General

• Patients treated with parenteral aminoglycosides should be under close clinical observation because these drugs have an inherent potential for causing ototoxicity and nephrotoxicity.Safety for treatment periods which are longer than 14 days has not been established.(amikacin)

Neurotoxicity

• Neurotoxicity, manifested as both bilateral auditory and vestibular ototoxicity, can occur in patients with pre-existing renal damage and in patients with normal renal function treated at higher doses and/or for periods longer than those recommended.
• The risk of aminoglycoside induced otoxicity is greater in patients with renal damage.
• High frequency deafness usually occurs first and can be detected only by audiometric testing.
• Vertigo may occur and may be evidence of vestibular injury. (amikacin, kanamycin)
• Other manifestations of neurotoxicity: numbness, skin tingling, muscle twitching and convulsions.
• The risk of hearing loss due to aminoglycosides increases with the degree of exposure to either high peak or high trough 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 drug is stopped.
• Aminoglycoside induced ototoxicity is usually irreversible.

Nephrotoxicity

• 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.
• Aminoglycoside nephrotoxicity usually is reversible.

Premature Infants & Neonates

• Use with caution because of renal immaturity and the resulting prolongation of serum half-life of the drug. 

Neuromuscular Blockade and Respiratory Paralysis

• 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 following oral use of aminoglycosides.
• The possiblity of these phenomena should be considered if aminoglycosides are administered by any route, especially in patients receiving anesthestics, neuromuscular blokcing agents (e.g., tubocurarine, succinylcholine, decamethonium) or in patients receiving massive transfusions of citrate anticoagulated blood.
• 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 oral or topical)

• Other aminoglycosides (e.g., amikacin, streptomycin, neomycin, kanamycin, gentamicin, and paromycin).
• Cumulative listing of drugs to avoid from all aminoglycoside package inserts include: amphotericin B, bacitracin, cephaloridine, cisplatin, colistin, polymixin B, vancomycin, viomycin.
• Avoid concurrent use of potent diuretics (e.g., ethacrynic acid, furosemide) as they increase risk of ototoxicity. (Kanamycin labeling states "Should not be given"). When administered intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.

Use in Pregnancy

• Aminoglycosides can cause fetal harm when administered during pregnancy.

Other Factors that Increase Toxicity Risk

• Advanced age, dehydration.

MONITORING RECOMMENDATIONS RELATED TO BLACK BOX DATA

Note: The following recommendations are included in the black box section of aminoglycoside labeling.
• Renal and eighth nerve function should be closely monitored in patients with known or suspected renal dysfunction at the onset of therapy and also in patients who develop signs of renal dysfunction during therapy.
• Monitor peak and trough concentrations during therapy to ensure appropriate levels and to avoid potentially toxic levels.
• Tobramycin, Gentamicin: Prolonged serum concentrations above 12 mcg/mL should be avoided. Rising trough levels (above 2 mcg/mL) may indicate tissue accumulation. Such accumulation, excessive peak concentrations, advanced age, and cumulative dose may contribute to ototoxicity and nephrotoxicity.
• Amikacin: Avoid potentially toxic levels and prolonged peak concentrations above 35 mcg/mL.
• Urine should be examined for decreased specific gravity and increased excretion of protein, and the presence of cells or casts. BUN, serum creatinine, and CrCl should be measured periodically.
• Audiograms: When feasible, it is recommended that serial audiograms be obtained in patients old enough to be tested, particuarly high-risk patients.
• Evidence of impairment of renal, vestibular, or auditory function requires discontinuation of the drug or dosage adjustment.
• Dosage adjustments required in renal impairment.
• Gentamicin: In the event of overdosage or toxic reaction, hemodialysis may aid in the removal of the drug from the blood, especially if renal function, is, or becomes, compromised. The rate of removal of gentamicin is considerably lower by peritoneal dialysis than it is by hemodialysis. In the newborn infant, exchange transfusions may also be considered.

Patient Counseling Information

• Amikacin Sulfate Injection, solution[Hospira]
• Amikacin Sulfate Injection, solution[Bristol-Myers Squibb Company]

Package Inserts

Amikin

Amikacin