OZURDEX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OZURDEX (OZURDEX).
Dexamethasone, a potent corticosteroid, reduces inflammation by inhibiting multiple inflammatory cytokines including prostaglandins, leukotrienes, and interleukins. It suppresses the migration of polymorphonuclear leukocytes and reverses increased capillary permeability. The mechanism involves binding to the glucocorticoid receptor, leading to regulation of gene expression that reduces production of inflammatory mediators.
| Metabolism | Dexamethasone is metabolized primarily in the liver via the cytochrome P450 enzyme CYP3A4. Metabolites are inactive and excreted in urine and feces. |
| Excretion | Primarily hepatic metabolism via CYP3A4; metabolites excreted in feces (≈70%) and urine (≈30%). Less than 1% excreted as unchanged drug. |
| Half-life | In the vitreous humor, the half-life is approximately 5-7 months following intravitreal implant administration. Systemic half-life is negligible due to low systemic exposure. |
| Protein binding | Approximately 68-89% bound to albumin, with less binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Systemic Vd is approximately 0.8 L/kg, indicating distribution mainly into plasma and extracellular fluid. For intravitreal administration, local Vd is limited to the vitreous chamber, estimated at 4-5 mL. |
| Bioavailability | Intravitreal implant: 100% local bioavailability. Systemic bioavailability is negligible (<0.1% of the administered dose) due to low systemic absorption from the vitreous. |
| Onset of Action | Intravitreal implant: Reduction in macular edema and improvement in visual acuity observed within 1-2 weeks; maximal effect by 2-3 months. |
| Duration of Action | Intravitreal implant: Single implant releases dexamethasone for up to 3-6 months; clinical effect may persist for 6 months or longer in some patients. Retreatment typically considered after 3-6 months based on disease recurrence. |
| Action Class | Intravitreal corticosteriod implants |
Single intravitreal implant of 0.7 mg (dexamethasone 700 mcg) in the affected eye; repeat dosing no sooner than 3 months after the prior implant.
| Dosage form | IMPLANT |
| Renal impairment | No dose adjustment required for renal impairment; data not available for GFR-based modifications. |
| Liver impairment | No dose adjustment required for hepatic impairment; not studied in Child-Pugh categories. |
| Pediatric use | Not recommended for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; caution for increased intraocular pressure and cataract formation, monitor closely. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OZURDEX (OZURDEX).
| Breastfeeding | Dexamethasone is excreted in human milk; M/P ratio not available. Systemic absorption after intravitreal OZURDEX is minimal; however, caution should be exercised. Manufacturer recommends discontinuing breastfeeding or drug based on importance. |
| Teratogenic Risk | FDA Pregnancy Category C. In animal studies, intravitreal dexamethasone caused fetal harm (cleft palate, fetal death) at systemic exposures 1.5 times the human dose. No adequate human studies. Avoid use in pregnant women unless benefit outweighs risk. First trimester: potential teratogenic effects; second/third trimesters: risk of preterm birth, low birth weight, and adrenal suppression in neonate if used systemically; however, intravitreal administration minimizes systemic exposure. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to dexamethasone or any component of the formulation","Active ocular infections (e.g., bacterial, fungal, viral, including herpes simplex)","Advanced glaucoma that is not adequately controlled by medications","Aphakia: Relative contraindication due to increased risk of steroid-induced glaucoma","Corneal or scleral thinning: Increased risk of perforation"]
| Precautions | ["Intravitreal injection associated risks: endophthalmitis, ocular inflammation, increased intraocular pressure, retinal detachment, and vitreous hemorrhage","Elevated intraocular pressure (IOP): May occur with treatment; monitor IOP regularly and manage appropriately","Corticosteroid-induced cataracts: Long-term use may lead to posterior subcapsular cataract formation","Delayed healing: Corticosteroids may delay wound healing","Exacerbation of infections: Use with caution in patients with active ocular infections; may mask signs of infection","Systemic effects: Prolonged use or use in susceptible patients may lead to systemic corticosteroid effects (e.g., adrenal suppression)","Use with caution in patients with glaucoma: Known steroid responders should be monitored closely","Not approved for use in children"] |
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| Fetal Monitoring | Monitor intraocular pressure (IOP) regularly; ultrasound monitoring for fetal growth if prolonged systemic exposure occurs (unlikely with single implant). In pregnant women, consider fetal assessment if signs of systemic corticosteroid effects appear. |
| Fertility Effects | In animal studies, dexamethasone decreased fertility and implantation. Human data lacking. Potential reversible suppression of hypothalamic-pituitary-adrenal axis may affect menstrual cycle. |