Dosing & Uses
Dosage Forms & Strengths
injectable solution
- 10mg/mL
- 40mg/mL
Solution reconstituted
- 1.2g
Bacterial Infections
3-6 mg/kg/day IV/IM divided q8hr OR
4-7 mg/kg/dose IV/IM qDay
Renal Impairment
Clcr >60 mL/min: q8hr
Clcr 40-60 mL/min: q12hr
Clcr 20-40 mL/min: q24hr
Clcr 10-20 mL/min: q48hr
Clcr <10 mL/min: q72hr
Following dialysis in ESRD
Monitor
Peak and trough concentrations, renal and auditory function
Life-threatening infection: 8-10 mcg/mL
Serious infection: 6-8 mcg/mL
UTIs: 4-6 mcg/mL
Synergy for infections caused by gram-positive organisms: 3-5 mcg/mL
Other Indications & Uses
May have increase activity against resistant Gram negatives
Citrobacter spp., E. coli, P. aeruginosa, Proteus spp. (indole-positive and negative), Providencia spp. (including Klebsiella-Enterobacter-Serratia), S. aureus (coagulase-positive and negative)
Dosage Forms & Strengths
injectable solution
- 10mg/mL
- 40mg/mL
Cystic Fibrosis
Neonates
<30 week gestation
- <28 days old: 2.5 mg/kg IV/IM qDay
- ≥28 days old: 3 mg/kg IV/IM qDay
30-36 week gestation
- <14 days old: 3 mg/kg IV/IM qDay
- ≥14 days old: 5 mg/kg/day IV/IM divided q12hr
>37 week gestation
- <7 days old: 5 mg/kg/day IV/IM divided q12hr
- ≥7 days old: 7.5 mg/kg/day IV/IM divided q8hr
Bacterial Infection
<5 years old: 2.5 mg/kg/dose IV/IM q8hr
≥5 years old: 2-2.5 mg/kg/dose IV/IM q8hr
Hemodialysis: 1.25-1.75 mg/kg/dose postdialysis
Monitor
Peak and trough concentrations, renal and auditory function
Life-threatening infection: 8-10 mcg/mL
Serious infection: 6-8 mcg/mL
UTIs: 4-6 mcg/mL
Synergy for infections caused by gram-positive organisms: 3-5 mcg/mL
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (22)
- amphotericin B deoxycholate
amphotericin B deoxycholate and tobramycin both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug.
- atracurium
tobramycin increases effects of atracurium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
- bacitracin
tobramycin and bacitracin both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug. Avoid concurrent use of bacitracin with other nephrotoxic drugs
- BCG vaccine live
tobramycin decreases effects of BCG vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.
- bumetanide
bumetanide, tobramycin. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of ototoxicity and nephrotoxicity.
- cholera vaccine
tobramycin, cholera vaccine. pharmacodynamic antagonism. Avoid or Use Alternate Drug. Avoid coadministration of cholera vaccine with systemic antibiotics since these agents may be active against the vaccine strain. Do not administer cholera vaccine to patients who have received oral or parenteral antibiotics within 14 days prior to vaccination.
- cidofovir
cidofovir and tobramycin both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug.
- cisatracurium
tobramycin increases effects of cisatracurium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
- ethacrynic acid
ethacrynic acid, tobramycin. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of ototoxicity and nephrotoxicity.
- furosemide
furosemide, tobramycin. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of ototoxicity and nephrotoxicity.
- incobotulinumtoxinA
tobramycin increases effects of incobotulinumtoxinA by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
- mannitol
mannitol increases levels of tobramycin by unspecified interaction mechanism. Contraindicated.
- neomycin PO
neomycin PO and tobramycin both increase nephrotoxicity and/or ototoxicity. Avoid or Use Alternate Drug.
- onabotulinumtoxinA
tobramycin increases effects of onabotulinumtoxinA by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
- pancuronium
tobramycin increases effects of pancuronium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
- quinidine
quinidine will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.
- rapacuronium
tobramycin increases effects of rapacuronium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
- rocuronium
tobramycin increases effects of rocuronium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
- succinylcholine
tobramycin increases effects of succinylcholine by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
- torsemide
torsemide, tobramycin. Either increases toxicity of the other by Mechanism: pharmacodynamic synergism. Avoid or Use Alternate Drug. Increased risk of ototoxicity and nephrotoxicity.
