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Tobramycin

PubChem CID
36294
Structure
Tobramycin_small.png
Tobramycin_3D_Structure.png
Molecular Formula
Synonyms
  • tobramycin
  • 32986-56-4
  • Nebramycin VI
  • Nebramycin 6
  • Nebramycin factor 6
Molecular Weight
467.5 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-03-27
  • Modify:
    2025-01-18
Description
Tobramycin Sulfate can cause developmental toxicity according to state or federal government labeling requirements.
Tobramycin is a amino cyclitol glycoside that is kanamycin B lacking the 3-hydroxy substituent from the 2,6-diaminoglucose ring. It has a role as an antibacterial agent, an antimicrobial agent and a toxin. It is functionally related to a kanamycin B. It is a conjugate base of a tobramycin(5+).
Aminoglycosides, many of which are derived directly from Streptomyces spp., are concentration-dependent bactericidal antibiotics with a broad spectrum of activity against Gram-positive and Gram-negative organisms. Inhaled tobramycin is notable for its use in treating chronic Pseudomonas aeruginosa infections in cystic fibrosis patients, as P. aeruginosa is notoriously inherently resistant to many antibiotics. However, tobramycin can also be administered intravenously and topically to treat a variety of infections caused by susceptible bacteria. Its use is limited in some cases by characteristic toxicities such as nephrotoxicity and ototoxicity, yet it remains a valuable option in the face of growing resistance to front-line antibiotics such as β-lactams and cephalosporins. Tobramycin was approved by the FDA in 1975 and is currently available in a variety of forms for administration by inhalation, injection, and external application to the eye (ophthalmic).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Tobramycin.png

1.2 3D Conformer

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(2S,3R,4S,5S,6R)-4-amino-2-[(1S,2S,3R,4S,6R)-4,6-diamino-3-[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy-2-hydroxycyclohexyl]oxy-6-(hydroxymethyl)oxane-3,5-diol
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C18H37N5O9/c19-3-9-8(25)2-7(22)17(29-9)31-15-5(20)1-6(21)16(14(15)28)32-18-13(27)11(23)12(26)10(4-24)30-18/h5-18,24-28H,1-4,19-23H2/t5-,6+,7+,8-,9+,10+,11-,12+,13+,14-,15+,16-,17+,18+/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

NLVFBUXFDBBNBW-PBSUHMDJSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C1[C@@H]([C@H]([C@@H]([C@H]([C@@H]1N)O[C@@H]2[C@@H]([C@H]([C@@H]([C@H](O2)CO)O)N)O)O)O[C@@H]3[C@@H](C[C@@H]([C@H](O3)CN)O)N)N
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C18H37N5O9
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

79645-27-5

2.3.3 Deprecated CAS

11098-01-4, 11111-45-8, 34337-51-4, 37321-13-4, 54330-95-9, 70322-33-7

2.3.4 European Community (EC) Number

2.3.5 UNII

2.3.6 ChEBI ID

2.3.7 ChEMBL ID

2.3.8 DrugBank ID

2.3.9 DSSTox Substance ID

2.3.10 HMDB ID

2.3.11 KEGG ID

2.3.12 Metabolomics Workbench ID

2.3.13 NCI Thesaurus Code

2.3.14 Nikkaji Number

2.3.15 NSC Number

2.3.16 PharmGKB ID

2.3.17 RXCUI

2.3.18 Wikidata

2.3.19 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • Brulamycin
  • Nebcin
  • Nebicin
  • Nebramycin Factor 6
  • Obracin
  • Sulfate, Tobramycin
  • Tobracin
  • Tobramycin
  • Tobramycin Sulfate

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
467.5 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
-6.2
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
10
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
14
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
6
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
467.25912777 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
467.25912777 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
268 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
32
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
609
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
14
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Experimental Properties

3.2.1 Physical Description

Solid

3.2.2 Color / Form

White to off-white powder
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1758
Crystals
Haynes, W.M. (ed.). CRC Handbook of Chemistry and Physics. 95th Edition. CRC Press LLC, Boca Raton: FL 2014-2015, p. 3-488

3.2.3 Solubility

freely soluble
FDA Label
Freely soluble in water (1 in 1.5 parts)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1758
Very slightly soluble in ethanol (1 in 2000 parts). Practically insoluble in chloroform, ether
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1758
5.37e+01 g/L

3.2.4 LogP

3.2.5 Stability / Shelf Life

Stable under recommended storage conditions.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
... Hygroscopic powder.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1758

3.2.6 Optical Rotation

Specific optical rotation: +129 deg at 20 °C/D (c = 1 in water)
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1758

3.2.7 Decomposition

Hazardous decomposition products formed under fire conditions - Carbon oxides, nitrogen oxides (NOx).
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
When heated to decomposition it emits toxic fumes of /nitrogen oxides/.
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3477

3.2.8 pH

Basic substance
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1758

3.2.9 Other Experimental Properties

Hygroscopic
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1758

3.3 Chemical Classes

3.3.1 Drugs

Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
Pharmaceuticals -> Antibiotics
S6 | ITNANTIBIOTIC | Antibiotic List from the ITN MSCA ANSWER | DOI:10.5281/zenodo.2621956
S57 | GREEKPHARMA | Suspect Pharmaceuticals from the National Organization of Medicine, Greece | DOI:10.5281/zenodo.3248883
3.3.1.1 Human Drugs
Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Aminoglycosides
Human drug -> Prescription
Human drug -> Prescription; Discontinued
Human drug -> Discontinued
Human drug -> Prescription; Discontinued; Active ingredient (TOBRAMYCIN SULFATE)
Human drug -> Prescription; Discontinued; Active ingredient (TOBRAMYCIN)
Human drugs -> Antibacterials for systemic use -> Human pharmacotherapeutic group -> EMA Drug Category
Human drugs -> Antibacterials for systemic use, Aminoglycoside antibacterials -> Human pharmacotherapeutic group -> EMA Drug Category
Paediatric drug
Ophthalmological preparations > Anti-infective agents

4 Spectral Information

4.1 Mass Spectrometry

4.1.1 GC-MS

1 of 2
Source of Spectrum
NP-15-4617-0
Copyright
Copyright © 2020-2024 John Wiley & Sons, Inc. All Rights Reserved.
Thumbnail
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2 of 2
Technique
DI/MS
Source of Spectrum
DigiLab GmbH (C) 2024
Copyright
Copyright © 2024 DigiLab GmbH and Wiley-VCH GmbH. All Rights Reserved.
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4.1.2 MS-MS

NIST Number
1168684
Instrument Type
IT/ion trap
Collision Energy
0
Spectrum Type
MS2
Precursor Type
[M+H]+
Precursor m/z
468.2664
Total Peaks
23
m/z Top Peak
324.1
m/z 2nd Highest
163.1
m/z 3rd Highest
205.1
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4.1.3 LC-MS

1 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
468.2663879394531
Instrument
Thermo Q Exactive HF
Instrument Type
ESI-QFT
Ionization Mode
positive
Collision Energy
65HCD
Top 5 Peaks

57.070629 100

344.828424 99.76

312.838631 94.40

353.841149 64.44

67.054904 54.91

Thumbnail
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2 of 3
View All
MS Category
Experimental
MS Type
LC-MS
MS Level
MS2
Precursor Type
[M+H]+
Precursor m/z
468.2663879394531
Instrument
Thermo Q Exactive HF
Instrument Type
ESI-QFT
Ionization Mode
positive
Collision Energy
45HCD
Top 5 Peaks

353.841111 100

336.838660 58.97

57.070613 51.36

394.844046 35.75

354.847208 22.01

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4.1.4 Other MS

MoNA ID
MS Category
Experimental
MS Type
Other
MS Level
MS2
Precursor Type
[M+Na]+
Precursor m/z
490.2483458
Ionization Mode
positive
Retention Time
2.2285484557309543
Top 5 Peaks

