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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 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.
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AMIKACIN SUMMARY
AMIKACIN Sulfate
Injection, USP
Fliptop Vial
Rx only
Amikacin sulfate is a semi-synthetic aminoglycoside antibiotic derived from kanamycin. It is C22H43N5O13• 2H2SO4 D-Streptamine, 0 -3-amino-3-deoxy-α-D-glucopyranosyl(1 — 6)- 0 -[6-amino-6-deoxy-α-D-glucopyranosyl(1— 4)]- N 1-(4-amino-2-hydroxy-1-oxobutyl)-2-deoxy-, (S)-, sulfate (1:2) (salt).
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.
Clinical studies have shown Amikacin Sulfate Injection, USP to be effective in bacterial septicemia (including neonatal sepsis); in serious infections of the respiratory tract, bones and joints, central nervous system (including meningitis) and skin and soft tissue; intra-abdominal infections (including peritonitis); and in burns and postoperative infections (including post-vascular surgery). Clinical studies have shown amikacin also to be effective in serious complicated and recurrent urinary tract infections due to these organisms. Aminoglycosides, including Amikacin Sulfate Injection, USP, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are not susceptible to antibiotics having less potential toxicity.
Bacteriologic studies should be performed to identify causative organisms and their susceptibilities to amikacin. Amikacin may be considered as initial therapy in suspected Gram-negative infections and therapy may be instituted before obtaining the results of susceptibility testing. Clinical trials demonstrated that amikacin was effective in infections caused by gentamicin and/or tobramycin-resistant strains of Gram-negative organisms, particularly Proteus rettgeri, Providencia stuartii, Serratia marcescens, and Pseudomonas aeruginosa. The decision to continue therapy with the drug should be based on results of the susceptibility tests, the severity of the infection, the response of the patient and the important additional considerations contained in the “WARNINGS” box above.
Amikacin has also been shown to be effective in staphylococcal infections and may be considered as initial therapy under certain conditions in the treatment of known or suspected staphylococcal disease such as, severe infections where the causative organism may be either a Gram-negative bacterium or a staphylococcus, infections due to susceptible strains of staphylococci in patients allergic to other antibiotics, and in mixed staphylococcal/Gram-negative infections.
In certain severe infections such as neonatal sepsis, concomitant therapy with a penicillin-type drug may be indicated because of the possibility of infections due to Gram-positive organisms such as streptococci or pneumococci.
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 antimicrobial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
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NEWS HIGHLIGHTS
Published Studies Related to Amikacin
Randomized controlled trial comparing oral amoxicillin-clavulanate and ofloxacin with intravenous ceftriaxone and amikacin as outpatient therapy in pediatric low-risk febrile neutropenia. [2009.09]
BACKGROUND: Outpatient oral therapy is infrequently used in pediatric low-risk febrile neutropenia (LRFN) as there is insufficient data regarding its equivalence as compared with parenteral therapy... CONCLUSIONS: Outpatient therapy is efficacious and safe in pediatric LRFN. There was no difference in outcome in oral versus IV outpatient therapy. Amoxycillin-clavulanate and ofloxacin may be the oral regimen of choice.
Cefepime monotherapy is as effective as ceftriaxone plus amikacin in pediatric patients with cancer and high-risk febrile neutropenia in a randomized comparison. [2009.04]
BACKGROUND AND PURPOSE: The empirical use of antibiotic therapy is widely accepted for patients with fever and neutropenia during cancer chemotherapy. The use of intravenous monotherapy with broad-spectrum antibiotics in patients at high risk for complications is an appropriate alternative. However, few data are available for pediatric patients. The aim of this study was to compare the efficacy and safety of cefepime (CFP) monotherapy with ceftriaxone plus amikacin (CFT+AK) in children and adolescents with febrile neutropenia (FN)... CONCLUSION: Monotherapy with CFP seems to be as effective and safe as CFT+AK for initial empirical therapy in children and adolescents with FN.
