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.

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 NOVADUR® solid polymer drug delivery system.

{ "type": "p", "children": [], "text": "Intravitreal implant containing dexamethasone 0.7 mg in the NOVADUR® solid polymer drug delivery system." }

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, 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.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Adverse reactions associated with ophthalmic steroids including OZURDEX® include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation, secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera.

Retinal Vein Occlusion and Posterior Segment Uveitis

The following information is based on the combined clinical trial results from 3 initial, randomized, 6-month, sham-controlled studies (2 for retinal vein occlusion and 1 for posterior segment uveitis):

<div class="scrollingtable"><table> <caption> <span>Table 1: Adverse Reactions Reported by Greater than 2% of Patients</span> </caption> <col width="216"/> <col width="114"/> <col width="102"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">MedDRA Term</span> <br/> </td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">OZURDEX</span><span class="Bold"><span class="Sup">®</span></span> <br/>N=497 (%)</td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Sham</span> <br/>N=498 (%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Intraocular pressure increased</td><td align="center" class="Lrule Rrule Toprule">125 (25%)</td><td align="center" class="Lrule Rrule Toprule">10 (2%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Conjunctival hemorrhage</td><td align="center" class="Lrule Rrule Toprule">108 (22%)</td><td align="center" class="Lrule Rrule Toprule">79 (16%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Eye pain</td><td align="center" class="Lrule Rrule Toprule">40 (8%)</td><td align="center" class="Lrule Rrule Toprule">26 (5%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Conjunctival hyperemia</td><td align="center" class="Lrule Rrule Toprule">33 (7%)</td><td align="center" class="Lrule Rrule Toprule">27 (5%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Ocular hypertension</td><td align="center" class="Lrule Rrule Toprule">23 (5%)</td><td align="center" class="Lrule Rrule Toprule">3 (1%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Cataract</td><td align="center" class="Lrule Rrule Toprule">24 (5%)</td><td align="center" class="Lrule Rrule Toprule">10 (2%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule">Vitreous detachment</td><td align="center" class="Lrule Rrule Toprule">12 (2%)</td><td align="center" class="Lrule Rrule Toprule">8 (2%)</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule Toprule">Headache</td><td align="center" class="Lrule Rrule Toprule">19 (4%)</td><td align="center" class="Lrule Rrule Toprule">12 (2%)</td> </tr> </tbody> </table></div>

Increased IOP with OZURDEX® peaked at approximately week 8. During the initial treatment period, 1% (3/421) of the patients who received OZURDEX® required surgical procedures for management of elevated IOP.

Following a second injection of OZURDEX® in cases where a second injection was indicated, the overall incidence of cataracts was higher after 1 year.

In a 2 year observational study, among patients who received >2 injections, the most frequent adverse reaction was cataract 54% (n= 96 out of 178 phakic eyes at baseline). Other frequent adverse reactions from the 283 treated eyes, regardless of lens status at baseline, were increased IOP 24% (n = 68) and vitreous hemorrhage 6.0% (n = 17).

Diabetic Macular Edema

The following information is based on the combined clinical trial results from 2 randomized, 3-year, sham-controlled studies in patients with diabetic macular edema. Discontinuation rates due to the adverse reactions listed in Table 2 were 3% in the OZURDEX® group and 1% in the Sham group. The most common ocular (study eye) and non-ocular adverse reactions are shown in Tables 2 and 3:

<div class="scrollingtable"><table> <caption> <span>Table 2: Ocular Adverse Reactions Reported by ≥ 1% of Patients and Non-ocular Adverse Reactions Reported by ≥ 5% of Patients</span> </caption> <col width="316"/> <col width="147"/> <col width="147"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">MedDRA Term</span> <br/> </td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">OZURDEX</span><span class="Bold"><span class="Sup">®</span></span> <br/>N=324 (%)</td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Sham</span> <br/>N=328 (%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Ocular</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Cataract<span class="Sup">1</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom">166/243<span class="Sup">2</span>  (68%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">49/230 (21%) </td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Conjunctival hemorrhage</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">73 (23%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">44 (13%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Visual acuity reduced</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">28 (9%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">13 (4%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Conjunctivitis</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">19 (6%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">8 (2%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Vitreous floaters</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">16 (5%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">6 (2%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Conjunctival edema</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">15 (5%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">4 (1%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Dry eye</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">15 (5%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">7 (2%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Vitreous detachment</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">14 (4%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">8 (2%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Vitreous opacities</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">11 (3%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">3 (1%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Retinal aneurysm</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">10 (3%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">5 (2%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Foreign body sensation</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">7 (2%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">4 (1%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Corneal erosion</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">7 (2%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">3 (1%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Keratitis</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">6 (2%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">3 (1%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Anterior Chamber Inflammation</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">6 (2%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">0 (0%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Retinal tear</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">5 (2%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">2 (1%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Eyelid ptosis</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">5 (2%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">2 (1%)</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom"><span class="Bold">Non-ocular</span></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"></td><td align="center" class="Lrule Rrule Toprule" valign="bottom"></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Hypertension</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">41 (13%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">21 (6%)</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule Toprule" valign="bottom">Bronchitis</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">15 (5%)</td><td align="center" class="Lrule Rrule Toprule" valign="bottom">8 (2%)</td> </tr> </tbody> </table></div>

1 Includes cataract, cataract nuclear, cataract subcapsular, lenticular opacities in patients who were phakic at baseline. Among these patients, 61% of OZURDEX® subjects vs. 8% of sham-controlled subjects underwent cataract surgery.

2 243 of the 324 OZURDEX® subjects were phakic at baseline; 230 of 328 sham-controlled subjects were phakic at baseline.

Increased Intraocular Pressure

<div class="scrollingtable"><table> <caption> <span>Table 3: Summary of Elevated Intraocular Pressure (IOP) Related Adverse Reactions</span> </caption> <col width="411"/> <col width="153"/> <col width="153"/> <tbody class="Headless"> <tr class="First"> <td class="Lrule Rrule Toprule"><span class="Bold">IOP</span></td><td align="center" class="Lrule Rrule Toprule" colspan="2"><span class="Bold"> Treatment: N (%)</span></td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule"><span class="Bold">OZURDEX</span><span class="Bold"><span class="Sup">®</span></span> <br/> <span class="Bold">N=324</span></td><td class="Lrule Rrule Toprule"><span class="Bold">Sham</span> <br/> <span class="Bold">N=328</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">IOP elevation ≥10 mm Hg from Baseline at any visit</td><td class="Lrule Rrule Toprule">91 (28%)</td><td class="Lrule Rrule Toprule">13 (4%)</td> </tr> <tr> <td class="Lrule Rrule Toprule">≥30 mm Hg IOP at any visit</td><td class="Lrule Rrule Toprule">50 (15%)</td><td class="Lrule Rrule Toprule">5 (2%)</td> </tr> <tr> <td class="Lrule Rrule Toprule">Any IOP lowering medication</td><td class="Lrule Rrule Toprule">136 (42%)</td><td class="Lrule Rrule Toprule">32 (10%)</td> </tr> <tr class="Last"> <td class="Lrule Rrule Toprule">Any surgical intervention for elevated IOP * </td><td class="Lrule Rrule Toprule">4 (1.2%)</td><td class="Lrule Rrule Toprule">1 (0.3%)</td> </tr> </tbody> </table></div>

* OZURDEX®: 1 surgical trabeculectomy for steroid-induced IOP increase, 1 surgical trabeculectomy for iris neovascularization, 1 laser iridotomy, 1 surgical iridectomySham: 1 laser iridotomy

The increase in mean IOP was seen with each treatment cycle, and the mean IOP generally returned to baseline between treatment cycles (at the end of the 6 month period) shown below:

Figure 1: Mean IOP during the study

Cataracts and Cataract Surgery

At baseline, 243 of the 324 OZURDEX® subjects were phakic; 230 of 328 sham-controlled subjects were phakic. The incidence of cataract development in patients who had a phakic study eye was higher in the OZURDEX® group (68%) compared with Sham (21%). The median time of cataract being reported as an adverse event was approximately 15 months in the OZURDEX® group and 12 months in the Sham group. Among these patients, 61% of OZURDEX® subjects vs. 8% of sham-controlled subjects underwent cataract surgery, generally between Month 18 and Month 39 (Median Month 21 for OZURDEX® group and 20 for Sham) of the studies.

The following reactions have been identified during post-marketing use of OZURDEX® in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to OZURDEX®, or a combination of these factors, include: complication of device insertion resulting in ocular tissue injury including sclera, subconjunctiva, lens and retina (implant misplacement), device dislocation with or without corneal edema, endophthalmitis, hypotony of the eye (associated with vitreous leakage due to injection), and retinal detachment.

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/m2 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/m2 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® 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.

{ "type": "p", "children": [], "text": "\nOZURDEX® 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, DL-Lactide and Glycolide (50:50) Copolymer 12000 Ethyl Ester, is ester terminated, and the other DL-Lactide and Glycolide (50:50) Copolymer 12000 Acid 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:

{ "type": "p", "children": [], "text": " 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, DL-Lactide and Glycolide (50:50) Copolymer 12000 Ethyl Ester, is ester terminated, and the other DL-Lactide and Glycolide (50:50) Copolymer 12000 Acid 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: C22H29FO5

{ "type": "p", "children": [], "text": "MW 392.47; molecular formula: C22H29FO5\n" }

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.

{ "type": "p", "children": [], "text": "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.

{ "type": "p", "children": [], "text": "The PLGA matrix slowly degrades to lactic acid and glycolic acid. " }

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 [14C]-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

{ "type": "p", "children": [], "text": "\nRetinal Vein Occlusion\n" }

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.

{ "type": "p", "children": [], "text": "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):

{ "type": "p", "children": [], "text": "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): " }

<div class="scrollingtable"><table> <caption> <span>Table 4: Number (Percent) of Patients with ≥ 15 Letters Improvement from Baseline in BCVA</span> </caption> <col width="100"/> <col width="93"/> <col width="87"/> <col width="84"/> <col width="91"/> <col width="85"/> <col width="83"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">Study Day</span></td><td align="center" class="Lrule Rrule Toprule" colspan="3"><span class="Bold">Study 1</span></td><td align="center" class="Lrule Rrule Toprule" colspan="3"><span class="Bold">Study 2</span></td> </tr> <tr> <td align="center" class="Lrule Rrule"></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">OZURDEX</span><span class="Bold"><span class="Sup">® </span></span>N=201</td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Sham</span> <br/>N=202</td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">p-value*</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">OZURDEX</span><span class="Bold"><span class="Sup">® </span></span>N=226</td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Sham</span> <br/>N=224</td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">p-value*</span></td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">Day 30</span></td><td align="center" class="Lrule Rrule Toprule">40 (20%)</td><td align="center" class="Lrule Rrule Toprule">15 (7%)</td><td align="center" class="Lrule Rrule Toprule">&lt; 0.01</td><td align="center" class="Lrule Rrule Toprule">51 (23%)</td><td align="center" class="Lrule Rrule Toprule">17 (8%)</td><td align="center" class="Lrule Rrule Toprule">&lt; 0.01</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">Day 60</span></td><td align="center" class="Lrule Rrule Toprule">58 (29%)</td><td align="center" class="Lrule Rrule Toprule">21 (10%)</td><td align="center" class="Lrule Rrule Toprule">&lt; 0.01</td><td align="center" class="Lrule Rrule Toprule">67 (30%)</td><td align="center" class="Lrule Rrule Toprule">27 (12%)</td><td align="center" class="Lrule Rrule Toprule">&lt; 0.01</td> </tr> <tr> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">Day 90</span></td><td align="center" class="Lrule Rrule Toprule">45 (22%)</td><td align="center" class="Lrule Rrule Toprule">25 (12%)</td><td align="center" class="Lrule Rrule Toprule">&lt; 0.01</td><td align="center" class="Lrule Rrule Toprule">48 (21%)</td><td align="center" class="Lrule Rrule Toprule">31 (14%)</td><td align="center" class="Lrule Rrule Toprule">0.039</td> </tr> <tr class="Last"> <td align="center" class="Lrule Rrule Toprule"><span class="Bold">Day 180</span></td><td align="center" class="Lrule Rrule Toprule">39 (19%)</td><td align="center" class="Lrule Rrule Toprule">37 (18%)</td><td align="center" class="Lrule Rrule Toprule">0.780</td><td align="center" class="Lrule Rrule Toprule">53 (24%)</td><td align="center" class="Lrule Rrule Toprule">38 (17%)</td><td align="center" class="Lrule Rrule Toprule">0.087</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Table 4: Number (Percent) of Patients with ≥ 15 Letters Improvement from Baseline in BCVA</span>\n</caption>\n<col width=\"100\"/>\n<col width=\"93\"/>\n<col width=\"87\"/>\n<col width=\"84\"/>\n<col width=\"91\"/>\n<col width=\"85\"/>\n<col width=\"83\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Study Day</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"3\"><span class=\"Bold\">Study 1</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\" colspan=\"3\"><span class=\"Bold\">Study 2</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule\"></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">OZURDEX</span><span class=\"Bold\"><span class=\"Sup\">® </span></span>N=201</td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Sham</span>\n<br/>N=202</td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">p-value*</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">OZURDEX</span><span class=\"Bold\"><span class=\"Sup\">® </span></span>N=226</td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Sham</span>\n<br/>N=224</td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">p-value*</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Day 30</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\">40 (20%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">15 (7%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">&lt; 0.01</td><td align=\"center\" class=\"Lrule Rrule Toprule\">51 (23%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">17 (8%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">&lt; 0.01</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Day 60</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\">58 (29%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">21 (10%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">&lt; 0.01</td><td align=\"center\" class=\"Lrule Rrule Toprule\">67 (30%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">27 (12%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">&lt; 0.01</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Day 90</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\">45 (22%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">25 (12%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">&lt; 0.01</td><td align=\"center\" class=\"Lrule Rrule Toprule\">48 (21%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">31 (14%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">0.039</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Day 180</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\">39 (19%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">37 (18%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">0.780</td><td align=\"center\" class=\"Lrule Rrule Toprule\">53 (24%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">38 (17%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">0.087</td>\n</tr>\n</tbody>\n</table></div>" }

