|indication=macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO),macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), diabetic macular edema
|adverseReactions=<!--Black Box Warning-->
|adverseReactions=eye pain, redness of eye, blurred vision
OZURDEX® (dexamethasone intravitreal implant) is indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).
* Dosing Information
1.2 Posterior Segment Uveitis
OZURDEX® is indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye.
:* Dosage
1.3 Diabetic Macular Edema
OZURDEX® is indicated for the treatment of diabetic macular edema.
=====Dosage=====
2.1 General Dosing Information
For ophthalmic intravitreal injection.
=====Condition2=====
2.2 Administration
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.
* Dosing Information
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.
:* Dosage
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.
=====Condition3=====
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.
* Dosing Information
:* Dosage
=====Condition4=====
* Dosing Information
:* Dosage
<!--Off-Label Use and Dosage (Adult)-->
<!--Guideline-Supported Use (Adult)-->
|offLabelAdultGuideSupport======Condition1=====
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
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.
|offLabelAdultGuideSupport=
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Non–Guideline-Supported Use (Adult)-->
<!--Non–Guideline-Supported Use (Adult)-->
|offLabelAdultNoGuideSupport======Condition1=====
|offLabelAdultNoGuideSupport=
* Dosing Information
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> ions and Dosage-->
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in adult patients.
<!--Pediatric Indications and Dosage-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
<!--FDA-Labeled Indications and Dosage (Pediatric)-->
|fdaLIADPed======Condition1=====
|fdaLIADPed=
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
There is limited information regarding <i>FDA-Labeled Use</i> of {{PAGENAME}} in pediatric patients.
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<!--Guideline-Supported Use (Pediatric)-->
<!--Guideline-Supported Use (Pediatric)-->
|offLabelPedGuideSupport======Condition1=====
|offLabelPedGuideSupport=
* Developed by:
* Class of Recommendation:
* Strength of Evidence:
* Dosing Information
:* Dosage
=====Condition2=====
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
<!--Non–Guideline-Supported Use (Pediatric)-->
<!--Non–Guideline-Supported Use (Pediatric)-->
|offLabelPedNoGuideSupport======Condition1=====
|offLabelPedNoGuideSupport=
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
* Dosing Information
<!--Contraindications-->
|contraindications=* 2.1 General Dosing Information
For ophthalmic intravitreal injection.
:* Dosage
2.2 Administration
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.
=====Condition2=====
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.
There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of {{PAGENAME}} in pediatric patients.
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.
<!--Contraindications-->
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.
|contraindications=* Condition1
<!--Warnings-->
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 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)].
====Precautions====
5.2 Steroid-related Effects
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)].
* Description
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.
<!--Adverse Reactions-->
<!--Adverse Reactions-->
<!--Clinical Trials Experience-->
<!--Clinical Trials Experience-->
|clinicalTrials=There is limited information regarding <i>Clinical Trial Experience</i> of {{PAGENAME}} in the drug label.
|clinicalTrials=6.1 Clinical Studies Experience
Because clinical studies 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.
=====Body as a Whole=====
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):
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
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.
=====Cardiovascular=====
|postmarketing=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 (implant misplacement), device dislocation with or without corneal edema, endophthalmitis, hypotony of the eye (associated with vitreous leakage due to injection), and retinal detachment.
|drugInteractions=*
|FDAPregCat=C
|useInPregnancyFDA=* Risk Summary
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
There are no adequate and well-controlled studies with OZURDEX® in pregnant women. Animal reproduction
studies using topical ocular administration of dexamethasone were conducted in mice and rabbits. Cleft palate and embryofetal death in mice and malformations of the intestines and kidneys in rabbits were observed. OZURDEX® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Animal Data
Topical ocular administration of 0.15% dexamethasone (0.375 mg/kg/day) on gestational days 10 to 13 produced embryofetal lethality and a high incidence of cleft palate in mice. A dose of 0.375 mg/kg/day in the mouse is approximately 3 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 (0.13 mg/kg/day, on gestational day 6 followed by 0.20 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.
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Postmarketing Experience-->
|postmarketing=There is limited information regarding <i>Postmarketing Experience</i> of {{PAGENAME}} in the drug label.
