DailyMed Label: OZURDEX

DailyMed Label: OZURDEX

2024

DailyMed Prescription

OZURDEX

dexamethasone

Allergan, Inc.

NDC: 0023-3348

NDC: 0023-3348

OZURDEX ® is a sterile intravitreal implant containing 0.7 mg (700 mcg) dexamethasone in the NOVADUR ® solid polymer sustained-release drug delivery system which does not contain an antimicrobial preservative.   OZURDEX ® is preloaded into a single-use, DDS ® applicator to facilitate injection of the rodshaped implant directly into the vitreous. The NOVADUR ®   system contains two poly D,L-lactide-co-glycolide (PLGA) polymer excipients. Both of these polymer materials have the same PLGA backbone, but the terminal end groups differ between them. One polymer, Resomer ® RG 502, is ester terminated, and the other Resomer ®  RG 502 H is acid terminated. The chemical name for dexamethasone is Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11β,16α)-. Its structural formula is: MW 392.47; molecular formula: C 22 H 29 FO 5 Dexamethasone occurs as a white to cream-colored crystalline powder having not more than a slight odor, and is practically insoluble in water and very soluble in alcohol. The PLGA matrix slowly degrades to lactic acid and glycolic acid. The structural formula for OZURDEX® is an intravitreal implant containing 0.7 mg (700 mcg) dexamethasone in the NOVADUR® solid polymer sustained-release drug delivery system. OZURDEX® is preloaded into a single-use, DDS® applicator to facilitate injection of the rod-shaped implant directly into the vitreous. The NOVADUR® system contains poly (D,L-lactide-co-glycolide) PLGA intravitreal polymer matrix without a preservative. The chemical name for dexamethasone is Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11β,16α)-.

OZURDEX ® is a corticosteroid indicated for: The treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) ( 1.1 ) The treatment of non-infectious uveitis affecting the posterior segment of the eye ( 1.2 ) The treatment of diabetic macular edema ( 1.3 ) OZURDEX ®   (dexamethasone intravitreal implant) is indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). OZURDEX ®   is indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye. OZURDEX ®   is indicated for the treatment of diabetic macular edema.

For ophthalmic intravitreal injection. ( 2.1 ) The intravitreal injection procedure should be carried out under controlled aseptic conditions. ( 2.2 ) Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. ( 2.2 ) For ophthalmic intravitreal injection. The intravitreal injection procedure should be carried out under controlled aseptic conditions which include the use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent). Adequate anesthesia and a broad-spectrum microbicide applied to the periocular skin, eyelid and ocular surface are recommended to be given prior to the injection. Remove the foil pouch from the carton and examine for damage. Then, open the foil pouch over a sterile field and gently drop the applicator on a sterile tray. Carefully remove the cap from the applicator. Hold the applicator in one hand and pull the safety tab straight off the applicator. Do not twist or flex the tab . The long axis of the applicator should be held parallel to the limbus, and the sclera should be engaged at an oblique angle with the bevel of the needle up (away from the sclera) to create a shelved scleral path. The tip of the needle is advanced within the sclera for about 1 mm (parallel to the limbus), then re-directed toward the center of the eye and advanced until penetration of the sclera is completed and the vitreous cavity is entered. The needle should not be advanced past the point where the sleeve touches the conjunctiva. Slowly depress the actuator button until an audible click is noted. Before withdrawing the applicator from the eye, make sure that the actuator button is fully depressed and has locked flush with the applicator surface. Remove the needle in the same direction as used to enter the vitreous. Following the intravitreal 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 any symptoms suggestive of endophthalmitis without delay. Each applicator can only be used for the treatment of a single eye. If the contralateral eye requires treatment, a new applicator must be used, and the sterile field, syringe, gloves, drapes, and eyelid speculum should be changed before OZURDEX ® is administered to the other eye.