*P-values were based on the Pearson’s chi-square test.

{ "type": "p", "children": [], "text": "*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.

{ "type": "p", "children": [], "text": "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.

{ "type": "p", "children": [], "text": "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

{ "type": "p", "children": [], "text": "\nPosterior Segment Uveitis\n" }

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. 

{ "type": "p", "children": [], "text": "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. \n" }

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.

{ "type": "p", "children": [], "text": "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

{ "type": "p", "children": [], "text": "\nDiabetic Macular Edema\n" }

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.

{ "type": "p", "children": [], "text": "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).

{ "type": "p", "children": [], "text": "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). " }

<div class="scrollingtable"><table> <caption> <span>Table 5: Visual Acuity outcomes at Month 39 (All randomized subjects with LOCF<span class="Sup">c</span>) </span> </caption> <col width="61"/> <col width="254"/> <col width="111"/> <col width="111"/> <col width="172"/> <tbody class="Headless"> <tr class="First"> <td class="Lrule Rrule Toprule"><span class="Bold">Study</span></td><td class="Lrule Rrule Toprule"><span class="Bold">Outcomes</span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">O</span><span class="Bold">ZURDEX</span><span class="Bold"><span class="Sup">®</span></span></td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Sham</span> <br/> </td><td align="center" class="Lrule Rrule Toprule"><span class="Bold">Estimated Difference (95% CI)</span></td> </tr> <tr> <td class="Lrule Rrule Toprule">1<span class="Sup">a</span> <br/> </td><td class="Lrule Rrule Toprule">Mean (SD) Baseline BCVA (Letters)</td><td align="center" class="Lrule Rrule Toprule">56 (10)<br/> </td><td align="center" class="Lrule Rrule Toprule">57 (9)<br/> </td><td align="center" class="Lrule Rrule Toprule"></td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Median (range) Baseline BCVA (Letters)</td><td align="center" class="Lrule Rrule Toprule">59 (34-95)</td><td align="center" class="Lrule Rrule Toprule">58 (34-74)</td><td align="center" class="Lrule Rrule Toprule"></td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Gain of ≥15 letters in BCVA (n(%))</td><td align="center" class="Lrule Rrule Toprule">34 (21%)</td><td align="center" class="Lrule Rrule Toprule">19 (12%)</td><td align="center" class="Lrule Rrule Toprule">9.3% (1.4%, 17.3%)</td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Loss of ≥15 letters in BCVA (n(%))</td><td align="center" class="Lrule Rrule Toprule">15 (9%)</td><td align="center" class="Lrule Rrule Toprule">17 (10%)</td><td align="center" class="Lrule Rrule Toprule">-1.1% (-7.5%, 5.3%)</td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Mean change in BCVA (SD)</td><td align="center" class="Lrule Rrule Toprule">4.1 (13.9)</td><td align="center" class="Lrule Rrule Toprule">0.9 (11.9)</td><td align="center" class="Lrule Rrule Toprule">3.2 (0.4, 5.9)</td> </tr> <tr> <td class="Lrule Rrule Toprule">2<span class="Sup">b</span> <br/> </td><td class="Lrule Rrule Toprule">Mean (SD) Baseline BCVA (Letters)</td><td align="center" class="Lrule Rrule Toprule">55 (10)<br/> </td><td align="center" class="Lrule Rrule Toprule">56 (9)<br/> </td><td class="Lrule Rrule Toprule"></td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Median (range) Baseline BCVA (Letters)</td><td align="center" class="Lrule Rrule Toprule">58 (34-72)</td><td align="center" class="Lrule Rrule Toprule">58 (36-82)</td><td align="center" class="Lrule Rrule Toprule"></td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Gain of ≥15 letters in BCVA (n(%))</td><td align="center" class="Lrule Rrule Toprule">30 (18%)</td><td align="center" class="Lrule Rrule Toprule">16 (10%)</td><td align="center" class="Lrule Rrule Toprule">8.4% (0.9%, 15.8%)</td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Loss of ≥15 letters in BCVA (n(%))</td><td align="center" class="Lrule Rrule Toprule">30 (18%)</td><td align="center" class="Lrule Rrule Toprule">18 (11%)</td><td align="center" class="Lrule Rrule Toprule">7.1% (-0.5%, 14.7%)</td> </tr> <tr class="Last"> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Mean change in BCVA (SD)</td><td align="center" class="Lrule Rrule Toprule">0.4 (17.5)</td><td align="center" class="Lrule Rrule Toprule">0.8 (13.6)</td><td align="center" class="Lrule Rrule Toprule">-0.7 (-4.1, 2.6)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Table 5: Visual Acuity outcomes at Month 39 (All randomized subjects with LOCF<span class=\"Sup\">c</span>) </span>\n</caption>\n<col width=\"61\"/>\n<col width=\"254\"/>\n<col width=\"111\"/>\n<col width=\"111\"/>\n<col width=\"172\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Study</span></td><td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Outcomes</span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">O</span><span class=\"Bold\">ZURDEX</span><span class=\"Bold\"><span class=\"Sup\">®</span></span></td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Sham</span>\n<br/>\n</td><td align=\"center\" class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Estimated Difference (95% CI)</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">1<span class=\"Sup\">a</span>\n<br/>\n</td><td class=\"Lrule Rrule Toprule\">Mean (SD) Baseline BCVA (Letters)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">56 (10)<br/>\n</td><td align=\"center\" class=\"Lrule Rrule Toprule\">57 (9)<br/>\n</td><td align=\"center\" class=\"Lrule Rrule Toprule\"></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Median (range) Baseline BCVA (Letters)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">59 (34-95)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">58 (34-74)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Gain of ≥15 letters in BCVA (n(%))</td><td align=\"center\" class=\"Lrule Rrule Toprule\">34 (21%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">19 (12%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">9.3% (1.4%, 17.3%)</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Loss of ≥15 letters in BCVA (n(%))</td><td align=\"center\" class=\"Lrule Rrule Toprule\">15 (9%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">17 (10%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">-1.1% (-7.5%, 5.3%)</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Mean change in BCVA (SD)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">4.1 (13.9)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">0.9 (11.9)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">3.2 (0.4, 5.9)</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\">2<span class=\"Sup\">b</span>\n<br/>\n</td><td class=\"Lrule Rrule Toprule\">Mean (SD) Baseline BCVA (Letters)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">55 (10)<br/>\n</td><td align=\"center\" class=\"Lrule Rrule Toprule\">56 (9)<br/>\n</td><td class=\"Lrule Rrule Toprule\"></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Median (range) Baseline BCVA (Letters)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">58 (34-72)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">58 (36-82)</td><td align=\"center\" class=\"Lrule Rrule Toprule\"></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Gain of ≥15 letters in BCVA (n(%))</td><td align=\"center\" class=\"Lrule Rrule Toprule\">30 (18%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">16 (10%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">8.4% (0.9%, 15.8%)</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Loss of ≥15 letters in BCVA (n(%))</td><td align=\"center\" class=\"Lrule Rrule Toprule\">30 (18%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">18 (11%)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">7.1% (-0.5%, 14.7%)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Mean change in BCVA (SD)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">0.4 (17.5)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">0.8 (13.6)</td><td align=\"center\" class=\"Lrule Rrule Toprule\">-0.7 (-4.1, 2.6)</td>\n</tr>\n</tbody>\n</table></div>" }

aStudy 1: OZURDEX®, N=163; Sham, N=165

{ "type": "p", "children": [], "text": "\naStudy 1: OZURDEX®, N=163; Sham, N=165" }

bStudy 2: OZURDEX®, N=165; Sham, N=163

{ "type": "p", "children": [], "text": "\nbStudy 2: OZURDEX®, N=165; Sham, N=163" }

c14% (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.

{ "type": "p", "children": [], "text": "\nc14% (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.

{ "type": "p", "children": [], "text": "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

{ "type": "p", "children": [], "text": "\nFigure 2: Proportion of Subjects with ≥ 15 Letters Improvement from Baseline BCVA in the Study Eye\n" }

Figure 3: Mean BCVA Change from Baseline

{ "type": "p", "children": [], "text": "\nFigure 3: Mean BCVA Change from Baseline\n" }

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.

{ "type": "p", "children": [], "text": "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. " }

