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WARNINGS
Patients treated with aminoglycosides should be under close clinical observation because of the potential toxicity associated with their use.
As with other aminoglycosides, gentamicin sulfate is potentially nephrotoxic. The risk of nephrotoxicity is greater in patients with impaired renal function and in those who receive high dosage or prolonged therapy.
Neurotoxicity manifested by ototoxicity, both vestibular and auditory, can occur in patients treated with gentamicin sulfate primarily in those with pre-existing renal damage and in patients with normal renal function treated with higher doses and/or for longer periods than recommended. Aminoglycoside-induced ototoxicity is usually irreversible. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching and convulsions.
Renal and eighth cranial nerve function should be closely monitored, especially in patients with known or suspected reduced renal function at onset of therapy and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Urine should be examined for decreased specific gravity, increased excretion of protein, and the presence of cells or casts. Blood urea nitrogen, serum creatinine, or creatinine clearance should be determined periodically. When feasible, it is recommended that serial audiograms be obtained in patients old enough to be tested, particularly high-risk patients. Evidence of ototoxicity (dizziness, vertigo, tinnitus, roaring in the ears or hearing loss) or nephrotoxicity requires dosage adjustment or discontinuance of the drug. As with the other aminoglycosides, on rare occasions changes in renal and eighth cranial nerve function may not become manifest until soon after completion of therapy.
Serum concentrations of aminoglycosides should be monitored when feasible to assure adequate levels and to avoid potentially toxic levels. When monitoring gentamicin peak concentrations, dosage should be adjusted so that prolonged levels above 12 mcg/mL are avoided. When monitoring gentamicin trough concentrations, dosage should be adjusted so that levels above 2 mcg/mL are avoided. Excessive peak and/or trough serum concentrations of aminoglycosides may increase the risk of renal and eighth cranial nerve toxicity. In the event of overdose or toxic reactions, hemodialysis may aid in the removal of gentamicin 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.
Concurrent and/or sequential systemic or topical use of other potentially neurotoxic and/or nephrotoxic drugs, such as cisplatin, cephaloridine, kanamycin, amikacin, neomycin, polymyxin B, colistin, paromomycin, streptomycin, tobramycin, vancomycin, and viomycin, should be avoided.
Other factors which may increase patient risk to toxicity are advanced age and dehydration.
The concurrent use of gentamicin with potent diuretics, such as ethacrynic acid or furosemide, should be avoided, since certain diuretics by themselves may cause ototoxicity. In addition, when administered intravenously, diuretics may enhance aminoglycoside toxicity by altering the antibiotic concentration in serum and tissue.
Aminoglycosides can cause fetal harm when administered to a pregnant woman (see WARNINGS).
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SUMMARY
Gentamicin Sulfate
in 0.9% Sodium Chloride Injection
Gentamicin Sulfate in 0.9% Sodium Chloride Injections are sterile, nonpyrogenic solutions of gentamicin sulfate in 0.9% sodium chloride injection. They are administered by the intravenous route as antibiotic infusions. They are premixed and require no further dilution. Each milliliter (mL) of the 50 mL size contains gentamicin sulfate equivalent to 1.2, or 1.6 mg gentamicin base with Sodium Chloride USP 9 mg in Water for Injection USP. Each milliliter (mL) of the 100 mL size contains gentamicin sulfate equivalent to 0.6, 0.8, or 1.0 mg gentamicin base with Sodium Chloride USP 9 mg in Water for Injection USP. Gentamicin Sulfate in 0.9% Sodium Chloride Injections have a calculated osmolarity of 290 mOsmol/liter; pH: 4.0 (3.0–5.5). May contain Sulfuric Acid NF and/or Sodium Hydroxide NF for pH adjustment. The solutions contain no bacteriostat, antimicrobial agent (except gentamicin) or buffer and are intended only for use as a single-dose injection. When smaller doses are required the unused portion should be discarded. Gentamicin is classified as a aminoglycoside antibiotic and is derived from Micromonospora purpurea, an actinomycete.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Gentamicin Sulfate in 0.9% Sodium Chloride Injection and other antibacterial drugs, Gentamicin Sulfate in 0.9% Sodium Chloride Injection 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.
