PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Aminoglycoside Antibiotics
    Ophthalmological Anti-infectives

    BOXED WARNING

    Dehydration, nephrotoxicity, renal disease, renal failure, renal impairment

    Patients receiving systemic or inhaled aminoglycosides, such as tobramycin, should be closely monitored for nephrotoxicity. Aminoglycosides are associated with major toxic effects on renal tubules. In patients with pre-existing renal impairment, renal failure, or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe nephrotoxic adverse reactions are sharply increased. Nephrotoxicity can manifest as decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine).  When monitoring serum concentrations, the manufacturer states that prolonged tobramycin peak concentrations above 12 mcg/mL should be avoided and trough concentrations above 2 mcg/mL should be avoided. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Renal function should be closely monitored. Evidence of nephrotoxicity requires dosage adjustment or discontinuance of therapy. Hemodialysis may aid in removal in the event of overdose or toxic reactions, especially if renal is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Avoid concurrent and/or sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic and/or neurotoxic because toxicity may be additive. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity.

    Hearing impairment, neurotoxicity, ototoxicity, tinnitus

    Patients receiving systemic and inhaled aminoglycosides, such as tobramycin, should be closely monitored for neurotoxicity, including ototoxicity and hearing impairment. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Neurotoxicity is manifested by bilateral auditory toxicity which often is permanent and, sometimes, by vestibular ototoxicity. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Vertigo may occur and may indicate vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of hearing loss increases with the degree of exposure and continues to progress after stopping the drug. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. In patients with pre-existing renal impairment or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe ototoxic adverse reactions are sharply increased. When monitoring tobramycin serum concentrations during use of conventional dose regimens, the manufacturer states that prolonged tobramycin peak concentrations above 12 mcg/mL should be avoided and trough concentrations above 2 mcg/mL should be avoided. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Eighth cranial nerve function should be closely monitored. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, or hearing loss) requires dosage adjustment or discontinuance of therapy. Aminoglycoside-induced ototoxicity is usually irreversible. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Aminoglycosides should not be given concomitantly with potent diuretics since certain diuretics by themselves may cause ototoxicity. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity. Audiology tests are recommended.

    Pregnancy

    Systemic exposure to tobramycin (e.g., injections, respiratory solutions for inhalation) and systemic exposure to other aminoglycosides may cause fetal harm during human pregnancy. Aminoglycosides cross the placenta. There have been reports of total irreversible bilateral congential deafness in newborns whose mothers received streptomycin, a related aminoglycoside, during pregnancy. Serious side effects to the mother, fetus, or newborn have not been reported with use of other aminoglycosides when used during pregnancy. If tobramycin injection is used during pregnancy or if the patient becomes pregnant during treatment with tobramycin, she should be apprised of the potential risk to the fetus. The risk with inhaled tobramycin is less well characterized. Tobramycin ophthalmic products may be used during pregnancy; reproduction studies in 3 types of animals at doses up to 33 times the normal human systemic dose have revealed no evidence of impaired fertility or harm to the fetus due to ophthalmic use of tobramycin. Because there have been no adequate studies investigating the safe use of ophthalmic tobramycin in pregnant women, it should only be used when the potential benefits to the mother outweigh possible risks to the fetus.

    DEA CLASS

    Rx

    DESCRIPTION

    Parenteral, inhaled, or ophthalmic aminoglycoside antibiotic
    Most active against aerobic gram-negative rods
    Risk of ototoxicity and renal toxicity with high serum concentration

    COMMON BRAND NAMES

    AK-Tob, BETHKIS, Kitabis Pak, Nebcin, Tobi, TOBI Podhaler, Tobrasol, Tobrex

    HOW SUPPLIED

    AK-Tob/Tobramycin/Tobrasol/Tobrex Ophthalmic Sol: 0.3%
    BETHKIS/Kitabis Pak/Tobi/Tobramycin/Tobramycin Sulfate Respiratory (Inhalation) Sol: 4mL, 5mL, 300mg
    Nebcin/Tobramycin/Tobramycin Sulfate Intramuscular Inj Sol: 1mL, 10mg, 40mg
    Nebcin/Tobramycin/Tobramycin Sulfate Intravenous Inj Sol: 1mL, 10mg, 40mg
    TOBI Podhaler Respiratory (Inhalation) Pwd: 28mg
    Tobramycin/Tobramycin Sulfate Intramuscular Inj Pwd F/Sol: 1.2g
    Tobramycin/Tobramycin Sulfate Intravenous Inj Pwd F/Sol: 1.2g
    Tobrex Ophthalmic Ointment: 0.3%

    DOSAGE & INDICATIONS

    For the treatment of bone and joint infections, skin and skin structure infections (burn wound infection), and meningitis.
    NOTE: Serum concentrations should be used to guide dosage adjustments. A 'dosing' weight should be used to calculate initial dosages in patients weighing more than their ideal body weight.
    For intrathecal† or intraventricular† administration in patients with meningitis.
    Intrathecal† or Intraventricular dosage†
    Adults

    5 to 20 mg intraventricularly once daily in combination with systemeic therapy.

    Infants, Children, and Adolescents

    5 to 20 mg intraventricularly once daily in combination with systemic therapy has been recommended in general without specific pediatric qualifications. Doses of 1.5 to 5 mg intraventricularly once daily and 2.5 mg intraventricularly every 8 hours have been used in pediatric case reports. Doses should be adjusted to maintain adequate CSF concentrations depending on the susceptibility of the infecting organism.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    3 mg/kg/day IV or IM given in 3 divided doses, while doses up to 5 mg/kg/day IV or IM in 3 to 4 divided doses may be required in life-threatening infections. Peak concentrations for these doses are expected to be approximately 4 to 6 mcg/mL. Adjust dosage based on serum concentration monitoring. Avoid peak concentrations more than 12 mcg/mL and trough concentrations more than 2 mcg/mL; use patient-specific information to guide the determination of adequate serum concentrations.

    Infants, Children, and Adolescents

    2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses (2 to 2.5 mg/kg every 8 hours or 1.5 to 1.89 mg/kg/dose IV or IM every 6 hours).

    Premature infants 30 days and older weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 8 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 8 to 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 to 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 7 days and younger; however, this dosing does not account for gestational age or birthweight.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 12 to 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 7 days and younger; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 to 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 7 days and younger; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Intravenous dosage (extended-interval dosing)†
    Adults

    5 to 7 mg/kg IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary.

    Infants, Children, and Adolescents

    5 to 8 mg/kg/dose IV every 24 hours has been recommended.

    Premature infants 30 days and older weighing less than 1,200 g

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2,000 g

    4 to 5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 24 to 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing less than 1,200 g

    5 mg/kg/dose IV every 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing more than 2,000 g

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 36 to 48 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing less than 1,200 g

    4 to 5 mg/kg/dose IV every 48 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    For the management of cystic fibrosis patients with Pseudomonas aeruginosa.
    Intravenous or Intramuscular dosage
    Adults, Adolescents, Children, and Infants

    10 mg/kg/dose IV every 24 hours. Doses as high as 12 to 15 mg/kg/dose IV every 24 hours have been used. Aminoglycosides have traditionally been administered as a three-times daily regimen; however, high dose extended-interval regimens are now preferred. The FDA-approved dose is 10 mg/kg/day IV or IM in 4 equally divided doses.

    Nebulized dosage (solution for inhalation)
    Adults, Adolescents, and Children 6 years and older

    300 mg (one ampule) via inhalation twice daily for 28 days. Administer in alternating 28-day periods (i.e., administer for 28 days, then 28 days off therapy, then resume therapy for the next 28 days). Administer the twice daily dose as close to 12 hours apart as possible; do not administer less than 6 hours apart. Safety and efficacy have not been demonstrated in patients with FEV1 less than 25% or more than 75% predicted (for TOBI) or FEV1 less than 40% or more than 80% predicted (for Bethkis), or in patients colonized with Burkholderia cepacia. A study evaluating the long term efficacy of this regimen in adolescents (age 13 to 17 years) noted improved lung function and weight gain.

    Oral inhalation dosage (powder for inhalation)
    Adults, Adolescents, and Children 6 years and older

    112 mg (four 28 mg capsules) via oral inhalation twice daily for 28 days. Administer in alternating 28-day periods (i.e., administer for 28 days, then 28 days off therapy, then resume therapy for the next 28 days). Administer the twice daily dose as close to 12 hours apart as possible; do not administer less than 6 hours apart. Safety and efficacy have not been demonstrated in patients with FEV1 less than 25% or more than 80% predicted, or in patients colonized with Burkholderia cepacia.

    For treatment of lower respiratory tract infections, including community-acquired pneumonia (CAP) and nosocomial pneumonia.
    NOTE: Serum concentrations should be used to guide dosage adjustments. A 'dosing' weight should be used to calculate initial dosages in patients weighing more than their ideal body weight.
    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    3 mg/kg/day IV or IM given in 3 divided doses, while doses up to 5 mg/kg/day IV or IM in 3 to 4 divided doses may be required in life-threatening infections. Peak concentrations for these doses are expected to be approximately 4 to 6 mcg/mL. Adjust dosage based on serum concentration monitoring. Avoid peak concentrations more than 12 mcg/mL and trough concentrations more than 2 mcg/mL; use patient-specific information to guide the determination of adequate serum concentrations. For CAP, clinical practice guidelines recommend an aminoglycoside in combination with an antipseudomonal beta-lactam and a respiratory fluoroquinolone (i.e., levofloxacin, moxifloxacin) or azithromycin for patients with risk factors for Pseudomonas infection. Clinical practice guidelines recommend treatment for a minimum of 5 days and the patient should be afebrile for 48 to 72 hours with no more than 1 sign of clinical instability before discontinuation. For patients with nosocomial pneumonia and risk factors for gram-negative resistance or with a high mortality risk, add as a second antipseudomonal agent. Clinical practice guidelines recommend treatment for 7 days. In patients with risk factors for MRSA, add vancomycin or linezolid.