<div class="scrollingtable"><table> <caption> <span>Table 6: Visual Acuity outcomes at Month 39 (Subgroup for pooled data with LOCF<span class="Sup">c</span>)</span> </caption> <col width="108"/> <col width="217"/> <col width="114"/> <col width="96"/> <col width="174"/> <tbody class="Headless"> <tr class="First"> <td class="Lrule Rrule Toprule"><span class="Bold">Subgroup</span> <br/> <span class="Bold">(Pooled)</span></td><td class="Lrule Rrule Toprule"><span class="Bold">Outcomes</span></td><td class="Lrule Rrule Toprule"><span class="Bold">OZURDEX</span><span class="Bold"><span class="Sup">®</span></span></td><td class="Lrule Rrule Toprule"><span class="Bold">Sham </span> <br/> </td><td class="Lrule Rrule Toprule"><span class="Bold">Estimated Difference (95% CI)</span></td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Sup">a</span>Pseudophakic</td><td class="Lrule Rrule Toprule">Gain of ≥15 letters in BCVA (n(%))</td><td class="Lrule Rrule Toprule">16 (20%)</td><td class="Lrule Rrule Toprule">11 (11%)</td><td class="Lrule Rrule Toprule">8.4% <br/>(-2.2%, 19.0%)</td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Loss of ≥15 letters in BCVA (n(%))</td><td class="Lrule Rrule Toprule">4 (5%)</td><td class="Lrule Rrule Toprule">7 (7%)</td><td class="Lrule Rrule Toprule">-2.2% (-9.1%, 4.7%)</td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Mean change in BCVA (SD)</td><td class="Lrule Rrule Toprule">5.8 (11.6)</td><td class="Lrule Rrule Toprule">1.4 (12.3)</td><td class="Lrule Rrule Toprule">4.2 (0.8, 7.6)</td> </tr> <tr> <td class="Lrule Rrule Toprule"><span class="Sup">b</span>Phakic</td><td class="Lrule Rrule Toprule">Gain of ≥15 letters in BCVA (n(%))</td><td class="Lrule Rrule Toprule">48 (20%)</td><td class="Lrule Rrule Toprule">24 (11%)</td><td class="Lrule Rrule Toprule">9.0% (2.7%, 15.4%)</td> </tr> <tr> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Loss of ≥15 letters in BCVA (n(%))</td><td class="Lrule Rrule Toprule">41 (17%)</td><td class="Lrule Rrule Toprule">28 (12%)</td><td class="Lrule Rrule Toprule">4.4% (-1.9%, 10.7%)</td> </tr> <tr class="Last"> <td class="Lrule Rrule"></td><td class="Lrule Rrule Toprule">Mean change in BCVA (SD)</td><td class="Lrule Rrule Toprule">1.0 (16.9)</td><td class="Lrule Rrule Toprule">0.6 (12.9)</td><td class="Lrule Rrule Toprule">0.3 (-2.4, 3.0)</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table>\n<caption>\n<span>Table 6: Visual Acuity outcomes at Month 39 (Subgroup for pooled data with LOCF<span class=\"Sup\">c</span>)</span>\n</caption>\n<col width=\"108\"/>\n<col width=\"217\"/>\n<col width=\"114\"/>\n<col width=\"96\"/>\n<col width=\"174\"/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Subgroup</span>\n<br/>\n<span class=\"Bold\">(Pooled)</span></td><td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Outcomes</span></td><td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">OZURDEX</span><span class=\"Bold\"><span class=\"Sup\">®</span></span></td><td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Sham </span>\n<br/>\n</td><td class=\"Lrule Rrule Toprule\"><span class=\"Bold\">Estimated Difference (95% CI)</span></td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Sup\">a</span>Pseudophakic</td><td class=\"Lrule Rrule Toprule\">Gain of ≥15 letters in BCVA (n(%))</td><td class=\"Lrule Rrule Toprule\">16 (20%)</td><td class=\"Lrule Rrule Toprule\">11 (11%)</td><td class=\"Lrule Rrule Toprule\">8.4% <br/>(-2.2%, 19.0%)</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Loss of ≥15 letters in BCVA (n(%))</td><td class=\"Lrule Rrule Toprule\">4 (5%)</td><td class=\"Lrule Rrule Toprule\">7 (7%)</td><td class=\"Lrule Rrule Toprule\">-2.2% (-9.1%, 4.7%)</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Mean change in BCVA (SD)</td><td class=\"Lrule Rrule Toprule\">5.8 (11.6)</td><td class=\"Lrule Rrule Toprule\">1.4 (12.3)</td><td class=\"Lrule Rrule Toprule\">4.2 (0.8, 7.6)</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule Toprule\"><span class=\"Sup\">b</span>Phakic</td><td class=\"Lrule Rrule Toprule\">Gain of ≥15 letters in BCVA (n(%))</td><td class=\"Lrule Rrule Toprule\">48 (20%)</td><td class=\"Lrule Rrule Toprule\">24 (11%)</td><td class=\"Lrule Rrule Toprule\">9.0% (2.7%, 15.4%)</td>\n</tr>\n<tr>\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Loss of ≥15 letters in BCVA (n(%))</td><td class=\"Lrule Rrule Toprule\">41 (17%)</td><td class=\"Lrule Rrule Toprule\">28 (12%)</td><td class=\"Lrule Rrule Toprule\">4.4% (-1.9%, 10.7%)</td>\n</tr>\n<tr class=\"Last\">\n<td class=\"Lrule Rrule\"></td><td class=\"Lrule Rrule Toprule\">Mean change in BCVA (SD)</td><td class=\"Lrule Rrule Toprule\">1.0 (16.9)</td><td class=\"Lrule Rrule Toprule\">0.6 (12.9)</td><td class=\"Lrule Rrule Toprule\">0.3 (-2.4, 3.0)</td>\n</tr>\n</tbody>\n</table></div>" }

a Pseudophakic: OZURDEX®, N=82; Sham, N=99

{ "type": "p", "children": [], "text": "\na Pseudophakic: OZURDEX®, N=82; Sham, N=99" }

b Phakic: OZURDEX®, N=246; Sham, N=229

{ "type": "p", "children": [], "text": "\nb Phakic: OZURDEX®, N=246; Sham, N=229" }

c14% (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.

{ "type": "p", "children": [], "text": "\nc14% (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." }

OZURDEX® (dexamethasone intravitreal implant) 0.7 mg is supplied in a foil pouch with 1 single-use plastic applicator, NDC 0023-3348-07.

{ "type": "p", "children": [], "text": "\nOZURDEX® (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 15oC to 30oC (59oF to 86oF).

{ "type": "p", "children": [], "text": "\nStorage: Store at 15oC to 30oC (59oF to 86oF)." }

Steroid-related Effects

{ "type": "p", "children": [], "text": "\nSteroid-related Effects \n" }

Advise patients that a cataract may occur after repeated treatment with OZURDEX®. If this occurs, advise patients that their vision will decrease, and they will need an operation to remove the cataract and restore their vision.

{ "type": "p", "children": [], "text": "Advise patients that a cataract may occur after repeated treatment with OZURDEX®. If this occurs, advise patients that their vision will decrease, and they will need an operation to remove the cataract and restore their vision. " }

Advise patients that they may develop increased intraocular pressure with OZURDEX® treatment, and the increased IOP will need to be managed with eye drops, and, rarely, with surgery.

{ "type": "p", "children": [], "text": "Advise patients that they may develop increased intraocular pressure with OZURDEX® treatment, and the increased IOP will need to be managed with eye drops, and, rarely, with surgery." }

Intravitreal Injection-related Effects

{ "type": "p", "children": [], "text": "\nIntravitreal Injection-related Effects\n" }

Advise patients that in the days following intravitreal injection of OZURDEX®, patients are at risk for potential complications including in particular, but not limited to, the development of endophthalmitis or elevated intraocular pressure.

{ "type": "p", "children": [], "text": "Advise patients that in the days following intravitreal injection of OZURDEX®, patients are at risk for potential complications including in particular, but not limited to, the development of endophthalmitis or elevated intraocular pressure. " }

When to Seek Physician Advice

{ "type": "p", "children": [], "text": "\nWhen to Seek Physician Advice\n" }

Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist.

{ "type": "p", "children": [], "text": "Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist. " }

Driving and Using Machines

{ "type": "p", "children": [], "text": "\nDriving and Using Machines \n" }

Inform patients that they may experience temporary visual blurring after receiving an intravitreal injection. Advise patients not to drive or use machines until this has been resolved.

{ "type": "p", "children": [], "text": "Inform patients that they may experience temporary visual blurring after receiving an intravitreal injection. Advise patients not to drive or use machines until this has been resolved." }

Distributed by:

{ "type": "p", "children": [], "text": "Distributed by:" }

AbbVie Inc.North Chicago, IL 60064

{ "type": "p", "children": [], "text": "AbbVie Inc.North Chicago, IL 60064" }

© 2025 AbbVie. All rights reserved.

{ "type": "p", "children": [], "text": "© 2025 AbbVie. All rights reserved." }

OZURDEX and its design are trademarks of Allergan, Inc., an AbbVie company.

{ "type": "p", "children": [], "text": "OZURDEX and its design are trademarks of Allergan, Inc., an AbbVie company." }

V5.0USPI3348

{ "type": "p", "children": [], "text": "V5.0USPI3348" }

NDC 0023-3348-07Ozurdex® (dexamethasoneintravitreal implant) 0.7 mg Allergan For Intravitreal InjectionContents include:  One Sterile, Use Applicator Rx Only

{ "type": "p", "children": [], "text": "NDC 0023-3348-07Ozurdex®\n(dexamethasoneintravitreal implant) 0.7 mg\nAllergan\nFor Intravitreal InjectionContents include: \n\nOne Sterile, Use Applicator\nRx Only" }

DEXTENZA is indicated for the treatment of ocular inflammation and pain following ophthalmic surgery (1.1).

DEXTENZA is indicated for the treatment of ocular itching associated with allergic conjunctivitis in adults and pediatric patients aged 2 years and older (1.2).

Limitations of Use

The use of DEXTENZA is not recommended for the treatment of ocular itching associated with allergic conjunctivitis in pediatric patients who require sedation for the insertion procedure [see Use in Specific Populations (8.4)].

DEXTENZA is an ophthalmic insert that is inserted in the lower lacrimal punctum into the canaliculus. A single DEXTENZA insert releases a 0.4 mg dose of dexamethasone for up to 30 days following insertion.

DEXTENZA is resorbable and does not require removal. Saline irrigation or manual expression can be performed to remove the insert if necessary. DEXTENZA is intended for single-use only.

Do not use if pouch has been damaged or opened. Do not re-sterilize.

Ophthalmic insert: fluorescent yellow, 3 mm cylindrical-shaped insert containing dexamethasone, 0.4 mg.

{ "type": "p", "children": [], "text": "Ophthalmic insert: fluorescent yellow, 3 mm cylindrical-shaped insert containing dexamethasone, 0.4 mg.\n" }

DEXTENZA is contraindicated in patients with active corneal, conjunctival or canalicular infections, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella; mycobacterial infections; fungal diseases of the eye, and dacryocystitis.

{ "type": "p", "children": [], "text": "DEXTENZA is contraindicated in patients with active corneal, conjunctival or canalicular infections, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella; mycobacterial infections; fungal diseases of the eye, and dacryocystitis.\n" }

Prolonged use of corticosteroids may result in glaucoma with damage to the optic nerve, defects in visual acuity and fields of vision. Steroids should be used with caution in the presence of glaucoma. Intraocular pressure should be monitored during the course of the treatment.

Corticosteroids may suppress the host response and thus increase the hazard for secondary ocular infections. In acute purulent conditions, steroids may mask infection and enhance existing infection [see Contraindications (4)].

Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex) [see Contraindications (4)].

Fungus invasion must be considered in any persistent corneal ulceration where a steroid has been used or is in use. Fungal culture should be taken when appropriate [see Contraindications (4)].

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation.

The initial prescription and renewal of the medication order of DEXTENZA should be made by a physician only after examination of the patient with the aid of magnification, such as slit lamp biomicroscopy, and, where appropriate, fluorescein staining. If signs and symptoms fail to improve after 2 days, the patient should be re-evaluated.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions associated with ophthalmic steroids include elevated intraocular pressure, which may be associated with optic nerve damage, visual acuity and field defects, posterior subcapsular cataract formation; delayed wound healing; secondary ocular infection from pathogens including herpes simplex, and perforation of the globe where there is thinning of the cornea or sclera [see Warnings and Precautions (5)].

DEXTENZA safety was studied in four randomized, vehicle-controlled studies (n = 567). The mean age of the population was 68 years (range 35 to 87 years), 59% were female, and 83% were white. Forty-seven percent had brown iris color and 30% had blue iris color. The most common ocular adverse reactions that occurred in patients treated with DEXTENZA were: anterior chamber inflammation including iritis and iridocyclitis (10%); intraocular pressure increased (6%); visual acuity reduced (2%); cystoid macular edema (1%); corneal edema (1%); eye pain (1%) and conjunctival hyperemia (1%).

The most common non-ocular adverse reaction that occurred in patients treated with DEXTENZA was headache (1%).

DEXTENZA safety was studied in four randomized, vehicle-controlled studies (n= 154). The mean age of the population was 41 years (range 19 to 69 years), 55 % were female and 61 % were white. Fifty seven percent had brown iris color and 20% had blue iris color. The most common ocular adverse reactions that occurred in patients treated with DEXTENZA were: intraocular pressure increased (3%), lacrimation increased (1%), eye discharge (1%), and visual acuity reduced (1%).

The most common non-ocular adverse reaction that occurred in patients treated with DEXTENZA was headache (1%).

Risk Summary

There are no adequate or well-controlled studies with DEXTENZA in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. In animal reproduction studies, administration of topical ocular dexamethasone to pregnant mice and rabbits during organogenesis produced embryofetal lethality, cleft palate and multiple visceral malformations (see Data).

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 a mouse study. A daily dose of 0.75 mg/kg/day in the mouse is approximately 5 times the entire dose of dexamethasone in the DEXTENZA product, on a mg/m2 basis. In a rabbit study, topical ocular administration of 0.1% dexamethasone throughout organogenesis (0.36 mg /day, on gestational day 6 followed by 0.24 mg/day on gestational days 7-18) produced intestinal anomalies, intestinal aplasia, gastroschisis and hypoplastic kidneys. A daily dose of 0.24 mg/day is approximately 6 times the entire dose of dexamethasone in the DEXTENZA product, on a mg/m2 basis.

