ILUVIEN APPROVED FOR A SECOND INDICATION

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office, and your patients?

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ILUVIEN APPROVED FOR A
SECOND INDICATION

What does this mean for you, your
office, and your patients?

Find out

This site is intended for US healthcare professionals only

Prescribing Information

Highlights of Prescribing Information

These highlights do not include all the information needed to use ILUVIEN® safely and effectively. See full prescribing information for ILUVIEN.

ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg
For Intravitreal Injection
Initial U.S. Approval: 1963

Download Prescribing Information

Indications and Usage

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)

Dosage and administration

  • 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)

Dosage Forms and Strength

Non-bioerodable intravitreal implant containing 0.19 mg fluocinolone acetonide in a drug delivery system. (3)

Contradictions

  • Ocular or periocular infections (4.1)
  • Glaucoma (4.2)
  • Hypersensitivity (4.3)

Warnings and Precautions

  • 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)

Adverse Reactions

In controlled studies, the most common adverse reactions reported were cataract development and increases in intraocular pressure. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Alimera Sciences, Inc. at 1-844-445-8843 or FDA at
1‑800-FDA-1088 or
www.fda.gov/medwatch.

See 17 for PATIENT COUNSELING INFORMATION 

Revised: 11/2016

Full Prescribing Informations: Contents*

  1. INDICATIONS AND USAGE
  2. DOSAGE AND ADMINISTRATION
    1. General Dosing Information
    2. Administration
  2. DOSAGE FORMS AND STRENGTHS
  3. CONTRAINDICATIONS
    1. Ocular or Periocular Infections
    2. Glaucoma
    3. Hypersensitivity
  4. WARNINGS AND PRECAUTIONS
    1. Intravitreal Injection-related Effects
    2. Steroid-related Effects
    3. Risk of Implant Migration
  5. ADVERSE REACTIONS
    1. Clinical Studies Experience
    2. Postmarketing Experience
  6.  
  7. USE IN SPECIFIC POPULATIONS
    1. Pregnancy
    2.  
    3. Nursing Mothers
    4. Pediatric Use
    5. Geriatric Use
  8.  
  9.  
  10. DESCRIPTION
  11. CLINICAL PHARMACOLOGY
    1. Mechanism of Action
    2. Pharmacokinetics
  12. NONCLINICAL TOXICOLOGY
    1. Carcinogenesis, Mutagenesis, Impairment of Fertility
  13. CLINICAL STUDIES
  14.  
  15. HOW SUPPLIED/STORAGE AND HANDLING
  16. PATIENT COUNSELING INFORMATION

*Sections or subsections omitted from the full prescribing information are not listed.

Contraindications

Full Prescribing Information

1 INDICATIONS AND USAGE  

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.

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Information

For ophthalmic intravitreal injection.

2.2 Administration

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:

  1. 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.
  2. Visually check through the viewing window of the preloaded applicator to ensure that there is a drug implant inside.
  3. 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.
  4. 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.
  5. 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.
  6. Inspect the tip of the needle to ensure it is not bent.
  7. 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.
  8. 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.

3 DOSAGE FORMS AND STRENGTHS

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.

4 CONTRAINDICATIONS

4.1 Ocular or Periocular Infections

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.

4.2 Glaucoma

ILUVIEN is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8.

4.3 Hypersensitivity

ILUVIEN is contraindicated in patients with known hypersensitivity to any components of this product.

5 WARNINGS AND PRECAUTIONS

5.1 Intravitreal Injection-related Effects

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)].

5.2 Steroid-related Effects

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.

5.3  Risk of Implant Migration

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.

6 ADVERSE REACTIONS

6.1 Clinical Studies Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions associated with ophthalmic steroids including ILUVIEN include cataract formation and subsequent cataract surgery, elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.

ILUVIEN was studied in two multicenter, randomized, sham-controlled, masked trials in which patients with diabetic macular edema (DME) were treated with either ILUVIEN (n=375) or sham (n=185).

Table 1 summarizes safety data available when the last subject completed the last 36 month follow up visit for the two primary ILUVIEN trials. In these trials, subjects were eligible for retreatment no earlier than 12 months after study entry.  Over the three year follow up period, approximately 75% of the ILUVIEN treated subjects received only one ILUVIEN implant.

The most common ocular (study eye) and non-ocular adverse reactions are shown in Tables 1 and 2.

