Patients treated with Nebcin (Tobramycin for Injection, USP)
and other aminoglycosides should be under close clinical observation,
because these drugs have an inherent potential for causing ototoxicity
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 above12 mcg/ mL should be avoided.
Rising trough levels (above 2 mcg/ mL) may indicate tissue
accumulation. Such accumulation, excessive peak concentrations,
advanced age, and cumulative dose may contribute to ototoxicity
and nephrotoxicity (see PRECAUTIONS).
Urine should be examined for decreased specific gravity and increased
excretion of protein, cells, and casts. Blood urea nitrogen, serum
creatinine, and creatinine clearance should be measured periodically.
When feasible, it is recommended that serial audiograms be obtained
in patients old enough to be tested, particularly high-risk patients.
Evidence of impairment of renal, vestibular, or auditory function
requires discontinuation of the drug or dosage adjustment.
Nebcin should be used with caution in premature and neonatal infants
because of their renal immaturity and the resulting prolongation
of serum half-life of the drug.
Concurrent and sequential use of other neurotoxic and/or nephrotoxic
antibiotics, particularly other aminoglycosides (e.g., amikacin,
streptomycin, neomycin, kanamycin, gentamicin, and paromomycin),
cephaloridine, viomycin, polymyxin B, colistin, cisplatin,
and vancomycin, should be avoided. Other factors that may increase
patient risk are advanced age and dehydration.
Aminoglycosides should not be given concurrently with potent diuretics,
such as ethacrynic acid and furosemide. Some diuretics themselves
cause ototoxicity, and intravenously administered diuretics enhance
aminoglycoside toxicity by altering antibiotic concentrations in
serum and tissue.
Aminoglycosides can cause fetal harm when administered to a pregnant
woman (see PRECAUTIONS).