Systemically administered corticosteroids appear in human milk and could suppress growth and interfere with endogenous corticosteroid production; however the systemic concentration of dexamethasone following administration of DEXTENZA is low [see Clinical Pharmacology (12.3)]. There is no information regarding the presence of DEXTENZA in human milk, the effects of the drug on the breastfed infant or the effects of the drug on milk production to inform risk of DEXTENZA to an infant during lactation. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for DEXTENZA and any potential adverse effects on the breastfed child from DEXTENZA.

The safety and effectiveness of DEXTENZA for the treatment of ocular inflammation and pain following ophthalmic surgery have been established in pediatric patients.

The safety and effectiveness of DEXTENZA for the treatment of ocular itching associated with allergic conjunctivitis have been established in pediatric patients aged 2 years and older. The use of DEXTENZA is not recommended for the treatment of ocular itching associated with allergic conjunctivitis in pediatric patients who require sedation for the insertion procedure.

Use of DEXTENZA for these indications is supported by evidence from adequate and well-controlled studies in adults with additional safety data from a single active-controlled study in pediatric patients aged birth to 5 years old [see Clinical Studies (14)]. A similar safety profile was observed between pediatric and adult patients.

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

DEXTENZA (dexamethasone ophthalmic insert) is a fluorescent yellow, 3 mm cylindrical-shaped, resorbable, sterile insert for intracanalicular use. DEXTENZA contains 0.4 mg dexamethasone in a polyethylene glycol (PEG) based hydrogel conjugated with fluorescein. DEXTENZA does not contain an antimicrobial preservative. The active ingredient is represented by the chemical structure:

{ "type": "p", "children": [], "text": "DEXTENZA (dexamethasone ophthalmic insert) is a fluorescent yellow, 3 mm cylindrical-shaped, resorbable, sterile insert for intracanalicular use. DEXTENZA contains 0.4 mg dexamethasone in a polyethylene glycol (PEG) based hydrogel conjugated with fluorescein. DEXTENZA does not contain an antimicrobial preservative. The active ingredient is represented by the chemical structure:\n" }

The chemical name for dexamethasone is 9-Fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. It has a molecular formula of C22H29FO5 and a molecular weight of 392.47 g/mol. Dexamethasone is a crystalline powder.

{ "type": "p", "children": [], "text": "The chemical name for dexamethasone is 9-Fluoro-11β,17,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. It has a molecular formula of C22H29FO5 and a molecular weight of 392.47 g/mol. Dexamethasone is a crystalline powder.\n" }

Each DEXTENZA contains: Active ingredients: 0.4 mg dexamethasone. Inactive ingredients: 4-arm polyethylene glycol (PEG) N-hydroxysuccinimidyl glutarate (20K), trilysine acetate, N-hydroxysuccinimide-fluorescein, sodium phosphate dibasic, sodium phosphate monobasic, water for injection.

{ "type": "p", "children": [], "text": "Each DEXTENZA contains: Active ingredients: 0.4 mg dexamethasone. Inactive ingredients: 4-arm polyethylene glycol (PEG) N-hydroxysuccinimidyl glutarate (20K), trilysine acetate, N-hydroxysuccinimide-fluorescein, sodium phosphate dibasic, sodium phosphate monobasic, water for injection.\n" }

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 samples were obtained from 16 healthy volunteers prior to insertion of DEXTENZA and on Day 1 (at 1, 2, 4, 8, 16 hours), 2 (24 hours), 4, 8, 15, 22 and 29 following the insertion of DEXTENZA.

Plasma concentrations of dexamethasone were detectable (above 50 pg/mL, the lower limit of quantification of the assay) in 11% of samples (21 of 189), and ranged from 0.05 ng/mL to 0.81 ng/mL.

No adequate studies in animals have been conducted to determine whether DEXTENZA has the potential for carcinogenesis.

Dexamethasone was not mutagenic in the Ames/Salmonella assay, both with and without metabolic activation. Dexamethasone was genotoxic in two in vitro assays using human lymphocytes (chromosomal aberration assay and sister chromatid exchange assay) and was genotoxic in two mouse in vivo assays (micronucleus assay and sister chromatid exchange assay).

Fertility studies have not been conducted in animals using DEXTENZA.

In three randomized, multicenter, double-masked, parallel group, vehicle-controlled efficacy trials, patients received DEXTENZA or its vehicle immediately upon completion of cataract surgery (NCT02034019, NCT02089113, NCT02736175). In all three trials, DEXTENZA had a higher proportion of patients than the vehicle group who were pain free on post-operative Day 8. On post-operative Day 14, in two of the three studies, DEXTENZA had a higher proportion of patients than the vehicle group who had an absence of anterior chamber cells that was statistically significant. Results are shown in Table 1 and Table 2.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 1: Percentage of Patients with Absence of Anterior Chamber Cells </span> </caption> <col align="left" width="5.883%"/> <col align="left" width="9.849%"/> <col align="left" width="8.424%"/> <col align="left" width="11.549%"/> <col align="left" width="2.150%"/> <col align="left" width="9.849%"/> <col align="left" width="8.424%"/> <col align="left" width="11.332%"/> <col align="left" width="2.150%"/> <col align="left" width="10.057%"/> <col align="left" width="8.783%"/> <col align="left" width="11.549%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Toprule" valign="middle"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="middle"><span class="Bold">Study 1</span></td><td align="center" class="Botrule Toprule" valign="middle"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="middle"><span class="Bold">Study 2</span></td><td align="center" class="Botrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Study 3</span></td> </tr> <tr> <td align="center" class="Lrule Rrule" valign="middle"></td><td align="center" valign="middle"><span class="Bold">dextenza</span> <br/> <span class="Bold">(N=164)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=83)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span></td><td align="center" valign="middle"></td><td align="center" valign="middle"><span class="Bold">dextenza</span> <br/> <span class="Bold">(N=161)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=80)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span></td><td align="center" valign="top"></td><td align="center" valign="middle"><span class="Bold">Dextenza</span> <br/> <span class="Bold">(N=216)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=222)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule" valign="middle"><span class="Bold">Visit</span></td><td align="center" class="Botrule" valign="middle"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="middle"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="middle"></td><td align="center" class="Botrule" valign="middle"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="middle"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="top"></td><td align="center" class="Botrule" valign="top"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="top"><span class="Bold">n (%)</span></td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule" valign="middle"><span class="Bold">Day 14</span></td><td align="center" class="Botrule" valign="middle">54 (33%) </td><td align="center" class="Botrule" valign="middle">12 (14%) </td><td align="center" class="Botrule Rrule" valign="middle">18% (8%, 29%) </td><td align="center" class="Botrule" valign="middle"></td><td align="center" class="Botrule" valign="middle">63 (39%) </td><td align="center" class="Botrule" valign="middle">25 (31%) </td><td align="center" class="Botrule Rrule" valign="middle">8% (-5%, 21%) </td><td align="center" class="Botrule" valign="middle"></td><td align="center" class="Botrule" valign="middle">113 (52%) </td><td align="center" class="Botrule" valign="middle">69 (31%) </td><td align="center" class="Botrule Rrule" valign="middle">21 % (12%, 30%) </td> </tr> </tbody> </table></div>

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 2: Percentage of Patients with Absence of Pain </span> </caption> <col align="left" width="5.868%"/> <col align="left" width="10.060%"/> <col align="left" width="8.426%"/> <col align="left" width="11.402%"/> <col align="left" width="2.275%"/> <col align="left" width="10.060%"/> <col align="left" width="8.426%"/> <col align="left" width="11.377%"/> <col align="left" width="2.100%"/> <col align="left" width="10.060%"/> <col align="left" width="8.693%"/> <col align="left" width="11.252%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Toprule" valign="middle"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="middle"><span class="Bold">Study 1</span></td><td align="center" class="Botrule Toprule" valign="middle"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="middle"><span class="Bold">Study 2</span></td><td align="center" class="Botrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Study 3</span></td> </tr> <tr> <td align="center" class="Lrule" valign="middle"></td><td align="center" valign="middle"><span class="Bold">Dextenza</span> <br/> <span class="Bold">(N=164)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=83)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span></td><td align="center" valign="middle"></td><td align="center" valign="middle"><span class="Bold">Dextenza</span> <br/> <span class="Bold">(N=161)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=80)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span></td><td align="center" valign="middle"></td><td align="center" valign="middle"><span class="Bold">Dextenza</span> <br/> <span class="Bold">(N=216)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=222)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span></td> </tr> <tr> <td align="center" class="Botrule Lrule" valign="middle"><span class="Bold">Visit</span></td><td align="center" class="Botrule" valign="middle"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="middle"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="middle"></td><td align="center" class="Botrule" valign="middle"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="middle"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="top"></td><td align="center" class="Botrule" valign="top"><span class="Bold">n (%)</span></td><td align="center" class="Botrule" valign="top"><span class="Bold">n (%)</span></td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule" valign="middle"><span class="Bold">Day 8</span></td><td align="center" class="Botrule" valign="middle">131 (80%) </td><td align="center" class="Botrule" valign="middle">36 (43%) </td><td align="center" class="Botrule Rrule" valign="middle">37% (24%, 49%) </td><td align="center" class="Botrule" valign="middle"></td><td align="center" class="Botrule" valign="middle">124 (77%) </td><td align="center" class="Botrule" valign="middle">47 (59%) </td><td align="center" class="Botrule Rrule" valign="middle">18% (6%, 31%) </td><td align="center" class="Botrule" valign="middle"></td><td align="center" class="Botrule" valign="middle">172 (80%) </td><td align="center" class="Botrule" valign="middle">136 (61%) </td><td align="center" class="Botrule Rrule" valign="middle">18% (10%, 27%) </td> </tr> </tbody> </table></div>

In three randomized, multicenter, double-masked, parallel group, vehicle-controlled efficacy trials, patients received DEXTENZA or its vehicle utilizing a repeat conjunctival allergen challenge model (NCT02445326, NCT02988882, NCT04050865). In all three trials, DEXTENZA resulted in lower mean ocular itching scores compared with the vehicle group at all time points throughout the one-month duration of the study. In two of the three studies, a higher proportion of patients had statistically significant reductions in ocular itching on Day 8, at 3 minutes, 5 minutes and 7 minutes post-challenge in the DEXTENZA group than in the vehicle group. Results are shown in Table 3.