152.06334433425897 0.04

207.03408633425897 0.02

128.06546433425896 0.02

404.28179967967037 0.02

158.09767333425896 0.02

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6 Chemical Vendors

7 Drug and Medication Information

7.1 Drug Indication

Inhaled tobramycin is indicated for the management of cystic fibrosis patients with _Pseudomonas aeruginosa_, but is not recommended in patients under six years of age, those with forced expiratory volume in 1 second (FEV1) 80% predicted, or in those with _Burkholderia cepacia_. Tobramycin applied topically to the eyes is indicated for the treatment of external eye (and adjoining structure) infections by susceptible bacteria. Tobramycin injection is indicated in adult and pediatric patients for the treatment of serious bacterial infections, including septicemia (caused by _P. aeruginosa_, _Escherichia coli_, and _Klebsiella_ spp.), lower respiratory tract infections (caused by _P. aeruginosa_, _Klebsiella_ spp., _Enterobacter_ spp., _Serratia_ spp., _E. coli_, and _Staphylococcus aureus_, both 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_ spp., and _Enterobacter_ spp.), skin, bone, and skin structure infections (caused by _P. aeruginosa_, _Proteus_ spp., _E. coli_, _Klebsiella_ spp., _Enterobacter_ spp., _Serratia_ spp. and _S. aureus_), and complicated and recurrent urinary tract infections (caused by _P. aeruginosa_, _Proteus_ spp., _E. coli_, _Klebsiella_ spp., _Enterobacter_ spp., _Serratia_ spp., _S. aureus_, _Providencia_ spp., and _Citrobacter_ spp.). Aminoglycosides, including tobramycin, should generally not be used in uncomplicated urinary tract infections or staphylococcal infections unless less toxic antibiotics cannot be used and the bacteria in question are known to be sensitive to aminoglycosides. As with all antibiotics, tobramycin use should be limited to cases where bacterial infections are known or strongly suspected to be caused by sensitive organisms, and the possible emergence of resistance should be monitored closely.
Vantobra is indicated for the management of chronic pulmonary infection due to Pseudomonas aeruginosa in patients aged 6 years and older with cystic fibrosis (CF). Consideration should be given to official guidance on the appropriate use of antibacterial agents.

7.2 LiverTox Summary

Tobramycin is a parenterally administered, broad spectrum aminoglycoside antibiotic that is widely used in the treatment of moderate to severe bacterial infections due to sensitive organisms. Despite its wide use, tobramycin has rarely been linked to instances of clinically apparent liver injury.

7.3 Drug Classes

Breast Feeding; Lactation; Milk, Human; Anti-Infective Agents; Antibacterial Agents; Aminoglycosides
Aminoglycosides

7.4 WHO Essential Medicines

Drug
Drug Classes
Ophthalmological preparations > Anti-infective agents
Formulation
Indication
(1) Other specified conjunctivitis; (2) Infectious blepharitis

7.5 FDA Approved Drugs

7.6 FDA Orange Book

7.7 FDA National Drug Code Directory

7.8 Drug Labels

Drug and label
Active ingredient and drug
Drug and label
Active ingredient and drug

7.9 Clinical Trials

7.9.1 ClinicalTrials.gov

7.9.2 EU Clinical Trials Register

7.9.3 NIPH Clinical Trials Search of Japan

7.10 EMA Drug Information

1 of 6
View All
Category
Human drugs
Therapeutic area
Respiratory Tract Infections; Cystic Fibrosis
Active Substance
Tobramycin
INN/Common name
tobramycin
Pharmacotherapeutic Classes
Antibacterials for systemic use
Status
This medicine is authorized for use in the European Union
Company
Pari Pharma GmbH
Market Date
2019-02-18
2 of 6
View All
Category
Human drugs
Therapeutic area
Cystic Fibrosis; Respiratory Tract Infections
Active Substance
Tobramycin
INN/Common name
tobramycin
Pharmacotherapeutic Classes
Antibacterials for systemic use
Status
This medicine is authorized for use in the European Union
Company
Viatris Healthcare Limited
Market Date
2011-07-20

7.11 Therapeutic Uses

Anti-Bacterial Agents
National Library of Medicine's Medical Subject Headings. Tobramycin. Online file (MeSH, 2016). Available from, as of December 5, 2016: https://www.nlm.nih.gov/mesh/2016/mesh_browser/MBrowser.html
/CLINICAL TRIALS/ ClinicalTrials.gov is a registry and results database of publicly and privately supported clinical studies of human participants conducted around the world. The Web site is maintained by the National Library of Medicine (NLM) and the National Institutes of Health (NIH). Each ClinicalTrials.gov record presents summary information about a study protocol and includes the following: Disease or condition; Intervention (for example, the medical product, behavior, or procedure being studied); Title, description, and design of the study; Requirements for participation (eligibility criteria); Locations where the study is being conducted; Contact information for the study locations; and Links to relevant information on other health Web sites, such as NLM's MedlinePlus for patient health information and PubMed for citations and abstracts for scholarly articles in the field of medicine. Tobramycin is included in the database.
NIH/NLM; ClinicalTrials.Gov. Available from, as of February 1, 2017: https://clinicaltrials.gov/ct2/results?term=TOBRAMYCIN&Search=Search
Tobramycin for Injection, USP 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 Proteus aeruginosa, Enterobacter coli, and Klebsiella spp. Lower respiratory tract infections caused by P. aeruginosa, Klebsiella spp, Enterobacter spp, Serratia spp, 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 spp, and Enterobacter spp. Skin, bone, and skin structure infections caused by P. aeruginosa, Proteus spp, E. coli, Klebsiella spp, Enterobacter spp, and S. aureus. Complicated and recurrent urinary tract infections caused by P. aeruginosa, Proteus spp, (indole-positive and indole-negative), E. coli, Klebsiella spp, Enterobacter spp, Serratia spp, S. aureus, Providencia spp, and Citrobacter spp. /Included in US product labeling/
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
Aminoglycosides, including tobramycin sulfate injection, USP 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 for Injection, USP 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.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
For more Therapeutic Uses (Complete) data for Tobramycin (9 total), please visit the HSDB record page.

7.12 Drug Warnings

/BOXED WARNING/ WARNINGS: Patients treated with tobramycin 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 preexisting 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 ug/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. 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.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
Serious allergic reactions including anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome have been reported rarely in patients on tobramycin therapy. Although rare, fatalities have been reported.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial agents, including Tobramycin for Injection, USP, and may range in severity from mild diarrhea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile. C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents. If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
Adverse effects on both the vestibular and auditory branches of the eighth nerve have been noted, especially in patients receiving high doses or prolonged therapy, in those given previous courses of therapy with an ototoxin, and in cases of dehydration. Symptoms include dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss. Hearing loss is usually irreversible and is manifested initially by diminution of high-tone acuity. Tobramycin and gentamicin sulfates closely parallel each other in regard to ototoxic potential.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
For more Drug Warnings (Complete) data for Tobramycin (41 total), please visit the HSDB record page.

8 Pharmacology and Biochemistry

8.1 Pharmacodynamics

Tobramycin is an aminoglycoside antibiotic derived from the actinomycete _Streptomyces tenebrarius_. It has a broad spectrum of activity against Gram-negative bacteria, including _Enterobacteriaceae_, _Escherichia coli_, _Klebsiella pneumoniae_, _Morganella morganii_, _Moraxella lacunata_, _Proteus_ spp., _Haemophilus_ spp., _Acinetobacter_ spp., _Neisseria_ spp., and, importantly, _Pseudomonas aeruginosa_. Aminoglycosides also generally retain activity against the biothreat agents _Yersinia pestis_ and _Francisella tularensis_. In addition, aminoglycosides are active against some Gram-positive bacteria such as _Staphylococcus_ spp., including methicillin-resistant (MRSA) and vancomycin-resistant strains, _Streptococcus_ spp., and _Mycobacterium_ spp. Like other aminoglycosides, tobramycin is taken up and retained by proximal tubule and cochlear cells in the kidney and ear, respectively, and hence carries a risk of nephrotoxicity and ototoxicity. There is also a risk of neuromuscular block, which may be more pronounced in patients with preexisting neuromuscular disorders such as myasthenia gravis or Parkinson's disease. Aminoglycosides can cross the placenta, resulting in total, irreversible, bilateral congenital deafness in babies born to mothers who were administered an aminoglycoside during pregnancy. Due to the low systemic absorption of inhaled and topical tobramycin formulations, these effects are more pronounced with injected tobramycin than with other formulations. However, all formulations carry a risk of hypersensitivity reactions, including potentially fatal cutaneous reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis.

