Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Implant, Intravitreal, as acetonide:
Iluvien: 0.19 mg (1 ea)
Retisert: 0.59 mg (1 ea)
Yutiq: 0.18 mg (1 ea)
Pharmacology
Mechanism of Action
Inhibit phospholipase A2 via lipocortin induction Lipocortins may control biosynthesis of prostaglandins and leukotrienes by inhibiting arachidonic acid. Arachidonic acid is released by membrane phospholipids by phospholipase A2.
Pharmacokinetics/Pharmacodynamics
Absorption
Systemic absorption is negligible
Distribution
Retisert: Aqueous and vitreous humor
Duration of Action
Iluvien, Yutiq: Releases fluocinolone acetonide at an initial rate of 0.25 mcg/day for 36 months
Retisert: Releases fluocinolone acetonide at an initial rate of 0.6 mcg/day, decreasing over 30 days to a steady-state release rate of 0.3 to 0.4 mcg/day for 30 months
Use: Labeled Indications
Diabetic macular edema (Iluvien): Treatment of diabetic macular edema in patients who have been previously treated with a course of corticosteroids and did not have a clinically significant rise in intraocular pressure.
Uveitis (Retisert, Yutiq): Treatment of chronic, noninfectious uveitis affecting the posterior segment of the eye
Contraindications
Hypersensitivity to fluocinolone, other corticosteroids, or any component of the formulation; active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella; active bacterial, mycobacterial or fungal infections of the eye.
Iluvien only: Glaucoma (in patients who have cup to disc ratios of >0.8).
Dosage and Administration
Dosing: Adult
Diabetic macular edema: Ocular implant (Iluvien): Intravitreal injection: One implant (0.19 mg) injected in affected eye. Note: Implant is designed to release fluocinolone at an initial rate of 0.25 mcg daily lasting 36 months.
Uveitis (chronic):
Ocular implant (Retisert): Intravitreal injection: One silicone-encased tablet (0.59 mg) surgically implanted into the posterior segment of the affected eye. Note: Implant is designed to initially release 0.6 mcg/day, decreasing over 30 days to a steady-state release rate of 0.3 to 0.4 mcg daily for 30 months. Recurrence of uveitis denotes depletion of tablet, requiring reimplantation.
Ocular implant (Yutiq): Intravitreal injection: One implant (0.18 mg) injected in affected eye. Note: Implant is designed to release fluocinolone at an initial rate of 0.25 mcg daily lasting 36 months.
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Uveitis, chronic: Children ≥12 years and Adolescents: Ocular implant (Retisert): Intravitreal injection: One silicone-encased tablet (0.59 mg) surgically implanted into the posterior segment of the affected eye. Note: Implant is designed to release 0.6 mcg/day, decreasing over 30 days to a steady-state release rate of 0.3 to 0.4 mcg daily for 30 months. Recurrence of uveitis denotes depletion of tablet, requiring reimplantation.
Administration
Ophthalmic implant (intravitreal injection): Administer under controlled aseptic conditions (eg, sterile gloves, sterile drape, sterile eyelid speculum). Administer adequate anesthesia and a broad-spectrum bactericidal to the periocular skin, eyelid, and ocular surfaces prior to injection. Refer to manufacturer’s prescribing information for administration technique.
Iluvien: Visually inspect preloaded applicator to ensure that it contains a drug implant. Optimal placement is inferior to optic disc and posterior to the equator of the eye
Retisert: Handle only by suture tab to avoid damaging the tablet integrity and adversely affecting release characteristics. Do not resterilize.
Yutiq: Optimal placement is inferior to optic disc and posterior to the equator of the eye.
Storage
Store at 15°C to 25°C (59°F to 77°F). Retisert: Protect from freezing.