<div class="scrollingtable"><table width="100%"> <caption> <span>Table 3: Reduction in Ocular Itching </span> </caption> <col align="left" width="6.570%"/> <col align="left" width="6.616%"/> <col align="left" width="9.093%"/> <col align="left" width="6.616%"/> <col align="left" width="12.924%"/> <col align="left" width="2.192%"/> <col align="left" width="7.831%"/> <col align="left" width="6.200%"/> <col align="left" width="12.193%"/> <col align="left" width="2.477%"/> <col align="left" width="8.270%"/> <col align="left" width="6.616%"/> <col align="left" width="12.401%"/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Toprule" valign="middle"></td><td align="center" class="Botrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="middle"><span class="Bold">Study 1</span></td><td align="center" class="Botrule Toprule" valign="middle"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="middle"><span class="Bold">Study 2</span></td><td align="center" class="Botrule Toprule" valign="top"></td><td align="center" class="Botrule Rrule Toprule" colspan="3" valign="top"><span class="Bold">Study 3</span></td> </tr> <tr> <td align="center" class="Lrule" valign="middle"></td><td align="center" valign="top"></td><td align="center" valign="middle"><span class="Bold">Dextenza</span> <br/> <span class="Bold">(N=35)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=38)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span></td><td align="center" valign="middle"></td><td align="center" valign="middle"><span class="Bold">Dextenza</span> <br/> <span class="Bold">(N=44)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=42)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span> <br/> </td><td align="center" valign="middle"></td><td align="center" valign="middle"><span class="Bold">Dextenza</span> <br/> <span class="Bold">(N=48)</span></td><td align="center" valign="middle"><span class="Bold">Vehicle</span> <br/> <span class="Bold">(N=48)</span></td><td align="center" class="Botrule Rrule" rowspan="2" valign="middle"><span class="Bold">Difference</span> <br/> <span class="Bold">(95% CI)</span> <br/> </td> </tr> <tr> <td align="center" class="Botrule Lrule" valign="middle"><span class="Bold">Visit</span></td><td align="center" class="Botrule" valign="top"><span class="Bold">Time Point</span></td><td align="center" class="Botrule" colspan="2" valign="middle"><span class="Bold">Least Square Means</span></td><td align="center" class="Botrule" valign="middle"></td><td align="center" class="Botrule" colspan="2" valign="middle"><span class="Bold">Least Square Means</span></td><td align="center" class="Botrule" valign="top"></td><td align="center" class="Botrule" colspan="2" valign="middle"><span class="Bold">Least Square Means</span></td> </tr> <tr> <td align="center" class="Botrule Lrule" rowspan="3" valign="middle"><span class="Bold">Day 8</span></td><td align="center" valign="top">3 min </td><td align="center" class="Rrule" valign="middle">1.9 </td><td align="center" class="Rrule" valign="middle">2.7 </td><td align="center" class="Rrule" valign="middle">-0.7 (-1.2, -0.3) </td><td align="center" class="Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle">2.1 </td><td align="center" class="Rrule" valign="middle">2.3 </td><td align="center" class="Rrule" valign="middle">-0.2 (-0.7, 0.3) </td><td align="center" class="Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle">1.8 </td><td align="center" class="Rrule" valign="middle">2.7 </td><td align="center" class="Rrule" valign="middle">-0.9 (-1.2, -0.4) </td> </tr> <tr> <td align="center" valign="top">5 min </td><td align="center" class="Rrule" valign="middle">2.1 </td><td align="center" class="Rrule" valign="middle">2.8 </td><td align="center" class="Rrule" valign="middle">-0.7 (-1.2, -0.3) </td><td align="center" class="Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle">2.1 </td><td align="center" class="Rrule" valign="middle">2.3 </td><td align="center" class="Rrule" valign="middle">-0.2 (-0.8, 0.3) </td><td align="center" class="Rrule" valign="middle"></td><td align="center" class="Rrule" valign="middle">1.8 </td><td align="center" class="Rrule" valign="middle">2.7 </td><td align="center" class="Rrule" valign="middle">-1.0 (-1.4, -0.6) </td> </tr> <tr class="Last"> <td align="center" class="Botrule" valign="top">7 min </td><td align="center" class="Botrule Rrule" valign="middle">1.9 </td><td align="center" class="Botrule Rrule" valign="middle">2.7 </td><td align="center" class="Botrule Rrule" valign="middle">-0.8 (-1.2, -0.4) </td><td align="center" class="Botrule Rrule" valign="middle"></td><td align="center" class="Botrule Rrule" valign="middle">2.1 </td><td align="center" class="Botrule Rrule" valign="middle">2.4 </td><td align="center" class="Botrule Rrule" valign="middle">-0.3 (-0.8, 0.3) </td><td align="center" class="Botrule Rrule" valign="middle"></td><td align="center" class="Botrule Rrule" valign="middle">1.7 </td><td align="center" class="Botrule Rrule" valign="middle">2.7 </td><td align="center" class="Botrule Rrule" valign="middle">-1.0 (-1.4, -0.6) </td> </tr> </tbody> </table></div>

Storage: Store refrigerated, between 2°C and 8°C (36°F and 46°F). Do not freeze. Protect from light, keep in package until use.

Advise patients to consult their eye care professional, if pain, redness, or itching develops.

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Ocular Therapeutix, Inc.Bedford, MA 01730 USA

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US Patent Nos.: 8,409,606; 8,563,027, 11,458041, 12,144,889, 12,150,896

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Principal Display Panel – Dextenza 1 ct Box Label

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NDC 70382-204-01

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0.4 mg insert

{ "type": "p", "children": [], "text": "\n0.4 mg insert\n" }

1 insert

{ "type": "p", "children": [], "text": "\n1 insert\n" }

Dextenza ®

{ "type": "p", "children": [], "text": "\nDextenza\n®\n" }

(dexamethasone ophthalmic insert) 0.4mg

{ "type": "p", "children": [], "text": "\n(dexamethasone ophthalmic insert) 0.4mg\n" }

for intracanalicular use

{ "type": "p", "children": [], "text": "\nfor intracanalicular use\n" }

Rx only

{ "type": "p", "children": [], "text": "Rx only\n" }

Ocular

{ "type": "p", "children": [], "text": "\nOcular\n" }

Therapeutix™

{ "type": "p", "children": [], "text": "Therapeutix™\n" }

Principal Display Panel – Dextenza 10 ct Box Label

{ "type": "p", "children": [], "text": "\nPrincipal Display Panel – Dextenza 10 ct Box Label\n" }

NDC 70382-204-10

{ "type": "p", "children": [], "text": "NDC 70382-204-10\n" }

0.4 mg insert

{ "type": "p", "children": [], "text": "\n0.4 mg insert\n" }

10 inserts

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Dextenza ®

{ "type": "p", "children": [], "text": "\nDextenza\n®\n" }

(dexamethasone ophthalmic insert) 0.4mg

{ "type": "p", "children": [], "text": "\n(dexamethasone ophthalmic insert) 0.4mg\n" }

for intracanalicular use

{ "type": "p", "children": [], "text": "\nfor intracanalicular use\n" }

Rx only

{ "type": "p", "children": [], "text": "Rx only\n" }

Ocular

{ "type": "p", "children": [], "text": "\nOcular\n" }

Therapeutix™

{ "type": "p", "children": [], "text": "Therapeutix™\n" }

Principal Display Panel – Dextenza Sample 1 ct Box Label

{ "type": "p", "children": [], "text": "\nPrincipal Display Panel – Dextenza Sample 1 ct Box Label\n" }

NDC 70382-204-99

{ "type": "p", "children": [], "text": "NDC 70382-204-99\n" }

0.4 mg insert

{ "type": "p", "children": [], "text": "\n0.4 mg insert\n" }

1 inserts

{ "type": "p", "children": [], "text": "\n1 inserts\n" }

Dextenza ®

{ "type": "p", "children": [], "text": "\nDextenza\n®\n" }

(dexamethasone ophthalmic insert) 0.4mg

{ "type": "p", "children": [], "text": "\n(dexamethasone ophthalmic insert) 0.4mg\n" }

for intracanalicular use

{ "type": "p", "children": [], "text": "\nfor intracanalicular use\n" }

Rx only

{ "type": "p", "children": [], "text": "Rx only\n" }

SAMPLE

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Not for resale.

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US Patent Nos.

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7,648,713 8,409,606 8,563,027 9,254,267

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Ocular

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Therapeutix™

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Principal Display Panel – Dextenza Pouch Label

{ "type": "p", "children": [], "text": "\nPrincipal Display Panel – Dextenza Pouch Label\n" }

Dextenza ®

{ "type": "p", "children": [], "text": "\nDextenza\n®\n" }

(dexamethasone ophthalmic insert) 0.4mg

{ "type": "p", "children": [], "text": "\n(dexamethasone ophthalmic insert) 0.4mg\n" }

for intracanalicular use

{ "type": "p", "children": [], "text": "\nfor intracanalicular use\n" }

Ocular Therapeutix, Inc.

{ "type": "p", "children": [], "text": "Ocular Therapeutix, Inc.\n" }

Bedford, MA 01730 USA

{ "type": "p", "children": [], "text": "Bedford, MA 01730 USA\n" }

NDC 70382-204-88

{ "type": "p", "children": [], "text": "NDC 70382-204-88\n" }

Rx only

{ "type": "p", "children": [], "text": "Rx only\n" }

LOT:

{ "type": "p", "children": [], "text": "\nLOT:\n" }

EXP DATE:

{ "type": "p", "children": [], "text": "\nEXP DATE:\n" }

DIRECTIONS FOR USE: See enclosed packageinsert. Do not use if pouch has been damagedor broken. DEXTENZA is intended for single dose only.

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CONTENTS: One DEXTENZA insert in foam carrier.

{ "type": "p", "children": [], "text": "\nCONTENTS: One DEXTENZA insert in foam carrier.\n" }

STORAGE: Refrigerate between 2 ° C - 8 ° C(36° F - 46° F). Do not freeze. Protect from light,keep in package until use.

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STERILE: Do not re-sterilize.

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PCR-780-12173

{ "type": "p", "children": [], "text": "PCR-780-12173\n" }

HEMADY is indicated in combination with other anti-myeloma products for the treatment of adults with multiple myeloma (MM).

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The recommended dosage of HEMADY is 20 mg or 40 mg, orally, once daily, on specific days depending on the treatment regimen. Refer to the Prescribing Information of the other anti-myeloma products used in combination with HEMADY for specific HEMADY dosing. HEMADY can be administered with or without food.

Dose-reduction for HEMADY is recommended for elderly patients, due to increased toxicity in these patients. Refer to the Prescribing Information of the other anti-myeloma products used as part of a combination regimen with HEMADY, for dosing recommendations in elderly patients.

Tablets: 20 mg white, round, biconvex tablet embossed with “20” on one side.

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HEMADY is contraindicated in patients with:

{ "type": "p", "children": [], "text": "HEMADY is contraindicated in patients with:" }

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{ "type": "ul", "children": [ "Systemic fungal infections. Corticosteroids may exacerbate systemic fungal infections [see Warnings and Precautions (5.2)].\n" ], "text": "" }

Corticosteroids , such as HEMADY, can cause serious and life-threatening alterations in endocrine function, especially with chronic use. Monitor patients receiving HEMADY for adrenal insufficiency after corticosteroid withdrawal and Cushing’s syndrome and hyperglycemia while receiving corticosteroids. In addition, patients with hypopituitarism, primary adrenal insufficiency, or congenital adrenal hyperplasia, altered thyroid function, or pheochromocytoma may be at risk for adverse endocrine events.

Risk of Adrenal Insufficiency Following Corticosteroid Withdrawal

Corticosteroids can produce reversible hypothalamic-pituitary adrenal (HPA) axis suppression, with the potential for the development of secondary adrenal insufficiency after withdrawal of corticosteroid treatment. Acute adrenal insufficiency can occur if glucocorticoids are withdrawn abruptly and can be fatal. The degree and duration of adrenocortical insufficiently produced is variable among patients and depends on the dose, frequency, and duration of glucocorticoid therapy. The risk may be reduced by gradually tapering the corticosteroid dose when withdrawing treatment. This insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, corticosteroid therapy should be reinstituted. For patients already taking corticosteroids during times of stress, the dosage may have to be increased.

A steroid “withdrawal syndrome”, seemingly unrelated to adrenocortical insufficiency, may also occur following abrupt discontinuance of corticosteroids. This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, and/or weight loss. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels.

Cushing’s Syndrome

Cushing’s syndrome (hypercortisolism) may occur with prolonged exposure to exogenous corticosteroids, including HEMADY. Symptoms include hypertension, truncal obesity and thinning of the limbs, purple striae, facial rounding, facial plethora, muscle weakness, easy and frequent bruising with thin fragile skin, posterior neck fat deposition, osteopenia, acne, amenorrhea, hirsutism and psychiatric abnormalities. Using the lowest dose of corticosteroid for the shortest duration possible may reduce the risk.

Hyperglycemia

Corticosteroids can increase blood glucose, worsen pre-existing diabetes, and predispose those on long-term therapy to diabetes mellitus, and may reduce the effect of the antidiabetic drugs. Monitor blood glucose at regular intervals. For patients with hyperglycemia, anti-diabetic treatment should be initiated or adjusted accordingly.

Considerations for Use in Patients with Altered Thyroid Function

Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. Changes in thyroid status of the patient may necessitate a dose adjustment of the corticosteroid. When concomitant administration of corticosteroids and levothyroxine is required, administration of corticosteroid should precede the initiation of levothyroxine therapy to avoid adrenal crisis.

Pheochromocytoma Crisis

There have been reports of pheochromocytoma crisis, which can be fatal, after administration of systemic corticosteroids. In patients with suspected or identified pheochromocytoma, consider the risk of pheochromocytoma crisis prior to administering HEMADY.

Corticosteroids, including HEMADY, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic.

Corticosteroids reduce resistance to new infections, exacerbate existing infections, increase the risk of disseminated infections, increase the risk of reactivation or exacerbation of latent infections, and mask some signs of infection. These infections can be severe, and at times fatal. The degree to which the dose, route, and duration of corticosteroid administration correlates with the specific risks of infection is not well characterized; however, the rate of occurrence of infectious complications increases with increasing doses of corticosteroids.

Monitor for the development of infection and consider withdrawal of HEMADY or reduction of the dose of corticosteroids as needed.