Table 1: Ocular Adverse Reactions Reported by ≥1% of Patients and Non-ocular Adverse Reactions Reported by ≥5% of Patients

Adverse ReactionsILUVIEN
(N=375)
n (%)		Sham
(N=185)
n (%)
Ocular
Cataract1
192/2352 (82%)
61/1212 (50%)
Myodesopsia80 (21%)17 (9%)
Eye pain57 (15%)25 (14%)
Conjunctival haemorrhage
50 (13%)21 (11%)
Posterior capsule opacification
35 (9%)6 (3%)
Eye irritation30 (8%)11 (6%)
Vitreous detachment
26 (7%)12 (7%)
Conjunctivitis14 (4%)5 (3%)
Corneal oedema
13 (4%)3 (2%)
Foreign body sensation in eyes
12 (3%)4 (2%)
Eye pruritus10 (3%)3 (2%)
Ocular hyperaemia
10 (3%)3 (2%)
Optic atrophy9 (2%)2 (1%)
Ocular discomfort
8 (2%)1 (1%)
Photophobia7 (2%)2 (1%)
Retinal exudates
7 (2%)0 (0%)
Anterior chamber cell
6 (2%)1 (1%)
Eye discharge6 (2%)1 (1%)
Non-ocular
Anemia40 (11%)10 (5%)
Headache33 (9%)11 (6%)
Renal Failure32 (9%)10 (5%)
Pneumonia28 (7%)8 (4%)
    1.  
  1. Includes cataract, cataract nuclear, cataract subcapsular, cataract cortical and cataract diabetic in patients who were phakic at baseline. Among these patients, 80% of ILUVIEN subjects vs. 27% of sham-controlled subjects underwent cataract surgery.
  2. 235 of the 375 ILUVIEN subjects were phakic at baseline; 121 of 185 sham-controlled subjects were phakic at baseline.

Increased intraocular Pressure

Table 2: Summary of Elevated IOP Related Adverse Reactions

Event
ILUVIEN
(N=375)
n (%)
Sham
(N=185)
n (%)
IOP elevation ≥ 10 mmHg from Baseline
127 (34%)18 (10%)
IOP elevation ≥ 30 mmHg
75 (20%)8 (4%)
Any IOP-lowering medication
144 (38%)26 (14%)
Any surgical intervention for elevated intraocular pressure
18 (5%)1 (1%)

Figure 1: Mean IOP during the study

Cataracts and Cataract Surgery

At baseline, 235 of the 375 ILUVIEN subjects were phakic; 121 of 185 sham-controlled subjects were phakic. The incidence of cataract development in patients who had a phakic study eye was higher in the ILUVIEN group (82%) compared with Sham (50%). The median time of cataract being reported as an adverse event was approximately 12 months in the ILUVIEN group and 19 months in the Sham group. Among these patients, 80% of ILUVIEN subjects vs. 27% of sham-controlled subjects underwent cataract surgery, generally within the first 18 months (Median Month 15 for both ILUVIEN group and for Sham) of the studies.

6.2 Postmarketing Experience

The following reactions have been identified during post-marketing use of ILUVIEN in clinical practice.  Because they are reported voluntarily estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to ILUVIEN, or a combination of these factors, include reports of drug administration error and reports of the drug being ineffective.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

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.

8.3 Nursing Mothers

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.

8.4 Pediatric Use

Safety and effectiveness of ILUVIEN in pediatric patients have not been established.

8.5 Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

11 DESCRIPTION

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 C24H30F206

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.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

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 A2 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 A2.

12.2 Pharmacokinetics

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.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility 

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.

14 CLINICAL STUDIES

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 1Study 2
 
ILUVIEN
(N=190)
Sham
(N=95)
ILUVIEN
(N=186)
Sham
(N=90)
Mean (SD)53 (13)55 (11)53 (12)55 (11)
Median (Range)
57 (19-75)58 (25-69)56 (20-70)58 (21-68)

aStudy 1: ILUVIEN, N=190; Sham, N=95
bStudy 2: ILUVIEN, N=186; Sham, N=90

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

Study 1: Phakic Subjects

Proportion (%) of Subjects Gaining ≥15 Letters (ITT LOCF)

Study 1: Pseudophakic Subjects

Proportion (%) of Subjects Gaining ≥15 Letters (ITT LOCF)

Study 2: Phakic Subjects

Proportion (%) of Subjects Gaining ≥15 Letters (ITT LOCF)

Study 2: Pseudophakic Subjects

Proportion (%) of Subjects Gaining ≥15 Letters (ITT LOCF)