8.2 MeSH Pharmacological Classification

Anti-Bacterial Agents
Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.)

8.3 FDA Pharmacological Classification

1 of 6
FDA UNII
VZ8RRZ51VK
Active Moiety
TOBRAMYCIN
Pharmacological Classes
Established Pharmacologic Class [EPC] - Aminoglycoside Antibacterial
Pharmacological Classes
Chemical Structure [CS] - Aminoglycosides
FDA Pharmacology Summary
Tobramycin is an Aminoglycoside Antibacterial.
2 of 6
Non-Proprietary Name
TOBRAMYCIN
Pharmacological Classes
Aminoglycosides [CS]; Aminoglycoside Antibacterial [EPC]
3 of 6
Non-Proprietary Name
TOBRAMYCIN INHALATION
Pharmacological Classes
Aminoglycosides [CS]; Aminoglycoside Antibacterial [EPC]
4 of 6
Non-Proprietary Name
TOBRAMYCIN INHALATION SOLUTION
Pharmacological Classes
Aminoglycosides [CS]; Aminoglycoside Antibacterial [EPC]
5 of 6
Non-Proprietary Name
TOBRAMYCIN OPHTHALMIC SOLUTION
Pharmacological Classes
Aminoglycoside Antibacterial [EPC]; Aminoglycosides [CS]
6 of 6
Non-Proprietary Name
TOBRAMYCIN SULFATE
Pharmacological Classes
Aminoglycosides [CS]; Aminoglycoside Antibacterial [EPC]

8.4 ATC Code

J01GB01
S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

J - Antiinfectives for systemic use

J01 - Antibacterials for systemic use

J01G - Aminoglycoside antibacterials

J01GB - Other aminoglycosides

J01GB01 - Tobramycin

S - Sensory organs

S01 - Ophthalmologicals

S01A - Antiinfectives

S01AA - Antibiotics

S01AA12 - Tobramycin

8.5 Absorption, Distribution and Excretion

Absorption
Tobramycin administered by inhalation in cystic fibrosis patients showed greater variability in sputum as compared to serum. After a single 112 mg dose, the serum Cmax was 1.02 ± 0.53 μg/mL, which was reached in one hour (Tmax), while the sputum Cmax was 1048 ± 1080 μg/g. Comparatively, for a 300 mg dose, the serum Cmax was 1.04 ± 0.58 μg/mL, which was also reached within one hour, while the sputum Cmax was 737 ± 1028 μg/g. The systemic exposure (AUC0-12) was also similar between the two doses, at 4.6 ± 2.0 μg∙h/mL for the 112 mg dose and 4.8 ± 2.5 μg∙h/mL for the 300 mg dose. When tobramycin was administered over a four-week cycle at 112 mg twice daily, the Cmax measured one hour after dosing ranged from 1.48 ± 0.69 μg/mL to 1.99 ± 0.59 μg/mL.
Route of Elimination
Tobramycin is primarily excreted unchanged in the urine.
Volume of Distribution
Inhalation tobramycin had an apparent volume of distribution in the central compartment of 85.1 L for a typical cystic fibrosis patient.
Clearance
Inhaled tobramycin has an apparent serum clearance of 14.5 L/h in cystic fibrosis patients aged 6-58 years.
Tobramycin is poorly absorbed from the GI tract.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 43
Tobramycin is rapidly absorbed following IM administration. Following IM administration of a single dose of tobramycin of 1 mg/kg in adults with normal renal function, peak serum tobramycin concentrations average 4-6 ug/mL and are attained within 30-90 minutes; at 6-8 hours after the dose, serum concentrations are 1 ug/mL or less. When the same dose is administered by IV infusion over 30-60 minutes, similar plasma concentrations of the drug are attained.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 43
In one study in neonates receiving IM tobramycin in a dosage of 2 mg/kg every 12 hours, peak serum concentrations of the drug were attained 0.5-1 hour after a dose and ranged from 4.9-5.2 ug/mL after the first dose and 4.5-5.1 ug/mL after 10-16 doses. In neonates 2-7 days of age receiving tobramycin in a dosage of 2.5 mg/kg by IV infusion every 12 hours, steady-state peak serum concentrations ranged from 3.5-9.9 ug/mL and trough serum concentrations ranged from 1.1-3.6 ug/mL in those weighing less than 2 kg. In those weighing 2 kg or more, peak serum concentrations ranged from 5-10.2 ug/mL and trough serum concentrations ranged from 0.7-2 ug/mL.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 43
Bioavailability of tobramycin administered by oral inhalation via a nebulizer may be variable because of individual differences in nebulizer performance and airway pathology. Following oral inhalation via nebulization, tobramycin remains concentrated principally in the airways; the drug does not readily cross epithelial membranes. Tobramycin sputum concentrations are highly variable following oral inhalation, but the drug does not appear to accumulate in sputum following multiple doses. Following an initial 300-mg dose of commercially available tobramycin solution for oral inhalation given via a nebulizer, sputum concentrations of the drug at 10 minutes averaged 1237 ug/g (range: 35-7414 ug/g). After 20 weeks of intermittent therapy (300-mg twice daily for 28 days followed by 28 days without the drug), sputum concentrations 10 minutes after administration averaged 1154 ug/g (range: 39-8085 ug/g) and sputum concentrations 2 hours after administration were approximately 14% of those obtained 10 minutes after administration. Following a single 300-mg dose of the commercially available tobramycin solution for oral inhalation given via nebulization in patients with cystic fibrosis, serum tobramycin concentrations averaged 0.95 ug/mL at 1 hour after administration; after 20 weeks of intermittent therapy (300 mg twice daily for 28 days followed by 28 days without the drug), serum tobramycin concentrations averaged 1.05 ug/mL at 1 hour after administration.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 43
For more Absorption, Distribution and Excretion (Complete) data for Tobramycin (15 total), please visit the HSDB record page.

8.6 Metabolism / Metabolites

Tobramycin is not appreciably metabolized.
Aminoglycosides are not metabolized and are excreted unchanged in the urine primarily by glomerular filtration. /Aminoglycosides/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 31

8.7 Biological Half-Life

Tobramycin has an apparent serum terminal half-life of ~3 hours following a single 112 mg inhaled dose in cystic fibrosis patients.
Total body clearance of tobramycin is approximately 20% higher in patients with cystic fibrosis than in patients without the disease; however, renal clearance is similar.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 43
When tobramycin is administered by oral inhalation using a nebulizer, any drug that is not absorbed systemically probably is eliminated principally in expectorated sputum.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 43
... Terminal elimination half-lives of greater than 100 hours have been reported in adults with normal renal function following repeated IM or IV administration of the drug.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 43
The plasma elimination half-life of tobramycin following parenteral administration usually is 2-3 hours in adults with normal renal function and has ranged from 50-70 hours in adults with impaired renal function. The serum elimination half-life of tobramycin is reported to average 4.6 hours in full-term infants weighing more than 2.5 kg and 8.7 hours in infants weighing less than 1.5 kg. In one study in neonates 2-7 days of age, elimination half-life ranged from 5.68-13.6 hours in those weighing less than 2 kg and 3.54-6.73 hours in those weighing 2 kg or more.
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 43