Varicella Zoster and Measles Viral Infections

Chickenpox caused by Varicella Zoster virus and measles can have a serious or even fatal course in non-immune children or adult on corticosteroids, including HEMADY. In patients who have not had these diseases, particular care should be taken to avoid exposure. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated. If a patient is exposed to measles, prophylaxis with immune globulin (IG) may be indicated. If chickenpox develops, treatment with antiviral agents may be considered.

Hepatitis B Virus Reactivation

Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers undergoing treatment with immunosuppressive drugs including corticosteroids. Reactivation can also occur in patients who appear to have resolved hepatitis B infection.

Fungal Infections

HEMADY is contraindicated in patients with systemic fungal infections. Corticosteroids may exacerbate systemic fungal infections. For patients on chronic corticosteroids who have developed systemic fungal infections, withdrawal of corticosteroids or reduction of the dose of corticosteroids is recommended.

The following infections have been reported during the use of corticosteroids to treat other conditions that HEMADY is not indicated for:

Amebiasis

Corticosteroids may activate latent amebiasis. Rule out latent amebiasis or active amebiasis before initiating corticosteroid therapy in any patient who has spent time in the tropics or any patient with unexplained diarrhea.

Strongyloides Infestation

In patients with known or suspected Strongyloides (threadworm) infestation, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia. For patients on HEMADY who develop known or suspected Strongyloides (threadworm) infection, withdrawal of corticosteroids or reduction of the dose of corticosteroids is recommended.

Tuberculosis

The use of corticosteroids in active tuberculosis should generally be limited to cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate anti-tuberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

Cerebral Malaria

Corticosteroids should not be used in cerebral malaria.

Corticosteroids, including HEMADY, can cause elevation of blood pressure, salt, and water retention, and increased excretion of potassium and calcium. Monitor blood pressure and assess for signs and symptoms of volume overload. Monitor serum potassium levels. Dietary salt restriction and potassium supplementation may be necessary. HEMADY should be used with caution in patients with congestive heart failure.

Literature reports suggest an association between use of corticosteroids and left ventricular free wall rupture after a recent myocardial infarction; therefore, therapy with HEMADY should be used with great caution in these patients.

Thromboembolism is a known adverse reaction of dexamethasone, including HEMADY. The risk for venous and arterial thromboembolism increases significantly when dexamethasone is administered with anti-myeloma products (e.g., thalidomide, lenalidomide, pomalidomide, and carfilzomib). Refer to the Prescribing Information of these anti-myeloma products for information about the risk of venous and arterial thromboembolism.

Consider thromboprophylaxis based on an assessment of individual patients’ underlying risk factors and the anti-myeloma drugs. Agents that also may increase the risk of thromboembolism should be used with caution in patients with multiple myeloma receiving combination regimens of HEMADY and anti-myeloma products.

Avoid administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids for the treatment of multiple myeloma. Killed or inactivated vaccines may be administered. However, the response to such vaccines cannot be predicted.

Use of corticosteroids may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses. Consider referral to an ophthalmologist for patients who develop ocular symptoms or use corticosteroid-containing products for more than 6 weeks. The use of oral corticosteroids is not recommended in the treatment of optic neuritis and may lead to an increase in the risk of new episodes. Corticosteroids should not be used in patients with active ocular herpes simplex.

Intraocular pressure may become elevated in some individuals. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.

There is an increased risk of gastrointestinal perforation during corticosteroid use in patients with certain gastrointestinal disorders such as active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis.

Signs of gastrointestinal perforation, such as peritoneal irritation, may be masked in patients receiving corticosteroids. Avoid corticosteroids if there is a possibility of impending perforation, abscess, or other pyrogenic infections; diverticulitis; fresh intestinal anastomoses; or active or latent peptic ulcer.

Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (i.e., decreasing absorption and increasing excretion) and inhibition of osteoblast function. This, together with a decrease in the protein matrix of the bone, secondary to an increase in protein catabolism, and reduced sex hormone production, may lead to inhibition of bone growth in pediatric patients and the development of osteoporosis at any age. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating HEMADY therapy.

An acute myopathy has been observed with the use of high doses of corticosteroids, most often occurring in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis), or in patients receiving concomitant therapy with neuromuscular blocking drugs (e.g., pancuronium). This acute myopathy is generalized, may involve ocular and respiratory muscles, and may result in quadriparesis. Elevation of creatine kinase may occur. Clinical improvement or recovery after stopping corticosteroids may require weeks to years.

Potentially severe psychiatric adverse reactions may occur with systemic corticosteroids, including HEMADY. Symptoms typically emerge within a few days or weeks of starting treatment and may be dose-related. These reactions may improve after either dose reduction or withdrawal, although pharmacologic treatment may be necessary. Psychiatric adverse reactions usually involve hypomanic or manic symptoms (e.g., euphoria, insomnia, mood swings) during treatment and depressive episodes after discontinuation of treatment. Inform patients and caregivers of the potential for behavioral and mood changes and encourage them to seek medical attention if psychiatric symptoms develop, especially if depressed mood or suicidal ideation is suspected.

Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy to treat other chronic conditions for which HEMADY is not indicated. Discontinuation of corticosteroids may result in clinical improvement.

HEMADY is administered in combination regimens with anti-myeloma products; please refer to the Prescribing Information of these products for additional information.

Based on findings from clinical and animal reproduction studies, corticosteroids, including HEMADY, can cause fetal harm when administered to a pregnant woman. Dexamethasone administration to pregnant women has resulted in adverse effects on fetal growth, skeletal development/osteogenesis and low birth weight with prolonged use. Dexamethasone administration to pregnant animals during organogenesis resulted in structural abnormalities, embryo-fetal mortality, functional impairment, and alterations to growth at doses equivalent to or below the recommended doses.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with HEMADY and for at least one month after the last dose [see Use in Specific Populations (8.1, 8.3)].

The following clinically significant adverse reactions are described in detail in other labeling sections:

{ "type": "p", "children": [], "text": "The following clinically significant adverse reactions are described in detail in other labeling sections:" }

{ "type": "ul", "children": [ "Hypersensitivity [see Contraindications (4)]\n", "Alterations in Endocrine Function [see Warnings and Precautions (5.1)]\n", "Immunosuppression and Increased Risk of Infections [see Warnings and Precautions (5.2)]\n", "Alterations in Cardiovascular/Renal Function [see Warnings and Precautions (5.3)]\n", "Venous and Arterial Thromboembolism [see Warnings and Precautions (5.4)]\n", "Vaccination [see Warnings and Precautions (5.5)]\n", "Ophthalmic Effects [see Warnings and Precautions (5.6)]\n", "Gastrointestinal Perforation [see Warnings and Precautions (5.7)]\n", "Osteoporosis [see Warnings and Precautions (5.8)]\n", "Myopathy [see Warnings and Precautions (5.9)]\n", "Behavioral and Mood Disturbances [see Warnings and Precautions (5.10)]\n", "Kaposi's Sarcoma [see Warnings and Precautions (5.11)]\n", "HEMADY in Combination with Anti-Myeloma Products [see Warnings and Precautions (5.12)]\n", "Embryo-Fetal Toxicity [see Warnings and Precautions (5.13)]\n" ], "text": "" }

The following adverse reactions associated with the use of HEMADY or other corticosteroids were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

{ "type": "p", "children": [], "text": "The following adverse reactions associated with the use of HEMADY or other corticosteroids were identified in clinical trials or postmarketing reports. Because these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure." }

Allergic reactions: Allergic or hypersensitivity reaction, anaphylaxis, angioedema.

{ "type": "p", "children": [], "text": "\nAllergic reactions: Allergic or hypersensitivity reaction, anaphylaxis, angioedema. " }

Blood and Lymphatic System Disorders: Leukocytosis.

{ "type": "p", "children": [], "text": "\nBlood and Lymphatic System Disorders: Leukocytosis." }

Cardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, edema, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis.

{ "type": "p", "children": [], "text": "\nCardiovascular: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, edema, pulmonary edema, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis." }

Dermatologic: Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, sterile abscess, rash, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria.

{ "type": "p", "children": [], "text": "\nDermatologic: Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scaly skin, ecchymoses and petechiae, edema, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, sterile abscess, rash, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria." }

Endocrine: Decreased carbohydrate and glucose tolerance, development of cushingoid state, hyperglycemia, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients.

{ "type": "p", "children": [], "text": "\nEndocrine: Decreased carbohydrate and glucose tolerance, development of cushingoid state, hyperglycemia, glycosuria, hirsutism, hypertrichosis, increased requirements for insulin or oral hypoglycemic agents in diabetes, manifestations of latent diabetes mellitus, menstrual irregularities, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), suppression of growth in pediatric patients. " }

Fluid and electrolyte disturbances: Fluid retention, hypokalemic alkalosis, potassium loss, sodium retention, increased urinary excretion of calcium, tumor lysis syndrome.

{ "type": "p", "children": [], "text": "\nFluid and electrolyte disturbances: Fluid retention, hypokalemic alkalosis, potassium loss, sodium retention, increased urinary excretion of calcium, tumor lysis syndrome. " }

Gastrointestinal: Abdominal distention, elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis.

{ "type": "p", "children": [], "text": "\nGastrointestinal: Abdominal distention, elevation in serum liver enzyme levels (usually reversible upon discontinuation), hepatomegaly, increased appetite, nausea, pancreatitis, peptic ulcer with possible perforation and hemorrhage, perforation of the small and large intestine (particularly in patients with inflammatory bowel disease), ulcerative esophagitis." }

Infection: Decreased resistance to infection, injection site infections following non-sterile administration.

{ "type": "p", "children": [], "text": "\nInfection: Decreased resistance to infection, injection site infections following non-sterile administration." }

Metabolic: Negative nitrogen balance due to protein catabolism.

{ "type": "p", "children": [], "text": "\nMetabolic: Negative nitrogen balance due to protein catabolism. " }

Musculoskeletal: Osteonecrosis of femoral and humeral heads, Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures.

{ "type": "p", "children": [], "text": "\nMusculoskeletal: Osteonecrosis of femoral and humeral heads, Charcot-like arthropathy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, steroid myopathy, tendon rupture, vertebral compression fractures." }

Neurological: Convulsions, epidural lipomatosis, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, neuritis, neuropathy, paresthesia, vertigo.

{ "type": "p", "children": [], "text": "\nNeurological: Convulsions, epidural lipomatosis, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, neuritis, neuropathy, paresthesia, vertigo." }

Ophthalmic: Central serous chorioretinopathy, exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, vision blurred.

{ "type": "p", "children": [], "text": "\nOphthalmic: Central serous chorioretinopathy, exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, vision blurred. " }

Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.

{ "type": "p", "children": [], "text": "\nOther: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain." }

Psychiatric: Depression, emotional instability, euphoria, insomnia, mood swings, personality changes, psychosis.

{ "type": "p", "children": [], "text": "\nPsychiatric: Depression, emotional instability, euphoria, insomnia, mood swings, personality changes, psychosis." }

Reproductive: Alteration in motility and number of spermatozoa.

{ "type": "p", "children": [], "text": "\nReproductive: Alteration in motility and number of spermatozoa." }

Strong CYP3A4 inhibitors

Coadministration of strong and moderate CYP3A4 inhibitors increased dexamethasone exposure [see Clinical Pharmacology (12.3)], which may increase the risk of adverse reactions [see Warnings and Precautions (5) and Adverse Reactions (6)]. Avoid coadministration of strong CYP3A4 inhibitors or consider alternative medication that are not strong CYP3A4 inhibitors. If concomitant use of strong CYP3A4 inhibitors cannot be avoided, closely monitor for adverse drug reactions.

Strong CYP3A4 inducers

Coadministration of strong CYP3A4 inducers may decrease dexamethasone exposure [see Clinical Pharmacology (12.3)], which may result in loss of efficacy. Avoid coadministration of strong CYP3A4 inducers or consider alternative medication that are not CYP3A4 inducers. If concomitant use strong CYP3A4 inducers cannot be avoided, consider increasing the dose of HEMADY.

Cholestyramine

Cholestyramine may increase the clearance of corticosteroids and potentially decrease corticosteroid exposure. Avoid coadministration of cholestyramine and HEMADY and consider alternative agents.

Anticholinesterases

Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, anticholinesterase agents should be withdrawn at least 24 hours before initiating corticosteroid therapy.