    Infants, Children, and Adolescents

    6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses (2 to 2.5 mg/kg every 8 hours or 1.5 to 1.89 mg/kg/dose IV or IM every 6 hours).

    Premature infants 30 days and older weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 WEEKS OR LESS: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA GREATER THAN 34 WEEKS: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 8 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 WEEKS OR LESS: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA GREATER THAN 34 WEEKS: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 WEEKS OR LESS: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA GREATER THAN 34 WEEKS: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 WEEKS OR LESS: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA GREATER THAN 34 WEEKS: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 WEEKS OR LESS: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA GREATER THAN 34 WEEKS: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 WEEKS OR LESS: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA GREATER THAN 34 WEEKS: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 WEEKS OR LESS: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA GREATER THAN 34 WEEKS: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Intravenous dosage (extended-interval dosing)†
    Adults

    5 to 7 mg/kg IV. Initial dosing intervals are often determined using a nomogram and then are adjusted based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24, 36, and, in some cases, 48 to 72 hours, may be necessary. For CAP, clinical practice guidelines recommend an aminoglycoside in combination with an antipseudomonal beta-lactam and a respiratory fluoroquinolone (i.e., levofloxacin, moxifloxacin) or azithromycin for patients with risk factors for Pseudomonas infection. Clinical practice guidelines recommend treatment for a minimum of 5 days and the patient should be afebrile for 48 to 72 hours with no more than 1 sign of clinical instability before discontinuation. For patients with nosocomial pneumonia and risk factors for gram-negative resistance or with a high mortality risk, add as a second antipseudomonal agent. Clinical practice guidelines recommend treatment for 7 days. In patients with risk factors for MRSA, add vancomycin or linezolid.

    Infants, Children, and Adolescents

    5 to 8 mg/kg/dose IV every 24 hours has been recommended.  

    Premature infants 30 days and older weighing less than 1,200 g

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2,000 g

    4 to 5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA LESS THAN 32 WEEKS: 4 mg/kg/dose IV every 48 hours; GA 32 TO 36 WEEKS: 4 mg/kg/dose IV every 36 hours; GA 37 WEEKS OR GREATER: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 24 to 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA LESS THAN 32 WEEKS: 4 mg/kg/dose IV every 48 hours; GA 32 TO 36 WEEKS: 4 mg/kg/dose IV every 36 hours; GA 37 WEEKS OR GREATER: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing less than 1,200 g

    5 mg/kg/dose IV every 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA LESS THAN 32 WEEKS: 4 mg/kg/dose IV every 48 hours; GA 32 TO 36 WEEKS: 4 mg/kg/dose IV every 36 hours; GA 37 WEEKS OR GREATER: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing more than 2,000 g

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA LESS THAN 32 WEEKS: 4 mg/kg/dose IV every 48 hours; GA 32 TO 36 WEEKS: 4 mg/kg/dose IV every 36 hours; GA 37 WEEKS OR GREATER: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 36 to 48 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA LESS THAN 32 WEEKS: 4 mg/kg/dose IV every 48 hours; GA 32 TO 36 WEEKS: 4 mg/kg/dose IV every 36 hours; GA 37 WEEKS OR GREATER: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing less than 1,200 g

    4 to 5 mg/kg/dose IV every 48 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA LESS THAN 32 WEEKS: 4 mg/kg/dose IV every 48 hours; GA 32 TO 36 WEEKS: 4 mg/kg/dose IV every 36 hours; GA 37 WEEKS OR GREATER: 4 mg/kg/dose IV every 24 hours.

    For the treatment of external infections of the eye including, of blepharitis, blepharoconjunctivitis, bacterial conjunctivitis, dacryocystitis, keratitis, keratoconjunctivitis, and acute meibomianitis.
    Ophthalmic dosage (ointment)
    Adults

    Apply a thin strip to the conjunctiva (about 1/2 inch) every 8 to 12 hours. For severe infections, apply every 3 to 4 hours until improvement, then reduce to less frequent intervals.

    Infants 2 months and older, Children, and Adolescents

    Apply a thin strip (about 1/2 inch) to the conjunctiva every 8 to 12 hours. For severe infections, apply every 3 to 4 hours until improvement, then reduce to less frequent intervals.

    Ophthalmic dosage (solution)
    Adults

    1 to 2 drops to the affected eye(s) every 4 hours. For severe infections, 2 drops every 1 hour until improvement, then reduce to less frequent intervals.

    Infants 2 months and older, Children, and Adolescents

    1 to 2 drops to the affected eye(s) every 4 hours. For severe infections, 2 drops every 1 hour until improvement, then reduce to less frequent intervals.

    For the treatment of complicated or recurrent urinary tract infection (UTI).
    NOTE: Serum concentrations should be used to guide dosage adjustments. A 'dosing' weight should be used to calculate initial dosages in patients weighing more than their ideal body weight.
    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    3 to 6 mg/kg/day IV/IM given in 2 to 3 divided doses. Lower doses can be used in uncomplicated, lower urinary tract infections. Higher doses may be required in infections due to more resistant organisms. The manufacturer recommends 3 to 5 mg/kg/day IV/IM given in 3 to 4 divided doses and that doses should not exceed 5 mg/kg/day unless serum concentrations are monitored.

    Infants, Children, and Adolescents

    6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses (2 to 2.5 mg/kg/dose IV or IM every 8 hours or 1.5 to 1.89 mg/kg/dose IV or IM every 6 hours). Treatment is recommended for 7 to 14 days.

    Premature Infants 30 days and older weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 8 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Intravenous dosage (extended-interval dosing)†
    Adults

    5 to 7 mg/kg IV. Dosing intervals are often determined using a nomogram and are frequently based on a random level drawn 8 to 12 hours after the first dose; dosing intervals of 24 hours, 36 hours, and in some cases, 48 to 72 hours, are used. For pyelonephritis, the Infectious Diseases Society of America (IDSA) recommends that aminoglycosides may be given alone or in combination with ampicillin or with an extended-spectrum cephalosporin or penicillin. A one-time extended interval dose of an aminoglycoside may also be used prior to oral therapy for patients who do not require hospitalization.

    Infants, Children, and Adolescents

    5 to 8 mg/kg/dose IV every 24 hours has been recommended. Treatment is recommended for 7 to 14 days.

    Premature Infants 30 days and older weighing less than 1,200 g

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2,000 g

    4 to 5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 24 to 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing less than 1,200 g

    5 mg/kg/dose IV every 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing more than 2,000 g

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 36 to 48 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing less than 1,200 g

    4 to 5 mg/kg/dose IV every 48 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    For the treatment of intraabdominal infections, including peritonitis.
    NOTE: Serum concentrations should be used to guide dosage adjustments. A 'dosing' weight should be used to calculate initial dosages in patients weighing more than their ideal body weight.
    For peritoneal dialysis-associated peritonitis in patients with end-stage renal disease.
    Intraperitoneal dosage
    Adults

    8 mg/L IP loading dose then 4 mg/L IP as continuous therapy in each dialysate exchange bag. For intermittent dosing, administer 0.6 mg/kg IP once daily in the exchange with the longest dwell time.

    Infants, Children, and Adolescents

    8 mg/L IP loading dose then 4 mg/L IP as continuous therapy in each dialysate exchange bag. For intermittent therapy, 0.6 mg/kg IP in anuric patients and 0.75 mg/kg IP in non-anuric patients administered during the longest daily dialysate dwell period.

    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    3 to 6 mg/kg/day IV/IM given in 2 to 3 divided doses. Higher doses may be required in infections due to more resistant organisms. The FDA-approved dose is 3 to 5 mg/kg/day IV/IM given in 3 to 4 divided doses and should not exceed 5 mg/kg/day unless serum concentrations are monitored. Treatment is recommended for 4 to 7 days.

    Infants, Children, and Adolescents

    3 to 7.5 mg/kg/day IV or IM divided every 8 hours per clinical practice guidelines. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses (2 to 2.5 mg/kg every 8 hours or 1.5 to 1.89 mg/kg/dose IV or IM every 6 hours). Treatment is recommended for 4 to 7 days.

    Premature infants 30 days and older and weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 8 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 7 days and younger; however, this dosing does not account for gestational age or birthweight.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Intravenous dosage (extended-interval dosing)†
    Adults

    5 to 7 mg/kg/dose IV. Dosing intervals are often determined using a nomogram and are frequently based on a random level drawn 8 to 12 hours after the first dose; dosing intervals of 24 hours, 36 hours, and in some cases, 48 to 72 hours, are used. Treatment is recommended for 4 to 7 days.

    Infants, Children, and Adolescents

    5 to 8 mg/kg/dose IV every 24 hours has been recommended. Treatment is recommended for 4 to 7 days.