8.8 Mechanism of Action

Tobramycin is a 4,6-disubstituted 2-deoxystreptamine (DOS) ring-containing aminoglycoside antibiotic with activity against various Gram-negative and some Gram-positive bacteria. The mechanism of action of tobramycin has not been unambiguously elucidated, and some insights into its mechanism rely on results using similar aminoglycosides. In general, like other aminoglycosides, tobramycin is bactericidal and exhibits both immediate and delayed killing, which are attributed to different mechanisms, as outlined below. Aminoglycosides are polycationic at physiological pH, such that they readily bind to bacterial membranes ("ionic binding"); this includes binding to lipopolysaccharide and phospholipids within the outer membrane of Gram-negative bacteria and to teichoic acid and phospholipids within the cell membrane of Gram-positive bacteria. This binding displaces divalent cations and increases membrane permeability, which allows aminoglycoside entry. Additional aminoglycoside entry ("energy-dependent phase I") into the cytoplasm requires the proton-motive force, allowing access of the aminoglycoside to its primary intracellular target of the bacterial 30S ribosome. Mistranslated proteins produced as a result of aminoglycoside binding to the ribosome (see below) integrate into and disrupt the cell membrane, which allows more of the aminoglycoside into the cell ("energy-dependent phase II"). Hence, tobramycin and other aminoglycosides have both immediate bactericidal effects through membrane disruption and delayed bactericidal effects through impaired protein synthesis; observed experimental data and mathematical modelling support this two-mechanism model. Inhibition of protein synthesis was the first recognized effect of aminoglycoside antibiotics. Structural and cell biological studies suggest that aminoglycosides bind to the 16S rRNA in helix 44 (h44), near the A site of the 30S ribosomal subunit, altering interactions between h44 and h45. This binding also displaces two important residues, A1492 and A1493, from h44, mimicking normal conformational changes that occur with successful codon-anticodon pairing in the A site. Overall, aminoglycoside binding has several negative effects, including inhibiting translation initiation and elongation and ribosome recycling. Recent evidence suggests that the latter effect is due to a cryptic second binding site situated in h69 of the 23S rRNA of the 50S ribosomal subunit. Also, by stabilizing a conformation that mimics correct codon-anticodon pairing, aminoglycosides promote error-prone translation; mistranslated proteins can incorporate into the cell membrane, inducing the damage discussed above. Although direct mutation of the 16S rRNA is a rare resistance mechanism, due to the gene being present in numerous copies, posttranscriptional 16S rRNA modification by 16S rRNA methyltransferases (16S-RMTases) at the N7 position of G1405 or the N1 position of A1408 are common resistance mechanisms in aminoglycoside-resistant bacteria. These mutants also further support the proposed mechanism of action of aminoglycosides. Direct modification of the aminoglycoside itself through acetylation, adenylation, and phosphorylation by aminoglycoside-modifying enzymes (AMEs) are also commonly encountered resistance mutations. Finally, due to the requirement for active transport of aminoglycosides across bacterial membranes, they are not active against obligately anaerobic bacteria.
Aminoglycosides are usually bacterial in action. Although the exact mechanism of action has not been fully elucidated, the drugs appear to inhibit protein synthesis in susceptible bacteria by irreversibly binding to 30S ribosomal subunits. /Aminoglycosides/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 29
... Aminoglycosides are aminocyclitols that kill bacteria by inhibiting protein synthesis as they bind to the 16S rRNA and by disrupting the integrity of bacterial cell membrane. Aminoglycoside resistance mechanisms include: (a) the deactivation of aminoglycosides by N-acetylation, adenylylation or O-phosphorylation, (b) the reduction of the intracellular concentration of aminoglycosides by changes in outer membrane permeability, decreased inner membrane transport, active efflux, and drug trapping, (c) the alteration of the 30S ribosomal subunit target by mutation, and (d) methylation of the aminoglycoside binding site. ... /Aminoglycosides/
Shakil S et al; J Biomed Sci 15 (1): 5-14 (2008)

8.9 Human Metabolite Information

8.9.1 Cellular Locations

Cytoplasm

8.9.2 Metabolite Pathways

9 Use and Manufacturing

9.1 Uses

MEDICATION (VET)
MEDICATION
Anti-Bacterial Agents
National Library of Medicine's Medical Subject Headings. Tobramycin. Online file (MeSH, 2016). Available from, as of December 5, 2016: https://www.nlm.nih.gov/mesh/2016/mesh_browser/MBrowser.html

Use (kg; approx.) in Germany (2009): >100

Use (kg; exact) in Germany (2009): 218

Use (kg) in USA (2002): 394

Consumption (g per capita; approx.) in Germany (2009): 0.00122

Consumption (g per capita; exact) in Germany (2009): 0.00266

Consumption (g per capita) in the USA (2002): 0.0014

Calculated removal (%): 92.1

9.1.1 Use Classification

Human drugs -> Antibacterials for systemic use -> Human pharmacotherapeutic group -> EMA Drug Category
Human drugs -> Antibacterials for systemic use, Aminoglycoside antibacterials -> Human pharmacotherapeutic group -> EMA Drug Category
Human Drugs -> EU pediatric investigation plans
Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

9.2 Methods of Manufacturing

An antibiotic entity separated from an antibiotic complex produced by Streptomyces tenebrarius.
Troy, D.B. (Ed); Remmington The Science and Practice of Pharmacy. 21 st Edition. Lippincott Williams & Williams, Philadelphia, PA 2005, p. 1652
Aminoglycoside antibiotic; component of the nebramycin complex produced by Streptomyces tenebrarius.
O'Neil, M.J. (ed.). The Merck Index - An Encyclopedia of Chemicals, Drugs, and Biologicals. Cambridge, UK: Royal Society of Chemistry, 2013., p. 1758

9.3 Formulations / Preparations

Table: Tobramycin Sulfate Preparations
Route of Administration
Parenteral
Dosage Form
For injection, concentrate for IV infusion
Strength
1.2 g (of tobramycin) pharmacy bulk package
Brand or Generic Form (Manufacturer)
Tobramycin Sulfate for Injection (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Parenteral
Dosage Form
For injection, concentrate for IV infusion
Strength
10 mg (of tobramycin) per mL (80 mg)
Brand or Generic Form (Manufacturer)
Tobramycin Sulfate ADD-Vantage (Hospira)
Route of Administration
Parenteral
Dosage Form
For injection, concentrate for IV infusion
Strength
10 mg (of tobramycin) per mL (80 mg)
Brand or Generic Form (Manufacturer)
(Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Parenteral
Dosage Form
Injection
Strength
10 mg (of tobramycin) per mL (20 mg)
Brand or Generic Form (Manufacturer)
Tabramycin Sulfate Pediatric Injection (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Parenteral
Dosage Form
Injection
Strength
40 mg (of tobramycin) per mL (80 mg or 1.2 g)
Brand or Generic Form (Manufacturer)
Tabramycin Sulfate Injection (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Parenteral
Dosage Form
Injection
Strength
40 mg (of tobramycin) per mL (2 g) pharmacy bulk package
Brand or Generic Form (Manufacturer)
Tabramycin Sulfate Injection (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 44
Table: Tobramycin Sulfate in Sodium Chloride Preparations
Route of Administration
Parenteral
Dosage Form
Injection, for IV infusion only
Strength
0.8 mg (of tobramycin) per mL (80 mg) in 0.9% Sodium Chloride
Brand or Generic Form (Manufacturer)
Tobramycin Sulfate in 0.9% Sodium Chloride Injection (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
Route of Administration
Parenteral
Dosage Form
Injection, for IV infusion only
Strength
1.2 mg (of tobramycin) per mL (60 mg) in 0.9% Sodium Chloride
Brand or Generic Form (Manufacturer)
Tobramycin Sulfate in 0.9% Sodium Chloride Injection (Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name)
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 44
Oral inhalation: Solution, for nebulization only: 300 mg/5 mL, Tobi (Chiron)
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 44
Ophthalmic: Suspension: 0.3% with Loteprednol Etabonate 0.5%, Zylet (Bausch & Lomb)
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016
For more Formulations/Preparations (Complete) data for Tobramycin (6 total), please visit the HSDB record page.