Figure 3: Mean BCVA Change from Baseline

Study 1: Phakic Subjects

Mean Change from Baseline in BCVA (ITT LOCF)

Study 1: Pseudophakic Subjects

Mean Change from Baseline in BCVA (ITT LOCF)

Study 2: Phakic Subjects

Mean Change from Baseline in BCVA (ITT LOCF)

Study 2: Pseudophakic Subjects

Mean Change from Baseline in BCVA (ITT LOCF)

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)

Lens StatusOutcomesILUVIENSham
Estimated Difference
(95% CI)
aPseudophakic
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)
bPhakic
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)

aPseudophakic: ILUVIEN, N=140; Sham, N=64
bPhakic: ILUVIEN, N=236; Sham, N=121

16 HOW SUPPLIED/STORAGE AND HANDLING

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).

17 PATIENT COUNSELING INFORMATION

Steroid-related Effects 

Advise patients that a cataract may occur after treatment with ILUVIEN.  If this occurs, advise patients that their vision will decrease, and they will need an operation to remove the cataract and restore their vision.

Advise patients that they may develop increased intraocular pressure with ILUVIEN treatment, and the increased IOP may need to be managed with eye drops, or surgery.

Intravitreal Injection-related Effects

Advise patients that in the days following intravitreal injection of ILUVIEN, patients are at risk for potential complications including in particular, but not limited to, the development of endophthalmitis or elevated intraocular pressure.

When to Seek Physician Advice

Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist.

Driving and Using Machines

Inform patients that they may experience temporary visual blurring after receiving an intravitreal injection. Advise patients not to drive or use machines until this has been resolved.

Manufactured for:
Alimera Sciences, Inc.
6310 Town Square, Suite 400
Alpharetta, GA 30005

Patented. See: www.alimerasciences.com

We are available to answer any questions about ILUVIEN. Please complete the following form to contact us today.

IMPORTANT SAFETY INFORMATION AND INDICATION

IMPORTANT SAFETY INFORMATION

Contraindications

  • ILUVIEN is contraindicated in patients with active or suspected ocular or periocular infections including most viral diseases 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.

Warnings and Precautions

  • Intravitreal Injection-related Effects: Intravitreal injections, including those with ILUVIEN, have been associated with endophthalmitis, eye inflammation, increased or decreased intraocular pressure, and choroidal or retinal detachments. Patients should be monitored following the intravitreal injection. Patients may experience temporary blurred vision after injection of the implant.
  • Intraocular Pressure (IOP) Increase: Prolonged use of corticosteroids may result in the development of 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. Intraocular pressure should be routinely monitored during the course of the treatment.
  • Cataracts: The use of corticosteroids may result in posterior subcapsular cataract formation.
  • Delayed Corneal Wound Healing: The use of corticosteroids after cataract surgery may delay healing and increase the incidence of bleb formation.
  • Corneal and Scleral Melting: Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of ophthalmic corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation of the globe.
  • Bacterial Infections: Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. Acute purulent or parasitic infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication. If signs and symptoms fail to improve after 2 days, the patient should be reevaluated.
  • Viral Infections: Use of ocular corticosteroids 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; frequent slit lamp microscopy is recommended.
  • Fungal Infections: Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local corticosteroid application. Fungus invasion should be suspected in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.
  • Risk of Implant Migration: 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.
  •  

Adverse Reactions

Diabetic Macular Edema
Ocular adverse reactions reported by greater than or equal to 1% of patients in the two combined 3-year clinical trials following injection of ILUVIEN for diabetic macular edema include: cataract (82%), myodesopsia (21%), eye pain (15%), conjunctival hemorrhage (13%), posterior capsule opacification (9%), eye irritation (8%), vitreous detachment (7%), conjunctivitis (4%), corneal oedema (4%), foreign body sensation in eyes (3%), eye pruritus (3%), ocular hyperaemia (3%), optic atrophy (2%), ocular discomfort (2%), photophobia (2%), retinal exudates (2%), anterior chamber cell (2%), and eye discharge (2%). Non-ocular adverse reactions reported by greater than or equal to 5% of patients include: anemia (11%), headache (9%), renal failure (9%), and pneumonia (7%)

Increased Intraocular Pressure: IOP elevation greater than or equal to 10 mm Hg from baseline at any visit was seen in 34% of ILUVIEN patients versus 10% of sham patients. IOP elevation greater than or equal to 30 mm Hg was seen in 20% of ILUVIEN patients versus 4% of sham patients. 38% of the patients who received ILUVIEN were subsequently treated with IOP-lowering medications during the study versus 14% of sham patients. 5% of the patients who received ILUVIEN needed surgical intervention for elevated IOP versus 1% of sham patients