Gentamicin Sulfate in 0.9% Sodium Chloride Injection is indicated in the treatment of serious infections caused by susceptible strains of the following microorganisms: Pseudomonas aeruginosa, Proteus species (indole-positive and indole-negative), Escherichia coli, Klebsiella - Enterobacter - Serratia species, Citrobacter species, and Staphylococcus species (coagulase-positive and coagulase-negative).
Clinical studies have shown gentamicin sulfate to be effective in bacterial neonatal sepsis; bacterial septicemia, and serious bacterial infections of the central nervous system (meningitis), urinary tract, respiratory tract, gastrointestinal tract (including peritonitis), skin, bone and soft tissue (including burns).
Aminoglycosides, including gentamicin, are not indicated in uncomplicated initial episodes of urinary tract infections unless the causative organisms are susceptible to these antibiotics and are not susceptible to antibiotics having less potential for toxicity.
Specimens for bacterial culture should be obtained to isolate and identify causative organisms and to determine their susceptibility to gentamicin.
Gentamicin may be considered as initial therapy in suspected or confirmed gram-negative infections, and therapy may be instituted before obtaining results of susceptibility testing. The decision to continue therapy with this drug should be based on the results of susceptibility tests, the severity of the infection, and the important additional concepts contained in the boxed WARNINGS. If the causative organisms are resistant to gentamicin, other appropriate therapy should be instituted.
In serious infections when the causative organisms are unknown, gentamicin may be administered as initial therapy in conjunction with a penicillin-type or cephalosporin-type drug before obtaining results of susceptibility testing. If anaerobic organisms are suspected as etiologic agents, consideration should be given to using other suitable antimicrobial therapy in conjunction with gentamicin. Following identification of the organism and its susceptibility, appropriate antibiotic therapy should then be continued.
Gentamicin has been used effectively in combination with carbenicillin for the treatment of life-threatening infections caused by Pseudomonas aeruginosa. It has also been found effective when used in conjunction with a penicillin-type drug for the treatment of endocarditis caused by group D streptococci.
Gentamicin has also been shown to be effective in the treatment of serious staphylococcal infections. While not the antibiotic of first choice, gentamicin may be considered when penicillins or other less potentially toxic drugs are contraindicated and bacterial susceptibility tests and clinical judgement indicate its use. It may also be considered in mixed infections caused by susceptible strains of staphylococci and gram-negative organisms.
In the neonate with suspected bacterial sepsis or staphylococcal pneumonia, a penicillin-type drug is also usually indicated as concomitant therapy with gentamicin.
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NEWS HIGHLIGHTS
Published Studies Related to Gentamicin Injection
Effect of silymarin and vitamin E on gentamicin-induced nephrotoxicity in dogs. [2007.10]
Drug-induced nephrotoxicity is an important cause of renal failure in dogs...
Population pharmacokinetics of a single daily intramuscular dose of gentamicin in children with severe malnutrition. [2007.04]
OBJECTIVES: The World Health Organization recommends that all children admitted with severe malnutrition should routinely receive parenteral ampicillin and gentamicin; despite this, mortality remains high. Since this population group is at risk of altered volume of distribution, we aimed to study the population pharmacokinetics of once daily gentamicin (7.5 mg/kg) in children with severe malnutrition and to evaluate clinical factors affecting pharmacokinetic parameters... CONCLUSIONS: Although a daily dose of 7.5 mg/kg achieves satisfactory gentamicin concentrations in the majority of patients, patients with renal impairment and shock may be at risk of accumulation with 24 hourly dosing. Further studies of gentamicin pharmacokinetics in this group are now needed to inform future international guideline recommendations.
Incidence, microbiological findings, and clinical presentation of sternal wound infections after cardiac surgery with and without local gentamicin prophylaxis. [2007.02]
Sternal wound infection (SWI) is a serious complication after cardiac surgery. In a previous randomized controlled trial, the addition of local collagen-gentamicin in the sternal wound before wound closure was found to significantly reduce the incidence of postoperative wound infections compared with the routine intravenous prophylaxis of isoxazolyl-penicillin only.