- typhoid vaccine live
tobramycin decreases effects of typhoid vaccine live by pharmacodynamic antagonism. Contraindicated. Wait until Abx Tx complete to administer live bacterial vaccine.
- vecuronium
tobramycin increases effects of vecuronium by pharmacodynamic synergism. Avoid or Use Alternate Drug. Risk of apnea.
Monitor Closely (66)
- abobotulinumtoxinA
tobramycin increases effects of abobotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Aminoglycosides may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.
- acyclovir
acyclovir and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- amikacin
amikacin and tobramycin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.
- amiodarone
amiodarone will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- bazedoxifene/conjugated estrogens
tobramycin will decrease the level or effect of bazedoxifene/conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- capreomycin
capreomycin and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- carboplatin
carboplatin and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- cephaloridine
cephaloridine and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- cisplatin
cisplatin and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- clarithromycin
clarithromycin will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- clotrimazole
clotrimazole will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- colistin
colistin and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- conjugated estrogens
tobramycin will decrease the level or effect of conjugated estrogens by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- contrast media (iodinated)
contrast media (iodinated) and tobramycin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.
- cyclosporine
cyclosporine and tobramycin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.
- daptomycin
tobramycin, daptomycin. Mechanism: unspecified interaction mechanism. Use Caution/Monitor. Tobramycin levels decrease and daptomycin levels increase when coadministered after single a dose.
- deferasirox
deferasirox, tobramycin. Other (see comment). Use Caution/Monitor. Comment: Acute renal failure has been reported during treatment with deferasirox. Coadministration of deferasirox with other potentially nephrotoxic drugs, including aminoglycosides, may increase the risk of this toxicity. Monitor serum creatinine and/or creatinine clearance in patients who are receiving deferasirox and nephrotoxic drugs concomitantly.
- dichlorphenamide
dichlorphenamide and tobramycin both decrease serum potassium. Use Caution/Monitor.
- digoxin
tobramycin will increase the level or effect of digoxin by altering intestinal flora. Applies only to oral form of both agents. Use Caution/Monitor.
- dronedarone
dronedarone will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
tobramycin and elvitegravir/cobicistat/emtricitabine/tenofovir DF both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- erythromycin base
erythromycin base will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin ethylsuccinate
erythromycin ethylsuccinate will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin lactobionate
erythromycin lactobionate will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- erythromycin stearate
erythromycin stearate will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- estradiol
tobramycin will decrease the level or effect of estradiol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- estrogens conjugated synthetic
tobramycin will decrease the level or effect of estrogens conjugated synthetic by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- estropipate
tobramycin will decrease the level or effect of estropipate by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- felodipine
felodipine will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- fosphenytoin
fosphenytoin will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- gentamicin
gentamicin and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- indinavir
indinavir will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- ioversol
ioversol and tobramycin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.
- ketoconazole
ketoconazole will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- levoketoconazole
levoketoconazole will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- loratadine
loratadine will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- magnesium supplement
magnesium supplement, tobramycin. Either increases toxicity of the other by pharmacodynamic synergism. Use Caution/Monitor. Each enhance the neuromuscular blocking effect of the other; may have negative respiratory effects.
- mestranol
tobramycin will decrease the level or effect of mestranol by altering intestinal flora. Applies only to oral forms of hormone. Low risk of contraceptive failure. Use Caution/Monitor.
- nefazodone
nefazodone will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nicardipine
nicardipine will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nifedipine
nifedipine will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- nilotinib
nilotinib will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- oxaliplatin
oxaliplatin and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- peramivir
tobramycin increases levels of peramivir by decreasing renal clearance. Use Caution/Monitor. Caution when peramivir coadministered with nephrotoxic drugs.
- phenobarbital
phenobarbital will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- phenytoin
phenytoin will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- polymyxin B
polymyxin B and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- prabotulinumtoxinA
tobramycin increases effects of prabotulinumtoxinA by pharmacodynamic synergism. Use Caution/Monitor. Aminoglycosides may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.