Intravitreal implant containing dexamethasone 0.7 mg in the N OVADUR ® solid polymer drug delivery system. Intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR ® solid polymer drug delivery system.   ( 3 )

Ocular or periocular infections ( 4.1 ) Glaucoma ( 4.2 ) Torn or ruptured posterior lens capsule ( 4.3 ) Hypersensitivity ( 4.4 ) OZURDEX ®   (dexamethasone intravitreal implant) 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. OZURDEX ® is contraindicated in patients with glaucoma, who have cup to disc ratios of greater than 0.8. OZURDEX ® is contraindicated in patients whose posterior lens capsule is torn or ruptured because of the risk of migration into the anterior chamber. Laser posterior capsulotomy in pseudophakic patients is not a contraindication for OZURDEX ® use. OZURDEX ® is contraindicated in patients with known hypersensitivity to any components of this product  [see Adverse Reactions ( 6 )] .

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 ) Intravitreal injections, including those with OZURDEX ® , have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored regularly following the injection [see Patient Counseling Information ( 17 )] . Use of corticosteroids including OZURDEX ®  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  [see Adverse Reactions ( 6.1 )] . 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.

In controlled studies, the most common adverse reactions reported by 20–70% of patients were cataract, increased intraocular pressure and conjunctival hemorrhage. (

Risk Summary There are no adequate and well-controlled studies with OZURDEX ® in pregnant women. Topical ocular administration of dexamethasone in mice and rabbits during the period of organogenesis produced cleft palate and embryofetal death in mice, and malformations of the abdominal wall/intestines and kidneys in rabbits at doses 5 and 4 times higher than the recommended human ophthalmic dose (RHOD) of OZURDEX ® (0.7 milligrams dexamethasone), respectively. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data Topical ocular administration of 0.15% dexamethasone (0.75 mg/kg/day) on gestational days 10 to 13 produced embryofetal lethality and a high incidence of cleft palate in mice. A dose of 0.75 mg/kg/day in the mouse is approximately 5 times an OZURDEX ® injection in humans (0.7 mg dexamethasone) on a mg/m 2 basis. In rabbits, topical ocular administration of 0.1% dexamethasone throughout organogenesis (0.20 mg/kg/day, on gestational day 6 followed by 0.13 mg/kg/day on gestational days 7-18) produced intestinal anomalies, intestinal aplasia, gastroschisis and hypoplastic kidneys. A dose of 0.13 mg/kg/day in the rabbit is approximately 4 times an OZURDEX ® injection in humans (0.7 mg dexamethasone) on a mg/m 2 basis. A no-observed-adverse-effect-level (NOAEL) was not identified in the mouse or rabbits studies. Risk Summary Systemically administered corticosteroids are present in human milk and can suppress growth and interfere with endogenous corticosteroid production or cause other unwanted effects. There is no information regarding the presence of dexamethasone in human milk, the effects on the breastfed infants, or the effects on milk production to inform risk of OZURDEX ® to an infant during lactation. The developmental and health benefits of breastfeeding should be considered, along with  the mother’s clinical need for OZURDEX ® and any potential adverse effects on the breastfed child from  OZURDEX ® . Safety and effectiveness of OZURDEX ® in pediatric patients have not been established. No overall differences in safety or effectiveness have been observed between elderly and younger patients.

OZURDEX ®   (dexamethasone intravitreal implant) 0.7 mg is supplied in a foil pouch with 1 single-use plastic applicator, NDC 0023-3348-07. Storage: Store at 15 o C to 30 o C (59 o F to 86 o F).

