

-The AAP states that higher doses (8 to 10 mg/kg/day) are appropriate for pulmonary exacerbations in patients with cystic fibrosis.

-In patients with cystic fibrosis, altered pharmacokinetics may result in reduced serum levels of aminoglycosides; measurement of tobramycin serum levels is recommended as basis for dose adjustment.

-The serum levels of tobramycin should be measured directly during therapy due to wide interpatient variability.

Inhalation Solution: 300 mg via nebulizer over approximately 15 minutes twice a day

Inhalation Powder: Using the Podhaler(TM) device, inhale the contents of four 28 mg capsules twice a day

Duration of therapy: 28 days

-Doses should be inhaled as close to 12 hours apart as possible and not less than 6 hours apart.

-Administer in alternating cycles of 28 days on and 28 days off.

-If patient is on multiple therapies, the following order of administration has been recommended: bronchodilator, chest physiotherapy, other inhaled medications, and lastly, inhaled tobramycin.

-Safety and efficacy have not been established in patients colonized with B cepacia.

-TOBI(R): Safety and efficacy have not been established in patients with FEV1 less than 25% or greater than 75% predicted.

-Bethkis(R): Safety and efficacy have not been established in patients with FEV1 less than 40% or greater than 80% predicted.

-TOBI(R) Podhaler(TM): Safety and efficacy have not been established in patients with FEV1 less than 25% or greater than 80% predicted.

Approved indication: The management of cystic fibrosis patients with P aeruginosa

Dosage should be adjusted in renal insufficiency. Various nomograms and methods have been proposed for determining the dosage in renally impaired adult patients - reduced doses at fixed intervals or normal doses at prolonged intervals. Regimens are ideally based on individualized pharmacokinetic dosing.

Manufacturer recommendations for patients with impaired renal function: Following a loading dose of 1 mg/kg, subsequent doses should be adjusted, either with reduced doses administered at 8-hour intervals or with normal doses given at prolonged intervals. Both methods are suggested as guides to be used when tobramycin serum levels cannot be measured directly. They are based on either the CrCl or the serum creatinine of the patient (these values correlate with the half-life of tobramycin). The regimens derived from either method should be used in conjunction with careful clinical and laboratory monitoring and should be modified as necessary.

CrCl 40 to 60 mL/min: Normal dose administered IV or IM every 12 hours

CrCl 20 to 40 mL/min: Normal dose administered IV or IM every 24 hours

CrCl 10 to 20 mL/min: Normal dose administered IV or IM every 48 hours

CrCl less than 10 mL/min: Normal dose administered IV or IM every 72 hours

CrCl 70 to 80 mL/min: 76% to 91% of the loading dose every 8 to 12 hours

CrCl 60 to 70 mL/min: 71% to 88% of the loading dose every 8 to 12 hours

CrCl 50 to 60 mL/min: 65% to 84% of the loading dose every 8 to 12 hours

CrCl 40 to 50 mL/min: 72% to 92% of the loading dose every 12 to 24 hours

CrCl 30 to 40 mL/min: 63% to 92% of the loading dose every 12 to 24 hours

CrCl 20 to 30 mL/min: 50% to 81% of the loading dose every 12 to 24 hours

CrCl 10 to 20 mL/min: 34% to 75% of the loading dose every 12 to 24 hours

CrCl less than 10 mL/min: 21% to 47% of the loading dose every 24 hours or a one-time loading dose with subsequent doses based on serum concentrations, estimated clearance and the patient's condition

CrCl 80 mL/min or more: 5 to 7 mg/kg every 24 hours

CrCl 60 to 79 mL/min: 4 to 5.5 mg/kg every 24 hours

CrCl 50 to 59 mL/min: 3.5 to 5 mg/kg every 24 hours

CrCl 40 to 49 mL/min: 2.5 to 3.5 mg/kg every 24 hours

CrCl 30 mL/min: 2 to 2.8 mg/kg every 24 hours

CrCl 20 mL/min: 4 to 5 mg/kg every 48 hours

CrCl 10 mL/min: 3 to 4 mg/kg every 48 hours

CrCl 61 mL/min or more: 7 mg/kg every 24 hours

CrCl 40 to 60 mL/min: 7 mg/kg every 36 hours

CrCl 20 to 40 mL/min: 7 mg/kg every 48 hours; monitor serum levels

CrCl less than 20 mL/min: 7 mg/kg once; repeat when trough level is less than 1 mcg/mL

If nephrotoxicity is suspected, therapy should be discontinued until tobramycin serum concentrations fall below 2 mcg/mL.