- quercetin
quercetin will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rifampin
rifampin will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- rimabotulinumtoxinB
tobramycin, rimabotulinumtoxinB. Either increases effects of the other by pharmacodynamic synergism. Use Caution/Monitor. Aminoglycosides may enhance botulinum toxin effects. Closely monitor for increased neuromuscular blockade.
- ritonavir
ritonavir will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sirolimus
sirolimus will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- sodium picosulfate/magnesium oxide/anhydrous citric acid
tobramycin decreases effects of sodium picosulfate/magnesium oxide/anhydrous citric acid by altering metabolism. Use Caution/Monitor. Coadministration with antibiotics decreases efficacy by altering colonic bacterial flora needed to convert sodium picosulfate to active drug.
- sodium sulfate/?magnesium sulfate/potassium chloride
sodium sulfate/?magnesium sulfate/potassium chloride increases toxicity of tobramycin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.
- sodium sulfate/potassium sulfate/magnesium sulfate
sodium sulfate/potassium sulfate/magnesium sulfate increases toxicity of tobramycin by Other (see comment). Use Caution/Monitor. Comment: Coadministration with medications that cause fluid and electrolyte abnormalities may increase the risk of adverse events of seizure, arrhythmias, and renal impairment.
- St John's Wort
St John's Wort will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- streptozocin
streptozocin and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
- tacrolimus
tacrolimus will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
tacrolimus and tobramycin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. - teicoplanin
teicoplanin and tobramycin both increase nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely.
- tenofovir DF
tenofovir DF and tobramycin both increase nephrotoxicity and/or ototoxicity. Use Caution/Monitor.
tobramycin increases levels of tenofovir DF by decreasing elimination. Use Caution/Monitor. - tolvaptan
tolvaptan will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- trazodone
trazodone will decrease the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- trimagnesium citrate anhydrous
tobramycin, trimagnesium citrate anhydrous. Either increases effects of the other by Other (see comment). Use Caution/Monitor. Comment: Coadministration of aminoglycosides with magnesium may increase risk of neuromuscular weakness and paralysis.
- verapamil
verapamil will increase the level or effect of tobramycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.
- voclosporin
voclosporin, tobramycin. Either increases toxicity of the other by nephrotoxicity and/or ototoxicity. Modify Therapy/Monitor Closely. Coadministration with drugs associated with nephrotoxicity may increase the risk for acute and/or chronic nephrotoxicity.
Minor (71)
- aceclofenac
aceclofenac increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- acemetacin
acemetacin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- adefovir
adefovir and tobramycin both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.
- aspirin
aspirin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- aspirin rectal
aspirin rectal increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- aspirin/citric acid/sodium bicarbonate
aspirin/citric acid/sodium bicarbonate increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- aztreonam
aztreonam, tobramycin. Either increases effects of the other by pharmacodynamic synergism. Minor/Significance Unknown. Combination may be used synergistically against Pseudomonas spp. and Enterobacteriaceae.
- balsalazide
tobramycin will decrease the level or effect of balsalazide by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
- biotin
tobramycin will decrease the level or effect of biotin by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
- calcium acetate
tobramycin decreases levels of calcium acetate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- calcium carbonate
tobramycin decreases levels of calcium carbonate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- calcium chloride
tobramycin decreases levels of calcium chloride by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- calcium citrate
tobramycin decreases levels of calcium citrate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- calcium gluconate
tobramycin decreases levels of calcium gluconate by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- celecoxib
celecoxib increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- choline magnesium trisalicylate
choline magnesium trisalicylate increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- clotrimazole
clotrimazole decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.
- cordyceps
cordyceps decreases toxicity of tobramycin by unspecified interaction mechanism. Minor/Significance Unknown.
- cyanocobalamin
tobramycin decreases levels of cyanocobalamin by inhibition of GI absorption. Applies only to oral form of both agents. Minor/Significance Unknown.
- diclofenac
diclofenac increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- diflunisal
diflunisal increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- entecavir
tobramycin, entecavir. Either increases effects of the other by decreasing renal clearance. Minor/Significance Unknown. Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase serum concentrations of either entecavir or the coadministered drug.
