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BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE Ocular Surgery DUREZOL ® (difluprednate ophthalmic emulsion) 0.05%, a topical corticosteroid, is indicated for the treatment of inflammation and pain associated with ocular surgery. Endogenous Anterior Uveitis DUREZOL ® Emulsion is also indicated for the treatment of endogenous anterior uveitis. DOSAGE AND ADMINISTRATION Ocular Surgery Instill one drop into the conjunctival sac of the affected eye 4 times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period, followed by 2 times daily for a week and then a taper based on the response. Endogenous Anterior Uveitis Instill one drop into the conjunctival sac of the affected eye 4 times daily for 14 days followed by tapering as clinically indicated. DOSAGE FORMS AND STRENGTHS DUREZOL ® Emulsion contains 0.05% difluprednate as a sterile preserved emulsion for topical ophthalmic administration. CONTRAINDICATIONS The use of DUREZOL ® Emulsion, as with other ophthalmic corticosteroids, is contraindicated in most active 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 disease of ocular structures. WARNINGS AND PRECAUTIONS IOP Increase Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. If this product is used for 10 days or longer, intraocular pressure should be monitored. Cataracts Use of corticosteroids may result in posterior subcapsular cataract formation. 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 beyond 28 days 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. 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. 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). 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. Fungal culture should be taken when appropriate. Topical Ophthalmic Use Only DUREZOL ® Emulsion is not indicated for intraocular administration. Contact Lens Wear DUREZOL ® Emulsion should not be instilled while wearing contact lenses. Remove contact lenses prior to instillation of DUREZOL ® Emulsion. The preservative in DUREZOL ® Emulsion may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of DUREZOL ® Emulsion. ADVERSE REACTIONS Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects; posterior subcapsular cataract formation; secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera. Ocular Surgery Ocular adverse reactions occurring in 5-15% of subjects in clinical studies with DUREZOL ® Emulsion included corneal edema, ciliary and conjunctival hyperemia, eye pain, photophobia, posterior capsule opacification, anterior chamber cells, anterior chamber flare, conjunctival edema, and blepharitis. Other ocular adverse reactions occurring in 1-5% of subjects included reduced visual acuity, punctate keratitis, eye inflammation, and iritis. Ocular adverse reactions occurring in < 1% of subjects included application site discomfort or irritation, corneal pigmentation and striae, episcleritis, eye pruritis, eyelid irritation and crusting, foreign body sensation, increased lacrimation, macular edema, sclera hyperemia, and uveitis. Most of these reactions may have been the consequence of the surgical procedure. Endogenous Anterior Uveitis A total of 200 subjects participated in the clinical trials for endogenous anterior uveitis, of which 106 were exposed to DUREZOL ® Emulsion. The most common adverse reactions of those exposed to DUREZOL ® Emulsion occurring in 5-10% of subjects included blurred vision, eye irritation, eye pain, headache, increased IOP, iritis, limbal and conjunctival hyperemia, punctate keratitis, and uveitis. Adverse reactions occurring in 2-5% of subjects included anterior chamber flare, corneal edema, dry eye, iridocyclitis, photophobia, and reduced visual acuity. USE IN SPECIFIC POPULATIONS Pregnancy Teratogenic Effects Pregnancy Category C. Difluprednate has been shown to be embryotoxic (decrease in embryonic body weight and a delay in embryonic ossification) and teratogenic (cleft palate and skeletal) anomalies when administered subcutaneously to rabbits during organogenesis at a dose of 1–10 mcg/kg/day. The no-observed-effect-level (NOEL) for these effects was 1 mcg/kg/day, and 10 mcg/kg/day was considered to be a teratogenic dose that was concurrently found in the toxic dose range for fetuses and pregnant females. Treatment of rats with 10 mcg/kg/day subcutaneously during organogenesis did not result in any reproductive toxicity, nor was it maternally toxic. At 100 mcg/kg/day after subcutaneous administration in rats, there was a decrease in fetal weights and delay in ossification, and effects on weight gain in the pregnant females. It is difficult to extrapolate these doses of difluprednate to maximum daily human doses of DUREZOL ® Emulsion, since DUREZOL ® Emulsion is administered topically with minimal systemic absorption, and difluprednate blood levels were not measured in the reproductive animal studies. However, since use of difluprednate during human pregnancy has not been evaluated and cannot rule out the possibility of harm, DUREZOL ® Emulsion should be used during pregnancy only if the potential benefit justifies the potential risk to the embryo or fetus. Nursing Mothers It is not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Caution should be exercised when DUREZOL ® Emulsion is administered to a nursing woman. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use No overall differences in safety or effectiveness have been observed between elderly and younger patients. Nonclinical Toxicology Carcinogenesis, Mutagenesis, and Impairment of Fertility Difluprednate was not genotoxic in vitro in the Ames test, and in cultured mammalian cells CHL/IU (a fibroblastic cell line derived from the lungs of newborn female Chinese hamsters). An in vivo micronucleus test of difluprednate in mice was also negative. Treatment of male and female rats with subcutaneous difluprednate up to 10 mcg/kg/day prior to and during mating did not impair fertility in either gender. Long term studies have not been conducted to evaluate the carcinogenic potential of difluprednate. Animal Toxicology and/or Pharmacology In multiple studies performed in rodents and non-rodents, subchronic and chronic toxicity tests of difluprednate showed systemic effects such as suppression of body weight gain; a decrease in lymphocyte count; atrophy of the lymphatic glands and adrenal gland; and for local effects, thinning of the skin; all of which were due to the pharmacologic action of the molecule and are well known glucocorticosteroid effects. Most, if not all of these effects were reversible after drug withdrawal. The NOEL for the subchronic and chronic toxicity tests were consistent between species and ranged from 1–1.25 mcg/kg/day. PATIENT COUNSELING INFORMATION Risk of Contamination This product is sterile when packaged. Patients should be advised not to allow the dropper tip to touch any surface, as this may contaminate the emulsion. Use of the same bottle for both eyes is not recommended with topical eye drops that are used in association with surgery. Risk of Secondary Infection If pain develops, or if redness, itching, or inflammation becomes aggravated, the patient should be advised to consult a physician. Contact Lens Wear DUREZOL ® Emulsion should not be instilled while wearing contact lenses. Patients should be advised to remove contact lenses prior to instillation of DUREZOL ® Emulsion. The preservative in DUREZOL ® Emulsion may be absorbed by soft contact lenses. Lenses may be reinserted after 10 minutes following administration of DUREZOL ® Emulsion. Revised: June 2012 U.S. Patent 6,114,319 Manufactured For Alcon Laboratories, Inc. 6201 South Freeway Fort Worth, Texas 76134 USA 1-800-757-9195 MedInfo@AlconLabs.com Manufactured By: Catalent Pharma Solutions Woodstock, IL 60098 © 2015 Novartis 1/15 DUR14090JAD-PI

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