    Premature infants 30 days and older weighing less than 1,200 g

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2,000 g

    4 to 5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 24 to 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing less than 1,200 g

    5 mg/kg/dose IV every 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing more than 2,000 g

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 36 to 48 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing less than 1,200 g

    4 to 5 mg/kg/dose IV every 48 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    For the treatment of bacteremia and sepsis.
    NOTE: Serum concentrations should be used to guide dosage adjustments. A 'dosing' weight should be used to calculate initial dosages in patients weighing more than their ideal body weight.
    Intravenous or Intramuscular dosage (conventional dosing)
    Adults

    3 mg/kg/day IV or IM given in 3 divided doses, while doses up to 5 mg/kg/day IV or IM in 3 to 4 divided doses may be required in life-threatening infections. Peak concentrations for these doses are expected to be approximately 4 to 6 mcg/mL. Adjust dosage based on serum concentration monitoring. Avoid peak concentrations more than 12 mcg/mL and trough concentrations more than 2 mcg/mL; use patient-specific information to guide the determination of adequate serum concentrations. Sepsis clinical practice guidelines suggest extended-interval dosing when possible. Start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Infants, Children, and Adolescents

    2.5 mg/kg/dose IV or IM every 8 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses (2 to 2.5 mg/kg every 8 hours or 1.5 to 1.89 mg/kg/dose IV or IM every 6 hours).

    Premature infants 30 days and older weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 8 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 8 to 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 8 to 29 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 to 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 6 to 7.5 mg/kg/day IV or IM given in 3 to 4 divided doses for neonates older than 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing more than 2,000 g

    2.5 mg/kg/dose IV or IM every 12 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    2.5 mg/kg/dose IV every 12 to 18 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Neonates 0 to 7 days weighing less than 1,200 g

    2.5 mg/kg/dose IV every 18 to 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA 34 weeks and younger: 2.5 mg/kg/dose IV every 18 hours or 3 mg/kg/dose IV every 24 hours; GA older than 34 weeks: 2.5 mg/kg/dose IV/IM every 12 hours. The FDA-approved dose is 4 mg/kg/day IV or IM given in 2 equal doses every 12 hours for premature or full-term neonates 0 to 7 days; however, this dosing does not account for gestational age or birthweight. In general, IM administration of drugs in very low birth weight premature neonates is not practical due to small muscle mass, and absorption is unreliable due to hemodynamic instability that is relatively common in this population.

    Intravenous dosage (extended-interval dosing)†
    Adults

    5 to 7 mg/kg/dose IV. Initial dosing intervals are often determined using a nomogram and are frequently based on a random concentration drawn 8 to 12 hours after the first dose; dosing intervals of 24 hours, 36 hours, and in some cases, 48 to 72 hours, are used. For sepsis, start within 1 hour of recognition as part of empiric multi-drug therapy. Duration of therapy is generally 7 to 10 days, but may be shorter or longer depending upon patient response, site of infection, and pathogen(s) isolated. Treatment may be narrowed with pathogen identification and/or adequate clinical response.

    Infants, Children, and Adolescents

    5 to 8 mg/kg/dose IV every 24 hours has been recommended.

    Premature infants 30 days and older weighing less than 1,200 g

    5 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing more than 2,000 g

    4 to 5 mg/kg/dose IV every 24 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 24 to 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 8 to 29 days weighing less than 1,200 g

    5 mg/kg/dose IV every 36 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing more than 2,000 g

    5 mg/kg/dose IV every 36 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing 1,200 to 2,000 g

    5 mg/kg/dose IV every 36 to 48 hours or 4 mg/kg/dose IV every 24 hours. In one gentamicin protocol (which could be extrapolated to tobramycin), the usual dose of 4 mg/kg/dose IV every 24 hours was extended to 4 mg/kg/dose IV every 48 hours if there was concurrent indomethacin. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    Neonates 0 to 7 days weighing less than 1,200 g

    4 to 5 mg/kg/dose IV every 48 hours. An alternative dosing regimen based on gestational age (GA) is also used which is as follows: GA younger than 32 weeks: 4 mg/kg/dose IV every 48 hours; GA 32 to 36 weeks: 4 mg/kg/dose IV every 36 hours; GA 37 weeks and older: 4 mg/kg/dose IV every 24 hours.

    For the treatment of infective endocarditis† due to Pseudomonas aeruginosa.
    NOTE: Serum tobramycin concentrations should be used to guide dosage adjustments. A 'dosing' weight should be used to calculate initial dosages in patients weighing more than their ideal body weight.
    Intravenous or Intramuscular dosage
    Adults

    8 mg/kg/day IV or IM in 1 dose is recommended by the American Heart Association (AHA) and the Infectious Diseases Society of America (IDSA).

    For the empiric treatment of febrile neutropenia†.
    For the treatment of febrile neutropenia in adults.
    Intravenous dosage (conventional dosing):
    Adults

    3 to 6 mg/kg/day IV given in 3 to 4 divided doses has been studied.

    For the treatment of febrile neutropenia in pediatric patients.
    Intravenous dosage (conventional dosing)
    Infants, Children, and Adolescents

    2 to 2.5 mg/kg/dose IV every 8 hours. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.

    Intravenous dosage (extended-interval dosing)
    Infants, Children, and Adolescents

    6 to 9 mg/kg/dose IV every 24 hours. In a pharmacokinetic analysis of a randomized controlled trial in pediatric patients with febrile neutropenia, age-specific initial doses of 10 mg/kg/dose IV (6 months to younger than 9 years), 8 mg/kg/dose IV (9 to 11 years), and 6 mg/kg/dose IV (12 years and older) given every 24 hours were recommended to achieve target serum tobramycin concentrations. Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.

    For surgical infection prophylaxis†.
    Intravenous or Intramuscular dosage
    Adults

    5 mg/kg IV or IM as a single preoperative dose as an alternative option as part of combination therapy for penicillin-allergic patients undergoing colorectal, gastroduodenal, biliary tract, or urologic procedures. Doses should be administered within 60 minutes prior to the surgical incision. No redosing is recommended; the duration of prophylaxis should be less than 24 hours for most procedures.

    Infants, Children, and Adolescents

    2.5 mg/kg IV or IM as a single preoperative dose as an alternative option as part of combination therapy for penicillin-allergic patients undergoing colorectal, gastroduodenal, biliary tract, or urologic procedures. Doses should be administered within 60 minutes prior to the surgical incision. No redosing is recommended; the duration of prophylaxis should be less than 24 hours for most procedures.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day oral powder for inhalation. Maximum dosage of ophthalmic ointment not established.

    Geriatric

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 7.5 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day oral powder for inhalation. Maximum dosage of ophthalmic ointment not established.

    Adolescents

    Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day oral powder for inhalation. Maximum dosage of ophthalmic ointment not established.

    Children

    6 to 12 years: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution; 600 mg/day nebulized solution for inhalation; 224 mg/day oral powder for inhalation. Maximum dosage of ophthalmic ointment not established.
    1 to 5 years: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution. Maximum dosage of ophthalmic ointment not established. The safety and efficacy of the nebulized or oral inhalation products have not been established.

    Infants

    2 to 12 months: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM; 48 drops/day ophthalmic solution. Maximum dosage of ophthalmic ointment not established. The safety and efficacy of the nebulized or oral inhalation products have not been established.
    1 month: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 10 mg/kg/day IV/IM. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.

    Neonates

    8 to 29 days: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 7.5 mg/kg/day IV/IM. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.
    0 to 7 days: Injectable aminoglycoside dosing is highly variable and dependent on several factors. The FDA-approved maximum is 4 mg/kg/day IV/IM. The safety and efficacy of the ophthalmic, nebulized, or oral inhalation products have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Tobramycin does not undergo hepatic metabolism. Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Conventional dosing:
    The manufacturer recommends either maintaining the standard dose and increasing the interval between doses or decreasing the dose while maintaining an every 8 hour dosing interval. To increase the dosing interval, the manufacturer recommends multiplying the patient's serum creatinine (mg/100 mL) by 6 to determine the dosing interval (i.e., serum creatinine of 2 mg/100 mL would yield a dosing interval of 12 hours). To decrease the dose, the manufacturer recommends dividing the patient's standard dose by the serum creatinine (mg/100 mL) to determine the lower recommended dose. For example, if a patient was receiving a standard dose of 60 mg IV every 8 hours and had a serum creatinine of 2 mg/100 mL, the dose would be adjusted to 30 mg IV every 8 hours. The manufacturer does suggest measuring serum concentrations and adjusting the dose accordingly. Additionally, the status of the renal function may change throughout the course of therapy. Several dosing regimens and nomograms designed to maintain traditional serum concentrations have been published in the literature for dosing in patients with renal impairment. However, these predictive dosage regimens and nomograms may result in serum concentrations outside the targeted range; therefore, doses should be adjusted based on patient-specific serum concentrations. Factors such as site of infection and organism susceptibility may alter the goals of therapy; thereby altering dosing in patients with renal impairment. The initial dosing interval should be individualized based on specific patient and disease-state characteristics, serum concentrations goals, site of infection, organism susceptibility, weight, age, and degree and stability of renal impairment (acute versus chronic). Further dosing should be guided by serum concentrations.
     
    Interval adjustment of extended-interval dosing of 5 or 7 mg/kg†:
    CrCl 60 mL/min or more: No dosage adjustment is needed. Adjust doses based on serum concentrations and organism MIC.
    CrCl 40 to 59 mL/min: 5 or 7 mg/kg IV every 36 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl 20 to 39 mL/min: 5 or 7 mg/kg IV every 48 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl less than 20 mL/min: 5 or 7 mg/kg IV once, then follow serial levels to determine time of next dose (serum concentration less than 1 mcg/mL). Adjust doses based on serum concentrations and organism MIC.
     
    Dose adjustment of extended dosing of 5 mg/kg†:
    CrCl 80 mL/min or more: No dosage adjustment is needed. Adjust doses based on serum concentrations and organism MIC.
    CrCl 60 to 79 mL/min: 4 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl 50 mL/min: 3.5 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl 40 mL/min: 2.5 mg/kg IV every 24 hours. Adjust doses based on serum concentrations and organism MIC.
    CrCl less than 30 mL/min: Use traditional dosing. Adjust doses based on serum concentrations and organism MIC.
     
