INDICATIONS AND USAGE 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 Sulfate in 0.9% Sodium Chloride Injection 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 Sulfate in 0.9% Sodium Chloride Injection 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 injection 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 injection 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 (see PRECAUTIONS, Pediatric Use and DOSAGE AND ADMINISTRATION sections).

WARNINGS (See boxed WARNINGS .) Aminoglycosides can cause fetal harm when administered to a pregnant woman.

Aminoglycoside antibiotics cross the placenta, and there have been several reports of total irreversible bilateral congenital deafness in children whose mothers received streptomycin during pregnancy.

Serious side effects to mother, fetus or newborn have not been reported in the treatment of pregnant women with other aminoglycosides.

Animal reproduction studies conducted on rats and rabbits did not reveal evidence of impaired fertility or harm to the fetus due to gentamicin sulfate.

It is not known whether gentamicin sulfate can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.

If gentamicin is used during pregnancy or if the patient becomes pregnant while taking gentamicin, she should be apprised of the potential hazard to the fetus.

Solutions containing sodium ions should be used with great care, if at all, in patients with congestive heart failure, severe renal insufficiency, and in clinical states in which there exists edema with sodium retention.

Risk of Ototoxicity Due to Mitochondrial DNA Variants Cases of ototoxicity with aminoglycosides have been observed in patients with certain variants in the mitochondrially encoded 12S rRNA gene ( MT-RNR1 ), particularly the m.1555A>G variant.

Ototoxicity occurred in some patients even when their aminoglycoside serum levels were within the recommended range.

Mitochondrial DNA variants are present in less than 1% of the general US population, and the proportion of the variant carriers who may develop ototoxicity as well as the severity of ototoxicity is unknown.

In case of known maternal history of ototoxicity due to aminoglycoside use or a known mitochondrial DNA variant in the patient, consider alternative treatments other than aminoglycosides unless the increased risk of permanent hearing loss is outweighed by the severity of infection and lack of safe and effective alternative therapies.

ADVERSE REACTIONS Nephrotoxicity - Adverse renal effects, as demonstrated by the presence of casts, cells, or protein in the urine or by rising BUN, NPN, serum creatinine and oliguria, have been reported.

They occur more frequently in patients with a history of renal impairment and in patients treated for longer periods or with larger dosages than recommended.

Neurotoxicity - Serious adverse effects on both vestibular and auditory branches of the eighth cranial nerve have been reported, primarily in patients with renal impairment (especially if hemodialysis is required) and in patients on high doses and/or prolonged therapy.

Symptoms include dizziness, vertigo, tinnitus, roaring in the ears and also hearing loss, which, as with the other aminoglycosides, may be irreversible.

Hearing loss is usually manifested initially by diminishing high-tone acuity.

Other factors which may increase the risk of toxicity include excessive dosage, dehydration and previous exposure to other ototoxic drugs.

Peripheral neuropathy or encephalopathy, including numbness, skin tingling, muscle twitching, convulsions, and a myasthenia gravis-like syndrome, have been reported.

Note : This risk of toxic reactions is low in patients with normal renal function who do not receive gentamicin sulfate at higher doses or for longer periods of time than recommended.

Other reported adverse reactions possibly related to gentamicin include: respiratory depression, lethargy, confusion, depression, visual disturbances, decreased appetite, weight loss, hypotension and hypertension; rash, itching, urticaria, generalized burning, laryngeal edema, anaphylactoid reactions, fever, and headache; nausea, vomiting, increased salivation, and stomatitis; purpura, pseudotumor cerebri, acute organic brain syndrome, pulmonary fibrosis, alopecia, joint pain, transient hepatomegaly, and splenomegaly.

Laboratory abnormalities possibly related to gentamicin include: increased levels of serum transaminase (SGOT, SGPT), serum LDH and bilirubin; decreased serum calcium, magnesium, sodium and potassium; anemia, leukopenia, granulocytopenia, transient agranulocytosis, eosinophilia, increased and decreased reticulocyte counts and thrombocytopenia.

While clinical laboratory test abnormalities may be isolated findings, they may also be associated with clinically related signs and symptoms.

For example, tetany and muscle weakness may be associated with hypomagnesemia, hypocalcemia, and hypokalemia.

While local tolerance of gentamicin sulfate is generally excellent, there has been an occasional report of pain at the injection site.

Subcutaneous atrophy or fat necrosis suggesting local irritation has been reported rarely.

Reactions which may occur because of the solution or the technique of administration include febrile response, infection at the site of injection, venous thrombosis or phlebitis extending from the site of injection, extravasation, and hypervolemia.

If an adverse reaction does occur, discontinue the infusion, evaluate the patient, institute appropriate therapeutic countermeasures, and save the remainder of the fluid for examination if deemed necessary.