No adjustment recommended.

Parenteral: In obese patients, the appropriate parenteral dose may be calculated by using the estimated lean body weight plus 40% of the excess as the basic weight on which to figure mg/kg.

Inhalation: No dosage adjustments are made.

-This drug should be considered a narrow therapeutic index (NTI) drug as small differences in dose or blood concentrations may lead to serious therapeutic failures or adverse drug reactions.

Recommendations:

- Generic substitution should be done cautiously, if at all, as current bioequivalence standards are generally insufficient for NTI drugs.

-Additional and/or more frequent monitoring should be done to ensure receipt of an effective dose while avoiding unnecessary toxicities.

Consult WARNINGS section for dosing related precautions.

In patients undergoing dialysis, 25% to 70% of the administered dose may be removed, depending on the duration and type of dialysis.

Intermittent hemodialysis (3 times/week, complete sessions): 2 to 3 mg/kg IV once as a loading dose, with subsequent doses based on serum concentrations, estimated clearance, and the patient's condition; doses should be administered following dialysis

Peritoneal dialysis: Normal dose administered IV or IM every 72 hours; concentrations should be monitored

1 month or older: 1.25 to 1.75 mg/kg/dose IV or IM after dialysis

Inhalation: Data not available

-Bethkis(R) should be administered using a handheld PARI LC(R) PLUS Reusable Nebulizer with a PARI Vios(R) air compressor over approximately 15 minutes and until the nebulizer output has sputtered for at least 1 minute.

-TOBI(R) should be administered using a handheld PARI LC(R) PLUS Reusable Nebulizer with a DeVilbiss Pulmo-Aide(R) compressor over approximately 15 minutes.

-The inhalation solution should not be diluted or mixed with dornase alfa or other medications in the nebulizer.

-TOBI(R) Podhaler(TM) capsules must not be swallowed; for use with the Podhaler(TM) device only.

-The manufacturer's product information should be consulted for additional administration information.

-The duration of therapy should be limited to short term. The usual duration of therapy for all patients is 7 to 10 days. In difficult and complicated infections, a longer course of therapy may be necessary. In such cases, monitoring of renal, auditory, and vestibular functions is recommended; neurotoxicity is more likely with treatment durations longer than 10 days.

-IV tobramycin should be infused over 20 to 60 minutes.

-Patients should be well-hydrated during aminoglycoside treatment.

-The inhalation solution ampules should be refrigerated (2C to 8C [36F to 46F]); if refrigerator is not available, may store at room temperature (up to 25C [77F]) for up to 28 days. Exposure to intense light should be avoided.

-The manufacturer's product information should be consulted.

-Tobramycin should not be physically premixed with other drugs.

-General: Peak and trough serum levels (periodically during parenteral therapy); serum levels in patients with auditory or renal dysfunction or patients treated with concomitant nephrotoxic or ototoxic drugs (at the physician's discretion during inhalation therapy)

-Metabolic: Serum calcium, magnesium, and sodium (during parenteral therapy)

-Nervous System: Serial audiograms in patients old enough to be tested, especially high-risk patients (during parenteral therapy); eighth-nerve function in patients with renal impairment and in patients who develop signs of renal dysfunction (during parenteral therapy)

-Renal: Urine for decreased specific gravity and increased excretion of protein, cells, and casts (during parenteral therapy); blood urea nitrogen, serum creatinine, CrCl (periodically during parenteral therapy); renal function in patients with renal impairment and in patients who develop signs of renal dysfunction (during parenteral therapy)