DailyMed Label: Iluvien

DailyMed Label: Iluvien

2023

DailyMed Prescription

Iluvien

fluocinolone acetonide

Alimera Sciences, Inc.

NDC: 68611-190

NDC: 68611-190

ILUVIEN is a sterile non-bioerodable intravitreal implant containing 0.19 mg (190 mcg) fluocinolone acetonide in a 36-month sustained-release drug delivery system. ILUVIEN is designed to release fluocinolone acetonide at an initial rate of 0.25 µg/day. ILUVIEN is preloaded into a single-use applicator to facilitate injection of the implant directly into the vitreous. The drug substance is a synthetic corticosteroid, fluocinolone acetonide. The chemical name for fluocinolone acetonide is (6α,11β, 16α)-6,9-difluoro-11,21-dihydroxy-16,17-[(1-methylethylidene)bis-(oxy)]-pregna-1,4-diene-3,20-dione. Its chemical structure is: MW 452.50; molecular formula C 24 H 30 F 2 0 6 Fluocinolone acetonide is a white or almost white, microcrystalline powder, practically insoluble in water, soluble in methanol, ethanol, chloroform and acetone, and sparingly soluble in ether. Each ILUVIEN consists of a light brown 3.5mm x 0.37mm implant containing 0.19 mg of the active ingredient fluocinolone acetonide and the following inactive ingredients: polyimide tube, polyvinyl alcohol, silicone adhesive and water for injection. iluvien-figure-2

ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg is indicated for the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure. ILUVIEN contains a corticosteroid and is indicated for the treatment of diabetic macular edema (DME) in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure. (1)

For ophthalmic intravitreal injection. (2.1) The intravitreal injection procedure should be carried out under aseptic conditions. (2.2) Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. (2.2) For ophthalmic intravitreal injection. The intravitreal injection procedure should be carried out under aseptic conditions, which include use of sterile gloves, a sterile drape, a sterile caliper, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide should be given prior to the injection. The injection procedure for ILUVIEN is as follows: The exterior of the tray should not be considered sterile. An assistant (non-sterile) should remove the tray from the carton and examine the tray and lid for damage. If damaged, do not use unit. If acceptable, the assistant should peel the lid from the tray without touching the interior surface. Visually check through the viewing window of the preloaded applicator to ensure that there is a drug implant inside. Remove the applicator from the tray with sterile gloved hands touching only the sterile interior tray surface and applicator. Prior to injection, the applicator tip must be kept above the horizontal plane to ensure that the implant is properly positioned within the applicator. To reduce the amount of air administered with the implant, the administration procedure requires two steps. Before inserting the needle into the eye, remove the protective cap then gently push the applicator button down and slide it to the first stop (at the curved black marks alongside the button track). At the first stop, release the button and it should move to the UP position. If the button does not rise to the UP position, do not proceed with this unit. Optimal placement of the implant is inferior to the optic disc and posterior to the equator of the eye. Measure 4 millimeters inferotemporal from the limbus with the aid of calipers for point of entry into the sclera. Inspect the tip of the needle to ensure it is not bent. Gently displace the conjunctiva so that after withdrawing the needle, the conjunctival and scleral needle entry sites will not align. Care should be taken to avoid contact between the needle and the lid margin or lashes. Insert the needle through the conjunctiva and sclera. To release the implant, while the button is in the UP position, advance the button by sliding it forward to the end of the button track and remove the needle. Note: Ensure that the button reaches the end of the track before removing the needle. Remove the lid speculum and perform indirect ophthalmoscopy to verify placement of the implant, adequate central retinal artery perfusion and absence of any other complications. Following the injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between two and seven days following the injection. Patients should be instructed to report without delay any symptoms suggestive of endophthalmitis.

ILUVIEN is a non-bioerodable intravitreal implant in a drug delivery system containing 0.19 mg fluocinolone acetonide, designed to release fluocinolone acetonide at an initial rate of 0.25 μg/day and lasting 36 months. Non-bioerodable intravitreal implant containing 0.19 mg fluocinolone acetonide in a drug delivery system. (3)

Ocular or periocular infections (4.1) Glaucoma (4.2) Hypersensitivity (4.3) ILUVIEN is contraindicated in patients with active or suspected ocular or periocular infections including most viral disease of the cornea and conjunctiva including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections and fungal diseases. ILUVIEN is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8. ILUVIEN is contraindicated in patients with known hypersensitivity to any components of this product.

Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored following the injection. (5.1) Use of corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. (5.2) The implant may migrate into the anterior chamber if the posterior lens capsule is not intact. (5.3) Intravitreal injections, including those with ILUVIEN , have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored following the intravitreal injection [see Patient Counseling Information (17) ] . Use of corticosteroids including ILUVIEN may produce posterior subcapsular cataracts, increased intraocular pressure and glaucoma. Use of corticosteroids may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Corticosteroids are not recommended to be used in patients with a history of ocular herpes simplex because of the potential for reactivation of the viral infection. Patients in whom the posterior capsule of the lens is absent or has a tear are at risk of implant migration into the anterior chamber.

In controlled studies, the most common adverse reactions reported were cataract development and increases in intraocular pressure.