10 Identification

10.1 Clinical Laboratory Methods

RADIOENZYMIC METHOD FOR DETERMINATION OF ANTIBIOTICS IN BODY FLUIDS USES GENTAMICIN ACETYLTRANSFERASES I & IV, CODED BY PLASMIDS PUZ 1 & PUX 2, RESPECTIVELY. APPLICABLE FOR TOBRAMYCIN.
SANCHEZ AGREDA M; IMMUNOLOGIKA (MADRID) 1 (1): 22-24, 26-28, 30-32, 34-35 (1979)
SERUM LEVELS WERE DETERMINED BY THE BACTEC 460. RESULTS WERE AT LEAST AS RELIABLE AS THOSE OBTAINED BY RADIOIMMUNOASSAY METHOD.
PHILLIPS ET AL; ANTIMICROB AGENTS CHEMOTHER 16 (4): 463-7 (1979)
DIFFUSION ASSAY PERFORMED AUTOMATICALLY IN PETRI DISHES USING PUNCH HOLE TECHNIQUE. RESULTS WITH TOBRAMYCIN SHOW THAT WITH BLOCK OF 6 DISHES, LIMITS OF ERRORS OF APPROX +- 2% CAN BE CONSTANTLY OBTAINED.
LIGHTBROWN ET AL; ANALYST 104 (MAR): 201-7 (1979)
HOMOGENOUS SUBSTRATE LABELED FLUORESCENT IMMUNOASSAY FOR DETERMINING TOBRAMYCIN CONCENTRATIONS IN HUMAN SERUM.
BURD ET AL; HOMOGENEOUS SUBSTRATE-LABELED FLUORESCENT IMMUNOASSAY FOR DETERMINING TOBRAMYCIN CONCENTRATIONS IN HUMAN SERUM; ENZYME LABELLED IMMUNOASSAY HORM DRUGS, PROC INT SYMP, 387-403 (1978)
FOLLOWING DILN OF SERUM SAMPLES WITH PHOSPHATE BUFFER, PROTEINS PPT WITH ACETONITRILE & SUPERNATANT PURIFIED BY 2-STEP PARTITION PROCEDURE, DERIV SEPARATED BY HIGH PRESSURE LIQ CHROMATOGRAPHY & DETECTED BY FLUOROMETRY
BAECK ET AL; CLIN CHEM (WINSTON-SALEM, NC) 25 (7): 1222-5 (1979)

11 Safety and Hazards

11.1 Hazards Identification

11.1.1 GHS Classification

1 of 2
View All
Note
Pictograms displayed are for 92.9% (13 of 14) of reports that indicate hazard statements. This chemical does not meet GHS hazard criteria for 7.1% (1 of 14) of reports.
Pictogram(s)
Irritant
Health Hazard
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H315 (50%): Causes skin irritation [Warning Skin corrosion/irritation]

H317 (14.3%): May cause an allergic skin reaction [Warning Sensitization, Skin]

H319 (42.9%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]

H335 (42.9%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure; Respiratory tract irritation]

H360 (21.4%): May damage fertility or the unborn child [Danger Reproductive toxicity]

H361 (14.3%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]

H400 (14.3%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

Precautionary Statement Codes

P203, P261, P264, P264+P265, P271, P272, P273, P280, P302+P352, P304+P340, P305+P351+P338, P318, P319, P321, P332+P317, P333+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 14 reports by companies from 12 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Reported as not meeting GHS hazard criteria per 1 of 14 reports by companies. For more detailed information, please visit ECHA C&L website.

There are 11 notifications provided by 13 of 14 reports by companies with hazard statement code(s).

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

11.1.2 Hazard Classes and Categories

Skin Irrit. 2 (50%)

Skin Sens. 1 (14.3%)

Eye Irrit. 2 (42.9%)

STOT SE 3 (42.9%)

Repr. 1B (21.4%)

Repr. 2 (14.3%)

Aquatic Acute 1 (14.3%)

Acute Tox. 3 (16.7%)

Acute Tox. 4 (16.7%)

Acute Tox. 3 (16.7%)

Acute Tox. 4 (50%)

Acute Tox. 3 (16.7%)

Acute Tox. 4 (50%)

Repr. 1B (50%)

Repr. 2 (33.3%)

Lact. (33.3%)

STOT RE 2 (16.7%)

11.2 Fire Fighting

11.2.1 Fire Fighting Procedures

Suitable extinguishing media: Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Advice for firefighters: Wear self-contained breathing apparatus for firefighting if necessary.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

11.3 Accidental Release Measures

11.3.1 Cleanup Methods

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains. Methods and materials for containment and cleaning up: Sweep up and shovel. Keep in suitable, closed containers for disposal.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

11.3.2 Disposal Methods

SRP: Expired or waste pharmaceuticals shall carefully take into consideration applicable DEA, EPA, and FDA regulations. It is not appropriate to dispose by flushing the pharmaceutical down the toilet or discarding to trash. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator.
Product: Offer surplus and non-recyclable solutions to a licensed disposal company; Contaminated packaging: Dispose of as unused product.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

11.3.3 Preventive Measures

ACCIDENTAL RELEASE MEASURES: Personal precautions, protective equipment and emergency procedures: Avoid dust formation. Avoid breathing vapors, mist or gas. Environmental precautions: Do not let product enter drains.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Precautions for safe handling: Provide appropriate exhaust ventilation at places where dust is formed.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Appropriate engineering controls: General industrial hygiene practice.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Gloves must be inspected prior to use. Use proper glove removal technique (without touching glove's outer surface) to avoid skin contact with this product. Dispose of contaminated gloves after use in accordance with applicable laws and good laboratory practices. Wash and dry hands.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
SRP: Local exhaust ventilation should be applied wherever there is an incidence of point source emissions or dispersion of regulated contaminants in the work area. Ventilation control of the contaminant as close to its point of generation is both the most economical and safest method to minimize personnel exposure to airborne contaminants. Ensure that the local ventilation moves the contaminant away from the worker.

11.4 Handling and Storage

11.4.1 Storage Conditions

Keep container tightly closed in a dry and well-ventilated place. Recommended storage temperature 2 - 8 °C.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

11.5 Exposure Control and Personal Protection

11.5.1 Personal Protective Equipment (PPE)

Eye/face protection: Use equipment for eye protection tested and approved under appropriate government standards such as NIOSH (US) or EN 166(EU).
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Skin protection: Handle with gloves.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Body Protection: Choose body protection in relation to its type, to the concentration and amount of dangerous substances, and to the specific work-place.
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html
Respiratory protection: Respiratory protection is not required. Where protection from nuisance levels of dusts are desired, use type N95 (US) or type P1 (EN 143) dust masks. Use respirators and components tested and approved under appropriate government standards such as NIOSH (US) or CEN (EU).
Sigma-Aldrich; Safety Data Sheet for Tobramycin. Product Number: T4014, Version 4.10 (Revision Date 05/11/2016). Available from, as of January 19, 2017: https://www.sigmaaldrich.com/safety-center.html

11.6 Regulatory Information

California Safe Cosmetics Program (CSCP) Reportable Ingredient

Hazard Traits - Developmental Toxicity

Authoritative List - Prop 65

Report - regardless of intended function of ingredient in the product

New Zealand EPA Inventory of Chemical Status
Tobramycin: Does not have an individual approval but may be used as a component in a product covered by a group standard. It is not approved for use as a chemical in its own right.

