RETISERT

RETISERT ® (fluocinolone acetonide intravitreal implant) 0.59 mg is a sterile implant designed to release fluocinolone acetonide locally to the posterior segment of the eye 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. The drug substance is the synthetic corticosteroid fluocinolone acetonide, represented by the following structural formula: C 24 H 30 F 2 O 6 Mol. Wt. 452.50 Chemical Name: Pregna-1,4-diene-3,20-dione,6,9-difluoro-11,21-dihydroxy-16,17-[(1-methyl-ethylidene)bis(oxy)],(6α,11β ,16α)-. Fluocinolone acetonide is a white crystalline powder, insoluble in water, and soluble in methanol. It has a melting point of 265-266ºC. Each RETISERT consists of a tablet containing 0.59 mg of the active ingredient, Fluocinolone Acetonide, USP, and the following inactives: magnesium stearate, microcrystalline cellulose, and polyvinyl alcohol. chemical structure

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)

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.

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.

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, contact Bausch & Lomb Incorporated at 1-800-553-5340 or 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.