Label: TOBRAMYCIN AND DEXAMETHASONE suspension/ drops

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 Empirical Formula: C 18H 37N 5O 9

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

Molecular Weight: 467.52

Dexamethasone Empirical Formula: C 22H 29FO 5

Chemical Name: 9-Fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione

Molecular Weight: 392.47

Each mL of tobramycin and dexamethasone ophthalmic suspension contains: Actives:tobramycin 0.3% (3 mg) and dexamethasone 0.1% (1 mg). Preservative:benzalkonium chloride 0.01%. Inactives:edetate disodium, hydroxyethyl cellulose, purified water, sodium chloride, sodium sulfate, sulfuric acid and/or sodium hydroxide (to adjust pH), and tyloxapol.

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 vitrostudies have demonstrated that tobramycin is active against susceptible strains of the following microorganisms:

Staphylococci,including S. aureusand 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 vulgarisstrains, Haemophilus influenzaeand H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticusand some Neisseriaspecies.

No data are available on the extent of systemic absorption from tobramycin and dexamethasone ophthalmic suspension; however, it is known that some systemic absorption can occur with ocularly applied drugs.

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. aureusand 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 vulgarisstrains, Haemophilus influenzaeand H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticusand some Neisseriaspecies.

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.

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.

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 tobramycin and dexamethasone ophthalmic suspension is administered to a nursing woman.

Safety and effectiveness in pediatric patients below the age of 2 years have not been established.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

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 (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.

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 PRECAUTIONSabove.

Sterile ophthalmic suspension in 2.5 mL (NDC61314-647-25), 5 mL (NDC61314-647-05) and 10 mL (NDC61314-647-10) dispensers.

STORAGE

Store at 8°C to 27°C (46°F to 80°F).

Store suspension upright and shake well before using.

After opening, tobramycin and dexamethasone ophthalmic suspension can be used until the expiration date on the bottle.

Distributed by Sandoz Inc.

Princeton, NJ 08540

May 2021

T2021-123

775950 US

NDC61314-647-25

Tobramycin and

Dexamethasone

Ophthalmic

Suspension

Rx only

STERILE

2.5 mL

FOR TOPICAL OPHTHALMIC USE

SANDOZ