- etodolac
etodolac increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- fenoprofen
fenoprofen increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- fluconazole
fluconazole decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.
- flurbiprofen
flurbiprofen increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- foscarnet
foscarnet and tobramycin both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.
- ibuprofen
ibuprofen increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- ibuprofen IV
ibuprofen IV increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- indomethacin
indomethacin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- ketoconazole
ketoconazole decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.
- ketoprofen
ketoprofen increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- ketorolac
ketorolac increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- ketorolac intranasal
ketorolac intranasal increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- levoketoconazole
levoketoconazole decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.
- lornoxicam
lornoxicam increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- magnesium chloride
tobramycin decreases levels of magnesium chloride by increasing renal clearance. Minor/Significance Unknown.
- magnesium citrate
tobramycin decreases levels of magnesium citrate by increasing renal clearance. Minor/Significance Unknown.
- magnesium hydroxide
tobramycin decreases levels of magnesium hydroxide by increasing renal clearance. Minor/Significance Unknown.
- magnesium oxide
tobramycin decreases levels of magnesium oxide by increasing renal clearance. Minor/Significance Unknown.
- magnesium sulfate
tobramycin decreases levels of magnesium sulfate by increasing renal clearance. Minor/Significance Unknown.
- meclizine
meclizine, tobramycin. Mechanism: unspecified interaction mechanism. Minor/Significance Unknown. Ototoxicity of aminoglycoside may be masked.
- meclofenamate
meclofenamate increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- mefenamic acid
mefenamic acid increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- meloxicam
meloxicam increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- methoxyflurane
methoxyflurane and tobramycin both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.
- miconazole vaginal
miconazole vaginal decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.
- nabumetone
nabumetone increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- naproxen
naproxen increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- oxaprozin
oxaprozin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- pantothenic acid
tobramycin will decrease the level or effect of pantothenic acid by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
- parecoxib
parecoxib increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- paromomycin
paromomycin and tobramycin both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.
- pentamidine
pentamidine and tobramycin both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.
- piperacillin
piperacillin increases effects of tobramycin by pharmacodynamic synergism. Minor/Significance Unknown.
- piroxicam
piroxicam increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- posaconazole
posaconazole decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.
- pyridoxine
tobramycin will decrease the level or effect of pyridoxine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
- pyridoxine (Antidote)
tobramycin will decrease the level or effect of pyridoxine (Antidote) by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
- salicylates (non-asa)
salicylates (non-asa) increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- salsalate
salsalate increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- streptomycin
streptomycin and tobramycin both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.
- sulfasalazine
sulfasalazine increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- sulindac
sulindac increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- thiamine
tobramycin will decrease the level or effect of thiamine by altering intestinal flora. Applies only to oral form of both agents. Minor/Significance Unknown.
- ticarcillin
ticarcillin decreases effects of tobramycin by altering metabolism. Minor/Significance Unknown. Increased risk in renal impairment.
- tolfenamic acid
tolfenamic acid increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- tolmetin
tolmetin increases levels of tobramycin by decreasing renal clearance. Minor/Significance Unknown. Interaction mainly occurs in preterm infants.
- vancomycin
tobramycin and vancomycin both increase nephrotoxicity and/or ototoxicity. Minor/Significance Unknown.
- voriconazole
voriconazole decreases levels of tobramycin by unknown mechanism. Minor/Significance Unknown.
- zoledronic acid
tobramycin, zoledronic acid. Mechanism: pharmacodynamic synergism. Minor/Significance Unknown. Additive hypocalcemia.