    Intermittent hemodialysis
    For adult patients, administer half of the full dose after hemodialysis. For pediatric patients, give 2 mg/kg IV/IM after the initial hemodialysis session. Factors such as patient size, site of infection, and organism susceptibility should also be considered. Subsequent doses should be guided by serum tobramycin concentrations and organism MIC.
     
    Peritoneal dialysis
    Give 1.5 to 2 mg/kg/dose IV/IM as indicated by serum concentrations.
     
    Continuous renal replacement therapy (CRRT)
    For adult patients, administer the full dose every 24 to 48 hours as guided by serum tobramycin concentrations. For pediatric patients, give 2 to 2.5 mg/kg dose IV/IM every 12 to 24 hours as guided by serum tobramycin concentrations.

    ADMINISTRATION

    For storage information, see specific product information within the How Supplied section.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    1.2 g Bulk Powder Vials for Injection
    Reconstitution:
    Reconstitute with 30 ml of sterile water for injection to provide a solution containing 40 mg/ml.
    The bulk vial should be penetrated one time with a suitable sterile dispensing set that allows measured distribution of the contents. The entire contents of the bulk vial should be used during reconstitution.
    Once penetration of the bulk vial has occurred, completion of reconstitution should take place within 24 hours.
    FURTHER DILUTION IS REQUIRED.
    Storage after reconstitution: Reconstituted vials are stable under refrigeration (20—25 degrees C or 68—77 degrees F) for 96 hours or at room temperature for 24 hours.
     
    Dilution:
    Dilute in a compatible solution of 50—100 ml. A maximum concentration of 5 mg/ml has been suggested.
     
    Solution for Injection Vials Dilution:
    Dilute in a compatible solution of 50—100 ml. A maximum concentration of 5 mg/ml has been suggested.
     
    Solution for Injection Bulk vials Dilution:
    The bulk vial should be penetrated one time with a suitable sterile dispensing set that allows measured distribution of the contents. 
    The entire contents of the bulk vial should be used during reconstitution. Any unused portion must be discarded within 4 hours.
    Dilute with a compatible solution of 50—100 ml. A maximum concentration of 5 mg/ml has been suggested.
     
    Pre-mixed IV Solution Preparation:
    Check for leaks by squeezing bag firmly. Do not add supplementary medication.
    Adjustments may be made to pre-mixed containers to either add or remove contents to provide an appropriate dose.
    Do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete.
     
    Intravenous injection:
    Infuse doses over 20—60 minutes.

    Intramuscular Administration

    Do not use solutions prepared from commercially available bulk packages and pre-mixed solutions for IM administration.
    Withdraw appropriate dose directly from the vial for solution. No dilution necessary. Inject deeply into a large muscle mass. Aspirate prior to injection to avoid injection into a blood vessel.

    Inhalation Administration

    Nebulized solution for inhalation:
    The solution for nebulization is administered by inhalation only. Do not administer subcutaneously, intravenously, or via intrathecally.
    Do not dilute or mix with other medicines in the nebulizer.
    Wash hands thoroughly with soap and water.
     
    Administration of the nebulized solution for inhalation:
    Administer via inhalation while the patient is sitting or standing upright and breathing normally through the mouthpiece of the nebulizer. Nose clips may help the patient breath through the mouth.
    The dose should be inhaled over approximately 15 minutes, using a hand-held nebulizer as recommended by the specific product manufacturer. Full treatment dose has been administered when the mouthpiece makes a spitting noise for at least 1 minute and the nebulizer cup is empty.
     
     
    Powder for inhalation:
    Capsules are to be used with a Podhaler device and the contents of the capsules are for oral inhalation only. Do not swallow the capsules.
    Each Podhaler device is used for only one week (7 days). After 7 days, discard the used Podhaler device and its storage case. A new Podhaler device will be supplied and should be used with each weekly pack of capsules.
    A reserve Podhaler device is provided and should be used if the original device is wet, dirty, broken, has been dropped, or does not seem to be piercing the capsules properly.
    Capsules should remain stored in the blister cards until immediately prior to administration.
    Administer after other inhaled medications and/or chest physiotherapy.
     
    Administration of the powder for inhalation:
    Thoroughly wash and dry hands.
    Hold the base of the Podhaler device and unscrew lid counter-clockwise. Stand the device upright.
    Unscrew the mouthpiece in a counter-clockwise direction while holding the body of the Podhaler.
    Tear the blister card in half lengthwise along the pre-cut lines.
    Peel back the foil covering the first capsule. Only unfoil and remove one capsule at a time, immediately prior to use.
    Place one capsule in the capsule chamber at the top of the Podhaler device. Do not insert directly into the top of the mouthpiece.
    Reattach the mouthpiece and tighten in a clockwise direction; do not overtighten.
    While holding Podhaler device with mouthpiece pointed downwards, press the blue button all the way down with your thumb. Release blue button; do not press more than once
    With mouth away from the mouthpiece, exhale completely.
    Place mouth over the mouthpiece, close lips tightly, and inhale deeply with a single breath. Hold breath for about 5 seconds, then exhale normally away from Podhaler device.
    After a few normal breaths away from from the device, repeat the exhale/inhale process using the same capsule.
    After the second inhalation from the Podhaler device, unscrew the mouthpiece and remove the capsule from the capsule chamber.
    Inspect the used capsule. It should be pierced and empty; if so, throw the capsule away. If the capsule is pierced but more than just a fine coating of powder remains, put the capsule back into the capsule chamber with pierced side pointed down. Reattach the mouthpiece and repeat the exhale/inhale process. If the capsule is not pierced, reinsert into the capsule chamber, reattach mouthpiece, and repeat the exhale/inhale process. If the capsule is still not pierced, use the reserve Podhaler device.
    Once the contents of the first capsule has been successully inhaled, repeat the process 3 more times until all four capsules have been inhaled (total dose = 4 capsules).
    Once the full dose has been administered, reattach mouthpiece onto Podhaler device and wipe with a clean, dry cloth. Throw away all empty capsules; do not store capsules in the Podhaler device.

    Ophthalmic Administration

    Ointment or solution:
    Instruct patient on proper instillation of eye ointment and/or solution.
    Do not to touch the tip of the dropper to the eye, fingertips, or other surface.

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Reconstituted product may be stored for 96 hours under refrigeration or 24 hours at room temperature
    - Store unreconstituted product at 68 to 77 degrees F
    AK-Tob:
    - Store between 36 to 77 degrees F
    BETHKIS:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store unused product in foil pouch
    - Unrefrigerated product can be stored at temperatures not exceeding 77 degrees F for 28 days
    Kitabis Pak:
    - After opening the foil pouch, store unused product in the foil pouch to protect it from light
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Product may be stored in the opened foil pouch for up to 28 days at room temperature (68 to 77 degrees F)
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    Nebcin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Tobi:
    - After opening the foil pouch, store unused product in the foil pouch to protect it from light
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Product may be stored in the opened foil pouch for up to 28 days at room temperature (68 to 77 degrees F)
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    TOBI Podhaler:
    - Product should always be stored in the blister and only removed immediately before use
    - Protect from moisture
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F
    Tobrasol :
    - Store between 36 to 77 degrees F
    Tobrex:
    - Store between 36 to 77 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Prescribing tobramycin in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

    Dehydration, nephrotoxicity, renal disease, renal failure, renal impairment

    Patients receiving systemic or inhaled aminoglycosides, such as tobramycin, should be closely monitored for nephrotoxicity. Aminoglycosides are associated with major toxic effects on renal tubules. In patients with pre-existing renal impairment, renal failure, or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe nephrotoxic adverse reactions are sharply increased. Nephrotoxicity can manifest as decreased creatinine clearance, the presence of cells or casts, oliguria, proteinuria, decreased urine specific gravity, or evidence of increasing nitrogen retention (increasing BUN, NPN, or serum creatinine).  When monitoring serum concentrations, the manufacturer states that prolonged tobramycin peak concentrations above 12 mcg/mL should be avoided and trough concentrations above 2 mcg/mL should be avoided. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Renal function should be closely monitored. Evidence of nephrotoxicity requires dosage adjustment or discontinuance of therapy. Hemodialysis may aid in removal in the event of overdose or toxic reactions, especially if renal is or becomes impaired. In rare cases, nephrotoxicity may not be evident until soon after completion of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible. Avoid concurrent and/or sequential coadministration of aminoglycosides with other drugs that are potentially nephrotoxic and/or neurotoxic because toxicity may be additive. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity.

    Hearing impairment, neurotoxicity, ototoxicity, tinnitus

    Patients receiving systemic and inhaled aminoglycosides, such as tobramycin, should be closely monitored for neurotoxicity, including ototoxicity and hearing impairment. Aminoglycosides are associated with major toxic effects on the auditory and vestibular branches of the eighth nerve. Neurotoxicity is manifested by bilateral auditory toxicity which often is permanent and, sometimes, by vestibular ototoxicity. High-frequency hearing loss usually occurs before there is noticeable clinical hearing loss; clinical symptoms may not be present to warn of developing cochlear damage. Vertigo may occur and may indicate vestibular injury. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of hearing loss increases with the degree of exposure and continues to progress after stopping the drug. Use aminoglycosides with caution in patients with preexisting hearing impairment, especially eighth-cranial-nerve impairment. In patients with pre-existing renal impairment or renal disease or in those with normal renal function who receive high doses or prolonged therapy, the risks of severe ototoxic adverse reactions are sharply increased. When monitoring tobramycin serum concentrations during use of conventional dose regimens, the manufacturer states that prolonged tobramycin peak concentrations above 12 mcg/mL should be avoided and trough concentrations above 2 mcg/mL should be avoided. However, single-daily dosing schemes that produce higher peak serum concentrations have been used without additional toxicity noted. Eighth cranial nerve function should be closely monitored. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, or hearing loss) requires dosage adjustment or discontinuance of therapy. Aminoglycoside-induced ototoxicity is usually irreversible. Patients of advanced age and patients with dehydration are at increased risk of developing toxicity. In the event of toxicity in newborns, exchange transfusions may be considered. Aminoglycosides should not be given concomitantly with potent diuretics since certain diuretics by themselves may cause ototoxicity. Intravenous diuretics may also alter aminoglycoside concentrations in serum and tissue and thereby enhance aminoglycoside toxicity. Audiology tests are recommended.

