AHFS Class:

• Corticosteroids 52:08.08

Generic Name(s):

• Fluocinolone Acetonide

Fluocinolone acetonide is a synthetic fluorinated corticosteroid.1

Uveitis

Fluocinolone acetonide is used for the management of chronic noninfectious uveitis affecting the posterior segment of the eye.1 Fluocinolone acetonide is designated an orphan drug by the US Food and Drug Administration (FDA) for this use.2,4

Safety and efficacy of fluocinolone acetonide have been evaluated in 2 multicenter, double-blind studies in patients with chronic (persisting for at least 1 year) noninfectious uveitis affecting the posterior segment of one or both eyes.1 In these studies, treatment with fluocinolone acetonide (one 0. 59-mg implant in one eye [in the more severely affected eye in patients with bilateral disease2 ]) reduced the recurrence rate of posterior uveitis in the treated eye from approximately 40-54% (for the 34-week period prior to implantation) to approximately 7-14% (for the 34-week period following implantation).1 The need for systemic corticosteroid and/or immunosuppressive therapy was reduced from 47-63% at baseline to 5-10% at 34 weeks after implantation, and the need for periocular corticosteroid injections was reduced from 50-65% to 3-6%.2 Visual acuity improvement of 3 or more lines was observed in 19-21% of treated eyes compared with 6-7% of untreated eyes.2

Topical Uses

For other uses of fluocinolone acetonide, see Fluocinolone Acetonide 84:06.08.

Administration

Fluocinolone acetonide is administered as an implant that is inserted intravitreally (through a pars plana incision) into the posterior segment of the affected eye.1 Simultaneous implantation into both eyes should be avoided to minimize the risk of bilateral postoperative infection.1 (See Increased Susceptibility to Infection under Warnings/Precautions: Warnings, in Cautions.)

Fluocinolone acetonide implants should be handled with extreme caution and only by the suture tab to avoid damaging the implant; damage to the implant may result in an increased rate of drug release.1 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.1

Aseptic technique should be maintained at all times prior to and during the surgical implantation procedure to ensure the sterility of the surgical field and of fluocinolone acetonide implants.1 Fluocinolone acetonide implants should not be resterilized by any method.1

Dosage

Dosage of fluocinolone acetonide is expressed in terms of the salt.1

The usual dosage of fluocinolone acetonide in adults and pediatric patients 12 years of age and older is 0.59 mg (1 implant) in each affected eye approximately every 30 months.1,3 The implant is designed to release fluocinolone acetonide locally to the posterior segment of the eye at a nominal initial rate of 0.6 mcg daily, which decreases over the first month to a steady state of 0.3-0.4 mcg daily for approximately 30 months.1 Following depletion of fluocinolone acetonide from the implant (as evidenced by recurrence of uveitis), the implant may be removed and replaced with a new implant to continue therapy.1

Special Populations

No special population recommendations at this time.3

Contraindications

Most viral diseases of the cornea and conjunctiva (including epithelial herpes simplex keratitis [dendritic keratitis], vaccinia, and varicella [chickenpox]); mycobacterial infections of the eye; and fungal diseases of ocular structures.1

Known or suspected hypersensitivity to fluocinolone acetonide, other corticosteroids, or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Surgical Complications

Insertion of fluocinolone acetonide implants may potentially result in complications, including cataract formation, choroidal detachment, temporary decrease in visual acuity, endophthalmitis, hypotony, increased intraocular pressure (IOP), exacerbation of intraocular inflammation, retinal detachment, vitreous hemorrhage, vitreous loss, and wound dehiscence.1

Immediate and temporary decrease in visual acuity in the implanted eye will occur in nearly all patients; this effect may persist for approximately 1-4 weeks following implantation.1

Ocular Effects

Glaucoma (with optic nerve damage and defects in visual acuity and fields of vision) may occur with long-term use of corticosteroids.1 Based on results of clinical studies with fluocinolone acetonide ocular implants, approximately 60% of patients will require drug therapy to reduce IOP within 34 weeks following implantation, and approximately 32% of patients are expected to require filtering procedures to control IOP within 2 years following implantation.1 Corticosteroids should be used with caution in patients with glaucoma, and patients must be monitored periodically for elevated IOP (e.g., every 3-6 months but more frequently in the immediate period following implantation).1,3

Posterior subcapsular cataract formation also may occur with prolonged use of corticosteroids.1 Within 2 years following insertion of fluocinolone acetonide implants, nearly all phakic eyes are expected to develop cataracts and require cataract surgery.1

