This vial is intended for use by the hospital pharmacist in the extemporaneous preparation of IV solutions.
PHARMACY BULK PACKAGE NOT FOR DIRECT INFUSION
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Tobramycin for Injection USP and other antibacterial drugs, tobramycin should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria.
Patients treated with tobramycin for injection USP and other aminoglycosides should be under close clinical observation, because these drugs have an inherent potential for causing ototoxicity and nephrotoxicity. Neurotoxicity, manifested as both auditory and vestibular ototoxicity, can occur. The auditory changes are irreversible, are usually bilateral, and may be partial or total. Eighth-nerve impairment and nephrotoxicity may develop, primarily in patients having preexisting renal damage and in those with normal renal function to whom aminoglycosides are administered for longer periods or in higher doses than those recommended. Other manifestations of neurotoxicity may include numbness, skin tingling, muscle twitching, and convulsions. The risk of aminoglycoside-induced hearing loss increases with the degree of exposure to either high peak or high trough serum concentrations. Patients who develop cochlear damage may not have symptoms during therapy to warn them of eighth-nerve toxicity, and partial or total irreversible bilateral deafness may continue to develop after the drug has been discontinued.
Rarely, nephrotoxicity may become apparent until the first few days after cessation of therapy. Aminoglycoside-induced nephrotoxicity usually is reversible.
Renal and eighth-nerve function should be closely monitored in patients with known or suspected renal impairment and also in those whose renal function is initially normal but who develop signs of renal dysfunction during therapy. Peak and trough serum concentrations of aminoglycosides should be monitored periodically during therapy to assure adequate levels and to avoid potentially toxic levels. Prolonged serum concentrations above 12 mcg/mL should be avoided. Rising trough levels (above 2 mcg/mL) may indicate tissue accumulation. Such accumulation, excessive peak concentrations, advanced age, and cumulative dose may contribute to ototoxicity and nephrotoxicity (see PRECAUTIONS). Urine should be examined for decreased specific gravity and increased excretion of protein, cells, and casts. Blood urea nitrogen, serum creatinine, and creatinine clearance should be measured periodically. When feasible, it is recommended that serial audiograms be obtained in patients old enough to be tested, particularly high-risk patients. Evidence of impairment of renal, vestibular, or auditory function requires discontinuation of the drug or dosage adjustment.
Tobramycin for injection USP should be used with caution in premature and neonatal infants because of their renal immaturity and the resulting prolongation of serum half-life of the drug.
Concurrent and sequential use of other neurotoxic and/or nephrotoxic antibiotics, particularly other aminoglycosides (eg. amikacin, streptomycin, neomycin, kanamycin, gentamicin, and paromomycin), cephaloridine, viomycin, polymycin B, colistin, cisplatin, and vancomycin, should be avoided. Other factors that may increase patient risk are advanced age and dehydration.
Aminoglycosides should not be given concurrently with potent diuretics, such as ethacrynic acid and furosemide. Some diuretics themselves cause ototoxicity, and intravenously administered diuretics enhance aminoglycoside toxicity by altering antibiotic concentrations in serum and tissue.
Aminoglycosides can cause fetal harm when administered to a pregnant woman (see PRECAUTIONS).
Description for Tobramycin Injection
Tobramycin sulfate, a water-soluble antibiotic of the aminoglycoside group, is derived from the actinomycete Streptomyces tenebrarius. Sterile tobramycin sulfate is supplied as a sterile dry powder and is intended for reconstitution with 30 mL of Sterile Water for Injection, USP. Sulfuric acid and/or sodium hydroxide may have been added during manufacture to adjust the pH. † Each vial contains tobramycin sulfate equivalent to 1200 mg of tobramycin. After reconstitution, the solution will contain 40 mg of tobramycin per mL. The product contains no preservative or sodium bisulfite.
Tobramycin sulfate is 0-3-amino-3-deoxy-a-D-glucopyranosyl-(1→4)- 0-[2,6-diamino-2,3,6-trideoxy-a-D-ribo-hexopyranosyl-(1→6)]-2-deoxy- L-streptamine, sulfate (2:5)(salt) and has the chemical formula (C18H37N5O9)2•5H2SO4. The molecular weight is 1425.45. The structural formula for tobramycin is as follows:
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The pharmacy bulk package of tobramycin for injection USP is a container of a sterile preparation for parenteral use that contains multiple single doses. It is intended for use in a pharmacy admixture program. Package use is restricted to the preparation of admixures for intravenous infusion or to the filling of empty sterile syringes for intravenous injections for patients with individualized dosing requirements.