11.6.1 FDA Requirements

The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including tobramycin, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act.
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 1, 2017: https://www.fda.gov/cder/ob/
The Approved Drug Products with Therapeutic Equivalence Evaluations identifies currently marketed prescription drug products, including tobramycin sulfate, approved on the basis of safety and effectiveness by FDA under sections 505 of the Federal Food, Drug, and Cosmetic Act. /Tobramycin sulfate/
DHHS/FDA; Electronic Orange Book-Approved Drug Products with Therapeutic Equivalence Evaluations. Available from, as of March 1, 2017: https://www.fda.gov/cder/ob/

11.7 Other Safety Information

11.7.1 Special Reports

KAHLMETER G; GENTAMICIN AND TOBRAMYCIN. CLINICAL PHARMACOKINETICS AND NEPHROTOXICITY. ASPECTS ON ASSAY TECHNIQUES; SCAND J INFECT DIS (SUPPL) 18: 40PP (1979). REVIEW WITH 149 REFERENCES ON PHARMACOKINETICS & NEPHROTOXICITY OF GENTAMICIN & TOBRAMYCIN.

12 Toxicity

12.1 Toxicological Information

12.1.1 Toxicity Summary

IDENTIFICATION AND USE: Tobramycin is aminoglycoside antibiotic. HUMAN EXPOSURE AND TOXICITY: Serious allergic reactions including anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome have been reported rarely in patients on tobramycin therapy. Although rare, fatalities have been reported. Adverse effects on both the vestibular and auditory branches of the eighth nerve have been noted, especially in patients receiving high doses or prolonged therapy, in those given previous courses of therapy with an ototoxin, and in cases of dehydration. Symptoms include dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss. Hearing loss is usually irreversible and is manifested initially by diminution of high-tone acuity. Renal function changes, as shown by rising BUN, NPN, and serum creatinine and by oliguria, cylindruria, and increased proteinuria, have been reported, especially in patients with a history of renal impairment who are treated for longer periods or with higher doses than those recommended. Adverse renal effects can occur in patients with initially normal renal function. Clostridium difficile associated diarrhea has been reported with use of nearly all antibacterial agents, including Tobramycin for Injection, USP, and may range in severity from mild diarrhea to fatal colitis. ANIMAL STUDIES: Tobramycin applied as 5% eyedrops to rabbit eyes caused only mild conjunctival erythema. However, 0.3% tobramycin eyedrops interfered with healing of rabbit corneal endothelium. The mean number of dose days required to produce vestibulotoxic effects, demonstrated by impaired righting reflex or locomotor ataxia, was from 41 to 61 in cats dosed with tobramycin. Histologic examination of the cochleae revealed degeneration of the hair cells and supporting sensory structures in the majority of cats dosed with tobramycin at 40 and 80 mg/kg. Renal toxicity was observed in pregnant rats and their fetuses after maternal administration of high doses of tobramycin, 30 or 60 mg/kg/day fo 10 days, during organogenesis. The dose-related fetal renal toxicity consisted of granularity and swelling of proximal tubule cells, poor glomerular differentiation, and increased glomerular density.

12.1.2 Hepatotoxicity

Intravenous and intramuscular therapy with tobramycin is usually associated with no increase in rates of serum aminotransferase or bilirubin elevations. Only isolated case reports of acute liver injury with jaundice have been associated with aminoglycoside therapy including tobramycin, not all of which are very convincing. The hepatic injury is typically mixed but can evolve into a cholestatic hepatitis. The latency to onset is rapid, occurring within 1 to 3 weeks and is typically associated with skin rash, fever and sometimes eosinophilia. Recovery typically occurs within 1 to 2 months and chronic injury has not been described. Aminoglycosides are not mentioned in large case series of drug induced liver disease and acute liver failure; thus, hepatic injury due to tobramycin is rare if it occurs at all.

12.1.3 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

Tobramycin is poorly excreted into breastmilk. Newborn infants apparently absorb small amounts of other aminoglycosides, but serum levels with three times daily dosages are far below those attained when treating newborn infections and systemic effects of tobramycin are unlikely. Older infants would be expected to absorb even less tobramycin. Because there is little variability in the milk tobramycin levels during multiple daily dose regimens, timing breastfeeding with respect to the dose is of little or no benefit in reducing infant exposure. Data are not available with single daily dose regimens. Monitor the infant for possible effects on the gastrointestinal flora, such as diarrhea, candidiasis (e.g., thrush, diaper rash) or rarely, blood in the stool indicating possible antibiotic-associated colitis.

Maternal use of an ear drop or eye drop that contains tobramycin presents little or no risk for the nursing infant. A task force respiratory experts from Europe, Australia and New Zealand found that inhaled tobramycin is compatible with breastfeeding.

◉ Effects in Breastfed Infants

An infant was breastfed (extent not stated) until the 4th month postpartum. At 2 months of age, his mother was given a 2-week course of tobramycin 150 mg three times daily plus meropenem for a cystic fibrosis exacerbation. infant displayed no change in stool pattern during the maternal treatment and had normal renal function at 6 months of age.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

12.1.4 Acute Effects

12.1.5 Interactions

Concomitant and/or sequential use of an aminoglycoside and other systemic, oral, or topical drugs that have neurotoxic, ototoxic, or nephrotoxic effects (e.g., other aminoglycosides, acyclovir, amphotericin B, bacitracin, capreomycin, certain cephalosporins, colistin, cisplatin, methoxyflurane, polymyxin B, vancomycin) may result in additive toxicity and should be avoided, if possible. /Aminoglycosides/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 29
Because of the possibility of an increased risk of ototoxicity due to additive effects or altered serum and tissue aminoglycoside concentrations, aminoglycosides should not be given concomitantly with potent diuretics such as ethacrynic acid, furosemide, urea, or mannitol. It has been suggested that concomitant use of certain anti-emetics that suppress nausea and vomiting of vestibular origin and vertigo (e.g., dimenhydrinate, meclizine) may mask symptoms of aminoglycoside-associated vestibular ototoxicity. /Aminoglycosides/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 29
Concurrent use of an aminoglycoside with general anesthetics or neuromuscular blocking agents (e.g., succinylcholine, rocuronium, tubocurarine) may potentiate neuromuscular blockade and cause respiratory paralysis. ... Aminoglycosides should be used with caution in patients receiving anesthetics or neuromuscular blocking agents, and patients should be closely observed for signs of respiratory depression. /Aminoglycosides/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 29
In vitro studies indicate that the antibacterial activity of aminoglycosides and beta-lactam antibiotics may be additive or synergistic against some organisms including Enterobacteriaceae, Pseudomonas aeruginosa, enterococci, and viridans streptococci. The synergistic effect of aminoglycosides and beta-lactams is used to therapeutic advantage, especially in the treatment of infections caused by enterococci or Ps. aeruginosa. Although the exact mechanism of this synergistic effect has not been determined, it appears that by inhibiting bacterial cell-wall synthesis the penicillin allows more effective ingress of the aminoglycoside to the ribosomal binding site. Synergism between aminoglycosides and extended-spectrum penicillins generally is unpredictable and antagonism has been reported rarely in vitro when these penicillins were used in conjunction with amikacin, gentamicin, or tobramycin. Therefore, some clinicians suggest that when concomitant therapy is indicated it may be advisable to use appropriate in vitro studies to demonstrate synergism against the isolated organism. Concomitant administration of an extended-spectrum penicillin and an aminoglycoside has resulted in decreased serum aminoglycoside concentrations and elimination half life, especially in patients with renal impairment. Therefore, serum aminoglycoside concentrations should be monitored in patients receiving concomitant therapy, especially when very high doses of an extended-spectrum penicillin are used or when the patient has impaired renal function. /Aminoglycosides/
American Society of Health-System Pharmacists 2016; Drug Information 2016. Bethesda, MD. 2016, p. 29
For more Interactions (Complete) data for Tobramycin (10 total), please visit the HSDB record page.