=====Body as a Whole=====
=====Cardiovascular=====
=====Digestive=====
=====Endocrine=====
=====Hematologic and Lymphatic=====
=====Metabolic and Nutritional=====
=====Musculoskeletal=====
=====Neurologic=====
=====Respiratory=====
=====Skin and Hypersensitivy Reactions=====
=====Special Senses=====
=====Urogenital=====
=====Miscellaneous=====
<!--Drug Interactions-->
|drugInteractions=* Drug
:* Description
<!--Use in Specific Populations-->
|useInPregnancyFDA=* '''Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
|useInPregnancyAUS=* '''Australian Drug Evaluation Committee (ADEC) Pregnancy Category'''
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of {{PAGENAME}} in women who are pregnant.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInLaborDelivery=There is no FDA guidance on use of {{PAGENAME}} during labor and delivery.
|useInNursing=There is no FDA guidance on the use of {{PAGENAME}} with respect to nursing mothers.
|useInNursing=Systemically administered corticosteroids are present in human milk and can suppress growth and interfere with endogenous corticosteroid production. The systemic concentration of dexamethasone following intravitreal treatment with OZURDEX® is low [see Clinical Pharmacology (12.3)]. It is not known whether intravitreal treatment with OZURDEX® could result in sufficient systemic absorption to produce detectable quantities in human milk. Exercise caution when OZURDEX® is administered to a nursing woman.
|useInPed=There is no FDA guidance on the use of {{PAGENAME}} with respect to pediatric patients.
|useInPed=Safety and effectiveness of OZURDEX® in pediatric patients have not been established.
|useInGeri=There is no FDA guidance on the use of {{PAGENAME}} with respect to geriatric patients.
|useInGeri=Safety and effectiveness of OZURDEX® in pediatric patients have not been established.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInGender=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific gender populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
|useInRace=There is no FDA guidance on the use of {{PAGENAME}} with respect to specific racial populations.
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<!--Administration and Monitoring-->
<!--Administration and Monitoring-->
|administration=* Oral
|administration=* Intravitreal
|monitoring=* 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.
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
* Intravenous
<!--Overdosage-->
|monitoring=There is limited information regarding <i>Monitoring</i> of {{PAGENAME}} in the drug label.
|drugBox=<!--Mechanism of Action-->
|mechAction=* 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.
* Description
<!--Structure-->
|structure=* OZURDEX® is an intravitreal implant containing 0.7 mg (700 mcg) dexamethasone in the NOVADUR® solid polymer sustained-release drug delivery system. OZURDEX® is preloaded into a single-use, DDS® applicator to facilitate injection of the rod-shaped implant directly into the vitreous. The NOVADUR® system contains poly (D,L-lactide-co-glycolide) PLGA intravitreal polymer matrix without a preservative. The chemical name for dexamethasone is Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11β,16α)-. Its structural formula is:
<!--IV Compatibility-->
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
|IVCompat=There is limited information regarding <i>IV Compatibility</i> of {{PAGENAME}} in the drug label.
<!--Pharmacodynamics-->
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
<!--Pharmacokinetics-->
|PK=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.
<!--Nonclinical Toxicology-->
|nonClinToxic=13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No adequate studies in animals have been conducted to determine whether OZURDEX® (dexamethasone intravitreal implant) has the potential for carcinogenesis.
<!--Overdosage-->
Although no adequate studies have been conducted to determine the mutagenic potential of OZURDEX®, dexamethasone has been shown to have no mutagenic effects in bacterial and mammalian cells in vitro or in the in vivo mouse micronucleus test.
|overdose====Acute Overdose===
====Signs and Symptoms====
Adequate fertility studies have not been conducted in animals.
|clinicalStudies=Retinal Vein Occlusion
* Description
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.
====Management====
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):
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
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.
* Description
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.
===Chronic Overdose===
Posterior Segment Uveitis
There is limited information regarding <i>Chronic Overdose</i> of {{PAGENAME}} in the drug label.
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.
<!--Pharmacology-->
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.
<!--Drug box 2-->
Diabetic Macular Edema
|drugBox=<!--Mechanism of Action-->
|mechAction=*
<!--Structure-->
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.
|structure=*
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).
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
: [[File:{{PAGENAME}}01.png|thumb|none|600px|This image is provided by the National Library of Medicine.]]
<!--Pharmacodynamics-->
|howSupplied=* OZURDEX® (dexamethasone intravitreal implant) 0.7 mg is supplied in a foil pouch with 1 single-use plastic applicator, NDC 0023-3348-07.
|PD=There is limited information regarding <i>Pharmacodynamics</i> of {{PAGENAME}} in the drug label.
|storage=Store at 15°-30°C (59°-86°F).
|packLabel=[[File:XXXXX.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
[[File:XXXXX.png|thumb|none|400px|This image is provided by the National Library of Medicine.]]
|fdaPatientInfo=Steroid-related Effects
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.
