Retisert

1 INDICATIONS AND USAGE RETISERT ® is indicated for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye. RETISERT is a corticosteroid indicated for the treatment of chronic noninfectious uveitis affecting the posterior segment of the eye. (1)

2 DOSAGE AND ADMINISTRATION RETISERT is surgically implanted into the posterior segment of the affected eye through a pars plana incision. (2.1) RETISERT is designed to release fluocinolone acetonide at a nominal initial rate of 0.6 mcg/day, decreasing over the first month to a steady state between 0.3-0.4 mcg/day over approximately 30 months. (2.1) Aseptic technique should be maintained at all times prior to and during the surgical implantation procedure. (2.2) 2.1 Dosing Information RETISERT is implanted into the posterior segment of the affected eye through a pars plana incision. The implant contains one tablet of 0.59 mg of fluocinolone acetonide. RETISERT is designed to release fluocinolone acetonide at a nominal initial rate of 0.6 mcg/day, decreasing over the first month to a steady state between 0.3-0.4 mcg/day over approximately 30 months. Following depletion of fluocinolone acetonide as evidenced by recurrence of uveitis, RETISERT may be replaced. 2.2 Handling of Implant Caution should be exercised in handling RETISERT in order to avoid damage to the implant, which may result in an increased rate of drug release from the implant. Thus, RETISERT should be handled only by the suture tab. Care should be taken during implantation and explantation to avoid sheer forces on the implant that could disengage the silicone cup reservoir (which contains a fluocinolone acetonide tablet) from the suture tab. Aseptic technique should be maintained at all times prior to and during the surgical implantation procedure. RETISERT should not be resterilized by any method.

4 CONTRAINDICATIONS Surgical placement of RETISERT is contraindicated in active viral, bacterial, mycobacterial and fungal infections of ocular structures. (4.1) 4.1 Viral, Bacterial, Mycobacterial and Fungal Infections of Ocular Structures Surgical placement of RETISERT is contraindicated in active viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in active bacterial, mycobacterial or fungal infections of the eye.

5 WARNINGS AND PRECAUTIONS Cataract formation: Nearly all phakic patients are expected to develop cataracts and require cataract surgery. (5.1) Endophthalmitis: Late onset endophthalmitis has been observed. (5.2) Increase in intraocular pressure: Use of corticosteroids may result in elevated IOP and/or glaucoma. (5.3) IOP lowering medications were required in > 75% of patients; filtering surgeries were required in > 35% of patients. (6.1) Separation of implant components: Physicians should periodically monitor the integrity of the implant by visual inspection. (5.4) 5.1 Cataract Formation Use of corticosteroids may result in posterior subcapsular cataract formation. Based on clinical trials with RETISERT, during the 3-year post-implantation period, nearly all phakic eyes are expected to develop cataracts and require cataract surgery. 5.2 Endophthalmitis and Surgical Complications Late onset endophthalmitis has been observed. These events are often related to the integrity of the surgical wound site. Careful attention to assure tight closure of the scleral wound and the integrity of the overlying conjunctiva at the wound site is important. Potential complications accompanying intraocular surgery to place RETISERT into the vitreous cavity may include, but are not limited to, the following: cataract formation, choroidal detachment, endophthalmitis, hypotony, increased intraocular pressure, exacerbation of intraocular inflammation, retinal detachment, vitreous hemorrhage, vitreous loss, and wound dehiscence. Following implantation of RETISERT, nearly all patients will experience an immediate and temporary decrease in visual acuity in the implanted eye which lasts for approximately one to four weeks post-operatively. 5.3 Increase in Intraocular Pressure Prolonged use of corticosteroids may result in elevated IOP and/or 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. Patients must be monitored for elevated IOP. Based on clinical trials with RETISERT, within 3-years post-implantation, approximately 77% of patients will require IOP lowering medications to control intraocular pressure and 37% of patients will require filtering procedures to control intraocular pressure [see Adverse Reactions ( 6.1 )] . 5.4 Separation of Implant Components In vitro stability studies show that the strength of the adhesive bond between the silicone cup reservoir and the suture tab is reduced with prolonged hydration, indicating a potential for the separation of these components. The suture tab composition is a silicone elastomer reinforced with a polyester mesh. Physicians should periodically monitor the integrity of the implant by visual inspection. 5.5 Other Corticosteroid Induced Adverse Reactions RETISERT should be used with caution in patients with a history of a viral, bacterial, mycobacterial or fungal infection of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia and varicella. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires great caution. Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections (bacterial, fungal, and viral). In acute purulent conditions of the eye, steroids may mask infection or enhance existing infection. Fungal and viral infections of the cornea are particularly prone to develop coincidentally with long-term application of steroids. The possibility of fungal invasion should be considered in any persistent corneal ulceration where steroid treatment has been used. Since resistance to infections is known to be reduced by corticosteroids, simultaneous bilateral implantation should not be carried out, in order to limit the potential for bilateral post-operative infection. Ocular administration of corticosteroids has also been associated with delayed wound healing and perforation of the globe where there is thinning of the sclera. The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.

6 ADVERSE REACTIONS Ocular adverse events included procedural complications, and eye pain (> 50%). Thirty-five to forty percent of patients reported ocular/conjunctival hyperemia, reduced visual acuity, and conjunctival hemorrhage. (6.1) The most common non-ocular event reported was headache (33%). (6.2) To report SUSPECTED ADVERSE REACTIONS, contactBausch & Lomb Incorporated at 1-800-553-5340or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience - Ocular Events The available safety data includes exposure to RETISERT in patients with chronic non-infectious uveitis affecting the posterior segment in two multicenter controlled clinical trials. Patients were randomized to dosage regimens of 0.59 mg or 2.1 mg implants. The most frequently reported ocular adverse events were cataract, increased intraocular pressure, procedural complication, and eye pain. These events occurred in approximately 50 - 90% of patients. Cataract includes aggravated cataract, and posterior capsular opacification. Procedural complications includes post-op complication, post-op wound complication, post-op wound site erythema, and wound dehiscense. Based on clinical trials with RETISERT, during the 3-year post-implantation period, nearly all phakic eyes are expected to develop cataracts and require cataract surgery. IOP lowering medications to lower intraocular pressure were required in approximately 77% of patients; filtering surgeries were required to control intraocular pressure in 37% of patients. Ocular adverse events occurring in approximately 10 - 40% of patients in decreasing order of incidence were ocular/conjunctival hyperemia, reduced visual acuity, glaucoma, conjunctival hemorrhage, blurred vision, abnormal sensation in the eye, eye irritation, maculopathy, vitreous floaters, hypotony, pruritus, ptosis, increased tearing, vitreous hemorrhage, dry eye, eyelid edema, macular edema and visual disturbance. Ocular adverse events occurring in approximately 5 - 9% of patients in decreasing order of incidence were eye discharge, photophobia, blepharitis, corneal edema, iris adhesions, choroidal detachment, diplopia, eye swelling, retinal detachment, photopsia, retinal hemorrhage and hyphema. 6.2 Clinical Trials Experience - Non-Ocular Events The most frequently reported non-ocular adverse event was headache (33%). Other non-ocular adverse events occurring in approximately 5-20% of patients in decreasing order of incidence were nasopharyngitis, arthralgia, sinusitis, dizziness, pyrexia, upper respiratory tract infection, influenza, vomiting, nausea, cough, back pain, limb pain, and rash.

8.1 Pregnancy Risk Summary Adequate and well-controlled studies with RETISERT have not been conducted in pregnant women to inform drug-associated risk. Animal reproduction studies have not been conducted with RETISERT. It is not known whether RETISERT can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. RETISERT should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.