Cataracts and Cataract Surgery: The incidence of cataract development in patients who had a phakic study eye was higher in the ILUVIEN group (82%) compared with sham (50%). The median time of cataract being reported as an adverse event was approximately 12 months in the ILUVIEN group and 19 months in the sham group. Among these patients, 80% of ILUVIEN subjects versus 27% of sham-controlled subjects underwent cataract surgery, generally within the first 18 months (median month 15 for both ILUVIEN group and for sham) of the studies.

INDICATION

ILUVIEN is a corticosteroid 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.

Please see full Prescribing Information.

IMPORTANT SAFETY INFORMATION

Contraindications

  • 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.

Warnings and Precautions

  • Intravitreal Injection-related Effects: Intravitreal injections, including those with ILUVIEN, have been associated with endophthalmitis, eye inflammation, increased or decreased intraocular pressure, and choroidal or retinal detachments. Patients should be monitored following the intravitreal injection. Patients may experience temporary blurred vision after injection of the implant.
  • Intraocular Pressure (IOP) Increase: Prolonged use of corticosteroids may result in the development of 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. Intraocular pressure should be routinely monitored during the course of the treatment.
  • Cataracts: The use of corticosteroids may result in posterior subcapsular cataract formation.
  • Delayed Corneal Wound Healing: The use of corticosteroids after cataract surgery may delay healing and increase the incidence of bleb formation.
  • Corneal and Scleral Melting: Various ocular diseases and long-term use of topical corticosteroids have been known to cause corneal and scleral thinning. Use of ophthalmic corticosteroids in the presence of thin corneal or scleral tissue may lead to perforation of the globe.
  • Bacterial Infections: Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. Acute purulent or parasitic infections of the eye may be masked or activity enhanced by the presence of corticosteroid medication. If signs and symptoms fail to improve after 2 days, the patient should be reevaluated.
  • Viral Infections: Use of ocular corticosteroids 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; frequent slit lamp microscopy is recommended.
  • Fungal Infections: Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local corticosteroid application. Fungus invasion should be suspected in any persistent corneal ulceration where a corticosteroid has been used or is in use. Fungal cultures should be taken when appropriate.
  • Risk of Implant Migration: 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.

Adverse Reactions

Diabetic Macular Edema
Ocular adverse reactions reported by greater than or equal to 1% of patients in the two combined 3-year clinical trials following injection of ILUVIEN for diabetic macular edema include: cataract (82%), myodesopsia (21%), eye pain (15%), conjunctival hemorrhage (13%), posterior capsule opacification (9%), eye irritation (8%), vitreous detachment (7%), conjunctivitis (4%), corneal oedema (4%), foreign body sensation in eyes (3%), eye pruritus (3%), ocular hyperaemia (3%), optic atrophy (2%), ocular discomfort (2%), photophobia (2%), retinal exudates (2%), anterior chamber cell (2%), and eye discharge (2%). Non-ocular adverse reactions reported by greater than or equal to 5% of patients include: anemia (11%), headache (9%), renal failure (9%), and pneumonia (7%)

Increased Intraocular Pressure: IOP elevation greater than or equal to 10 mm Hg from baseline at any visit was seen in 34% of ILUVIEN patients versus 10% of sham patients. IOP elevation greater than or equal to 30 mm Hg was seen in 20% of ILUVIEN patients versus 4% of sham patients. 38% of the patients who received ILUVIEN were subsequently treated with IOP-lowering medications during the study versus 14% of sham patients. 5% of the patients who received ILUVIEN needed surgical intervention for elevated IOP versus 1% of sham patients

Cataracts and Cataract Surgery: The incidence of cataract development in patients who had a phakic study eye was higher in the ILUVIEN group (82%) compared with sham (50%). The median time of cataract being reported as an adverse event was approximately 12 months in the ILUVIEN group and 19 months in the sham group. Among these patients, 80% of ILUVIEN subjects versus 27% of sham-controlled subjects underwent cataract surgery, generally within the first 18 months (median month 15 for both ILUVIEN group and for sham) of the studies.

INDICATION

ILUVIEN is a corticosteroid 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.

Please see full Prescribing Information.