    Aminoglycoside hypersensitivity

    Patients with aminoglycoside hypersensitivity should not receive tobramycin. Allergic reactions to aminoglycosides are generally uncommon, but hypersensitivity with one agent may demonstrate cross sensitivity with another aminoglycoside.

    Botulism, electrolyte imbalance, myasthenia gravis, neuromuscular disease, parkinsonism, respiratory depression, respiratory insufficiency

    Systemic aminoglycosides, such as tobramycin, are associated with neuromuscular blockade and may cause severe neuromuscular weakness lasting hours to days. Respiratory paralysis, respiratory insufficiency, or respiratory depression may occur when aminoglycosides are instilled after local irrigation and after topical application during surgical procedures. Neuromuscular blockade has also been reported with both oral and parenteral use of aminoglycosides. Clinicians should be aware of the possibility of neuromuscular blockade and respiratory paralysis if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular-blocking agents (e.g., tubocurarine, succinylcholine, decamethonium, or in patients receiving massive transfusions of citrate-anticoagulated blood). If neuromuscular blockade occurs, calcium salts may reduce these effects but mechanical respiratory assistance may be needed. Corrective therapy is required for any electrolyte imbalance, which may aggravate risk for neuromuscular/neurological symptoms. During or after aminoglycoside therapy, paresthesias, tetany, positive Chvostek and Trousseau signs, and mental confusion have been described in patients with hypomagnesemia, hypocalcemia, and hypokalemia. In infants, tetany and muscle weakness have been described. Aminoglycosides may aggravate muscle weakness in patients with neuromuscular disease such as myasthenia gravis, botulism, or parkinsonism.

    Colitis, diarrhea, GI disease, inflammatory bowel disease, pseudomembranous colitis, ulcerative colitis

    Almost all antibacterial agents have been associated with pseudomembranous colitis (antibiotic-associated colitis) which may range in severity from mild to life-threatening. In the colon, overgrowth of Clostridia may exist when normal flora is altered subsequent to antibacterial administration. The toxin produced by Clostridium difficile is a primary cause of pseudomembranous colitis. It is known that systemic use of antibiotics predisposes patients to development of pseudomembranous colitis. Consideration should be given to the diagnosis of pseudomembranous colitis in patients presenting with diarrhea following antibacterial administration. Systemic antibiotics should be prescribed with caution to patients with inflammatory bowel disease such as ulcerative colitis or other GI disease. If diarrhea develops during therapy, the drug should be discontinued. Following diagnosis of pseudomembranous colitis, therapeutic measures should be instituted. In milder cases, the colitis may respond to discontinuation of the offending agent. In moderate to severe cases, fluids and electrolytes, protein supplementation, and treatment with an antibacterial effective against Clostridium difficile may be warranted. Products inhibiting peristalsis are contraindicated in this clinical situation. Practitioners should be aware that antibiotic-associated colitis has been observed to occur over two months or more following discontinuation of systemic antibiotic therapy; a careful medical history should be taken.

    Acute bronchospasm, corneal abrasion

    Use of ophthalmic ointments, such as tobramycin ophthalmic ointment, may delay healing of corneal abrasion or lesions. Acute bronchospasm can occur with tobramycin inhalation products. Bronchospasm that occurs during the use of tobramycin inhalation solution should be treated as medically appropriate.

    Pregnancy

    Systemic exposure to tobramycin (e.g., injections, respiratory solutions for inhalation) and systemic exposure to other aminoglycosides may cause fetal harm during human pregnancy. Aminoglycosides cross the placenta. There have been reports of total irreversible bilateral congential deafness in newborns whose mothers received streptomycin, a related aminoglycoside, during pregnancy. Serious side effects to the mother, fetus, or newborn have not been reported with use of other aminoglycosides when used during pregnancy. If tobramycin injection is used during pregnancy or if the patient becomes pregnant during treatment with tobramycin, she should be apprised of the potential risk to the fetus. The risk with inhaled tobramycin is less well characterized. Tobramycin ophthalmic products may be used during pregnancy; reproduction studies in 3 types of animals at doses up to 33 times the normal human systemic dose have revealed no evidence of impaired fertility or harm to the fetus due to ophthalmic use of tobramycin. Because there have been no adequate studies investigating the safe use of ophthalmic tobramycin in pregnant women, it should only be used when the potential benefits to the mother outweigh possible risks to the fetus.

    Breast-feeding

    Aminoglycosides are generally excreted into human breast milk in low concentrations. Tobramycin breast milk concentrations after systemic administration are around 0.52 mcg/mL. Serum concentrations after nebulized tobramycin peak at approximately 1 mcg/mL. Because of the potential toxicity to nursing infants from inhaled and systemic tobramycin products, many of the manufacturers recommend that a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. However, aminoglycosides are poorly absorbed from the gastrointestinal tract and are not likely to cause adverse events in nursing infants; thus ophthalmic, topical, systemic, and inhaled aminoglycosides are generally considered compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Neonates, premature neonates

    Use tobramycin with caution in neonates and premature neonates due to renal immaturity and the prolongation of serum half-life of the drug, which increases the risk of aminoglycoside-induced toxicity. When tobramycin is used in the neonatal population, careful monitoring is warranted for signs and symptoms of toxicity including auditory, vestibular, and renal toxicity and neuromuscular blockade.

    Geriatric

    Geriatric patients may be at increased risk of tobramycin neurotoxicity and nephrotoxicity. Elderly patients may have decreased renal function; therefore, care should be taken in dose selection and tobramycin monitoring when using systemic or inhaled tobramycin therapy. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, use of parenteral tobramycin must be accompanied by monitoring of renal function tests, including a baseline value, and serum tobramycin concentrations, with the exception of single dose prophylactic administration. Serious consequences may occur insidiously if adequate monitoring does not occur; the drug may cause or worsen hearing loss and renal failure. Use of antibiotics should be limited to confirmed or suspected bacterial infections. Antibiotics are non-selective and may result in the eradication of beneficial microorganisms while promoting the emergence of undesired ones, causing secondary infections such as oral thrush, colitis, or vaginitis. Any antibiotic may cause diarrhea, nausea, vomiting, anorexia, and hypersensitivity reactions.

    ADVERSE REACTIONS

    Severe

    bronchospasm / Rapid / 0.5-5.0
    exfoliative dermatitis / Delayed / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    toxic epidermal necrolysis / Delayed / 0-1.0
    erythema multiforme / Delayed / 0-1.0
    hyposthenuria / Delayed / Incidence not known
    renal tubular acidosis (RTA) / Delayed / Incidence not known
    proteinuria / Delayed / Incidence not known
    renal tubular necrosis / Delayed / Incidence not known
    azotemia / Delayed / Incidence not known
    hearing loss / Delayed / Incidence not known
    seizures / Delayed / Incidence not known
    aphonia / Delayed / Incidence not known

    Moderate

    dyspnea / Early / 12.4-33.7
    chest pain (unspecified) / Early / 4.5-26.0
    hemoptysis / Delayed / 12.4-19.4
    dysphonia / Delayed / 3.8-13.6
    wheezing / Rapid / 5.0-6.8
    erythema / Early / 0-3.0
    eosinophilia / Delayed / 2.0-2.0
    pyuria / Delayed / Incidence not known
    ataxia / Delayed / Incidence not known
    myasthenia / Delayed / Incidence not known
    superinfection / Delayed / Incidence not known
    pseudomembranous colitis / Delayed / Incidence not known
    leukopenia / Delayed / Incidence not known
    anemia / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    impaired wound healing / Delayed / Incidence not known
    confusion / Early / Incidence not known
    hyponatremia / Delayed / Incidence not known
    hypokalemia / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known
    hyperbilirubinemia / Delayed / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known