Adverse Effects
1-10%
Ototoxicity
Nephrotoxicity
Neurotoxicity (neuromuscular blockade)
<1%
Hypotension
Drug fever
Drowsiness
Headache
Paresthesia
Tremor
Rash
Nausea
Vomiting
Anemia
Eosinophilia
Arthralgia
Weakness
Eyelid edema
Itching eyes
Keratitis
Lacrimation
Dyspnea
Warnings
Black Box Warnings
Neurotoxicity, manifested as both bilateral auditory and vestibular ototoxicity, can occur in patients with preexisting renal damage and in patients with normal renal function treated at higher doses and/or for periods longer than those recommended; high-frequency deafness usually occurs first and can be detected only by audiometric testing; vertigo may occur and may be evidence of vestibular injury
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
When feasible, 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 drug or dosage adjustment
Aminoglycosides are potentially nephrotoxic; risk is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy; rarely, nephrotoxicity may not become apparent until the first few days after cessation of therapy
Use with caution in premature infants and neonates because of renal immaturity and the resulting prolongation of serum half-life of the drug
Neuromuscular blockade and respiratory paralysis have been reported following parenteral injection, topical instillation (as in orthopedic and abdominal irrigation or in local treatment of empyema), and oral use of aminoglycosides, especially when given soon after anesthesia or muscle relaxants; if blockage occurs, calcium salts may reverse these phenomena, but mechanical respiratory assistance may be necessary
Avoid concurrent or sequential use of neurotoxic and/or nephrotoxic drugs including other aminoglycosides (eg, amikacin, streptomycin, neomycin, kanamycin, gentamicin, paromomycin
Cumulative listing of drugs to avoid from all aminoglycoside package inserts includes amphotericin B, bacitracin, cephaloridine, cisplatin, colistin, polymyxin B, vancomycin, and viomycin. Avoid potent diuretics (eg, ethacrynic acid, furosemide) because they increase risk of ototoxicity. When administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue
Contraindications
Documented hypersensitivity to any aminoglycoside or history of hypersensitivity or serious toxic reactions to aminoglycosides
Cautions
Serious allergic sometimes fatal reactions including anaphylaxis and dermatologic reactions including exfoliative dermatitis, toxic epidermal necrolysis, erythema multiforme, and Stevens-Johnson Syndrome reported rarely; discontinue therapy If allergic reaction occurs, drug should be discontinued and appropriate therapy instituted
Serum and urine specimens for examination should be collected during therapy; serum calcium, magnesium, and sodium should be monitored
Cross-allergenicity among aminoglycosides has been demonstrated
In patients with extensive burns or cystic fibrosis, altered pharmacokinetics may result in reduced serum concentrations of aminoglycosides; in such patients treated with tobramycin, measurement of serum concentration is especially important as a basis for determination of appropriate dosage
Elderly patients may have reduced renal function that may not be evident in results of routine screening tests, such as BUN or serum creatinine; a creatinine clearance determination may be more useful; monitoring of renal function during treatment with aminoglycosides is particularly important in such patients
An increased incidence of nephrotoxicity reported following concomitant administration of aminoglycoside antibiotics and cephalosporins
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 potential curare-like effect on neuromuscular function
Aminoglycosides may be absorbed in significant quantities from body surfaces after local irrigation or application and may cause neurotoxicity and nephrotoxicity
Aminoglycosides have not been approved for intraocular and/or subconjunctival use; physicians are advised that macular necrosis has been reported following administration of aminoglycosides, including tobramycin, by these routes
The inactivation of tobramycin and other aminoglycosides by ß-lactam-type antibiotics (penicillins or cephalosporins) has been demonstrated in vitro and in
patients with severe renal impairment; such inactivation has not been found in patients with normal renal function who have been given the drugs by separate routes of administration
Therapy with tobramycin may result in overgrowth of nonsusceptible organisms; if overgrowth of nonsusceptible organisms occurs, appropriate therapy should be initiated
Clostridium difficile
- Clostridium difficile associated diarrhea (CDAD) reported; may range
- in severity from mild diarrhea to fatal colitis; treatment with antibacterial agents alters normal flora of colon leading to overgrowth of C. difficile
- C. difficile produces toxins A and B which contribute to 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
Peak and trough levels
- Peak and trough serum levels should be measured periodically during therapy; prolonged concentrations above 12 mcg/mL should be avoided
- Rising trough levels (above 2 mcg/mL) may indicate tissue accumulation; such accumulation, advanced age, and cumulative dosage may contribute to ototoxicity and nephrotoxicity; it is particularly important to monitor serum levels closely in patients with known renal impairment.
