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TobraDex® (tobramycin and dexamethasone ophthalmic ointment) Sterile

DESCRIPTION: TOBRADEX® (tobramycin and dexamethasone ophthalmic ointment) is a sterile, multiple
dose antibiotic and steroid combination for topical ophthalmic use. The chemical structures for tobramycin and
dexamethasone are presented below:

.
Each gram of TOBRADEX® (tobramycin and dexamethasone ophthalmic ointment) contains: Actives:
tobramycin 0.3% (3 mg) and dexamethasone 0.1% (1 mg). Preservative: chlorobutanol 0.5%. Inactives:
mineral oil and white petrolatum.

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, Acinetobacter calcoaceticus and some Neisseria species.
No data are available on the extent of systemic absorption from TOBRADEX® (tobramycin and dexamethasone
ophthalmic ointment); however, it is known that some systemic absorption can occur with ocularly applied
drugs.

INDICATIONS AND USAGE: TOBRADEX (tobramycin and dexamethasone ophthalmic ointment) is

indicated for steroid-responsive inflammatory ocular conditions for which a corticosteroid is indicated and

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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. 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 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:
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

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product, discontinue use and institute appropriate therapy.

Ophthalmic ointment may retard corneal wound healing.
Patients should be advised not to wear contact lenses if they have signs and symptoms of bacterial
ocular infection.
Information for Patients: Do not touch tube tip to any surface, as this may contaminate the contents.
Contact lenses should not be worn during the use of this product.
Do not use the product if the imprinted carton seals have been damaged, or removed.
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 ointment) 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 ointment) 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 clinical differences in safety or effectiveness have been observed between the
elderly and other adult 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
ointment) 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 intraocular pressure with possible development of
glaucoma, and infrequent optic nerve damage; posterior subcapsular cataract formation; and delayed wound
healing.

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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.

DOSAGE AND ADMINISTRATION: Apply a small amount (approximately ½ inch ribbon) into the
conjunctival sac(s) up to three or four times daily.
How to apply TOBRADEX® (tobramycin and dexamethasone ophthalmic ointment):
1. Tilt your head back.
2. Place a finger on your cheek just under your eye and gently pull down until a "V" pocket is formed between
your eyeball and your lower lid.
3. Place a small amount (about ½ inch) of TOBRADEX ® (tobramycin and dexamethasone ophthalmic
ointment). Do not let the tip of the tube touch your eye.
4. Look downward before closing your eye.
Not more than 8 g should be prescribed initially and the prescription should not be refilled without further
evaluation as outlined in PRECAUTIONS above.

HOW SUPPLIED: 3.5 g STERILE ointment supplied in an aluminum tube with a white polyethylene tip and
white polyethylene cap (NDC 0078-0876-01).

STORAGE: Store at 2°C to 25°C (36°F to 77°F).

After opening, TOBRADEX (tobramycin and dexamethasone ophthalmic ointment) can be used until the
expiration date on the tube.

Distributed by:
Novartis Pharmaceuticals Corporation
East Hanover, New Jersey 07936

© Novartis

Revised: 5/2021

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