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WARNINGS
Patients treated with Tobramycin Injection and other aminoglycosides should be under close clinical observation, because these drugs have an inherent potential for causing ototoxicity and nephrotoxicity.
Neurotoxicity, manifested as both auditory and vestibular ototoxicity, can occur. The auditory changes are irreversible, are usually bilateral, and may be partial or total. Eighth-nerve impairment and nephrotoxicity may develop, primarily in patients having pre-existing renal damage and in those with normal renal function to whom aminoglycosides are administered for longer periods or in higher doses than those recommended. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of aminoglycoside-induced hearing loss increases with the degree of exposure to either high peak or high trough serum concentrations. Patients who develop cochlear damage may not have symptoms during therapy to warn them of eighth-nerve toxicity, and partial or total irreversible bilateral deafness may continue to develop after the drug has been discontinued. Rarely, nephrotoxicity may not become apparent until the first few days after cessation of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible.
Renal and eighth-nerve function should be closely monitored in patients with known or suspected renal impairment and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Peak and trough serum concentrations of aminoglycosides should be monitored periodically during therapy to assure adequate levels and to avoid potentially toxic levels. Prolonged serum concentrations above 12 mcg/mL should be avoided. Rising trough levels (above 2 mcg/mL) may indicate tissue accumulation. Such accumulation, excessive peak concentrations, advanced age, and cumulative dose may contribute to ototoxicity and nephrotoxicity (see PRECAUTIONS). Urine should be examined for decreased specific gravity and increased excretion of protein, cells, and casts. Blood urea nitrogen, serum creatinine, and creatinine clearance should be measured periodically. When feasible, it is recommended that serial audiograms be obtained in patients old enough to be tested, particularly high-risk patients. Evidence of impairment of renal, vestibular, or auditory function requires discontinuation of the drug or dosage adjustment.
Tobramycin should be used with caution in premature and neonatal infants because of their renal immaturity and the resulting prolongation of serum half-life of the drug.
Concurrent and sequential use of other neurotoxic and/or nephrotoxic antibiotics, particularly other aminoglycosides (e.g., amikacin, streptomycin, neomycin, kanamycin, gentamicin, and paromomycin), cephaloridine, viomycin, polymyxin B, colistin, cisplatin, and vancomycin, should be avoided. Other factors that may increase patient risk are advanced age and dehydration.
Aminoglycosides should not be given concurrently with potent diuretics, such as ethacrynic acid and furosemide. Some diuretics themselves cause ototoxicity, and intravenously administered diuretics enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.
Aminoglycosides can cause fetal harm when administered to a pregnant woman (see PRECAUTIONS).
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TOBRAMYCIN SUMMARY
TOBRAMYCIN
INJECTION, USP
Tobramycin sulfate, a water-soluble antibiotic of the aminoglycoside group, is derived from the actinomycete Streptomyces tenebrarius. Tobramycin Injection, USP is a clear and colorless sterile aqueous solution for parenteral administration. Each mL contains tobramycin sulfate equivalent to 10 mg tobramycin; sodium metabisulfite added as an antioxidant, 1.5 mg; and edetate disodium added as a stabilizer, 0.1 mg. Contains sulfuric acid and may contain sodium hydroxide for pH adjustment. pH 4.5 (3.0 to 6.5). Tobramycin sulfate is O -3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)- O -[2,6-diamino-2,3,6-trideoxy-α-D- ribo -hexopyranosyl-(1→6)]-2-deoxy-,L-streptamine sulfate (2:5)(salt) and has the chemical formula (C18H37N5O9)2• 5H2SO4.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of tobramycin and other antibacterial drugs, tobramycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Tobramycin is indicated for the treatment of serious bacterial infections caused by susceptible strains of the designated microorganisms in the diseases listed below:
Septicemia in the pediatric patient and adult caused by P aeruginosa, E coli, and Klebsiella sp
Lower respiratory tract infections caused by P aeruginosa, Klebsiella sp, Enterobacter sp, Serratia sp, E coli, and S aureus (penicillinase and non-penicillinase-producing strains)
Serious central-nervous-system infections (meningitis) caused by susceptible organisms
Intra-abdominal infections, including peritonitis, caused by E coli, Klebsiella sp, and Enterobacter sp
Skin, bone, and skin-structure infections caused by P aeruginosa, Proteus sp, E coli, Klebsiella sp, Enterobacter sp, and S aureus
Complicated and recurrent urinary tract infections caused by P aeruginosa, Proteus sp (indole-positive and indole-negative), E coli, Klebsiella sp, Enterobacter sp, Serratia sp, S aureus, Providencia sp, and Citrobacter sp
Aminoglycosides, including tobramycin, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are not susceptible to antibiotics having less potential toxicity. Tobramycin may be considered in serious staphylococcal infections when penicillin or other potentially less toxic drugs are contraindicated and when bacterial susceptibility testing and clinical judgment indicate its use.
Bacterial cultures should be obtained prior to and during treatment to isolate and identify etiologic organisms and to test their susceptibility to tobramycin. If susceptibility tests show that the causative organisms are resistant to tobramycin, other appropriate therapy should be instituted. In patients in whom a serious life-threatening gram-negative infection is suspected, including those in whom concurrent therapy with a penicillin or cephalosporin and an aminoglycoside may be indicated, treatment with tobramycin may be initiated before the results of susceptibility studies are obtained. The decision to continue therapy with tobramycin should be based on the results of susceptibility studies, the severity of the infection, and the important additional concepts discussed in the WARNINGS box above.
