RETISERT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for RETISERT (RETISERT).
Fluocinolone acetonide is a corticosteroid that binds to glucocorticoid receptors, inhibiting inflammatory mediators such as prostaglandins and leukotrienes, and suppressing immune response.
| Metabolism | Primarily hepatic via CYP3A4; undergoes reduction, hydroxylation, and glucuronidation. |
| Excretion | Primarily hepatic metabolism; renal excretion as metabolites (approximately 50% within 40 days, with ~20% unchanged). Fecal excretion accounts for ~30%. |
| Half-life | Terminal half-life is approximately 110 days (range 50-150 days) in the systemic circulation following intravitreal implantation, reflecting slow release from the implant. |
| Protein binding | Approximately 99% bound primarily to albumin and corticosteroid-binding globulin (CBG). |
| Volume of Distribution | Fluocinolone acetonide exhibits a large apparent volume of distribution (Vd approximately 6.2 L/kg after IV administration), indicating extensive tissue distribution. |
| Bioavailability | Intravitreal implant: 100% (direct delivery to vitreous). Oral: Not applicable; systemic bioavailability negligible due to extensive first-pass metabolism. |
| Onset of Action | Intravitreal implant: Clinical effect (reduction in inflammation) typically observed within 2-4 weeks post-implantation. |
| Duration of Action | The implant provides sustained release for up to 30 months (2.5 years) in the vitreous cavity, with therapeutic effects lasting throughout the implant's lifespan. |
Intravitreal implant containing 0.59 mg fluocinolone acetonide; one implant inserted into the vitreous cavity via pars plana injection; release fluocinolone for up to 30 months; single dose per eye.
| Dosage form | IMPLANT |
| Renal impairment | No specific GFR-based dose adjustment required; renal impairment does not significantly affect systemic exposure due to local administration. |
| Liver impairment | No specific Child-Pugh-based dose adjustment required; hepatic impairment is unlikely to alter local drug action; use caution in severe hepatic disease due to corticosteroid systemic effects. |
| Pediatric use | Not approved in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; monitor for intraocular pressure elevation and cataract formation, which may be more frequent in elderly; use same dosing as adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for RETISERT (RETISERT).
| Breastfeeding | It is not known whether fluocinolone acetonide is excreted in human milk after intravitreal administration. Systemic absorption is negligible, but caution should be exercised. No M/P ratio is available. Due to the low systemic exposure, the risk to the nursing infant is considered minimal, but professional judgment should be used. |
| Teratogenic Risk | FDA Pregnancy Category C. In animal studies, fluocinolone acetonide (the active ingredient in RETISERT) has been shown to be teratogenic at subcutaneous doses of 0.1 mg/kg/day in rabbits and 0.05 mg/kg/day in rats, causing fetal abnormalities including cleft palate and umbilical hernia. There are no adequate and well-controlled studies in pregnant women. The intravitreal implant results in minimal systemic exposure; however, theoretical risk exists. Use during pregnancy only if potential benefit justifies the potential risk to the fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to fluocinolone acetonide or any component","Active ocular infections (including viral, bacterial, fungal, mycobacterial)","Posterior lens capsule rupture"]
| Precautions | ["Increased intraocular pressure (IOP) and glaucoma","Cataract formation","Endophthalmitis","Retinal detachment","Mydriasis","Delayed wound healing"] |
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| Fetal Monitoring | Monitor intraocular pressure regularly (e.g., at 1 week, 1 month, and then every 3 months post-implant). Assess for endophthalmitis, retinal detachment, and cataract formation. In pregnant women, consider fetal ultrasound monitoring if systemic exposure is a concern, though exposure is minimal. |
| Fertility Effects | In animal studies, fluocinolone acetonide at subcutaneous doses up to 0.5 mg/kg/day in rats did not impair fertility. No specific human data are available for intravitreal use. The implant's local action and low systemic levels suggest minimal impact on fertility. |