Amikacin Sulfate

AMIKACIN SULFATE — amikacin sulfate injection, solution
Fresenius Kabi USA, LLC

Rx only

To reduce the development of drug-resistant bacteria and maintain the effectiveness of the amikacin and other antibacterial drugs, amikacin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.

BOXED WARNINGS

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 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 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 injection, USP is a semi-synthetic aminoglycoside antibiotic derived from kanamycin. It is O -3-amino-3-deoxy-α-D-glucopyranosyl-(1→4)-O -[6-amino-6-deoxy-α-D-glucopyranosyl-(1→6)]-N3 -(4-amino-L-2-hydroxybutyryl)-2-deoxy-L-streptamine sulfate (1:2).

structure
(click image for full-size original)

C22 H43 N5 O13 • 2H2 SO4 M.W. 781.76

The dosage form is supplied as a sterile, colorless to light straw colored solution for IM or IV use. The 100 mg per 2 mL vial contains per each mL: 50 mg amikacin (as the sulfate), 0.13% sodium metabisulfite, 0.5% sodium citrate dihydrate, water for injection qs, with pH adjusted to 4.5 with sulfuric acid. The 500 mg per 2 mL vial and 1 gram per 4 mL vial contains per each mL: 250 mg amikacin (as the sulfate), 0.66% sodium metabisulfite, 2.5% sodium citrate dihydrate, water for injection qs, with pH adjusted to 4.5 with sulfuric acid.

CLINICAL PHARMACOLOGY:

Microbiology

Mechanism of Action

Amikacin, an aminoglycoside, binds to the prokaryotic ribosome, inhibiting protein synthesis in susceptible bacteria. It is bactericidal in vitro against Gram-positive and Gram-negative bacteria.


Mechanism of Resistance

Aminoglycosides are known to be ineffective against Salmonella and Shigella species in patients. Therefore, in vitro susceptibility test results should not be reported.

Amikacin resists degradation by certain aminoglycoside inactivating enzymes known to affect gentamicin, tobramycin, and kanamycin.

Aminoglycosides in general have a low order of activity against Gram-positive organisms other than Staphylococcal isolates.


Interactions with Other Antimicrobials

In vitro studies have shown that amikacin sulfate combined with a beta-lactam antibiotic acts synergistically against many clinically significant Gram-negative organisms.


Antibacterial Activity

Amikacin has been shown to be active against the following bacteria, both in vitro and in clinical infections (see INDICATIONS AND USAGE).


Gram-Positive Bacteria

Staphylococcus species

Gram-Negative Bacteria

Pseudomonas species

Escherichia coli

Proteus species (indole-positive and indole-negative)

Klebsiella species

Enterobacter species

Serratia species

Acinetobacter species

Amikacin has demonstrated in vitro activity against the following bacteria. The safety and effectiveness of amikacin in treating clinical infections due to these bacteria have not been established in adequate and well-controlled trials.

Citrobacter freundii


Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC

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 species, Enterobacter species, Serratia species, and Acinetobacter species.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amikacin and other antibacterial drugs, amikacin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

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