† Each vial contains tobramycin sulfate equivalent to 1200 mg of tobramycin.
Uses for Tobramycin Injection
TOBRADEX® (tobramycin and dexamethasone ophthalmic suspension) is indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and where superficial bacterial ocular infection or a risk of bacterial ocular infection exists.
Ocular steroids are indicated in inflammatory conditions of the palpebral and bulbar conjunctiva, cornea and anterior segment of the globe where the inherent risk of steroid use in certain infective conjunctivitides is accepted to obtain a diminution in edema and inflammation. They are also indicated in chronic anterior uveitis and corneal injury from chemical, radiation or thermal burns, or penetration of foreign bodies.
The use of a combination drug with an anti-infective component is indicated where the risk of superficial ocular infection is high or where there is an expectation that potentially dangerous numbers of bacteria will be present in the eye.
The particular anti-infective drug in this product is active against the following common bacterial eye pathogens:
Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulase-negative), including penicillin-resistant strains.
Streptococci, including some of the Group A-beta-hemolytic species, some nonhemolytic species, and some Streptococcus pneumoniae.
Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus mirabilis, Morganella morganii, most Proteus vulgaris strains, Haemophilus influenzae and H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticus and some Neisseria species.
Dosage for Tobramycin Injection
One or two drops instilled into the conjunctival sac(s) every four to six hours. During the initial 24 to 48 hours, the dosage may be increased to one or two drops every two (2) hours. Frequency should be decreased gradually as warranted by improvement in clinical signs. Care should be taken not to discontinue therapy prematurely.
Not more than 20 mL should be prescribed initially and the prescription should not be refilled without further evaluation as outlined in PRECAUTIONS above.
HOW SUPPLIED
Sterile ophthalmic suspension in 2.5 mL (NDC 0065-0647-25), 5 mL (NDC 0065-064705) and 10 mL (NDC 0065-0647-10) dispensers.
Storage
Store at 8°C to 27°C (46°F to 80°F). Store suspension upright and shake well before using.
After opening, TOBRADEX® (tobramycin and dexamethasone ophthalmic suspension) can be used until the expiration date on the bottle.
Distributed by: Novartis Pharmaceuticals Corporation East Hanover, New Jersey 07936. Revised: May 2021
Side Effects for Tobramycin Injection
Adverse reactions have occurred with steroid/anti-infective combination drugs which can be attributed to the steroid component, the anti-infective component, or the combination. Exact incidence figures are not available.
The most frequent adverse reactions to topical ocular tobramycin [TOBREX (tobramycin ophthalmic solution) 0.3%] are hypersensitivity and localized ocular toxicity, including lid itching and swelling, and conjunctival erythema. These reactions occur in less than 4% of patients.
The reactions due to the steroid component are: elevation of IOP with possible development of glaucoma, and infrequent optic nerve damage; posterior subcapsular cataract formation; and delayed wound healing.
Secondary Infection
The development of secondary infection has occurred after use of combinations containing steroids and antimicrobials. Fungal infections of the cornea are particularly prone to develop coincidentally with long-term applications of steroids. The possibility of fungal invasion must be considered in any persistent corneal ulceration where steroid treatment has been used. Secondary bacterial ocular infection following suppression of host responses also occurs.
Postmarketing Experience
Additional adverse reactions identified from postmarketing use include anaphylactic reaction, erythema multiforme.
The following additional adverse reactions have been reported with the individual components listed below:
Dexamethasone
Cushing's syndrome and adrenal suppression may occur after use of dexamethasone in excess of the listed dosing instructions in predisposed patients, including children and patients treated with CYP3A4 inhibitors.
Aminoglycosides
Neurotoxicity, ototoxicity, and nephrotoxicity have occurred in patients receiving systemic aminoglycoside therapy. Aminoglycosides may aggravate muscle weakness in patients with known or suspected neuromuscular disorders, such as myasthenia gravis or Parkinson's disease, because of their potential effect on neuromuscular function.