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This site is for US audiences only. © Copyright 2025 ANI Pharmaceuticals, Inc. All rights reserved.
ILUVIEN is a registered trademark of Alimera Sciences, Inc., an ANI Pharmaceuticals, Inc. Company.
US-IL-2400025 10/2025

Reference

  1. ILUVIEN. Prescribing information. Alimera Sciences, Inc.

References

  1. Campochiaro PA, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125-2132.
  2. Campochiaro PA et al. for the FAMOUS Study Group. Aqueous Levels of FAc after Administration of FAc Inserts or FAc Implants. Ophthalmology 2013; 120:583-587.
  3. Kane F and Green K. Ocular Pharmacokinetics of Fluocinolone Acetonide Following ILUVIEN Implantation in the Vitreous Humor of Rabbits. J Ocul Pharmacol Ther. 2015; 31 (1):11-16.
  4. Merrill PT, et al. The 0.19-mg Fluocinolone Acetonide Intravitreal Implant Reduces Treatment Burden in Diabetic Macular Edema. Am J Ophthalmol. 2023;248:16-23.

References

  1. Campochiaro PA, et al. Ophthalmol. 2013;120:583-587.
  2. Romera-Aroca et al. Journal of Diabetes Research. 2016;2016:2156273.
  3. Rübsam et al. International Journal of Molecular Sciences. 2018;19(4):942.
  4. Merrill PT, et al. The 0.19-mg Fluocinolone Acetonide Intravitreal Implant Reduces Treatment Burden in Diabetic Macular Edema. Am J Ophthalmol. 2023;248:16-23.
  5. Data on file. Alimera Sciences, Inc. MI-DOF-064

Reference

  1. ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg full US Prescribing Information. Alimera Sciences, Inc. 

Phakic Eyes

Consider ILUVIEN for phakic patients with DME, particularly those aged > 50 years and/or with developing cataracts

Patients with diabetes are 2 to 5 times more prone to cataract development2

In the ILUVIEN Phase 3 clinical trials:

  • 92% of patients were aged > 50 years3,4
  • 65% of all patients were phakic5
  • 83% of phakic patients had evidence of some cataract at baseline3
  • After cataract extraction, phakic patients treated with ILUVIEN had long-term VA outcomes similar to those observed in pseudophakic patients in the Phase 3 clinical trials6

References

  1. ILUVIEN® [package insert]. Alpharetta, GA: Alimera Sciences, Inc.
  2. Javadi MA, Zari-Ghanavati S. Cataracts in diabetic patients: A review article. J Ophthalmic Vis Rec. 2008;3(1):52-65.
  3. Data on file. Alimera Sciences, Inc.
  4. Mordi JA, Ciuffreda KJ. Statis aspects of accommodation: age and presbyopia. Vision Res. 1998;38:1643-1653.

Vitrectomized Eyes

Observations from a small, real-world cohort of vitrectomized patients with DME treated with ILUVIEN

  • In this retrospective study of 26 vitrectomized eyes treated with ILUVIEN, visual acuity and retinal thickness improved (mean follow-up 8.5 months)1
  • 31% of patients had increases in intraocular pressure (IOP) that were managed with drops; none required surgery at the time of study publication
  • 2 patients in this study experienced migration of the ILUVIEN implant to the anterior chamber. In both cases, there was a history of capsular tear and ILUVIEN was surgically repositioned without further complication
  • Patients in whom the posterior capsule of the lens is absent or has a tear are at risk of implant migration into the anterior chamber1

Reference

  1. Meireles A, Goldsmith C, El-Ghrably I, et al. Efficacy of 0.2 µg/day fluocinolone acetonide implant (ILUVIEN) in eyes with diabetic macular edema and prior vitrectomy. Eye (Lond). 2017;31(5):684-690.

References

  1. Singer MA, et al. Three-Safety and Efficacy of the 0.19-mg Fluocinolone Acetonide Intravitreal Implant for Diabetic Macular Edema: The PALADIN Study. Ophthalmology. 2022;129(6):605-613.
  2. Eaton A, et al. The USER Study: A Chart Review of Patients Receiving a 0.2 µg/day Fluocinolone Acetonide Implant for Diabetic Macular Edema. Ophthalmol Ther. 2019;8(1):51-62.
  3. Data on file. Alimera Sciences, Inc. MI-DOF-064.