12.1.6 Antidote and Emergency Treatment

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160
/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160
/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/
Currance, P.L. Clements, B., Bronstein, A.C. (Eds).; Emergency Care For Hazardous Materials Exposure. 3rd revised edition, Elsevier Mosby, St. Louis, MO 2007, p. 160-1

12.1.7 Human Toxicity Excerpts

/SIGNS AND SYMPTOMS/ Clinically apparent signs and symptoms of an overdose of tobramycin ophthalmic solution (punctate keratitis, erythema, increased lacrimation, edema and lid itching) may be similar to adverse reaction effects seen in some patients.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Solution/Drops) (Updated: May 2015). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=019172e3-bf24-4b76-9253-f58765d7b4f3
/SIGNS AND SYMPTOMS/ Serious allergic reactions including anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome have been reported rarely in patients on tobramycin therapy. Although rare, fatalities have been reported.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
/SIGNS AND SYMPTOMS/ Adverse effects on both the vestibular and auditory branches of the eighth nerve have been noted, especially in patients receiving high doses or prolonged therapy, in those given previous courses of therapy with an ototoxin, and in cases of dehydration. Symptoms include dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss. Hearing loss is usually irreversible and is manifested initially by diminution of high-tone acuity. Tobramycin and gentamicin sulfates closely parallel each other in regard to ototoxic potential.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
/SIGNS AND SYMPTOMS/ Renal function changes, as shown by rising BUN, NPN, and serum creatinine and by oliguria, cylindruria, and increased proteinuria, have been reported, especially in patients with a history of renal impairment who are treated for longer periods or with higher doses than those recommended. Adverse renal effects can occur in patients with initially normal renal function.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
For more Human Toxicity Excerpts (Complete) data for Tobramycin (11 total), please visit the HSDB record page.

12.1.8 Non-Human Toxicity Excerpts

/LABORATORY ANIMALS: Acute Exposure/ .../Tobramycin/ applied as 5% eyedrops to rabbit eyes caused only mild conjunctival erythema... However, 0.3% tobramycin eyedrops interfered with healing of rabbit corneal endothelium.
Grant, W.M. Toxicology of the Eye. 3rd ed. Springfield, IL: Charles C. Thomas Publisher, 1986., p. 925
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ In this study, mixed-breed cats (four/group) were given daily sc injections of netilmicin (20, 40, and 80 mg/kg), gentamicin (20 and 40 mg/kg), or tobramycin (20, 40, and 80 mg/kg) for up to 30 weeks or until ototoxicity was observed. The animals were examined throughout the study for effects on cochlear and vestibular function. Hematologic, serum chemical, and drug-serum (24-hr postdose) assays were performed at approximate monthly intervals during the dosing period. The cochleae, kidneys, and liver were examined microscopically. The mean number of dose days required to produce vestibulotoxic effects, demonstrated by impaired righting reflex or locomotor ataxia, was from 41 to 61 in cats dosed with tobramycin (40 and 80 mg/kg) or gentamicin. No vestibular dysfunction was observed in any of the netilmicin 20-mg/kg-dosed cats, in two cats each of the tobramycin 20-mg/kg and netilmicin 40-mg/kg groups, and in one netilmicin 80-mg/kg-dosed animal. Histologic examination of the cochleae revealed degeneration of the hair cells and supporting sensory structures in the majority of cats dosed with gentamicin at 20 and 40 mg/kg and tobramycin at 40 and 80 mg/kg. Less than 50% of the tissues from cats of the tobramycin 20-mg/kg and netilmicin 40- and 80-mg/kg-dosed groups had similar degenerative cochlear changes. No cochlear damage was noted in any of the cats given netilmicin at 20 mg/kg. Results of the clinical laboratory determinations were generally unremarkable. Proximal tubular degeneration was the principal finding observed in the kidneys of the animals. Under the conditions of this study, at least a twofold (vestibular) to fourfold (cochlear) relative safety margin for ototoxicity was established in favor of netilmicin over tobramycin and gentamicin.
McCormick GC et al; Toxicol Appl Pharmacol 77 (3): 479-89 (1985)
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /The purpose of this study was/ to investigate the possible differences in cochleotoxic effects in rabbits between twice-daily administration of topical gentamicin and tobramycin throughout the perforated tympanic membrane with the use of distortion-product otoacoustic emissions (DPOAEs). Twenty female rabbits were studied prospectively daily for 21 days. The rabbits' ears were divided into two groups: right and left ear groups. Twice-daily for 21 days after paracentesis, 0.3% gentamicin was administered topically in the left ears, and 0.3% tobramycin was administered topically in the right ears. For 21 days, the cochlear activity of the right and left ears of all rabbits was examined every 7 days using DPOAEs. The numerical values of the distortion product (DP) intensity recorded on days 7, 14 and 21 of drug administration were compared between the two groups. Cochlear activity was reduced earlier in the gentamicin group in the 2-4 kHz frequencies compared to the tobramycin group in the second DPOAE measurement (day 7 of the experiment). In two rabbits in the gentamicin group, the third DPOAE measurement showed that cochlear activity was reduced in all frequencies. In six rabbits in the tobramycin group, the third DPOAE measurement showed that cochlear activity was reduced in all frequencies. There was no statistical significance between the two groups except day 7 in the 2 and 3 kHz frequencies (p<0.05). We concluded that low frequencies (2 and 3 kHz) are more sensitive to the administration of topical gentamicin than to topical tobramycin. Early cessation of tobramycin drops may be minimally cochlear toxic compared to gentamicin within the first 7 days when these drugs are misused in treating chronic otitis media.
Oghan F et al; Int J Pediatr Otorhinolaryngol 75 (7): 915-8 (2011)
/LABORATORY ANIMALS: Subchronic or Prechronic Exposure/ /The purpose of the research was/ to study the possible age-dependent ototoxic effects of tobramycin a subacute toxicity study was performed. To young adult (3 months) and old (27-30 months) female Wag-Rij rats 0, 10, 40, and 160 mg tobramycin sulfate/kg was administered subcutaneously in two doses a day. After 14 days all animals were autopsied. The cochlea was fixed by perfusion through the opened oval window and prepared for scanning electron microscopy. The rat cochlea consists of two turns. In all animals of the young control group the row of inner hair cells (IHC) as well as the three rows of outer hair cells (OHC) of the organ of Corti were fully intact. IHC as well as OHC are provided with three rows of stereocilia, from inside to outside with increasing length. The stereocilia of OHC are arranged in a characteristic W-configuration. In the young low dose group effects were focally seen in only 1 of 10 rats, consisting of shortened, disoriented or partly disappeared stereocilia of IHC and OHC in the basal turn. In the young mid dose group 4 of 10 animals had focally shortened, disoriented, and less stereocilia in the first row of OHC in the basal turn, and once of IHC and OHC in the apical turn. Seven of 8 animals of the young high dose group showed effects consisting of focal loss or shortening of stereocilia of IHC and OHC of the apical turn (3x), of OHC in the basal turn (3x), and once of stereocilia of IHC only. In the old control group the stereocilia of IHC were fully intact. However, many OHC, independent of row or turn, had no stereocilia at all. The percentages of OHC without stereocilia in the three rows of the apical and basal turns were 44-10-50 and 40-20-50, respectively. In the old low, mid, and high dose group the percentages of OHC without stereocilia were nearly identical to those of the old control group. In the old low and high dose group a reduced number of stereocilia per IHC occurred in half of the number of animals, while in the mid dose group the IHC were fully intact. In young adult animals the number of mildly affected cochleae increased as well as the extent of the lesion increased with increasing dose of tobramycin. The lesions of IHC and OHC, consisting of a decrease in number or shortening of stereocilia, were restricted mainly to (the last part of) the basal turn. As old control rats showed already a large number of OHC without stereocilia, the possible ototoxic effects of tobramycin were not detected against this "background" of stereociliary loss, consistent with aging. The damage in old rats was certainly not greater than in young adult rats. In conclusion, old rats were not more sensitive to the possible ototoxic effects of tobramycin than young adult rats.
Dormans JA et al; Toxicol Appl Pharmacol 136 (1): 179-85 (1996)
For more Non-Human Toxicity Excerpts (Complete) data for Tobramycin (9 total), please visit the HSDB record page.