    Mild

    cough / Delayed / 10.0-46.1
    pharyngitis / Delayed / 38.0-38.0
    asthenia / Delayed / 35.7-35.7
    rhinitis / Early / 34.5-34.5
    fever / Early / 12.4-32.9
    headache / Early / 11.4-26.7
    anorexia / Delayed / 18.6-18.6
    vomiting / Early / 5.7-14.0
    abdominal pain / Early / 12.8-12.8
    nausea / Early / 7.5-11.2
    weight loss / Delayed / 10.1-10.1
    sinusitis / Delayed / 8.1-8.1
    nasal congestion / Early / 7.2-8.1
    otalgia / Early / 7.4-7.4
    back pain / Delayed / 7.0-7.0
    epistaxis / Delayed / 1.9-7.0
    dysgeusia / Early / 0.5-6.6
    diarrhea / Early / 1.9-6.2
    malaise / Early / 6.2-6.2
    dizziness / Early / 5.8-5.8
    rash (unspecified) / Early / 2.3-5.4
    hyperventilation / Early / 5.4-5.4
    myalgia / Early / 4.7-4.7
    throat irritation / Early / 1.9-4.5
    laryngitis / Delayed / 4.3-4.3
    tinnitus / Delayed / 3.1-3.1
    ocular irritation / Rapid / 0-3.0
    ocular pruritus / Rapid / 0-3.0
    cylindruria / Delayed / Incidence not known
    vertigo / Early / Incidence not known
    weakness / Early / Incidence not known
    injection site reaction / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    urticaria / Rapid / Incidence not known
    leukocytosis / Delayed / Incidence not known
    lethargy / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acetaminophen; Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Acyclovir: (Major) Additive nephrotoxicity is possible if systemic aminoglycosides are used with acyclovir. Carefully monitor renal function during concomitant therapy.
    Adefovir: (Moderate) Chronic coadministration of adefovir with nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity, even in patients who have normal renal function.
    Aldesleukin, IL-2: (Moderate) Aldesleukin, IL 2 may cause nephrotoxicity. Concurrent administration of drugs possessing nephrotoxic effects, such as the aminoglycosides, with Aldesleukin, IL 2 may increase the risk of kidney dysfunction. In addition, reduced kidney function secondary to Aldesleukin, IL 2 treatment may delay elimination of concomitant medications and increase the risk of adverse events from those drugs.
    Aminosalicylate sodium, Aminosalicylic acid: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Amobarbital: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving tobramycin.
    Amphotericin B cholesteryl sulfate complex (ABCD): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tobramycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B lipid complex (ABLC): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tobramycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B liposomal (LAmB): (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tobramycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Amphotericin B: (Major) Additive nephrotoxicity can occur if amphotericin B is given concomitantly with tobramycin. Intensive monitoring of renal function is recommended. Amphotericin B dosage reduction may be necessary if renal impairment occurs.
    Aprotinin: (Moderate) The manufacturer recommends using aprotinin cautiously in patients that are receiving drugs that can affect renal function, such as the aminoglycosides, as the risk of renal impairment may be increased.
    Aspirin, ASA: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Carisoprodol: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Dipyridamole: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Omeprazole: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Oxycodone: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Aspirin, ASA; Pravastatin: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Atracurium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Atropine; Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Minor) Antiemetics, like scopolamine, should be used carefully with amikacin because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Azelastine; Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bacitracin: (Minor) Additive nephrotoxicity may occur with concurrent use of bacitracin and other nephrotoxic agents. When possible, avoid concomitant administration of systemic bacitracin and other nephrotoxic drugs such as aminoglycosides (particularly kanamycin, streptomycin, and neomycin).Use of topically administrated preparations containing bacitracin, especially when applied to large surface areas, with aminoglycosides may have additive nephrotoxic potential.
    Beclomethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Betamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bismuth Subsalicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Bleomycin: (Moderate) Previous treatment with nephrotoxic agents, like aminoglycosides, may result in decreased clearance of bleomycin if renal function has been impaired.
    Botulinum Toxins: (Moderate) The effects of botulinum toxin can be potentiated by systemic aminoglycosides or other drugs that interfere with neuromuscular transmission. Monitor aminoglycoside concentrations, and monitor for evidence of neurotoxicity including systemic neuromuscular blockade.
    Budesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Budesonide; Formoterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Bumetanide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Capreomycin: (Major) The concomitant use of capreomycin and aminoglycosides may increase the risk of nephrotoxicity and neurotoxicity. Since capreomycin is eliminated by the kidney, coadministration of capreomycin with other potentially nephrotoxic drugs, including aminoglycosides may increase serum concentrations of either capreomycin or aminoglycosides. Theoretically, coadministration may increase the risk of developing nephrotoxicity, even in patients who have normal renal function. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with capreomycin resulting from administration of large doses or rapid intravenous infusion. Aminoglycosides have also been reported to interfere with nerve transmission at the neuromuscular junction. Concomitant administration of capreomycin with aminoglycosides should be avoided if possible; however, if they must be coadministered, use extreme caution.
    Carbetapentane; Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Carboplatin: (Moderate) Patients previously or currently treated with other potentially nephrotoxic agents, such as systemic aminoglycosides, can have a greater risk of developing carboplatin-induced nephrotoxicity. These patients may benefit from hydration prior to carboplatin therapy to lessen the incidence of nephrotoxicity. Monitor renal function closely.
    Cefepime: (Minor) Cefepime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotaxime: (Minor) Cefotaxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefotetan: (Minor) Cefotetan's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefoxitin: (Minor) Cefoxitin's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefprozil: (Minor) Cefprozil's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftazidime; Avibactam: (Minor) Ceftazidime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Ceftizoxime: (Minor) Ceftizoxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Cefuroxime: (Minor) Cefuroxime's product label states that cephalosporins may potentiate the adverse renal effects of nephrotoxic agents, such as aminoglycosides and loop diuretics. Carefully monitor renal function, especially during prolonged therapy or use of high aminoglycoside doses. The majority of reported cases involve the combination of aminoglycosides and cephalothin or cephaloridine, which are associated with dose-related nephrotoxicity as singular agents. Limited but conflicting data with other cephalosporins have been noted.
    Chlorpheniramine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Codeine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Phenylephrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpheniramine; Pseudoephedrine: (Minor) Chlorpheniramine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Chlorpromazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Choline Salicylate; Magnesium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Ciclesonide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cidofovir: (Severe) The administration of cidofovir with other potentially nephrotoxic agents, such as aminoglycosides, is contraindicated. These agents should be discontinued at least 7 days prior to beginning cidofovir.
    Cisatracurium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Cisplatin: (Major) Aminoglycosides should be used cautiously in patients receiving cisplatin. Aminoglycosides can aggravate the nephrotoxicity and electrolyte loss seen with cisplatin if given concurrently or shortly after cisplatin therapy. Concurrent use of cisplatin and other nephrotoxic agents also known to be ototoxic (i.e., aminoglycosides) may increase the risk of cisplatin-induced ototoxicity.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Codeine; Phenylephrine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Codeine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Corticosteroids: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Corticotropin, ACTH: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Cyclizine: (Minor) Cyclizine may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Cyclosporine: (Major) Additive nephrotoxicity can occur if cyclosporine is administered with other nephrotoxic drugs such as aminoglycosides.
    Daptomycin: (Moderate) The pharmacokinetics of daptomycin and tobramycin may be altered when the two antibiotics are coadministered. The serum concentration of daptomycin may be increased and the serum concentration of tobramycin may be decreased. The manufacturer recommends caution when daptomycin is coadministered with tobramycin.
    Deferasirox: (Moderate) Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and aminoglycosides concomitantly.
    Deflazacort: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Dexamethasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Dextromethorphan; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Dimenhydrinate: (Minor) Dimenhydrinate and other antiemetics should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity, including nausea secondary to vertigo.
    Diphenhydramine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Ibuprofen: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Naproxen: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Diphenhydramine; Phenylephrine: (Minor) Diphenhydramine may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Doxacurium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Efavirenz; Emtricitabine; Tenofovir: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Emtricitabine; Tenofovir disoproxil fumarate: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Entecavir: (Moderate) Because entecavir is primarily eliminated by the kidneys and aminoglycosides can affect renal function, concurrent administration with aminoglycosides may increase the serum concentrations of entecavir and adverse events. The manufacturer of entecavir recommends monitoring for adverse effects when these drugs are coadministered.
    Ethacrynic Acid: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Fludrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Flunisolide: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluphenazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by aminoglycosides.
    Fluticasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Salmeterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Fluticasone; Vilanterol: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Formoterol; Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Foscarnet: (Major) The risk of renal toxicity may be increased if foscarnet is used in conjunction with other nephrotoxic agents such as aminoglycosides.
    Furosemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Gallium Ga 68 Dotatate: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including intravenous mannitol. In addition, intravenous mannitol may alter the serum and tissue concentrations of tobramycin, thereby, increasing the risk for aminoglycoside toxicities. If possible, avoid concurrent use. If these drugs must be used together, it would be prudent to monitor renal function, serum electrolytes, and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates). Studies to evaluate a potential interaction between inhaled formulations of mannitol and tobramycin have not been conducted.
    Gallium: (Severe) Concurrent use of gallium nitrate with other potentially nephrotoxic drugs, such as aminoglycosides, may increase the risk for developing severe renal insufficiency. If use of an aminoglycoside is indicated, gallium nitrate administration should be discontinued, and hydration for several days after administration of the aminoglycoside is recommended. Serum creatinine concentrations and urine output should be closely monitored during and subsequent to this period. Gallium nitrate should be discontinued if the serum creatinine concentration exceeds 2.5 mg/dl.
    Ganciclovir: (Major) Concurrent use of nephrotoxic agents, such as the aminoglycosides, with ganciclovir should be done cautiously to avoid additive nephrotoxicity.
    General anesthetics: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving tobramycin.
    Ginger, Zingiber officinale: (Minor) Ginger may mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by aminoglycosides. Antiemetics block the histamine or acetylcholine response that causes nausea due to vestibular emetic stimuli such as motion.
    Gold: (Minor) Both aminoglycosides and gold compounds can cause nephrotoxicity. Auranofin has been reported to cause a nephrotic syndrome or glomerulonephritis with proteinuria and hematuria. Monitor renal function carefully during concurrent therapy.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
    Hydrocortisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Ibandronate: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Ibuprofen lysine: (Moderate) Use caution in combining ibuprofen lysine with renally eliminated medications, like aminoglycosides, as ibuprofen lysine may reduce the clearance of aminoglycosides. Closely monitor renal function and adjust aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