Drug Interactions for Tobramycin Injection
No Information provided
Warnings for Tobramycin Injection
FOR TOPICAL OPHTHALMIC USE. NOT FOR INJECTION INTO THE EYE. Sensitivity to topically applied aminoglycosides may occur in some patients. Severity of hypersensitivity reactions may vary from local effects to generalized reactions, such as erythema, itching, urticaria, skin rash, anaphylaxis, anaphylactoid reactions, or bullous reactions. If a sensitivity reaction does occur, discontinue use.
Prolonged use of steroids may result in glaucoma, with damage to the optic nerve, defects in visual acuity and fields of vision, and posterior subcapsular cataract formation. Intraocular pressure (IOP) should be routinely monitored even though it may be difficult in pediatric patients and uncooperative patients. Prolonged use may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions and parasitic infections of the eye, steroids may mask infection or enhance existing infection.
In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids.
Precautions for Tobramycin Injection
General
The possibility of fungal infections of the cornea should be considered after long-term steroid dosing. As with other antibiotic preparations, prolonged use may result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, appropriate therapy should be initiated. When multiple prescriptions are required, or whenever clinical judgement dictates, the patient should be examined with the aid of magnification, such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.
Cross-sensitivity to other aminoglycoside antibiotics may occur; if hypersensitivity develops with this product, discontinue use and institute appropriate therapy.
Nonclinical Toxicology
Carcinogenesis, Mutagenesis, Impairment Of Fertility
No studies have been conducted to evaluate the carcinogenic or mutagenic potential. No impairment of fertility was noted in studies of subcutaneous tobramycin in rats at doses of 50 and 100 mg/kg/day.
Pregnancy
Corticosteroids have been found to be teratogenic in animal studies. Ocular administration of 0.1% dexamethasone resulted in 15.6% and 32.3% incidence of fetal anomalies in two groups of pregnant rabbits. Fetal growth retardation and increased mortality rates have been observed in rats with chronic dexamethasone therapy. Reproduction studies have been performed in rats and rabbits with tobramycin at doses up to 100 mg/kg/day parenterally and have revealed no evidence of impaired fertility or harm to the fetus.
There are no adequate and well-controlled studies in pregnant women. However, prolonged or repeated corticoid use during pregnancy has been associated with an increased risk of intra-uterine growth retardation. TOBRADEX (tobramycin and dexamethasone ophthalmic suspension) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Infants born of mothers who have received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism.
Nursing Mothers
Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in human milk. Because many drugs are excreted in human milk, caution should be exercised when TOBRADEX (tobramycin and dexamethasone ophthalmic suspension) is administered to a nursing woman.
Pediatric Use
Safety and effectiveness in pediatric patients below the age of 2 years have not been established.
Geriatric Use
No overall differences in safety or effectiveness have been observed between elderly and younger patients.
Overdose Information for Tobramycin Injection
No Information provided
Contraindications for Tobramycin Injection
Epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, and many other viral diseases of the cornea and conjunctiva. Mycobacterial infection of the eye. Fungal diseases of ocular structures. Hypersensitivity to a component of the medication.
Clinical Pharmacology for Tobramycin Injection
Corticoids suppress the inflammatory response to a variety of agents and they probably delay or slow healing. Since corticoids may inhibit the body's defense mechanism against infection, a concomitant antimicrobial drug may be used when this inhibition is considered to be clinically significant. Dexamethasone is a potent corticoid.
The antibiotic component in the combination (tobramycin) is included to provide action against susceptible organisms. In vitro studies have demonstrated that tobramycin is active against susceptible strains of the following microorganisms:
Staphylococci, including S. aureus and S. epidermidis (coagulase-positive and coagulase-negative), including penicillin-resistant strains.
Streptococci, including some of the Group A-beta-hemolytic species, some nonhemolytic species, and some Streptococcus pneumoniae.
Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes, Proteus mirabilis, Morganella morganii, most Proteus vulgaris strains, Haemophilus influenzae and H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticus and some Neisseria species.
No data are available on the extent of systemic absorption from TOBRADEX; however, it is known that some systemic absorption can occur with ocularly applied drugs.
From 
Infectious Disease Resources
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