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TobraDex®
(tobramycin and dexamethasone ophthalmic suspension) Sterile
DESCRIPTION: TOBRADEX® (tobramycin and dexamethasone ophthalmic suspension) is a sterile, multiple dose
antibiotic and steroid combination for topical ophthalmic use.
The chemical structures for tobramycin and dexamethasone are presented below:
[Tobramycin Structure]
Tobramycin
Empirical Formula: C18 H37 N5 O9
Chemical Name:
O-3-Amino-3-deoxy- α-D-glucopyranosyl-(1→4)-O-[2,6-diamino-2,3,6-trideoxy-α-D-ribo-
hexopyranosyl-(1→6)]-2-deoxy-L-streptamine
[Dexamethasone Structure]
Dexamethasone
Empirical Formula: C22 H29 F O5
Chemical Name:
9-Fluoro-11ß,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione
Each mL of TOBRADEX® (tobramycin and dexamethasone ophthalmic suspension) contains:
Active: Tobramycin 0.3% (3 mg) and Dexamethasone 0.1% (1 mg). Preservative: Benzalkonium Chloride 0.01%.
Inactives: tyloxapol, edetate disodium, sodium chloride, hydroxyethyl cellulose, sodium sulfate, sulfuric acid and/or
sodium hydroxide (to adjust pH) and purified water.
CLINICAL PHARMACOLOGY: 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, and
Acinetobacter calcoaceticus and some Neisseria species.
Bacterial susceptibility studies demonstrate that in some cases microorganisms resistant to gentamicin remain susceptible to
tobramycin.
No data are available on the extent of systemic absorption from TOBRADEX (tobramycin and dexamethasone ophthalmic
suspension); however, it is known that some systemic absorption can occur with ocularly applied drugs. If the maximum
dose of TOBRADEX (tobramycin and dexamethasone ophthalmic suspension) is given for the first 48 hours (two drops in
each eye every 2 hours) and complete systemic absorption occurs, which is highly unlikely, the daily dose of
dexamethasone would be 2.4 mg. The usual physiologic replacement dose is 0.75 mg daily. If TOBRADEX (tobramycin
and dexamethasone ophthalmic suspension) is given after the first 48 hours as two drops in each eye every 4 hours, the
administered dose of dexamethasone would be 1.2 mg daily.
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INDICATIONS AND USAGE: 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.
CONTRAINDICATIONS: 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.
WARNINGS: FOR TOPICAL OPHTHALMIC USE ONLY. NOT FOR INJECTION INTO THE EYE.
Sensitivity to topically applied aminoglycosides may occur in some patients. 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 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 those diseases causing thinning of the cornea or sclera, perforations have been
known to occur with the use of topical steroids. In acute purulent conditions of the eye, steroids may mask infection or
enhance existing infection.
PRECAUTIONS:
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.
Information for Patients: Do not touch dropper or tube tip to any surface, as this may contaminate the contents. Contact
lenses should not be worn during the use of this product.
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 Category C. 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
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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. TOBRADEX® Ophthalmic Suspension should be used during pregnancy only if the potential benefit
justifies the potential risk to the fetus.
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® 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.
ADVERSE REACTIONS: 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)]
are hypersensitivity and localized ocular toxicity, including lid itching and swelling, and conjunctival erythema. These
reactions occur in less than 4% of patients. Similar reactions may occur with the topical use of other aminoglycoside
antibiotics. Other adverse reactions have not been reported; however, if topical ocular tobramycin is administered
concomitantly with systemic aminoglycoside antibiotics, care should be taken to monitor the total serum concentration. The
reactions due to the steroid component are: elevation of intraocular pressure (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.
OVERDOSAGE: Clinically apparent signs and symptoms of an overdose of TOBRADEX Ophthalmic Suspension
(punctate keratitis, erythema, increased lacrimation, edema and lid itching) may be similar to adverse reaction effects seen
in some patients.
DOSAGE AND ADMINISTRATION: 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 0065-0647-05) and 10
mL (NDC 0065-0647-10) DROP-TAINER® dispensers.
STORAGE: Store at 8º -27ºC (46º - 80ºF).
Store suspension upright and shake well before using.
Rx only
U.S. Patent No. 5,149,694
©2002 Alcon Laboratories, Inc.
Alcon® Ophthalmic (logo)
ALCON LABORATORIES, INC.
Fort Worth, Texas 76134 USA
Printed in USA
Revised August 2002 TobGer-0802
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