- A useful guideline would be to perform serum level assays after 2 or 3 doses, so that dosage could be adjusted if necessary, and at 3- to 4-day intervals during therapy
- In the event of changing renal function, more frequent serum levels should be obtained and the dosage or dosage interval adjusted according to guidelines
- In order to measure the peak level, a serum sample should be drawn about 30 minutes following intravenous infusion or 1 hour after an intramuscular injection
- Trough levels are measured by obtaining serum samples at 8 hours or just prior to next dose; these suggested time intervals are intended only as guidelines and may vary according to institutional practices
- It is important, that there be consistency within individual patient program unless computerized pharmacokinetic dosing programs are available in the institution
- Serum-level assays may be especially useful for monitoring treatment of severely ill patients with changing renal function or of those infected with less susceptible organisms or those receiving maximum dosage
Ototoxicity
- Ototoxicity may occur in some patients even when their aminoglycoside serum levels are within recommended range
- Postmarketing experience, patients receiving therapy have reported hearing loss; vestibular toxicity may be manifested by vertigo, ataxia or dizziness; patients with known or suspected auditory or vestibular dysfunction should be closely monitored when receiving therapy; monitoring might include obtaining audiometric evaluations and serum tobramycin levels;
- Mitochondrial DNA variants are present in <1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity as well as severity of ototoxicity is unknown
- In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than aminoglycosides unless increased risk of permanent hearing loss is outweighed by severity of infection and lack of safe and effective alternative therapies
Neuromuscular blockade
- Neuromuscular blockade and respiratory paralysis have been reported in cats receiving very high doses of tobramycin (40 mg/kg)
- Possibility of prolonged or secondary apnea should be considered if tobramycin is administered to anesthetized patients who are also receiving neuromuscular blocking agents, such as succinylcholine, tubocurarine, or decamethonium, or to patients receiving massive transfusions of citrated blood
- If neuromuscular blockade occurs, may be reversed by administration of calcium salts
Pregnancy & Lactation
Pregnancy
Therapy, can cause fetal harm when administered to a pregnant woman; published literature reports that use of streptomycin, an aminoglycoside, can cause total, irreversible, bilateral congenital deafness when administered to a pregnant woman
Animal data
- In animal reproduction studies with subcutaneous administration of tobramycin in pregnant rats and rabbits during organogenesis, there were no adverse developmental outcomes at doses up to 3.2 times and 1.3 times maximum recommended clinical dose based on body surface area; however, ototoxicity was not evaluated in offspring from these studies; advise pregnant women of potential risk to a fetus
Lactation
Limited published data with tobramycin for injection in lactating women indicate that tobramycin is present in human milk; there are no data on effects of drug on milk production; drug may cause alteration in the intestinal flora of breastfeeding infant; advise a woman to monitor breastfed infant for loose or bloody stools and candidiasis (thrush, diaper rash).
Developmental and health benefits of breastfeeding should be considered along with mother's clinical need for therapy and any potential adverse effects on breastfed infant from drug or from underlying maternal condition
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Inhibits protein synthesis by irreversibly binding to bacterial 30S and 50S ribosomes
Absorption
Absorption: IM: rapid and complete
Peak Plasma Time: IM: 30-60 min; IV: ~30 min
Distribution
Distribution: to extracellular fluid including serum, abscesses, ascitic, pericardial, pleural, synovial, lymphatic, and peritoneal fluids; crosses placenta; poor penetration into CSF, eye, bone, prostate
Protein Bound: <30%
Vd: 0.2-0.3 L/kg; pediatrics: 0.2-0.7 L/kg
Elimination
Half-Life: 2-3 hr (normal renal function)
Excretion: ~90%-95% in urine within 24 hr (normal renal function)
Administration
IV Incompatibilities
Additive: cefamandole, cefepime, cefotaxime, cefotetan, floxacillin, heparin, penicillins
Syringe: cefamandole, clindamycin, heparin
Y-site: allopurinol, amphotericin B cholesteryl sulfate, cefoperazone, heparin, hetastarch, indomethacin, propofol, sargramostim
IV Preparation
Standard diluent: 50-100 mL of D5W or NS
IV Administration
Infuse over 30-60 min
Give penicillins or cephalosporins at least 1 hr apart from tobramycin
Storage
Stable at room temp both as the clear, colorless solution & as the dry powder
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Formulary
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