Ephedrine

Ephedrine may decrease dexamethasone exposure. Decreased exposure may result in loss of efficacy. Consider increasing the dose of HEMADY when used concomitantly with ephedrine.

Estrogens, Including Oral Contraceptives

Estrogens may decrease the hepatic metabolism of certain corticosteroids and increase exposures, which may increase the risk of adverse reactions [see Warnings and Precautions (5) and Adverse Reactions (6)].

CYP3A4 Substrates

Coadministration of dexamethasone with drugs that are CYP3A4 substrates may decrease the concentration of these drugs. This may result in loss of efficacy of these drugs.

Oral Anticoagulants

Coadministration of anticoagulants with corticosteroids may reduce the response to anticoagulants [see Adverse Reactions (6)]. Frequently monitor coagulation indices to maintain the desired anticoagulant effect when administered with HEMADY.

Amphotericin B Injection and Potassium-Depleting Agents

Sodium retention with resultant edema and potassium loss may occur in patients receiving corticosteroids [see Warnings and Precautions (5.3), and Adverse Reactions (6)]. Closely monitor potassium levels when potassium-depleting agents are coadministered with HEMADY. In addition, there have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.

Antidiabetics

Corticosteroids, including HEMADY, may increase blood glucose concentrations [see Warnings and Precautions (5.1) and Adverse Reactions (6)]. Consider adjusting the dose of antidiabetic agents, as necessary, when coadministered with HEMADY.

Isoniazid

Serum concentrations of isoniazid may be decreased with corticosteroids.

Cyclosporine

Increased activity of both cyclosporine and corticosteroids may occur when the two are used concurrently. Convulsions have been reported with this concurrent use.

Digitalis Glycosides

Patients on digitalis glycosides may be at increased risk of arrhythmias due to hypokalemia [see Warnings and Precautions (5.3) and Adverse Reactions (6)].

Nonsteroidal Anti-Inflammatory Agents (NSAIDS)

Concomitant use of aspirin (or other nonsteroidal anti-inflammatory agents) and corticosteroids increases the risk of gastrointestinal side effects [see Warnings and Precautions (5.7) and Adverse Reactions (6)]. The clearance of salicylates may be increased with concurrent use of corticosteroids. Monitor for toxicity when aspirin is used in conjunction with HEMADY in hypoprothrombinemia.

Phenytoin

In post-marketing experience, there have been reports of both increases and decreases in phenytoin levels with dexamethasone coadministration, leading to alterations in seizure control.

Vaccines

Patients on corticosteroid therapy may exhibit a diminished response to toxoids and live or inactivated vaccines due to inhibition of antibody response. Corticosteroids may also potentiate the replication of some organisms contained in live attenuated vaccines. If possible, defer routine administration of vaccines or toxoids until HEMADY therapy is discontinued [see Warnings and Precautions (5.5)].

Concomitant Therapies that May Increase the Risk of Thromboembolism

Erythropoietic agents, or other agents that may increase the risk of thromboembolism, such as estrogen containing therapies, coadministered with HEMADY may increase the risk of thromboembolism. Monitor for risk of thromboembolism in patients with MM receiving anti-myeloma products with HEMADY [see Warnings and Precautions (5.4)].

Thalidomide

Toxic epidermal necrolysis has been reported with concomitant use of thalidomide. Closely monitor for toxicity when thalidomide is coadministered with HEMADY.

Skin Tests

Corticosteroids may suppress reactions to skin tests.

Risk Summary

Corticosteroids, including HEMADY, readily cross the placenta. Adverse developmental outcomes including orofacial clefts (cleft lip with or without cleft palate), intrauterine growth restriction, and decreased birth weight have been reported with maternal use of corticosteroids, including HEMADY, during pregnancy. In animal developmental and reproductive toxicology studies administration of corticosteroids to pregnant animals during organogenesis resulted in structural abnormalities, embryo-fetal mortality, functional impairment, and alterations to growth at doses equivalent to or below the recommended doses (see Data).

Advise pregnant women of the potential risk to a fetus.

HEMADY is administered in combination with anti-myeloma products that can cause embryo-fetal harm and are contraindicated for use in pregnancy. Refer to the Prescribing Information of the other anti-myeloma products used in combination with HEMADY for additional information.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Data

Human Data

HEMADY should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Multiple courses of antenatal dexamethasone had been associated with reduced birth weight, susceptibility to infections, and increase blood glucose level in the newborns. Neonatal hypoglycemia was also reported. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Animal Data

In pregnant animals administered dexamethasone during organogenesis, doses equivalent to or below the recommended human dose have caused adverse developmental outcomes including structural abnormalities (cleft palate), alterations to growth (growth restrictions including reduced bone lengths and fetal weights), functional impairment (neurodevelopmental and metabolic effects), and embryo-fetal mortality (reduced number of embryonic implantations and fewer live fetuses).

Risk Summary

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Advise women not to breastfeed during treatment and for 2 weeks after the last dose.

Pregnancy Testing

Pregnancy testing is recommended for females of reproductive potential prior to initiating HEMADY [see Use in Specific Populations (8.1)].

HEMADY is used in combination with other anti-myeloma products that require pregnancy testing in females of reproductive potential. Refer to the Prescribing Information for the products used in combination with HEMADY.

Contraception

Advise patients of reproductive potential to use effective contraception during treatment with HEMADY and for at least one month following the final dose of HEMADY. HEMADY is used in combination with other anti-myeloma products that require contraception in females and males of reproductive potential. Refer to the Prescribing Information for the products used in combination with HEMADY.

Infertility

Males

Steroids may increase or decrease motility and number of spermatozoa in some patients. In animals, dexamethasone affects male spermatogenesis [see Nonclinical Toxicology (13.1)].

Safety and effectiveness in pediatric patients have not been established.

No overall differences in safety or effectiveness were observed between elderly subjects and younger subjects, and other reported clinical experience with dexamethasone has not identified differences in responses between the elderly and younger patients. However, the incidence of corticosteroid-induced adverse reactions may be increased in geriatric patients and are dose-related.

Osteoporosis is the most frequently encountered complication, which occurs at a higher incidence rate in corticosteroid-treated geriatric patients as compared to younger populations and in age-matched controls. Losses of bone mineral density appear to be greatest early on in the course of treatment and may recover over time after steroid withdrawal or use of lower doses. Higher doses increase the relative risk of both vertebral and nonvertebral fractures, even in the presence of higher bone density compared to patients with involution osteoporosis. Perform routine screening of geriatric patients, including regular assessments of bone mineral density and institution of fracture prevention strategies, along with regular review of the dose of and need for continued dexamethasone therapy [see Warnings and Precautions (5.8)].

HEMADY is used in combination with other anti-myeloma products. Refer to the Prescribing Information of the other anti-myeloma products used as part of a combination regimen with HEMADY, for information on the use of those products in elderly patients.

Treatment of overdosage is by supportive and symptomatic therapy. In the case of acute overdosage, according to the patient’s condition, supportive therapy may include gastric lavage or induced vomiting.

{ "type": "p", "children": [], "text": "Treatment of overdosage is by supportive and symptomatic therapy. In the case of acute overdosage, according to the patient’s condition, supportive therapy may include gastric lavage or induced vomiting." }

HEMADY (dexamethasone, USP) is an anti-inflammatory, 9-fluoro-glucocorticoid. The chemical name is 9-fluoro-11β,17,21trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. The molecular weight is 392.47 g/mol. The molecular formula is C22H29FO5. The structural formula is: 

{ "type": "p", "children": [], "text": "HEMADY (dexamethasone, USP) is an anti-inflammatory, 9-fluoro-glucocorticoid. The chemical name is 9-fluoro-11β,17,21trihydroxy-16α-methylpregna-1,4-diene-3,20-dione. The molecular weight is 392.47 g/mol. The molecular formula is C22H29FO5. The structural formula is:  " }

Dexamethasone is a white to practically white, odorless, crystalline powder. It is stable in air. It is practically insoluble in water. HEMADY for oral administration is available as an immediate-release tablet in a strength of 20 mg. Each tablet contains dexamethasone USP and the following inactive ingredients: corn starch NF, lactose monohydrate NF, magnesium stearate NF, povidone NF, and sodium starch glycolate NF.

{ "type": "p", "children": [], "text": "Dexamethasone is a white to practically white, odorless, crystalline powder. It is stable in air. It is practically insoluble in water.\n HEMADY for oral administration is available as an immediate-release tablet in a strength of 20 mg. Each tablet contains dexamethasone USP and the following inactive ingredients: corn starch NF, lactose monohydrate NF, magnesium stearate NF, povidone NF, and sodium starch glycolate NF." }

Dexamethasone is a corticosteroid with anti-inflammatory effects and low mineralocorticoid activity. The precise mechanism of action in multiple myeloma is unknown. Dexamethasone induces apoptosis of multiple myeloma cells.

Following oral administration of a single dose of dexamethasone tablet to healthy subjects, the decrease in mean baseline cortisol concentration was maximal by 12 hours post-dose, with mean cortisol concentrations returning to near baseline approximately 3 days after drug administration.

The pharmacokinetics of oral dexamethasone were dose proportional between single dose of 0.5 to 40 mg. Following a single HEMADY dose of 20 mg, the geometric mean (coefficient of variation, %CV) dexamethasone peak concentrations (Cmax) was 247 ng/mL (31%) and area under the curve over time to infinity (AUCinf) was 1271 ng.hr/mL (31%) in subjects.

Absorption

Following 20 mg dose of HEMADY, dexamethasone median time to peak concentrations (Tmax) was 1 hour (range: 0.5 to 4 hours).

Effect of Food

A high-fat, high-calorie (total 800-1000 calories: approximately 60% from fat, 25% from carbohydrate and 15% from protein) meal had no effect on AUCinf and decreased Cmax by 23% of a single 20 mg dose of HEMADY.

Distribution

Dexamethasone is about 77% bound to human plasma proteins in vitro.

Elimination

The mean terminal half-life (coefficient of variation) of dexamethasone is 4 hours (18%) and oral clearance (CL/F) was 15.7 L/hr following a single dose of HEMADY.

Metabolism 

Dexamethasone is metabolized by CYP3A4.

Excretion 

Renal excretion of dexamethasone is less than 10% of total body clearance. Less than 10% of dexamethasone is excreted in the urine.

Specific Populations

The effect of baseline renal and hepatic impairment on the pharmacokinetics of dexamethasone has not been studied.

Drug Interactions Studies

Effect of Strong and Moderate CYP3A4 Inhibitors

Coadministration of itraconazole (strong CYP3A4 inhibitor: 200 mg once daily x 4 days) with a single dose of oral dexamethasone (4.5 mg) increased dexamethasone AUCinf by 3.7-fold [see Drug Interactions (7.1)].

Coadministration of aprepitant (moderate CYP3A4 inhibitor: 125 mg on Day 1, and 80 mg once daily on Days 2 to 5) with oral dexamethasone (20 mg on Day 1, and 8 mg once daily on Day 2-5) increased dexamethasone AUCinf by 2.2 -fold on Day 1 and 5 [see Drug Interactions (7.1)].

Effects of Other Anti-Myeloma Products

Coadministration of thalidomide, lenalidomide, pomalidomide, ixazomib, bortezomib or carfilzomib with dexamethasone is not expected to affect the pharmacokinetics of dexamethasone.

Effect on Other Anti-Myeloma Products 

Coadministration of dexamethasone had no effect on the mean AUCinf of lenalidomide, pomalidomide, ixazomib, and bortezomib.

Coadministration of dexamethasone with carfilzomib or thalidomide is not expected to affect the pharmacokinetics of these drugs, as these drugs are not primarily metabolized by CYP3A4 in vitro.

For additional information on the drug interaction studies with dexamethasone and other anti-myeloma products, refer to the Prescribing Information of the other anti-myeloma products.

No adequate studies have been conducted in animals to determine whether corticosteroids have a potential for carcinogenesis.

Dexamethasone was tested for in vitro and in vivo genotoxic potential and was positive in the following assays: chromosomal aberrations and sister-chromatid exchanges in human lymphocytes, and micronuclei and sister-chromatid exchanges in mouse bone marrow. The Ames/Salmonella assay, with and without S9 mix, did not show an increase in His+ revertants.

