ILUVIEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ILUVIEN (ILUVIEN).
Fluocinolone acetonide, a corticosteroid, suppresses inflammation by inhibiting phospholipase A2, reducing arachidonic acid release and subsequent prostaglandin and leukotriene synthesis. It also inhibits cytokine production and endothelial cell adhesion molecule expression.
| Metabolism | Fluocinolone acetonide is metabolized primarily by cytochrome P450 3A4 (CYP3A4) to 6α-hydroxyfluocinolone acetonide and other metabolites. |
| Excretion | Fluocinolone acetonide is primarily eliminated via hepatic metabolism and subsequent fecal/biliary excretion. Approximately 50-70% of a dose is excreted in feces as metabolites, with less than 20% recovered in urine as unchanged drug or metabolites. |
| Half-life | Intravitreal terminal half-life of fluocinolone acetonide from the Iluvien implant is approximately 30 months (range 18-36 months), providing sustained release over 36 months in the vitreous cavity. |
| Protein binding | Fluocinolone acetonide is approximately 90% bound to plasma proteins, primarily albumin and corticosteroid-binding globulin (CBG). |
| Volume of Distribution | Volume of distribution (Vd) for fluocinolone acetonide after systemic administration is approximately 0.8 L/kg, indicating extensive tissue distribution. For intravitreal delivery, Vd is limited to the vitreous cavity (~4 mL), with negligible systemic distribution. |
| Bioavailability | Intravitreal: 100% (local delivery, no first-pass metabolism). Systemic: negligible (<0.1%) after intravitreal implantation due to the slow release and low dose. |
| Onset of Action | Onset of clinical effect (reduction in diabetic macular edema) is typically observed within 2-4 weeks after intravitreal implantation, with maximal effect seen by 3-6 months. |
| Duration of Action | Duration of action is up to 36 months (3 years) from a single intravitreal implant, with sustained release of fluocinolone acetonide. Clinical effect persists for the implant's lifespan; retreatment may be needed after 3 years. |
Intravitreal implant containing 0.19 mg fluocinolone acetonide, designed to release drug over approximately 36 months. Administered as a single injection into the vitreous cavity of the eye.
| Dosage form | IMPLANT |
| Renal impairment | No dose adjustment required based on renal function; systemic exposure is negligible. |
| Liver impairment | No dose adjustment required based on hepatic function; systemic exposure is negligible. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; use not recommended. |
| Geriatric use | No specific dose adjustment for elderly; clinical studies included patients aged 65 and older with no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ILUVIEN (ILUVIEN).
| Breastfeeding | Excretion in human milk unknown; negligible systemic absorption after intravitreal injection suggests minimal exposure. M/P ratio not determined. Caution advised; consider benefit of therapy and risk to infant. |
| Teratogenic Risk | No adequate and well-controlled studies in pregnant women. In animal studies, intravitreal administration of fluocinolone acetonide at doses 0.5-2 times the recommended human dose resulted in teratogenicity (cleft palate, omphalocele) and embryotoxicity. Based on mechanism, corticosteroids are associated with increased risk of cleft lip/palate in first trimester. Risk cannot be ruled out; use only if potential benefit justifies risk. |
■ FDA Black Box Warning
Not applicable.
| Serious Effects |
["Active ocular or periocular infections (including viral, fungal, or mycobacterial infections).","Known hypersensitivity to fluocinolone acetonide or any component of the product."]
| Precautions | ["Elevated intraocular pressure (IOP): Monitor IOP regularly; may require management with topical medications or surgical intervention.","Cataract formation: Posterior subcapsular cataracts are common post-implantation; may require cataract surgery.","Endophthalmitis: Risk with implant procedure; monitor for signs of infection.","Retinal detachment: Risk during implantation or with vitreous loss.","Steroid-induced glaucoma: Can lead to permanent vision loss."] |
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| Fetal Monitoring | Monitor intraocular pressure (IOP) and signs of infection. In pregnant patients, consider fetal ultrasound for cleft palate if exposed in first trimester. |
| Fertility Effects | No human data. In animal studies, no effects on male or female fertility at clinically relevant doses. |