Dexamethasone, a corticosteroid, has been shown to suppress inflammation by inhibiting multiple inflammatory cytokines resulting in decreased edema, fibrin deposition, capillary leakage and migration of inflammatory cells. Plasma concentrations were obtained from 21 patients with macular edema due to branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO), and 21 patients with diabetic macular edema (DME) prior to dosing and at 4 to 5 additional post-dose timepoints on Days 1, 7, 21, 30, 45, 60, and 90 following the administration of the first intravitreal implant containing 0.7 mg dexamethasone.   In RVO and DME patients, the majority of plasma dexamethasone concentrations were below the lower limit of quantitation (LLOQ = 50 pg/mL). Plasma dexamethasone concentrations from 12% of samples were above the LLOQ, ranging from 52 pg/mL to 102 pg/mL.   Plasma dexamethasone concentration did not appear to be related to age, body weight, or sex of patients. In an in vitro metabolism study, following the incubation of [ 14 C]-dexamethasone with human cornea, iris-ciliary body, choroid, retina, vitreous humor, and sclera tissues for 18 hours, no metabolites were observed.

Animal studies have not been conducted to determine whether OZURDEX ®   (dexamethasone intravitreal implant) has the potential for carcinogenesis or mutagenesis.  Fertility studies have not been conducted in animals.