Drug Interactions
Nonsteroidal Anti-Inflammatory Agents (Ophthalmic): May enhance the adverse/toxic effect of Corticosteroids (Ophthalmic). Healing of ophthalmic tissue during concomitant administration of ophthalmic products may be delayed. Monitor therapy
Ritodrine: Corticosteroids may enhance the adverse/toxic effect of Ritodrine. Monitor therapy
Adverse Reactions
>10%:
Central nervous system: Headache (9% to 33%), dizziness (5% to 20%)
Dermatologic: Skin rash (5% to 20%)
Gastrointestinal: Nausea (5% to 20%), vomiting (5% to 20%)
Hematologic & oncologic: Anemia (11%)
Infection: Influenza (5% to 20%)
Neuromuscular & skeletal: Back pain (5% to 20%), limb pain (5% to 20%), arthralgia (2% to 20%)
Ophthalmic: Cataract (50% to 90%), increased intraocular pressure (50% to 90%; ≥10 mm Hg: 22% to 34%; ≥30 mm Hg: 12% to 20%), eye pain (8% to 90%), abnormal sensation in eyes (10% to 40%), blepharoptosis (10% to 40%), blurred vision (10% to 40%), decreased visual acuity (immediate; duration 1 to 4 weeks; 10% to 40%), eyelid edema (10% to 40%), macular edema (10% to 40%), maculopathy (10% to 40%), visual disturbance (10% to 40%), conjunctival hemorrhage (8% to 40%), decreased intraocular pressure (ocular hypotony: 7% to 40%), dry eye syndrome (4% to 40%), eye pruritus (3% to 40%), vitreous opacity (3% to 40%), conjunctival hyperemia (2% to 40%), glaucoma (2% to 40%), vitreous hemorrhage (2% to 40%), eye irritation (1% to 40%), lacrimation (1% to 40%)
Respiratory: Cough (5% to 20%), nasopharyngitis (5% to 20%), sinusitis (5% to 20%), upper respiratory tract infection (5% to 20%)
Miscellaneous: Procedural complications (eg, cataract fragments, implant migration, wound complications; 50% to 90%), fever (5% to 20%)
1% to 10%
Cardiovascular: Hypertension (3%)
Central nervous system: Foreign body sensation of eye (3%)
Ophthalmic: Uveitis (10%), anterior chamber eye hemorrhage (5% to 9%), blepharitis (5% to 9%), choroidal detachment (5% to 9%), diplopia (5% to 9%), retinal detachment (5% to 9%), retinal hemorrhage (5% to 9%), swelling of eye (5% to 9%), synechiae of iris (5% to 9%), corneal edema (4% to 9%), posterior capsule opacification (4% to 9%), eye discharge (2% to 9%), photophobia (2% to 9%), photopsia (2% to 9%), anterior chamber inflammation (5%), conjunctivitis (4%), ocular hyperemia (3% to 4%), ophthalmic inflammation (3%), vitreous disorder (floaters: 3%), eye discomfort (2%), hypopyon (2%), optic atrophy (2%), retinal exudates (2%), retinopathy (macular fibrosis: 2%), chorioretinitis (1%), iridocyclitis (1%), visual field defect (1%,)
Renal: Renal failure (9%)
Respiratory: Pneumonia (7%)
Postmarketing and/or case reports: Endophthalmitis (late onset), secondary infection (bacterial, viral, or fungal)
Warnings/Precautions
Concerns related to adverse effects:
- Cataract formation: Use of corticosteroids may result in posterior subcapsular cataract formation.
- Glaucoma: Use of corticosteroids (especially long-term use) may cause increased intraocular pressure and glaucoma. Use with caution in patients with glaucoma. Monitor IOP in all patients; within 3 years postimplantation, most patients will require IOP lowering medications and/or filtering procedures to control IOP.
- Immunosuppression: May enhance development of secondary bacterial, fungal, or viral infections. Not recommended in patients with a history of ocular herpes simplex (potential for reactivation). Use with caution in patients with a history of bacterial, mycobacterial, fungal, or viral infections or the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella. In acute purulent conditions, may mask infection. Fungal and viral infections are of particular concern. If corneal ulceration persists, consider fungal infection.
- Ocular effects: Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure and retinal detachment. Monitor carefully after intravitreal injection. Complications may also include cataract formation, choroidal detachment, hypotony, vitreous hemorrhage, vitreous loss, and wound dehiscence. Procedure may cause optic nerve injury. Visual defects in acuity and field of vision may occur (lasting 1 to 4 weeks postoperatively). Late-onset endophthalmitis has been observed, often associated with surgical site integrity.
- Ocular effects: Retisert: Perforation may occur with topical steroids in diseases which thin the cornea or sclera. Steroid use may delay healing after cataract surgery and increase bleb formation incidence.
Dosage form specific issues:
- Ocular implant: Iluvien, Yutiq: In patients in whom the posterior capsule of the lens is absent or has a tear, implant may migrate into the anterior chamber.
- Ocular implant: Retisert: Recommend unilateral implantation only to minimize risk of postoperative infections developing in both eyes. Due to the potential for separation of the silicone cup reservoir from the suture tab, implant integrity should be monitored during eye exams. Assure tight closure of scleral wound and integrity of overlying conjunctiva at the wound site.
Monitoring Parameters
Iluvien, Yutiq: Following injection, monitor for increased intraocular pressure and endophthalmitis; check for perfusion of optic nerve head immediately after injection, tonometry within 30 minutes, and biomicroscopy between 2 to 7 days after injection.
Retisert: Periodically monitor integrity of implant by visual inspection; recurrence of uveitis (may indicate need for reimplantation); IOP.
Pregnancy
Pregnancy Considerations
Animal studies have not been conducted with this product; however, adverse events have been observed with corticosteroids in animal reproduction studies. Systemic absorption is below the limit of quantification following ocular administration.
Patient Education
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache or blurred vision. Have patient report immediately to prescriber vision changes, eye pain, severe eye irritation, eye redness, unable to pass urine, change in amount of urine passed, sensitivity to light, or severe loss of strength and energy (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.