Cost effectiveness of local collagen-gentamicin as prophylaxis for sternal wound infections in different risk groups. [2006.04]
OBJECTIVES: In a randomized trial addition of local collagen-gentamicin in the sternal wound reduced the rate of sternal wound infection (SWI) to about 50% compared to intravenous prophylaxis alone. The aim of the present study was to evaluate the economic rationale for its use in every-day clinical practice. This includes the question whether high-risk groups that may have particular benefit should be identified... CONCLUSION: The addition of local collagen-gentamicin to intravenous antibiotic prophylaxis was dominant, i.e. resulted in both lower costs and fewer wound infections.
Gentamicin concentrations in synovial fluid and joint tissues during intravenous administration or continuous intra-articular infusion of the tarsocrural joint of clinically normal horses. [2006.03]
OBJECTIVE: To compare gentamicin concentrations achieved in synovial fluid and joint tissues during IV administration and continuous intra-articular (IA) infusion of the tarsocrural joint in horses. ANIMALS: 18 horses with clinically normal tarsocrural joints... CONCLUSIONS AND CLINICAL RELEVANCE: Continuous IA infusion of gentamicin achieves higher drug concentrations in joint tissues of normal tarsocrural joints of horses, compared with concentrations after IV administration.
Clinical Trials Related to Gentamicin Injection
Gentamicin Treatment of Muscular Dystrophy [Completed]
This study will evaluate the antibiotic gentamicin for treating patients with muscular
dystrophy caused by a specific genetic abnormality known as a nonsense mutation. In studies
of mice with this type of muscular dystrophy, gentamicin treatment produced positive changes
in muscle tissue.
Patients with Duchenne or Becker muscular dystrophy caused by nonsense mutations by may be
eligible for this 2-week study. Before starting treatment, patients will have evaluations of
muscle strength and general well being. Two muscle tissue samples will be taken by needle
biopsy, under local anesthetic and sedation. Because of potential risks of hearing loss and
kidney toxicity associated with gentamicin, patients will also have a hearing test and blood
and urine tests for kidney function before starting treatment. (Currently, gentamicin is
commonly prescribed for serious infections of the lungs, heart, and digestive and urinary
tracts; adverse effects of hearing loss and kidney toxicity can occur with excessively high
drug doses.)
Patients will be hospitalized during drug treatment. Gentamicin will be given intravenously
(through a vein) once a day for 14 days. Blood samples will be collected daily to monitor
drug levels and determine dosage adjustments, if necessary. Urine samples will be collected
to assess kidney function. Hearing tests will be done on days 7 and 10.
On the last day of the study, hearing, kidney function, and muscle strength will be tested
and the results compared with pre-treatment levels. Blood and muscle samples will also be
taken again for pre-treatment comparison. Hearing, blood, urine, and muscle strength tests
will be repeated one month after treatment ends for comparison with previous results.
Determination of Gentamicin Dosing in Neonatal Patients [Active, not recruiting]
The purpose of this study is to determine what dosage of gentamicin for use in one-time
administration device (Uniject) is appropriate.
Topical Gentamicin Cream Versus Alternating Gentamicin and Mupirocin Cream in Peritoneal Dialysis [Not yet recruiting]
Catheter-related infection, namely exit site infection and peritonitis, is the commonest
complication of peritoneal dialysis. This complication causes significant morbidity and
mortality in patients requiring peritoneal dialysis. Topical application of mupirocin 2%
cream was first proven to be effective in reduction of staphylococcus-related catheter
infection in 1990s. Subsequent randomized trial published in 2005 showed that gentamicin
cream was superior to mupirocin 2% cream in reducing both Gram's positive and Gram's
negative related catheter infection. However, a retrospective report published in 2007 puts
the use of prophylactic antibiotic cream into a question. It reported an emergency of
non-tuberculous mycobacterial infection in a dialysis center in Hong Kong after practising
prophylactic application of gentamicin cream at the catheter exit site. The following
prospective, randomized and open-label study aims to find out an optimal regimen of topical
antibiotic prophylaxis in patients requiring peritoneal dialysis.
Six Month Study of Gentamicin in Duchenne Muscular Dystrophy With Stop Codons [Recruiting]
The purpose of this study is to determine the safety of giving intravenous (IV) gentamicin to
boys with Duchenne muscular dystrophy who have stop codon mutations.
Comparison of Once Daily Versus 8 Hour Dosing of Gentamicin for the Treatment of Intrapartum Chorioamnionitis [Active, not recruiting]
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Page last updated: 2008-01-02
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