Tobradex ST

5 WARNINGS AND PRECAUTIONS Intraocular Pressure (IOP) Increase : Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. If this product is used for 10 days or longer, IOP should be monitored. ( 5.1 ). Sensitivity to topically applied aminoglycosides may occur. ( 5.2 ) Cataracts : Use of corticosteroids may result in posterior subcapsular cataract formation. ( 5.3 ) Delayed Healing : The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. ( 5.4 ) Bacterial Infections : Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated. ( 5.5 ) Viral Infections : Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). ( 5.6 ) Fungal Infections : Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. ( 5.7 ) Vision Blurred : Vision may be temporarily blurred following dosing with TOBRADEX ST. Care should be exercised in operating machinery or driving a motor vehicle. ( 5.8 ) 5.1 Intraocular Pressure Increase Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. If this product is used for 10 days or longer, intraocular pressure (IOP) should be monitored. 5.2 Aminoglycoside Sensitivity Sensitivity to topically applied aminoglycosides may occur. 5.3 Cataracts Use of corticosteroids may result in posterior subcapsular cataract formation. 5.4 Delayed Healing The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of topical steroids. The initial prescription and renewal of the medication order should be made by a physician only after examination of the patient with the aid of magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining. 5.5 Bacterial Infections Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection. If signs and symptoms fail to improve after 2 days, the patient should be reevaluated. 5.6 Viral Infections Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). 5.7 Fungal Infections Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. 5.8 Vision Blurred Vision may be temporarily blurred following dosing with TOBRADEX ST. Care should be exercised in operating machinery or driving a motor vehicle. 5.9 Risk of Contamination Do not touch the dropper tip of the bottle to any surface, as this may contaminate the contents. 5.10 Contact Lens Use TOBRADEX ST contains benzalkonium chloride, an antimicrobial preservative, that may be absorbed by soft contact lenses. Contact lenses should not be worn during the use of TOBRADEX ST.

6 ADVERSE REACTIONS 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.