12.1.9 Non-Human Toxicity Values

LD50 Guinea pig sc 676 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3477
LD50 Mouse im 440 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3477
LD50 Mouse iv 72,500 ug/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3477
LD50 Mouse sc 367 mg/kg
Lewis, R.J. Sr. (ed) Sax's Dangerous Properties of Industrial Materials. 11th Edition. Wiley-Interscience, Wiley & Sons, Inc. Hoboken, NJ. 2004., p. 3477
For more Non-Human Toxicity Values (Complete) data for Tobramycin (8 total), please visit the HSDB record page.

12.1.10 Ongoing Test Status

EPA has released the Interactive Chemical Safety for Sustainability (iCSS) Dashboard. The iCSS Dashboard provides an interactive tool to explore rapid, automated (or in vitro high-throughput) chemical screening data generated by the Toxicity Forecaster (ToxCast) project and the federal Toxicity Testing in the 21st century (Tox21) collaboration. /The title compound was tested by ToxCast and/or Tox21 assays/[USEPA; ICSS Dashboard Application; Available from, as of December 8, 2016: http://actor.epa.gov/dashboard/]

12.1.11 Populations at Special Risk

Renal function changes, as shown by rising blood urea nitrogen (BUN), non-protein nitrogen (NPN), and serum creatinine and by oliguria, cylindruria, and increased proteinuria, have been reported, especially in patients with a history of renal impairment ... .
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
Tobramycin is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Dose reduction is required for patients with impaired renal function. Elderly patients may have reduced renal function that may not be evident in the results of routine screening tests, such as blood urea nitrogen (BUN) or serum creatinine. A creatinine clearance determination may be more useful. Monitoring of renal function during treatment with aminoglycosides is particularly important in the elderly.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
Aminoglycosides should be used with caution in patients with muscular disorders, such as myasthenia gravis or parkinsonism, since these drugs may aggravate muscle weakness because of their potential curare-like effect on neuromuscular function. /Aminoglycosides/
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
Elderly patients may be at a higher risk of developing nephrotoxicity and ototoxicity while receiving tobramycin.
NIH; DailyMed. Current Medication Information for Tobramycin (Tobramycin Sulfate Injection, Powder, For Solution) (Updated: January 2016). Available from, as of February 13, 2017: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d62ff359-912b-4be1-9fc2-2dde8777eefb
For more Populations at Special Risk (Complete) data for Tobramycin (6 total), please visit the HSDB record page.

12.1.12 Protein Binding

Tobramycin binding to serum proteins is negligible.

13 Associated Disorders and Diseases

14 Literature

14.1 Consolidated References

14.2 NLM Curated PubMed Citations

14.3 Springer Nature References

14.4 Thieme References

14.5 Nature Journal References

14.6 Chemical Co-Occurrences in Literature

14.7 Chemical-Gene Co-Occurrences in Literature

14.8 Chemical-Disease Co-Occurrences in Literature

15 Patents

15.1 Depositor-Supplied Patent Identifiers

15.2 WIPO PATENTSCOPE

15.3 FDA Orange Book Patents

15.4 Chemical Co-Occurrences in Patents

15.5 Chemical-Disease Co-Occurrences in Patents

15.6 Chemical-Gene Co-Occurrences in Patents

16 Interactions and Pathways

16.1 Protein Bound 3D Structures

16.1.1 Ligands from Protein Bound 3D Structures

PDBe Ligand Code
PDBe Structure Code
PDBe Conformer

16.2 Chemical-Target Interactions

16.3 Drug-Drug Interactions

16.4 Pathways

17 Biological Test Results

17.1 BioAssay Results

18 Taxonomy

The LOTUS Initiative for Open Natural Products Research: frozen dataset union wikidata (with metadata) | DOI:10.5281/zenodo.5794106

19 Classification

19.1 MeSH Tree

19.2 NCI Thesaurus Tree

19.3 ChEBI Ontology

19.4 KEGG: Drug

19.5 KEGG: USP

19.6 KEGG: ATC

19.7 KEGG: JP15

19.8 KEGG: Drug Groups

19.9 KEGG : Antimicrobials

19.10 KEGG: Drug Classes

19.11 WHO ATC Classification System

19.12 FDA Pharm Classes

19.13 ChemIDplus

19.14 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

19.15 ChEMBL Target Tree

19.16 UN GHS Classification

19.17 NORMAN Suspect List Exchange Classification

19.18 EPA DSSTox Classification

19.19 The Natural Products Atlas Classification

19.20 LOTUS Tree

19.21 FDA Drug Type and Pharmacologic Classification

19.22 EPA Substance Registry Services Tree

19.23 MolGenie Organic Chemistry Ontology

20 Information Sources

  1. California Office of Environmental Health Hazard Assessment (OEHHA)
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    (2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)oxane-3,5-diol
    https://echa.europa.eu/substance-information/-/substanceinfo/100.120.947
    (2S,3R,4S,5S,6R)-4-amino-2-{[(1S,2S,3R,4S,6R)-4,6-diamino-3-{[(2R,3R,5S,6R)-3-amino-6-(aminomethyl)-5-hydroxyoxan-2-yl]oxy}-2-hydroxycyclohexyl]oxy}-6-(hydroxymethyl)oxane-3,5-diol (EC: 616-717-2)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/73223
  16. FDA Global Substance Registration System (GSRS)
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  17. Hazardous Substances Data Bank (HSDB)
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  19. ChEMBL
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    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  20. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  21. Comparative Toxicogenomics Database (CTD)
    LICENSE
    It is to be used only for research and educational purposes. Any reproduction or use for commercial purpose is prohibited without the prior express written permission of NC State University.
    http://ctdbase.org/about/legal.jsp
  22. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  23. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  24. Therapeutic Target Database (TTD)
  25. DailyMed
  26. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  27. Drugs and Lactation Database (LactMed)
  28. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  29. WHO Model Lists of Essential Medicines
    LICENSE
    Permission from WHO is not required for the use of WHO materials issued under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Intergovernmental Organization (CC BY-NC-SA 3.0 IGO) license.
    https://www.who.int/about/policies/publishing/copyright
  30. EU Clinical Trials Register
  31. FDA Orange Book
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  32. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Tobramycin
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  33. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  34. National Drug Code (NDC) Directory
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  35. Japan Chemical Substance Dictionary (Nikkaji)
  36. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Therapeutic category of drugs in Japan
    http://www.genome.jp/kegg-bin/get_htext?br08301.keg
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Drugs listed in the Japanese Pharmacopoeia
    http://www.genome.jp/kegg-bin/get_htext?br08311.keg
  37. MassBank of North America (MoNA)
    LICENSE
    The content of the MoNA database is licensed under CC BY 4.0.
    https://mona.fiehnlab.ucdavis.edu/documentation/license
  38. Metabolomics Workbench
  39. Nature Chemical Biology
  40. NIPH Clinical Trials Search of Japan
  41. NIST Mass Spectrometry Data Center
    LICENSE
    Data covered by the Standard Reference Data Act of 1968 as amended.
    https://www.nist.gov/srd/public-law
  42. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  43. PharmGKB
    LICENSE
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    https://www.pharmgkb.org/page/policies
  44. Protein Data Bank in Europe (PDBe)
  45. RCSB Protein Data Bank (RCSB PDB)
    LICENSE
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    https://www.rcsb.org/pages/policies
  46. SpectraBase
    4,6-Diamino-3-[(3-amino-3-deoxyhexopyranosyl)oxy]-2-hydroxycyclohexyl 2,6-diamino-2,3,6-trideoxyhexopyranoside
    https://spectrabase.com/spectrum/1Gi59aVj8QI
  47. Springer Nature
  48. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  49. Wikidata
  50. Wikipedia
  51. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
  52. PubChem
  53. GHS Classification (UNECE)
  54. The Natural Products Atlas
    LICENSE
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    https://www.npatlas.org/terms
    The Natural Products Atlas Classification
    https://www.npatlas.org/
  55. EPA Substance Registry Services
  56. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  57. PATENTSCOPE (WIPO)
  58. NCBI
CONTENTS