Efficacy and safety evaluation of fixed dose combination of cefepime and amikacin in comparison with cefepime alone in treatment of nosocomial pneumonia patients. [2008.05]
Nosocomial pneumonia is the most frequent and leading cause of morbidity and mortality... In conclusion, fixed dose combination of Cefepime and Amakacin was more effective in the treatment of nosocomial pneumonia than Cefepime alone.
Efficacy and renal toxicity of one daily dose of amikacin versus conventional dosage regime. [2007.02]
This study assessed the efficacy and renal toxicity of one daily dose of amikacin versus several doses in infected full-term newborns. A clinical trial was conducted with 120 patients who were divided into two groups: group A (n = 60), infants who received amikacin 20 mg/kg/d in one dose; and group B (n = 60), infants who received amikacin 10 mg/kg/d every 12 hours...
Single daily amikacin versus cefotaxime in the short-course treatment of spontaneous bacterial peritonitis in cirrhotics. [2005.11.21]
CONCLUSION: In this study, single daily doses of amikacin in the treatment of SBP in cirrhotics were not associated with an increased incidence of renal impairment or nephrotoxicity. However, a 5-d regimen of amikacin is less effective than a 5-d regimen of cefotaxime in the SBP treatment.
Clinical Trials Related to Amikacin
Once-Daily Amikacin Plus Cloxacillin in Febrile Neutropenic Children [Completed]
Once-daily dose administration of aminoglycoside in adults is effective and economical.
However, its value in febrile neutropenic children, especially in Thailand, is less well
researched. In the area where Pseudomonas aeruginosa prevalence in febrile neutropenic
children is low, the combination of cloxacillin and amikacin is an appropriate approach. This
study would like to compare the efficacy and safety including cost between these two amikacin
administrations (once-daily or twice-daily) in combination with cloxacillin as an empirical
therapy in febrile neutropenic children.
Hypothesis: Once-daily amikacin plus cloxacillin can be used to treat febrile neutropenic
children in Khon Kaen, Thailand.
Amikacin Penetration Into the Cerebrospinal Fluid [Withdrawn]
The limited available data precludes establishing an antibiotic regimen in patients suffering
from bacterial meningitis after head trauma, or spontaneous bleeding Understanding the
disposition of Amikacin administered intrathecally will enable to propose rational treatment
of these patients.
A Phase II/III Trial of Rifampin, Ciprofloxacin, Clofazimine, Ethambutol, and Amikacin in the Treatment of Disseminated Mycobacterium Avium Infection in HIV-Infected Individuals. [Completed]
To compare the effectiveness and toxicity of two combination drug treatment programs for the
treatment of disseminated Mycobacterium avium infection in HIV seropositive patients. [Per
03/06/92 amendment: to evaluate the efficacy of azithromycin when given in conjunction with
either ethambutol or clofazimine as maintenance therapy.] Disseminated M. avium infection is
the most common systemic bacterial infection complicating AIDS in the United States. The
prognosis of patients with disseminated M. avium is extremely poor, particularly when it
follows other opportunistic infections or is associated with anemia. Test tube studies and
clinical data indicate that the best treatment program may include clofazimine, ethambutol, a
rifamycin derivative, and ciprofloxacin. Test tube and animal studies indicate that amikacin
is a bactericidal (bacteria destroying) drug that works better when used with ciprofloxacin.
Its role in treatment programs is a key issue because of toxicity and because it must be
administered parenterally (by injection or intravenously).
Pharmacokinetics of Nebulized Amikacin in Patients With Pneumonia Undergoing Mechanical Ventilation [Recruiting]
Impact of Imipenem With Amikacin Pharmacokinetic and Pharmacodynamic Parameters Variability on Gram Negative Bacilli Ventilator-associated Pneumonia Outcome [Recruiting]
The study is a prospective open trial conducted in 4 centers, and designed to determine if
pharmacokinetic (PK) and pharmacodynamic (PD) parameters of imipenem, associated with
amikacin as empirical therapy, impact microbiological and clinical outcome of patients with
Gram negative bacilli (GNB) ventilator-associated pneumonia (VAP).
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Page last updated: 2009-10-20
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