AMIKACIN SULFATE- amikacin sulfate injection, solution
Hospira, Inc.
ARNINGS
Patients treated with parenteral aminoglycosides should be under close clinical observation because of the potential ototoxicity and nephrotoxicity associated with their use. Safety for treatment periods which are longer than 14 days has not been established.
Neurotoxicity, manifested as vestibular and permanent bilateral auditory 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. The risk of aminoglycoside-induced ototoxicity 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. Other manifestations of neurotoxicity may include 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 serum concentrations. Patients developing cochlear damage may not have symptoms during therapy to warn them of developing eighth-nerve toxicity, and total or partial irreversible bilateral deafness may occur after the drug has been discontinued. Aminoglycoside-induced ototoxicity is usually irreversible.
Aminoglycosides are potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high doses or prolonged therapy.
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 possibility of these phenomena should be considered if aminoglycosides are administered by any route, especially in patients receiving anesthetics, neuromuscular blocking agents such as 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.
Renal and eighth-nerve function should be closely monitored especially in patients with known or suspected renal impairment at the onset of therapy and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Serum concentrations of amikacin should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels and prolonged peak concentrations above 35 micrograms per mL. Urine should be examined for decreased specific gravity, increased excretion of proteins, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be measured periodically. Serial audiograms should be obtained where feasible in patients old enough to be tested, particularly high risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears, and hearing loss) or nephrotoxicity requires discontinuation of the drug or dosage adjustment.
Concurrent and/or sequential systemic, oral, or topical use of other neurotoxic or nephrotoxic products, particularly bacitracin, cisplatin, amphotericin B, cephaloridine, paromomycin, viomycin, polymyxin B, colistin, vancomycin, or other aminoglycosides should be avoided. Other factors that may increase risk of toxicity are advanced age and dehydration.
The concurrent use of amikacin with potent diuretics (ethacrynic acid, or furosemide) should be avoided since diuretics by themselves may cause ototoxicity. In addition, when administered, intravenously, diuretics may enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.
DESCRIPTION
Amikacin sulfate is semi-synthetic aminoglycoside antibiotic derived from kanamycin. It is C22 H43 N5 O13 2H2 SO4 D-Streptamine, 0-3-amino-3-deoxy-?-D-glucopyranosyl)-0-[6-amino-6-deoxy-?-D-glucopyranosyl)]-N1 -(4-amino-2-hydroxy-1-oxobutyl)-2-deoxy-, (S)-, sulfate (1:2) (salt).
Molecular weight is 781.75.
The dosage form is supplied as sterile, colorless to light straw colored solution, for I.M. or I.V. use. The 100 mg per mL vial contains, in addition to amikacin sulfate, 0.12% sodium metabisulfite and 0.57% sodium citrate, dihydrate. Nitrogen gassed. Contains sulfuric acid for pH adjustment. pH 4.5 (3.5 to 5.5). The 500 mg per mL vial and syringe, and the gram per mL vial contain 0.6% sodium metabisulfite and 2.9% sodium citrate, dihydrate. Contains sulfuric acid for pH adjustment. pH 4.5 (3.5 to 5.5). Amikacin Sulfate Injection, USP is oxygen sensitive.
Microbiology
Gram-negative-Amikacin is active in vitro against Pseudomonas species, Escherichia coli, Proteus species (indole-positive and indole-negative), Providencia species, Klebsiella-Enterobacter-Serratia species, Acinetobacter (formerly Mima-Herellea) species, and Citrobacter freundii.
When strains of the above organisms are found to be resistant to other aminoglycosides, including gentamicin, tobramycin and kanamycin, many are susceptible to amikacin in vitro.
Gram-positive-Amikacin is active in vitro against penicillinase and nonpenicillinase-producing Staphylococcus species including methicillin-resistant strains. However, aminoglycosides in general have low order of activity against other Gram-positive organisms: viz, Streptococcus pyogenes, enterococci, and Streptococcus pneumoniae (formerly Diplococcus pneumoniae).
Amikacin resists degradation by most aminoglycoside inactivating enzymes known to affect gentamicin, tobramycin, and kanamycin.
In vitro studies have shown that amikacin sulfate combined with beta-lactam antibiotic acts synergistically against many clinically significant Gram-negative organisms.
INDICATIONS AND USAGE
Amikacin Sulfate Injection, USP is indicated in the short-term treatment of serious infections due to susceptible strains of Gram-negative bacteria, including Pseudomonas species, Escherichia coli, species of indole-positive and indole-negative Proteus, Providencia species, Klebsiella-Enterobacter-Serratia species, and Acinetobacter (Mima-Herellea) species.
CONTRAINDICATIONS
A history of hypersensitivity to amikacin is contraindication for its use. history of hypersensitivity or serious toxic reactions to aminoglycosides may contraindicate the use of any other aminoglycoside because of the known cross-sensitivities of patients to drugs in this class
PRECAUTIONS
Aminoglycosides are quickly and almost totally absorbed when they are applied topically, except to the urinary bladder, in association with surgical procedures. Irreversible deafness, renal failure, and death due to neuromuscular blockade have been reported following irrigation of both small and large surgical fields with an aminoglycoside preparation.
Amikacin Sulfate Injection, USP is potentially nephrotoxic, ototoxic and neurotoxic. The concurrent or serial use of other ototoxic or nephrotoxic agents should be avoided either systemically or topically because of the potential for additive effects. Increased nephrotoxicity has been reported following concomitant parenteral administration of aminoglycoside antibiotics and cephalosporins. Concomitant cephalosporins may spuriously elevate creatinine determinations.
Pregnancy-Category D
info. for Patients
Patients should be counseled that antibacterial drugs including amikacin should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When an antibacterial drug product is prescribed to treat bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may decrease the effectiveness of the immediate treatment and increase the likelihood that bacteria will develop resistance and will not be treatable by amikacin or other antibacterial drugs in the future
DOSAGE AND ADMINISTRATION
The patient?s pretreatment body weight should be obtained for calculation of correct dosage. Amikacin Sulfate Injection, USP may be given intramuscularly or intravenously.
The status of renal function should be estimated by measurement of the serum creatinine concentration or calculation of the endogenous creatinine clearance rate. The blood urea nitrogen (BUN) is much less reliable for this purpose. Reassessment of renal function should be made periodically during therapy.