Retinal Vein Occlusion The efficacy of OZURDEX ®   for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) was assessed in two, multicenter, double-masked, randomized, parallel studies. Following a single injection, OZURDEX ® demonstrated the following clinical results for the percent of patients with ≥ 15 letters of improvement from baseline in best-corrected visual acuity (BCVA): Table 4: Number (Percent) of Patients with ≥ 15 Letters Improvement from Baseline in BCVA Study Day Study 1 Study 2 OZURDEX ® N=201 Sham N=202 p-value* OZURDEX ® N=226 Sham N=224 p-value* Day 30 40 (20%) 15 (7%) < 0.01 51 (23%) 17 (8%) < 0.01 Day 60 58 (29%) 21 (10%) < 0.01 67 (30%) 27 (12%) < 0.01 Day 90 45 (22%) 25 (12%) < 0.01 48 (21%) 31 (14%) 0.039 Day 180 39 (19%) 37 (18%) 0.780 53 (24%) 38 (17%) 0.087 *P-values were based on the Pearson’s chi-square test. In each individual study and in a pooled analysis, time to achieve ≥ 15 letters (3-line) improvement in BCVA cumulative response rate curves were significantly faster with OZURDEX ® compared to sham (p < 0.01), with OZURDEX ®   treated patients achieving a 3-line improvement in BCVA earlier than sham-treated patients. The onset of a ≥ 15 letter (3-line) improvement in BCVA with OZURDEX ® occurs within the first two months after   implantation in approximately 20-30% of subjects. The duration of effect persists approximately one to three months after onset of this effect. Posterior Segment Uveitis The efficacy of OZURDEX ® was assessed in a single, multicenter, masked, randomized study of 153 patients with non-infectious uveitis affecting the posterior segment of the eye.   After a single injection, the percent of patients reaching a vitreous haze score of 0 (where a score of 0 represents no inflammation) was statistically significantly greater for patients receiving OZURDEX ® versus sham at week 8 (primary time point) (47% versus 12%). The percent of patients achieving a 3-line improvement from baseline BCVA was 43% for patients receiving OZURDEX ® versus 7% for sham at week 8. Diabetic Macular Edema The efficacy of OZURDEX ® for the treatment of diabetic macular edema was assessed in two, multicenter, masked, randomized, sham-controlled studies. Subjects were to be evaluated for retreatment eligibility every three months starting from Month 6 but could only receive successive treatments at least 6 months apart. Retreatment was based on physician’s discretion after examination including Optical Coherence Tomography. Patients in the OZURDEX ® arm received an average of 4 treatments during the 36 months. The primary endpoint was the proportion of patients with 15 or more letters improvement in BCVA from baseline at Month 39 or final visit for subjects who exited the study at or prior to Month 36. The Month 39 extension was included to accommodate the evaluation of safety and efficacy outcomes for subjects who received re-treatment at Month 36. Only fourteen percent of the study patients completed the Month 39 visit (16.8% from OZURDEX ® and 12.2% from Sham). Table 5: Visual Acuity outcomes at Month 39 (All randomized subjects with LOCF c ) Study Outcomes O ZURDEX ® Sham Estimated Difference (95% CI) 1 a Mean (SD) Baseline BCVA (Letters) 56 (10) 57 (9) Median (range) Baseline BCVA (Letters) 59 (34-95) 58 (34-74) Gain of ≥15 letters in BCVA (n(%)) 34 (21%) 19 (12%) 9.3% (1.4%, 17.3%) Loss of ≥15 letters in BCVA (n(%)) 15 (9%) 17 (10%) -1.1% (-7.5%, 5.3%) Mean change in BCVA (SD) 4.1 (13.9) 0.9 (11.9) 3.2 (0.4, 5.9) 2 b Mean (SD) Baseline BCVA (Letters) 55 (10) 56 (9) Median (range) Baseline BCVA (Letters) 58 (34-72) 58 (36-82) Gain of ≥15 letters in BCVA (n(%)) 30 (18%) 16 (10%) 8.4% (0.9%, 15.8%) Loss of ≥15 letters in BCVA (n(%)) 30 (18%) 18 (11%) 7.1% (-0.5%, 14.7%) Mean change in BCVA (SD) 0.4 (17.5) 0.8 (13.6) -0.7 (-4.1, 2.6) a Study 1: OZURDEX ® , N=163; Sham, N=165 b Study 2: OZURDEX ® , N=165; Sham, N=163 c 14% (16.8% from OZURDEX ® and 12.2% from Sham) of patients had BCVA outcome at Month 39, for the remaining patients, the data at Month 36 or earlier was carried forward. 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. The visual acuity improvement from baseline increases during a treatment cycle, peaks at approximately 3 Months posttreatment and diminishes thereafter. Patients who were pseudophakic at baseline achieved greater mean BCVA change from baseline at the final study visit. Figure 2 : Proportion of Subjects with ≥ 15 Letters Improvement from Baseline BCVA in the Study Eye Figure 3 : Mean BCVA Change from Baseline The best corrected visual acuity outcomes for the Pseudophakic and Phakic subgroups from Studies 1 and 2 at Month 39 are presented in Table 6. Table 6: Visual Acuity outcomes at Month 39 (Subgroup for pooled data with LOCF c ) Subgroup (Pooled) Outcomes OZURDEX ® Sham Estimated Difference (95% CI) a Pseudophakic Gain of ≥15 letters in BCVA (n(%)) 16 (20%) 11 (11%) 8.4% (-2.2%, 19.0%) Loss of ≥15 letters in BCVA (n(%)) 4 (5%) 7 (7%) -2.2% (-9.1%, 4.7%) Mean change in BCVA (SD) 5.8 (11.6) 1.4 (12.3) 4.2 (0.8, 7.6) b Phakic Gain of ≥15 letters in BCVA (n(%)) 48 (20%) 24 (11%) 9.0% (2.7%, 15.4%) Loss of ≥15 letters in BCVA (n(%)) 41 (17%) 28 (12%) 4.4% (-1.9%, 10.7%) Mean change in BCVA (SD) 1.0 (16.9) 0.6 (12.9) 0.3 (-2.4, 3.0) a Pseudophakic: OZURDEX ® , N=82; Sham, N=99 b Phakic: OZURDEX ® , N=246; Sham, N=229 c 14% (16.8% from OZURDEX ® and 12.2% from Sham) of patients had BCVA outcome at Month 39, for the remaining patients the data at Month 36 or earlier was used in the analysis. Figure 2: Proportion of Subjects with ≥ 15 Letters Improvement from Baseline BCVA in the Study Eye Figure 3: Mean BCVA Change from Baseline

NDC 0023-3348-07 Ozurdex ® (dexamethasone intravitreal implant) 0.7 mg Allergan For Intravitreal Injection Contents include:   One Sterile, Use Applicator Rx Only PRINCIPAL DISPLAY PANEL NDC 0023-3348-07 Ozurdex® (dexamethasone intravitreal implant) 0.7 mg Allergan For Intravitreal Injection Contents include: One Sterile, Use Applicator Rx Only