Limitations of the USER Study

  • Data are based on clinical practice, where the reporting of data is not standardized, and the data may not be as rigorous as in a clinical trial where the data collected are monitored.
  • USER involved the collection of data up to 3 years prior to ILUVIEN (when available) and all available data post-ILUVIEN — Mean follow-up after ILUVIEN was 403 days, with 102 eyes followed up for 6 months, 92 for 12 months, and 50 for 18 months.
  • Optical coherence tomography (OCT) data were only available for 120 eyes.

Limitations of the Study

  • This is a small, retrospective study
  • Data were based on clinical practice, where there is reporting of non-standardized data, and the data may not be as rigorous as in a clinical trial where the data collection is monitored
  • The effect of the vitrectomy procedure on the duration of the intravitreal therapy is not fully understood
  • Further studies are required to confirm the current findings and assess the effect of ILUVIEN over a longer period of follow-up
  • The collection and reporting of this retrospective data with a relatively small number of patients and short period of follow-up post-therapy with ILUVIEN (mean = 8.5 months) should not be compared with the FAME pivotal studies, which provided 36 months of follow-up data
  • Study was performed in Europe, where clinical practice may be different. In Europe, ILUVIEN is approved for the treatment of visual impairment due to chronic DME considered insufficiently responsive to available therapies

Conflicts of Interest

Authors of this study received compensation from Alimera. Two authors received speaker honoraria from Alimera, and two authors were consultants. One author received reimbursement of travel expenses and study support from Alimera.

Studies Design: FAME

FAME A and B were randomized, double-masked, sham injection–controlled, parallel-group, multicenter studies conducted under a single protocol over 36 months.

Study arms:

561 subjects randomized 2:1

  • 0.2 μg/day FAc intravitreal insert
  • Sham injection

Primary endpoint:

Proportion of subjects with improvement in BCVA ≥ 15 letters at 24 months

Inclusion criteria:

Foveal thickness ≥ 250 μm despite ≥ 1 prior focal/grid macular laser photocoagulation treatments and BCVA in ETDRS letter score between 19 and 68 (20/50-20/400).

Exclusion criteria:

Glaucoma, ocular hypertension, IOP > 21 mm Hg, or using IOP-lowering drops.

Reference:

  • Campochiaro PA, Brown DM, Pearson A, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125-2132.

Reference

1. ILUVIEN® [package insert]. Alpharetta, GA: Alimera Sciences, Inc.

References

1. ILUVIEN® [package insert]. Alpharetta, GA: Alimera Sciences, Inc.

2. Parrish RK, Campochiaro PA, Pearson PA, Green K, Traverso CE, FAME Study Group. Characterization of intraocular pressure increases and management strategies following treatment with fluocinolone acetonide intravitreal implants in the FAME trials. Ophthalmic Surg Lasers Imaging Retina. 2016;47:426-435.

References

  1. Campochiaro PA, et al. Sustained delivery fluocinolone acetonide vitreous inserts provide benefit for at least 3 years in patients with diabetic macular edema. Ophthalmology. 2012;119(10):2125-2132.
  2. ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg full US Prescribing Information. Alimera Sciences, Inc.

Reference

  1. ILUVIEN® (fluocinolone acetonide intravitreal implant) 0.19 mg full US Prescribing Information. Alimera Sciences, Inc. 

Reference

1. Meireles A, Goldsmith C, El-Ghrably I, et al. Efficacy of 0.2 µg/day fluocinolone acetonide implant (ILUVIEN) in eyes with diabetic macular edema and prior vitrectomy. Eye (Lond). 2017;31(5):684-690.

References

1. ILUVIEN® [package insert]. Alpharetta, GA: Alimera Sciences, Inc.

2. Javadi MA, Zari-Ghanavati S. Cataracts in diabetic patients: A review article. J Ophthalmic Vis Rec. 2008;3(1):52-65.

3. Data on file. Alimera Sciences, Inc.

4. Mordi JA, Ciuffreda KJ. Statis aspects of accommodation: age and presbyopia. Vision Res. 1998;38:1643-1653.

5. Campochiaro PA, Brown DM, Pearson A, et al. Long-term benefit of sustained-delivery fluocinolone acetonide vitreous inserts for diabetic macular edema. Ophthalmology. 2011;118:626-635.

6. Yang Y, Bailey C, Holz FG, et al. Long-term outcomes of phakic patients with diabetic macular oedema treated with intravitreal fluocinolone acetonide (FAc) implants. Eye (Lond). 2015;29:1173-1180.

Reference

1. Data on file. Alimera Sciences, Inc.

Reference

1. Data on file. Alimera Sciences, Inc.