Pregnancy Category C There are no adequate and well-controlled studies of ILUVIEN in pregnant women. Animal reproduction studies have not been conducted with fluocinolone acetonide. Corticosteroids have been shown to be teratogenic in laboratory animals when administered systemically at relatively low dosage levels. ILUVIEN should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Systemically administered corticosteroids are present in human milk and could suppress growth and interfere with endogenous corticosteroid production. The systemic concentration of fluocinolone acetonide following intravitreal treatment with ILUVIEN is low [see Clinical Pharmacology (12.3) ]. It is not known whether intravitreal treatment with ILUVIEN could result in sufficient systemic absorption to produce detectable quantities in human milk. Exercise caution when ILUVIEN is administered to a nursing woman. Safety and effectiveness of ILUVIEN in pediatric patients have not been established. No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg is supplied in a sterile single use preloaded applicator with a 25-gauge needle, packaged in a tray sealed with a lid inside a carton. NDC 68611-190-02 Storage: Store at 15° - 30° C (59° - 86° F).

Corticosteroids inhibit inflammatory responses to a variety of inciting agents including multiple inflammatory cytokines. They inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. Corticosteroids are thought to act by inhibition of phospholipase A 2 via induction of inhibitory proteins collectively called lipocortins. It is postulated that these proteins control biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting release of the common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A 2 . In a human pharmacokinetic study of ILUVIEN , fluocinolone acetonide concentrations in plasma were below the lower limit of quantitation of the assay (100 pg/mL) at all post-administration time points from Day 7 through Month 36 following intravitreal administration of a 0.2 mcg/day or 0.5 mcg/day fluocinolone acetonide insert.

Long-term animal studies have not been conducted to determine the carcinogenic potential or the effect on fertility of ILUVIEN . Fluocinolone acetonide was not genotoxic in vitro in the Ames test (S. typhimurium and E. coli) and the mouse lymphoma TK assay, or in vivo in the mouse bone marrow micronucleus assay.

The efficacy of ILUVIEN was assessed in two three year, randomized (2:1, active: sham), multicenter, double-masked, parallel-groups studies that enrolled patients with diabetic macular edema (DME) that had previously been treated with laser photocoagulation. The primary efficacy endpoint in both trials was the proportion of subjects in whom vision had improved by 15 letters or more from baseline after 24 months of follow-up. Table 3: Baseline BCVA (Letters) Study 1 Study 2 ILUVIEN (N=190) Sham (N=95) ILUVIEN (N=186) Sham (N=90) Mean (SD) Median (Range) 53 (13) 57 (19-75) 55 (11) 58 (25-69) 53 (12) 56 (20-70) 55 (11) 58 (21-68) Table 4: Visual Acuity outcomes at Month 24 (All randomized subjects with LOCF)      a Study 1: ILUVIEN , N=190; Sham, N=95      b Study 2: ILUVIEN , N=186; Sham, N=90   Study        Outcomes   ILUVIEN   Sham   Estimated Difference (95% CI)      1 a   Gain of ≥15 letters in BCVA (n (%))   51 (27%)   14 (15%)   12.1% (2.6%, 21.6%)   Loss of ≥15 letters in BCVA (n (%))   26 (14%)   5 (5%)   8.4% (1.8%, 15.1%)   Mean change from baseline in BCVA (SD)   3.7 (18.7)   3.2 (13.1)   1.8 (-2.8, 6.3)      2 b   Gain of ≥15 letters in BCVA (n (%))   57 (31%)   16 (18%)   13.0% (2.7%, 23.4%)   Loss of ≥15 letters in BCVA (n (%))   22 (12%)   9 (10%)   1.8% (-5.9%, 9.6%)   Mean change from baseline in BCVA (SD)   5.2 (18.0)   0.0 (15.6)   6.1 (1.4, 10.8) Visual acuity outcomes by lens status (Phakic or Pseudophakic) at different visits are presented in Figure 2 and Figure 3 . The occurrence of cataracts impacted visual acuity during the study. Patients who were pseudophakic at baseline achieved greater mean BCVA change from baseline at the Month 24 study visit. Figure 2: Proportion of subjects with >=15 Letters Improvement from Baseline BCVA in the Study Eye Figure 3: Mean BCVA Change from Baseline The BCVA outcomes for the Pseudophakic and Phakic subgroups from Studies 1 and 2 at Month 24 are presented in Table 5 . Table 5: Visual Acuity outcomes at Month 24 (Subgroup for pooled data with LOCF)      a Pseudophakic : ILUVIEN , N=140; Sham, N=64      b Phakic: ILUVIEN , N=236; Sham, N=121   Lens Status   Outcomes   ILUVIEN   Sham   Estimated Difference   (95% CI)       a Pseudophakic   Gain of ≥15 letters in BCVA (n (%))   39 (28%)   8 (13%)   15.4% (4.4%, 26.3%)   Loss of ≥15 letters in BCVA (n (%))   7 (5%)   7 (11%)   -5.9% (-14.4%, 2.5%)   Mean change from baseline in BCVA   (SD)   7.1 (14.5)   1.5 (17.4)   5.6 (0.7, 10.6)       b Phakic   Gain of ≥15 letters in BCVA (n (%))   69 (29%)   22 (18%)   11.1% (2.1%, 20.1%)   Loss of ≥15 letters in BCVA (n (%))   41 (17%)   7 (6%)   11.6% (5.2%, 18%)   Mean change from baseline in BCVA   (SD)   2.8 (20.1)   1.8 (12.6)   1 (-2.5 ,4.4) iluvien-figure-3 iluvien-figure-4

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