    Ifosfamide: (Moderate) Nephrotoxic agents, such as the aminoglycosides, can increase the nephrotoxicity of ifosfamide. Damaged kidney tubules may be less likely to convert mesna to its active kidney protecting form, which may contribute to the potential for increased ifosfamide toxicity. Clinicians should be alert for an increased risk of ifosfamide toxicity, including neurotoxicity, renal toxicity, and bone marrow suppression.
    Immune Globulin IV, IVIG, IGIV: (Moderate) Immune globulin (IG) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients receiving known nephrotoxic drugs like aminoglycosides. Coadminister IG products at the minimum concentration available and the minimum rate of infusion practicable. Closely monitor renal function.
    Iohexol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iopamidol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Iopromide: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Ioversol: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Isosulfan Blue: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Lithium: (Moderate) Moderate to significant dietary sodium changes, or changes in sodium and fluid intake, may affect lithium excretion. Systemic sodium chloride administration may result in increased lithium excretion and therefore, decreased serum lithium concentrations. In addition, high fluid intake may increase lithium excretion. For patients receiving sodium-containing intravenous fluids, symptom control and lithium concentrations should be carefully monitored. It is recommended that patients taking lithium maintain consistent dietary sodium consumption and adequate fluid intake during the initial stabilization period and throughout lithium treatment. Supplemental oral sodium and fluid should be only be administered under careful medical supervision.
    Magnesium Salicylate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Mannitol: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including intravenous mannitol. In addition, intravenous mannitol may alter the serum and tissue concentrations of tobramycin, thereby, increasing the risk for aminoglycoside toxicities. If possible, avoid concurrent use. If these drugs must be used together, it would be prudent to monitor renal function, serum electrolytes, and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates). Studies to evaluate a potential interaction between inhaled formulations of mannitol and tobramycin have not been conducted.
    Meclizine: (Minor) Meclizine and other antiemetics should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo).
    Meperidine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Mesoridazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms (e.g. dizziness, tinnitus, or vertigo) that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Methohexital: (Moderate) Patients receiving general anesthetics should be observed for exaggerated effects if they are receiving tobramycin.
    Methylprednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Mivacurium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Mometasone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Mycophenolate: (Minor) Drugs that alter the gastrointestinal flora may interact with mycophenolate by disrupting enterohepatic recirculation. Tobramycin may decrease normal GI flora levels and thus lead to less free mycophenolate available for absorption.
    Neuromuscular blockers: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Non-Ionic Contrast Media: (Moderate) Because the use of other nephrotoxic drugs, such as aminoglycoside antibiotics, is an additive risk factor for nephrotoxicity in patients receiving radiopaque contrast agents, concomitant use should be avoided when possible.
    Nonsteroidal antiinflammatory drugs: (Moderate) It is possible that additive nephrotoxicity may occur in patients who receive nonsteroidal anti-inflammatory drugs (NSAIDs) concurrently with other nephrotoxic agents, such as tobramycin.
    Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
    Pamidronate: (Moderate) Coadministration of pamidronate with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity following pamidronate administration, even in patients who have normal renal function.
    Pancuronium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Pentamidine: (Major) Additive nephrotoxicity may be seen with the combination of pentamidine and other agents that cause nephrotoxicity, such as systemic aminoglycosides. Renal function and aminoglycoside concentratons should be closely monitored.
    Perphenazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Perphenazine; Amitriptyline: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Phenylephrine; Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Polymyxin B: (Major) The concomitant use of systemic Polymyxin B with systemic aminoglycosides increases the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. Monitor patients for changes in renal function if these drugs are coadministered. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
    Polymyxins: (Major) The concomitant use of colistimethate sodium with systemic aminoglycosides may increase the risk of nephrotoxicity, ototoxicity, and neurotoxicity. Since polymyxins and aminoglycosides are both eliminated by the kidney, coadministration may increase serum concentrations of either drug class. If these drugs are used in combination, monitor renal function and patients for increased adverse effects. Additionally, neuromuscular blockade has been associated with both polymyxins and aminoglycosides, and is more likely to occur in patients with renal dysfunction.
    Prednisolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Prednisone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Promethazine: (Minor) Antiemetics, like promethazine, should be used carefully with aminoglycosides because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Pyridostigmine: (Moderate) Aminoglycosides have been associated with neuromuscular blockade when used as an abdominal irrigant intraoperatively. Although the risk of neuromuscular blockade is remote with parenteral aminoglycoside therapy, these antibiotics should be used cautiously in myasthenic patients. This represents a pharmacodynamic interaction with cholinesterase inhibitors when used to treat myasthenia gravis, rather than a pharmacokinetic interaction.
    Rapacuronium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Rocuronium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Salicylates: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Salsalate: (Minor) Due to the inhibition of renal prostaglandins by salicylates, concurrent use of salicylates and other nephrotoxic agents like the aminoglycosides may lead to additive nephrotoxicity.
    Scopolamine: (Minor) Antiemetics, like scopolamine, should be used carefully with amikacin because they can mask symptoms of ototoxicity (e.g., nausea secondary to vertigo). These agents block the histamine or acetylcholine response that causes nausea due to vestibular (inner ear) emetic stimuli such as motion.
    Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
    Streptozocin: (Moderate) Because streptozocin is nephrotoxic, concurrent or subsequent administration of other nephrotoxic agents, including aminoglycosides, could exacerbate the renal insult.
    Succinylcholine: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Surfactants: (Major) Some surfactant anti infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant.
    Tacrolimus: (Moderate) Additive nephrotoxicity is possible if aminoglycosides are used with tacrolimus. Care should be taken in using tacrolimus with other nephrotoxic drugs. Assessment of renal function in patients who have received tacrolimus is recommended, as the tacrolimus dosage may need to be reduced
    Telavancin: (Major) Concurrent or sequential use of telavancin with other potentially nephrotoxic drugs (e.g., systemic aminoglycosides) may lead to additive nephrotoxicity. Televancin is closely related to vancomycin. In one clinical study, vancomycin coadministration, high aminoglycoside trough levels, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Closely monitor renal function and adjust telavancin doses based on creatinine clearance/renal function, and aminoglycoside doses based on renal function and serum aminoglycoside concentrations as clinically indicated.
    Tenofovir Alafenamide: (Moderate) Tenofovir-containing products, should be avoided with concurrent or recent use of a nephrotoxic agent, such as aminoglycosides. Tenofovir is primarily excreted via the kidneys by a combination of glomerular filtration and active tubular secretion. Coadministration of tenofovir alafenamide with drugs that are eliminated by active tubular secretion may increase concentrations of tenofovir, and/or the co-administered drug. Drugs that decrease renal function may also increase concentrations of tenofovir. Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Monitor patients receiving concomitant nephrotoxic agents for changes in serum creatinine and phosphorus, and urine glucose and protein.
    Tenofovir, PMPA: (Moderate) Renal impairment, which may include hypophosphatemia, has been reported with the use of tenofovir with a majority of the cases occurring in patients who have underlying systemic or renal disease or who are concurrently taking nephrotoxic agents. Tenofovir should be avoided with concurrent or recent use of a nephrotoxic agent; patients receiving concomitant nephrotoxic agents should be carefully monitored for changes in serum creatinine and phosphorus.
    Thioridazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may effectively mask vestibular symptoms that are associated with ototoxicity induced by various medications, including the aminoglycosides.
    Tolvaptan: (Moderate) Coadministration of tolvaptan and hypertonic saline (e.g., 3% NaCl injection solution) is not recommended. The use of hypertonic sodium chloride in combination with tolvaptan may result in a too rapid correction of hyponatremia and increase the risk of osmotic demyelination (i.e., central pontine myelinolysis).
    Torsemide: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including loop diuretics. If loop diuretics and aminoglycosides are used together, it would be prudent to monitor renal function parameters, serum electrolytes, and serum aminoglycoside concentrations during therapy. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Triamcinolone: (Moderate) Concomitant use of systemic sodium chloride, especially at high doses, and corticosteroids may result in sodium and fluid retention. Assess sodium chloride intake from all sources, including intake from sodium-containing intravenous fluids and antibiotic admixtures. Carefully monitor sodium concentrations and fluid status if sodium-containing drugs and corticosteroids must be used together.
    Trifluoperazine: (Minor) When used for the treatment of nausea and vomiting, antiemetic phenothiazines may mask symptoms that are associated with ototoxicity induced by the aminoglycosides.
    Trimethobenzamide: (Minor) Because of trimethobenzamide's antiemetic pharmacology, the drug may effectively mask dizziness, tinnitus, or vertigo that are associated with ototoxicity induced by various medications, including the aminoglycosides. Clinicians should be aware of this potential interaction and take it into consideration when monitoring for aminoglycoside-induced side effects.
    Tubocurarine: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Urea: (Moderate) The risk of ototoxicity or nephrotoxicity secondary to aminoglycosides may be increased by the addition of concomitant therapies with similar side effects, including urea. In addition, urea may alter the serum and tissue concentrations of tobramycin, thereby, increasing the risk for aminoglycoside toxicities. If possible, avoid concurrent use. If these drugs must be used together, it would be prudent to monitor renal function, serum electrolytes, and serum aminoglycoside concentrations. Audiologic monitoring may be advisable during high dose therapy or therapy of long duration, when hearing loss is suspected, or in selected risk groups (e.g., neonates).
    Valganciclovir: (Major) Concurrent use of nephrotoxic agents, such as aminoglycosides, with valganciclovir should be done cautiously to avoid additive nephrotoxicity.
    Vancomycin: (Major) Concomitant use of parenteral vancomycin with other nephrotoxic drugs, such as aminoglycosides, can lead to additive nephrotoxicity. Both vancomycin and aminoglycosides may cause ototoxicity as well. In a clinical study, vancomycin coadministration, high aminoglycoside trough concentrations, and heart failure independently predicted acute kidney injury during aminoglycoside treatment. Renal function should be monitored closely, and vancomycin and aminoglycoside doses should be adjusted according to serum concentrations as clinically indicated.
    Vecuronium: (Moderate) Aminoglycosides traditionally have been associated with neuromuscular blockade, but this event is most likely to occur when aminoglycoside solutions are used to irrigate wounds intraoperatively. Neuromuscular blockers should be used cautiously in patients receiving aminoglycosides.
    Warfarin: (Moderate) The concomitant use of warfarin with many classes of antibiotics, including aminoglycosides, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary.
    Zalcitabine, ddC: (Moderate) Drugs such as parenteral aminoglycosides may increase the risk of developing peripheral neuropathy or other zalcitabine-associated adverse events by interfering with the renal clearance of zalcitabine and thereby raising systemic drug exposure. Coadministration of these drugs with zalcitabine requires frequent clinical and laboratory monitoring, with dosage adjustment for any significant change in renal function.
    Zoledronic Acid: (Moderate) Since zoledronic acid is eliminated by the kidney, coadministration of zoledronic acid with other potentially nephrotoxic drugs may increase serum concentrations of either zoledronic acid and/or these coadministered drugs. Theoretically, the chronic coadministration of zoledronic acid with other nephrotoxic drugs, such as aminoglycosides, may increase the risk of developing nephrotoxicity.