Increased Susceptibility to Infection

Ophthalmic corticosteroids may mask, prolong, or exacerbate existing ocular infections (e.g., herpes simplex).1 Corticosteroids should be used with extreme caution in patients with a history of herpes simplex virus infections.1

Development of secondary ocular infection (bacterial, fungal, or viral) has occurred following use of ophthalmic corticosteroids.1 Fungal and viral infections of the cornea are particularly prone to develop following long-term use of these agents.1 The possibility of fungal infection should be considered in patients receiving corticosteroids who present with persistent corneal ulceration.1

Wound Healing Complications

Use of ophthalmic corticosteroids after cataract surgery may delay healing and increase the risk of bleb formation.1

General Precautions

Proper Handling of Implants

Exercise caution in order to maintain sterility of and avoid damage to the implant.1 (See Dosage and Administration: Administration.)

Specific Populations

Pregnancy

Category C.1 (See Users Guide.)

Lactation

Systemically administered corticosteroids are distributed into milk and may suppress growth, interfere with endogenous corticosteroid production, or cause other adverse effects.1 Not known whether ocular administration of fluocinolone acetonide could result in sufficient systemic absorption to produce detectable quantities in milk; caution if used in nursing women.1

Pediatric Use

Safety and efficacy not established in children younger than 12 years of age.1

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1

Common Adverse Effects

Adverse ocular effects reported in 50-90% of patients receiving fluocinolone acetonide implants include cataract, increased IOP, ocular pain, and surgical complications (e.g., cataract fragments in the eye; injury; mechanical complication, migration, or expulsion of implant; wound complications or dehiscence).1 Adverse ocular effects reported in 10-35% of patients include reduced visual acuity, conjunctival hemorrhage, conjunctival hyperemia, glaucoma, blurred vision, abnormal sensation in the eye, ocular irritation, hypotony, pruritus, vitreous floaters, maculopathy, vitreous hemorrhage, ptosis, ocular inflammation, eyelid edema, increased tearing, and dry eye.1

The most common adverse systemic effect reported in patients receiving fluocinolone acetonide implants was headache (31%).1

No formal drug interaction studies have been performed to date.3 However, because of limited systemic exposure, only intraocular interactions would be expected.3

Description

Fluocinolone acetonide is a synthetic fluorinated corticosteroid.1 Corticosteroids inhibit the inflammatory response to mechanical, chemical, or immunologic agents.1,3 Corticosteroids inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.1 Although the precise mechanism of the ocular effects of corticosteroids is unknown, corticosteroids are thought to act by inducing phospholipase A₂ inhibitory proteins (collectively referred to as lipocortins); these proteins are postulated to control the biosynthesis of potent inflammatory mediators (e.g., prostaglandins, leukotrienes) by inhibiting the release of their common precursor, arachidonic acid.1

Fluocinolone acetonide is commercially available as a sterile intravitreal implant.1 The implant consists of a tablet encased in a silicone elastomer cup containing a release orifice and a polyvinyl alcohol membrane positioned between the tablet and the orifice; the silicone elastomer cup assembly is attached to a polyvinyl alcohol suture tab with silicone adhesive.1 The implant is designed to release fluocinolone acetonide locally to the posterior segment of the eye at a nominal initial rate of 0.6 mcg daily, decreasing over the first month to a steady state of 0.3-0.4 mcg daily over approximately 30 months.1 Following insertion of the implant, plasma concentrations of fluocinolone acetonide at weeks 1, 4, and 34 were below the limit of detection (0.2 ng/mL).1 Concentrations of the drug in aqueous and vitreous humor appeared to be highly variable, ranging from below the limit of detection to 589 ng/mL throughout the 34-month observation period.1

Advice to Patients

Importance of informing patients that fluocinolone acetonide treats ocular inflammation only and does not treat the underlying disease.1 Drugs used to treat the underlying disease may be prescribed concomitantly as deemed appropriate by a clinician.1

Importance of advising patients to return to clinician's office for follow-up ophthalmologic examinations of both eyes at appropriate intervals following insertion of the fluocinolone acetonide implant.1

Risks of surgical complications, adverse ocular effects, and ocular infections.1

Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

Importance of informing patients of other important precautionary information.1 (See Cautions.)

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

1. Bausch & Lomb Incorporated. Retisert^® (fluocinolone acetonide intravitreal implant) 0.59 mg prescribing information. Rochester, NY; 2005 Apr.

2. Bausch & Lomb. Retisert^® (fluocinolone acetonide intravitreal implant) 0.59 mg formulary kit. Tampa, FL; 2005 May.

3. Bausch & Lomb, Rochester, NY: Personal communication.

4. Food and Drug Administration. Orphan designation pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD. From FDA website ([Web]).