TOBRADEX ST

TOBRADEX ST (tobramycin and dexamethasone ophthalmic suspension) 0.3%/0.05% is a sterile, isotonic, white, aqueous antibiotic and steroid suspension with a pH of approximately 5.7 and an osmolality of approximately 290 mOsm/kg. The chemical name of tobramycin is 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. It has a molecular formula of C 18 H 37 N 5 O 9 and a molecular weight of 467.52 g/mol. The chemical structure is: The chemical name of dexamethasone is 9-fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. It has a molecular formula of C 22 H 29 FO 5 and a molecular weight of 392.47 g/mol. The chemical structure is: Each mL of TOBRADEX ST contains: Actives: tobramycin 3 mg and dexamethasone 0.5 mg. Preservative: benzalkonium chloride 0.1 mg. Inactives: edetate disodium, hydrochloric acid and/or sodium hydroxide (to adjust pH), propylene glycol, purified water, sodium chloride, sodium sulfate, tyloxapol, and xanthan gum. Chemical Structure Chemical Structure

TOBRADEX ST 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. epidermidi s (coagulase-positive and coagulase-negative), including penicillin-resistant isolates. Streptococci , including some Group A and other 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 isolates, Haemophilus influenzae, H. aegyptius, Moraxella lacunata, Acinetobacter calcoaceticus , and some Neisseria species . TOBRADEX ST is a topical antibiotic and corticosteroid combination 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. ( 1 ).

Instill one drop into the conjunctival sac(s) every 4 to 6 hours. ( 2.1 ) During the initial 24 to 48 hours, dosage may be increased to one drop every 2 hours. ( 2.1 ) Frequency should be decreased gradually as warranted by improvement in clinical signs, but care should be taken not to discontinue therapy prematurely. ( 2.1 ) 2.1 Initiation and Continuation of Treatment Evaluate intraocular pressure (IOP) prior to the initial prescription and renewal of the medication order [see Warnings and Precautions (5.1) ] . Perform ophthalmic examination with the aid of magnification, such as slit lamp biomicroscopy, and, where appropriate, fluorescein staining, prior to the initial prescription and renewal of the medication order. Re-evaluate the patient if signs and symptoms fail to improve after 2 days [see Warnings and Precautions (5.4 , 5.5) ] . Not more than one bottle should be prescribed initially, and the prescription should not be refilled without further evaluation. 2.2 Recommended Dosage Instill one drop into the conjunctival sac(s) every 4 to 6 hours. During the initial 24 to 48 hours, the dosage may be increased to one drop every 2 hours. Frequency should be decreased gradually as warranted by improvement in clinical signs. Care should be taken not to discontinue therapy prematurely. Shake well before use.

TOBRADEX ST, as with other ophthalmic corticosteroids, is contraindicated in most viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. ( 4.1 ) Hypersensitivity to any component of the medication ( 4.2 ) 4.1 Nonbacterial Etiology TOBRADEX ST, as with other ophthalmic corticosteroids, is contraindicated in most viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal diseases of ocular structures. 4.2 Hypersensitivity Hypersensitivity to a component of the medication.

Most common adverse reactions to topical ocular tobramycin are hypersensitivity and localized ocular toxicity, including eye pain, eyelids pruritus, eyelid edema, and conjunctival hyperemia. The reactions due to the steroid component are increases in IOP with possible development of glaucoma. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Harrow at 1-833-4HARROW(427769) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 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 ® ) are hypersensitivity and localized ocular toxicity, including eye pain, eyelids pruritus, eyelid edema, and conjunctival hyperemia. These reactions occur in less than 4% of patients. The reactions due to the steroid component are: increased IOP with possible development of glaucoma, and infrequent optic nerve disorder; subcapsular cataract; and impaired healing [see Warnings and Precautions (5.1 , 5.3 , 5.4) ] . 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 [see Warnings and Precautions (5.7) ] . 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. Non-ocular adverse events occurring at an incidence of 0.5% to 1% included headache and increased blood pressure. The following additional adverse reactions have been reported with the individual components below: 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. 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. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of TOBRADEX ST. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Additional adverse reactions identified from postapproval use include, anaphylactic reaction, and erythema multiforme.

Storage Store at 2°C to 25°C (36°F to 77°F). Protect from light. After opening, TOBRADEX ST can be used until the expiration date on the bottle.