    PREGNANCY AND LACTATION

    Pregnancy

    Systemic exposure to tobramycin (e.g., injections, respiratory solutions for inhalation) and systemic exposure to other aminoglycosides may cause fetal harm during human pregnancy. Aminoglycosides cross the placenta. There have been reports of total irreversible bilateral congential deafness in newborns whose mothers received streptomycin, a related aminoglycoside, during pregnancy. Serious side effects to the mother, fetus, or newborn have not been reported with use of other aminoglycosides when used during pregnancy. If tobramycin injection is used during pregnancy or if the patient becomes pregnant during treatment with tobramycin, she should be apprised of the potential risk to the fetus. The risk with inhaled tobramycin is less well characterized. Tobramycin ophthalmic products may be used during pregnancy; reproduction studies in 3 types of animals at doses up to 33 times the normal human systemic dose have revealed no evidence of impaired fertility or harm to the fetus due to ophthalmic use of tobramycin. Because there have been no adequate studies investigating the safe use of ophthalmic tobramycin in pregnant women, it should only be used when the potential benefits to the mother outweigh possible risks to the fetus.

    Aminoglycosides are generally excreted into human breast milk in low concentrations. Tobramycin breast milk concentrations after systemic administration are around 0.52 mcg/mL. Serum concentrations after nebulized tobramycin peak at approximately 1 mcg/mL. Because of the potential toxicity to nursing infants from inhaled and systemic tobramycin products, many of the manufacturers recommend that a decision be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. However, aminoglycosides are poorly absorbed from the gastrointestinal tract and are not likely to cause adverse events in nursing infants; thus ophthalmic, topical, systemic, and inhaled aminoglycosides are generally considered compatible with breast-feeding. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Tobramycin is bactericidal in action. Similar to other aminoglycosides, it works by inhibiting bacterial protein synthesis through irreversible binding to the 30 S ribosomal subunit of susceptible bacteria. Tobramycin is actively transported into the bacterial cell where it binds to receptors present on the 30 S ribosomal subunit. This binding interferes with messenger RNA (mRNA). As a result, abnormal, nonfunctional proteins are formed due to misreading of the bacterial DNA. Eventually, susceptible bacteria die because of the lack of functional proteins. One aspect essential to aminoglycoside lethality is the need to achieve intracellular concentrations in excess of extracellular. Anaerobic bacteria are not susceptible to aminoglycosides due, at least in part, to a lack of an active transport mechanism for aminoglycoside uptake. The uptake of aminoglycosides may be facilitated by the presence of inhibitors of the bacterial cell wall (i.e. beta-lactams, vancomycin).
     
    Against gram-negative aerobic rods, aminoglycosides exhibit 'concentration-dependent killing' and a 'post-antibiotic effect' (PAE). 'Concentration-dependent killing' describes the principle that bactericidal effects increase as the concentration increases. PAE is where suppression of bacterial growth continues after the antibiotic concentration falls below the bacterial MIC. The PAE can be bacteria specific, as well as drug specific. The PAE of aminoglycosides is short for most gram-positive organisms (< 2 hours) and longer for gram-negative organisms (2—8 hours), such as E. coli, K. pneumoniae, and Ps. aeruginosa. Both of these phenomena are being exploited in designing dosage regimens that employ higher doses administered at longer intervals. The major pharmacodynamic parameter that determines efficacy of aminoglycosides is the serum peak concentration to MIC ratio (peak:MIC). Both time-kill studies as well as studies in humans have shown that a peak:MIC of > 8—12:1 is associated with successful regimens.
     
    The mechanism of renal toxicity with aminoglycosides is associated with accumulation in the renal tubule, which is a saturable process. Elevated serum trough concentrations are associated with an increased risk of toxicity.
     
    The mechanism of ototoxicity relates to the aminoglycoside-induced destruction of sensory hair cells of the inner ear. The cochlear sensory cells that are most vulnerable are in the basal end, thereby leading to high-frequency hearing loss first. As ototoxicity ascends toward the apex of the cochlea, the lower frequencies are affected. Sensory cells that deal with vestibular function may also be affected. Aminoglycosides may cause free-radical damage to sensory cells and neurons. Biochemically, they may bind to polyphospoinositides, which are part of the transmembrane signaling system mediating physiological effects of hormones, neurotransmitters, and neuromodulators which may interfere with essential mechanisms of cell physiology. Neural destruction without any cochlear hair cell damage has also been described. There may also be a genetic mitochondrial RNA mutation that may predispose some patients to aminoglycoside ototoxicity. Aminoglycosides enter the inner ear rapidly, but it is suggested that concentrations do not correlate with the development of ototoxicity. Likely, aminoglycoside concentrations in the inner ear dissipate slowly, which is consistent with the possibility of developing ototoxicity days to weeks after drug discontinuation.
     
    For gram-negative organisms and Staphylococcus aureus the Clinical and Laboratory Standards Institute (CLSI) defines MICs of <= 4 mcg/ml as susceptible, 8 mcg/ml as intermediate, and >= 16 mcg/ml as resistant for gentamicin.
     
    Aminoglycoside resistance is well documented. There are a variety of resistance mechanisms employed by different pathogens. Enzymatic inhibition by gram-negative pathogens and Enterococcus sp. via aminoglycoside-modifying enzymes is achieved by modification of the aminoglycoside as it is transported across the cytoplasmic membrane. Alterations in the inner membrane porin channels by Pseudomonas aeruginosa decrease antimicrobial penetration to the site of activity within the bacterial cell. Some gram-negative organisms and Enterococcus sp. can alter the ribosomal target sites of the aminoglycosides to decrease binding, thereby decreasing antimicrobial activity.

    PHARMACOKINETICS

    Tobramycin is administered intravenously, by oral inhalation, and by ophthalmic administration. Tobramycin is not absorbed orally, and serum concentrations are unpredictable after IM injection. Since penetration into the CNS is poor, tobramycin also has been given intrathecally or intraventricularly in conjunction with parenteral therapy for treating CNS infections. Tobramycin distributes into extracellular fluid; the volume of distribution is approximately 0.25—0.3 L/kg. However, critically-ill patients, and patients with burns, ascites, or heart failure usually have larger volumes of distribution, often in the range of 0.3—0.4 L/kg. Protein binding of tobramycin is negligible.
     
    Tobramycin is not metabolized. Elimination is almost exclusively via glomerular filtration. Thus, elimination half-life varies according to renal function. In adults with normal renal function, the plasma elimination half-life of injectable tobramycin is about 2—3 hours; elimination half-lives for the inhaled formulations are approximately 3 hours for TOBI Podhaler and 4.4 hours for Bethkis.

    Intravenous Route

    Peak serum concentrations following an intravenous infusion of tobramycin are proportional to the dose; a peak serum concentration of 6—8 mcg/ml is usually achieved with an intravenous dose of 2 mg/kg infused over 30 minutes.

    Inhalation Route

    Tobramycin administered via inhalation concentrates primarily in the airways, with bioavailability varying based on airway pathology and nebulizer performance.
    Solution for inhalation:  The average tobramycin concentration in sputum is 1237 mcg/g (range: 35—7414 mcg/g) after 10 minutes and 814 mcg/g (range: 23—2843 mcg/g) after 30 minutes. Tobramycin does not accumulate in sputum with repeated dosing. The mean serum tobramycin concentration one hour after inhalation of a single 300 mg dose by cystic fibrosis patients is 0.95 mcg/ml (range: 0.06-1.89 mcg/ml); after repeated dosing for 20 weeks, the average serum concentration is 1.05 mcg/ml.
    Powder for inhalation: Following a single 112 mg dose in cystic fibrosis patients, the mean sputum tobramycin concentration is 1048 +/- 1080 mcg/g. A mean peak serum concentration of 1.02 +/- 0.53 mcg/ml is achieved approximately 1 hour post-dose, which is comparable to concentrations observed with a 300 mg dose of TOBI. Systemic exposure is also comparable to the 300 mg TOBI dose (4.6 +/- 2.0 mcg x hr/ml vs. 4.8 +/- 2.5 mcg x hr/ml). After a 28 day dosing cycle, peak serum concentrations range from 1.48 +/- 0.69 mcg/ml to 1.99 +/- 0.59 mcg/ml.

    Other Route(s)

    Ophthalmic Route
    The pharmacokinetics of tobramycin after ophthalmic administration are not well known.