Published literature identified reduced testicular spermatozoids and reduced spermatogenesis in male mice dosed intraperitoneally for 7 days at doses equivalent to the human dose based on a mg/m2 body surface area comparison.

How Supplied

{ "type": "p", "children": [], "text": "\nHow Supplied\n" }

20 mg tablet: white, round, biconvex tablets embossed "20" on one side.

{ "type": "p", "children": [], "text": "20 mg tablet: white, round, biconvex tablets embossed \"20\" on one side." }

NDC 72893-015-24: Bottle of 24,

{ "type": "p", "children": [], "text": "NDC 72893-015-24: Bottle of 24," }

NDC 72893-015-06: Bottle of 100

{ "type": "p", "children": [], "text": "NDC 72893-015-06: Bottle of 100" }

Storage

{ "type": "p", "children": [], "text": "\nStorage\n" }

Store at 20°C to 25°C (68°F to 77°F) excursions permitted 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant, child resistant container.

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F) excursions permitted 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant, child resistant container." }

Discuss the following with patients prior to treatment with HEMADY:

{ "type": "p", "children": [], "text": "Discuss the following with patients prior to treatment with HEMADY:" }

Administration

{ "type": "p", "children": [], "text": "\nAdministration\n" }

{ "type": "ul", "children": [ "HEMADY is administered as part of combination regimens with anti-myeloma products; instruct patients to take HEMADY exactly as prescribed in the Prescribing Information of the anti-myeloma products administered with HEMADY [see Dosage and Administration (2.1) and Warning and Precautions (5.12)]." ], "text": "" }

{ "type": "ul", "children": [ "Inform elderly patients regarding dose-reduction, if needed [see Dosage and Administration (2.2) and Use in Specific Populations (8.5)]." ], "text": "" }

{ "type": "ul", "children": [ "Warn patients to not stop taking HEMADY abruptly or without first checking with their healthcare providers as there may be a need for gradual dose reduction to decrease the risk of adrenal insufficiency [see Warnings and Precautions (5.1)]." ], "text": "" }

{ "type": "ul", "children": [ "HEMADY may be taken with or without food." ], "text": "" }

 Alterations in Endocrine Function Advise patients to inform any medical attendants that they are taking corticosteroids, as prolonged use may cause adrenal insufficiency, Cushing's syndrome and make patients dependent on corticosteroids. Instruct patients to notify their healthcare provider if they have diabetes, or thyroid gland problems as the dose of medications used to control these other conditions may need to be adjusted while they are taking HEMADY [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "  Alterations in Endocrine Function\n Advise patients to inform any medical attendants that they are taking corticosteroids, as prolonged use may cause adrenal insufficiency, Cushing's syndrome and make patients dependent on corticosteroids. Instruct patients to notify their healthcare provider if they have diabetes, or thyroid gland problems as the dose of medications used to control these other conditions may need to be adjusted while they are taking HEMADY [see Warnings and Precautions (5.1)]. " }

Advise the patient that, following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including myalgia, arthralgia, and malaise. Advise patients to not discontinue use of HEMADY abruptly or without medical supervision [see Warnings and Precautions (5.1)].

{ "type": "p", "children": [], "text": "Advise the patient that, following prolonged therapy, withdrawal of corticosteroids may result in symptoms of the corticosteroid withdrawal syndrome including myalgia, arthralgia, and malaise. Advise patients to not discontinue use of HEMADY abruptly or without medical supervision [see Warnings and Precautions (5.1)]." }

Immunosuppression and Increased Risk of Infections Advise patients that they are at increased risk of infection. Tell patients to inform their healthcare provider if they have had recent or ongoing infections or if they have recently received a vaccine. Medical advice should be sought immediately if the patient develops fever or other signs of infection. Patients should be made aware that some infections can potentially be severe and fatal [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "\nImmunosuppression and Increased Risk of Infections\n Advise patients that they are at increased risk of infection. Tell patients to inform their healthcare provider if they have had recent or ongoing infections or if they have recently received a vaccine. Medical advice should be sought immediately if the patient develops fever or other signs of infection. Patients should be made aware that some infections can potentially be severe and fatal [see Warnings and Precautions (5.2)]." }

Warn patients who are on corticosteroids to avoid exposure to chickenpox or measles and to alert their healthcare provider immediately if they are exposed [see Warnings and Precautions (5.2)].

{ "type": "p", "children": [], "text": "Warn patients who are on corticosteroids to avoid exposure to chickenpox or measles and to alert their healthcare provider immediately if they are exposed [see Warnings and Precautions (5.2)]." }

Alterations in Cardiovascular/Renal Function Inform patients that HEMADY can cause an increase in blood pressure and water retention. If this occurs, dietary salt restriction and potassium supplementation may be needed [see Warnings and Precautions (5.3)].

{ "type": "p", "children": [], "text": "\nAlterations in Cardiovascular/Renal Function \n Inform patients that HEMADY can cause an increase in blood pressure and water retention. If this occurs, dietary salt restriction and potassium supplementation may be needed [see Warnings and Precautions (5.3)]." }

Venous and Arterial Thromboembolism Inform patients of the potential risk of developing venous and arterial thromboembolism and discuss the need for appropriate prophylactic treatment [see Warnings and Precautions (5.4)].

{ "type": "p", "children": [], "text": "\nVenous and Arterial Thromboembolism\n Inform patients of the potential risk of developing venous and arterial thromboembolism and discuss the need for appropriate prophylactic treatment [see Warnings and Precautions (5.4)]." }

Vaccination Inform patients that they may receive concurrent vaccinations with use of HEMADY, except for live-attenuated or live vaccines [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "\nVaccination \n Inform patients that they may receive concurrent vaccinations with use of HEMADY, except for live-attenuated or live vaccines [see Warnings and Precautions (5.5)]." }

Ophthalmic Effects Inform patients that HEMADY may cause cataracts or glaucoma and advise monitoring if corticosteroid therapy is continued for more than 6 weeks [see Warnings and Precautions (5.6)].

{ "type": "p", "children": [], "text": "\nOphthalmic Effects\n Inform patients that HEMADY may cause cataracts or glaucoma and advise monitoring if corticosteroid therapy is continued for more than 6 weeks [see Warnings and Precautions (5.6)]." }

Gastrointestinal Perforation HEMADY may increase the risk of developing gastrointestinal perforation. Advise patients to promptly seek medical attention if they develop unusually severe, persistent or worsening abdominal pain. Warn patients to avoid corticosteroids if there is a possibility of gastrointestinal perforation [see Warnings and Precautions (5.7)].

{ "type": "p", "children": [], "text": "\nGastrointestinal Perforation\n HEMADY may increase the risk of developing gastrointestinal perforation. Advise patients to promptly seek medical attention if they develop unusually severe, persistent or worsening abdominal pain. Warn patients to avoid corticosteroids if there is a possibility of gastrointestinal perforation [see Warnings and Precautions (5.7)]." }

Osteoporosis Advise patients about the risk of osteoporosis with prolonged use of HEMADY, which can predispose the patient to vertebral and long bone fractures [see Warnings and Precautions (5.8)].

{ "type": "p", "children": [], "text": "\nOsteoporosis\n Advise patients about the risk of osteoporosis with prolonged use of HEMADY, which can predispose the patient to vertebral and long bone fractures [see Warnings and Precautions (5.8)]." }

Myopathy Advise patients to contact their healthcare provider if they experience new or worsening symptoms of myopathy such as unexplained muscle pain, tenderness or weakness [see Warnings and Precautions (5.9)].

{ "type": "p", "children": [], "text": "\nMyopathy\n Advise patients to contact their healthcare provider if they experience new or worsening symptoms of myopathy such as unexplained muscle pain, tenderness or weakness [see Warnings and Precautions (5.9)]." }

Behavioral and Mood Disturbances Advise patients about the potential for severe behavioral and mood changes with HEMADY and encourage them to seek medical attention if psychiatric symptoms develop [see Warnings and Precautions (5.10)].

{ "type": "p", "children": [], "text": "\nBehavioral and Mood Disturbances\n Advise patients about the potential for severe behavioral and mood changes with HEMADY and encourage them to seek medical attention if psychiatric symptoms develop [see Warnings and Precautions (5.10)]." }

Kaposi’s Sarcoma Advise patients about the risk of Kaposi’s sarcoma in patients receiving corticosteroid therapy. Advise patients to discontinue HEMADY in case Kaposi’s sarcoma is diagnosed [see Warnings and Precautions (5.11)].

{ "type": "p", "children": [], "text": "\nKaposi’s Sarcoma \n Advise patients about the risk of Kaposi’s sarcoma in patients receiving corticosteroid therapy. Advise patients to discontinue HEMADY in case Kaposi’s sarcoma is diagnosed [see Warnings and Precautions (5.11)]. " }

HEMADY in Combination with Anti-Myeloma Products Advise patients about the risk of adverse reactions which may occur when HEMADY is taken in combination with anti-myeloma products. Inform patients of the possible adverse reactions that could occur with the prescribed combination regimen, as detailed in the Prescribing Information of these products [see Warnings and Precautions (5.12)].

{ "type": "p", "children": [], "text": "\nHEMADY in Combination with Anti-Myeloma Products \n Advise patients about the risk of adverse reactions which may occur when HEMADY is taken in combination with anti-myeloma products. Inform patients of the possible adverse reactions that could occur with the prescribed combination regimen, as detailed in the Prescribing Information of these products [see Warnings and Precautions (5.12)]. " }

Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus. Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with HEMADY [see Warnings and Precautions (5.13) and Use in Specific Populations (8.1)].

{ "type": "p", "children": [], "text": "\nEmbryo-Fetal Toxicity \n Advise females of reproductive potential of the potential risk to a fetus. Advise females to contact their healthcare provider if they become pregnant, or if pregnancy is suspected, during treatment with HEMADY [see Warnings and Precautions (5.13) and Use in Specific Populations (8.1)]." }

Drug Interactions Certain medications can cause an interaction with HEMADY. Advise patients to inform their healthcare provider of all the medicines the patient is taking, including over-the-counter medicines, dietary supplements, and herbal products. Inform patients that alternate therapy, dosage adjustment, and/or special test(s) may be needed during the treatment [see Drug Interactions (7.1, 7.2)].

{ "type": "p", "children": [], "text": "\nDrug Interactions \n Certain medications can cause an interaction with HEMADY. Advise patients to inform their healthcare provider of all the medicines the patient is taking, including over-the-counter medicines, dietary supplements, and herbal products. Inform patients that alternate therapy, dosage adjustment, and/or special test(s) may be needed during the treatment [see Drug Interactions (7.1, 7.2)]." }

Females and Males of Reproductive Potential Advise patients of reproductive potential to use effective contraception during treatment with HEMADY and for at least one month after the last dose [see Use in Specific Populations (8.3)].

{ "type": "p", "children": [], "text": "\nFemales and Males of Reproductive Potential\n Advise patients of reproductive potential to use effective contraception during treatment with HEMADY and for at least one month after the last dose [see Use in Specific Populations (8.3)]." }

Lactation Advise women not to breastfeed during treatment with HEMADY and for 2 weeks after the last dose [see Use in Specific Populations (8.2)].

{ "type": "p", "children": [], "text": "\nLactation \n Advise women not to breastfeed during treatment with HEMADY and for 2 weeks after the last dose [see Use in Specific Populations (8.2)]." }

Manufactured for: Dexcel Pharma Technologies Ltd Nahum Haftzadi 21, Givat Shaul Jerusalem, Israel 9548402

{ "type": "p", "children": [], "text": "Manufactured for: Dexcel Pharma Technologies Ltd Nahum Haftzadi 21, Givat Shaul Jerusalem, Israel 9548402" }

Distributed by: Acrotech Biopharma Inc East Windsor, NJ 08520

{ "type": "p", "children": [], "text": "Distributed by: Acrotech Biopharma Inc East Windsor, NJ 08520" }

Carton-24 Tablets-20 mg

{ "type": "p", "children": [], "text": "\nCarton-24 Tablets-20 mg\n" }

Carton-100 Tablets-20 mg

{ "type": "p", "children": [], "text": "\nCarton-100 Tablets-20 mg\n" }

 Label-24 Tablets-20 mg

{ "type": "p", "children": [], "text": "\n Label-24 Tablets-20 mg\n" }

Label-100 Tablets-20 mg

{ "type": "p", "children": [], "text": "\nLabel-100 Tablets-20 mg\n" }