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NEWS HIGHLIGHTS
Published Studies Related to Tobramycin
Pharmacokinetics of tobramycin in ducks and sex-related differences. [2009.03]
The aims of the present study were to determine the disposition of tobramycin after single intravenous (IV) and intramuscular (IM) injections in ducks, and to establish any sex-related differences. Tobramycin sulfate was administered as a 2.5% water solution in a cross-over design at a dose of 5mg/kg to 12 healthy ducks (six males and six females)...
Effects of loteprednol/tobramycin versus dexamethasone/tobramycin on intraocular pressure in healthy volunteers. [2008.01]
PURPOSE: To compare the steroid-induced intraocular pressure (IOP) and other ocular adverse effects of loteprednol etabonate 0.5% and tobramycin 0.3% ophthalmic suspension with those of dexamethasone 0.1% and tobramycin 0.3% ophthalmic suspension... CONCLUSIONS: Loteprednol/tobramycin was significantly less likely to produce elevations in IOP than was dexamethasone/tobramycin in healthy subjects treated for 28 days. Both loteprednol etabonate/tobramycin and dexamethasone/tobramycin were well tolerated with low risks for systemic AEs and ocular AEs other than elevation in IOP for dexamethasone/tobramycin.
Comparison of the safety and efficacy of loteprednol 0.5%/tobramycin 0.3% with dexamethasone 0.1%/tobramycin 0.3% in the treatment of blepharokeratoconjunctivitis. [2008.01]
CONCLUSIONS: LE/T satisfied the condition of non-inferiority to DM/T in decreasing the signs and symptoms of ocular inflammation associated with blepharokeratoconjunctivitis. Subjects treated with DM/T experienced more of an increase in IOP. Limitation: Although the single-masked design of this study could be considered a limitation, care was taken to ensure that the investigator was masked.
Population pharmacokinetics of tobramycin administered thrice daily and once daily in children and adults with cystic fibrosis. [2007.09]
BACKGROUND: Tobramycin pharmacokinetics have not been evaluated previously in a large series of data collected in children and adults with CF receiving once (OD) or three times daily (TD) tobramycin... CONCLUSIONS: The reduced elimination rate in OD may either be caused by circadian pharmacokinetic behaviour of tobramycin or indicates early renal damage caused by high tobramycin doses not detected by biochemical measurements. However, results of our previous work suggest that OD tobramycin may be less nephrotoxic. The higher V1 in children implies that a relative higher tobramycin dose in these patients is needed for the same target peak serum concentration.
Phase 3 Safety Comparisons for 1.0% Azithromycin in Polymeric Mucoadhesive Eye Drops versus 0.3% Tobramycin Eye Drops for Bacterial Conjunctivitis. [2007.08]
PURPOSE: To compare the safety and tolerability of 1.0% azithromycin in a polymeric mucoadhesive delivery system with 0.3% tobramycin ophthalmic solution for the treatment of bacterial conjunctivitis... CONCLUSIONS: This is the first report of the safety and tolerability of a commercially manufactured preparation of azithromycin for ophthalmic use. Azithromycin 1% in DuraSite is safe and can be administered in a regimen of less frequent doses than can tobramycin, while producing an equivalent clinical outcome. The formulation is well tolerated in patients over the age of 1 year for the eradication of bacteria commonly associated with conjunctivitis. (ClinicalTrials.gov number, NCT00105469.).
Clinical Trials Related to Tobramycin
Tobramycin Inhalation Solution Administered by eFlow Rapid Nebulizer: Scintigraphy Study [Completed]
This study assesses the aerosol delivery characteristics (measured by in vivo lung
deposition, nebulization time, serum tobramycin concentrations, and pharmacokinetic
parameters) and safety of tobramycin inhalation solution administered for inhalation by PARI
eFlow rapid electronic nebulizer (no compressor) vs. PARI LC PLUS Jet Nebulizer (with
compressor) in healthy subjects and in subjects with cystic fibrosis.
Tobramycin Administered by eFlow Rapid Nebulizer: Pharmacokinetic Study [Completed]
This study assesses the aerosol delivery characteristics (measured by nebulization time,
serum and sputum tobramycin pharmacokinetic parameters) and safety of tobramycin administered
for inhalation by PARI eFlow rapid electronic nebulizer (no compressor) vs. PARI LC PLUS Jet
Nebulizer (with compressor) in subjects with cystic fibrosis.
The Tobramycin Study [Completed]
Evaluate if tobramycin given once a day is at least as efficacious as the traditional
tobramycin given three times a day, given with penicillin G, til patients with febrile
neutropenia.
Efficacy and Safety of 28 or 56 Days Treatment With Inhaled Tobramycin Nebuliser Solution for Pseudomonas Aeruginosa Infection in Children With Cystic Fibrosis. [Active, not recruiting]
This study assesses time to recurrence of infection with Pseudomonas aeruginosa following
treatment of the initial infection with tobramycin nebuliser solution. The safety of the
initial tobramycin treatment will be monitored over the first 3 months of the study and
patients will be followed for a further 24 months.
Tobramycin Inhalation Powder (TIP) in Cystic Fibrosis Subjects [Terminated]
Lung infections are a chronic problem for patients with cystic fibrosis (CF). Some patients
with CF may have a type of bacteria called Pseudomonas aeruginosa in their lungs that can
cause infections or make their symptoms worse. Tobramycin inhalation solution (TOBI) is an
approved antibiotic, which is inhaled directly into the lungs, and can be used to manage
these infections. Tobramycin inhalation powder (TIP) is a new, experimental powder
formulation of tobramycin that is inhaled directly into the lungs using a T-326 inhaler. The
purpose of this research study is to determine if TIP is safe and effective when compared to
placebo (a powder with no medicine) treatment.
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Page last updated: 2009-10-20
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