Intravitreal Injection-related Effects
<!--Pharmacokinetics-->
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.
|PK=There is limited information regarding <i>Pharmacokinetics</i> of {{PAGENAME}} in the drug label.
<!--Nonclinical Toxicology-->
When to Seek Physician Advice
|nonClinToxic=There is limited information regarding <i>Nonclinical Toxicology</i> of {{PAGENAME}} in the drug label.
<!--Clinical Studies-->
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.
|clinicalStudies=There is limited information regarding <i>Clinical Studies</i> of {{PAGENAME}} in the drug label.
<!--How Supplied-->
Driving and Using Machines
|howSupplied=*
|packLabel=<!--Patient Counseling Information-->
|fdaPatientInfo=There is limited information regarding <i>Patient Counseling Information</i> of {{PAGENAME}} in the drug label.
<!--Precautions with Alcohol-->
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.
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
|alcohol=* Alcohol-{{PAGENAME}} interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
<!--Brand Names-->
<!--Brand Names-->
|brandNames=* ®<ref>{{Cite web | title = | url = }}</ref>
|brandNames=* OZURDEX®<ref>{{Cite web | title =OZURDEX - dexamethasone implant | url =http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4b204f44-6e8a-4d17-803c-268f0b04679f#section-9 }}</ref>
<!--Look-Alike Drug Names-->
<!--Look-Alike Drug Names-->
|lookAlike=* A® — B®<ref name="www.ismp.org">{{Cite web | last = | first = | title = http://www.ismp.org | url = http://www.ismp.org | publisher = | date = }}</ref>
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Overview
Dexamethasone implant is a steroid that is FDA approved for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO),macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO), diabetic macular edema. Common adverse reactions include eye pain, redness of eye, blurred vision.
Adult Indications and Dosage
FDA-Labeled Indications and Dosage (Adult)
Indication
1.1 Retinal Vein Occlusion
OZURDEX® (dexamethasone intravitreal implant) is indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).
1.2 Posterior Segment Uveitis
OZURDEX® is indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye.
1.3 Diabetic Macular Edema
OZURDEX® is indicated for the treatment of diabetic macular edema.
Dosage
2.1 General Dosing Information
For ophthalmic intravitreal injection.
2.2 Administration
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.
Off-Label Use and Dosage (Adult)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Dexamethasone implant in adult patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use ions and Dosage-->
Pediatric Indications and Dosage
FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Dexamethasone implant in pediatric patients.
Off-Label Use and Dosage (Pediatric)
Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Dexamethasone implant in pediatric patients.
Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Dexamethasone implant in pediatric patients.
Contraindications
2.1 General Dosing Information
For ophthalmic intravitreal injection.
2.2 Administration
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.
Warnings
5.1 Intravitreal Injection-related Effects
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)].
5.2 Steroid-related Effects
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.
Adverse Reactions
Clinical Trials Experience
6.1 Clinical Studies Experience
Because clinical studies 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):
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.
Postmarketing Experience
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 (implant misplacement), device dislocation with or without corneal edema, endophthalmitis, hypotony of the eye (associated with vitreous leakage due to injection), and retinal detachment.
There are no adequate and well-controlled studies with OZURDEX® in pregnant women. Animal reproduction
studies using topical ocular administration of dexamethasone were conducted in mice and rabbits. Cleft palate and embryofetal death in mice and malformations of the intestines and kidneys in rabbits were observed. OZURDEX® should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Animal Data
Topical ocular administration of 0.15% dexamethasone (0.375 mg/kg/day) on gestational days 10 to 13 produced embryofetal lethality and a high incidence of cleft palate in mice. A dose of 0.375 mg/kg/day in the mouse is approximately 3 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 (0.13 mg/kg/day, on gestational day 6 followed by 0.20 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.
Pregnancy Category (AUS):
Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Dexamethasone implant in women who are pregnant.
Labor and Delivery
There is no FDA guidance on use of Dexamethasone implant during labor and delivery.
Nursing Mothers
Systemically administered corticosteroids are present in human milk and can suppress growth and interfere with endogenous corticosteroid production. The systemic concentration of dexamethasone following intravitreal treatment with OZURDEX® is low [see Clinical Pharmacology (12.3)]. It is not known whether intravitreal treatment with OZURDEX® could result in sufficient systemic absorption to produce detectable quantities in human milk. Exercise caution when OZURDEX® is administered to a nursing woman.
Pediatric Use
Safety and effectiveness of OZURDEX® in pediatric patients have not been established.
Geriatic Use
Safety and effectiveness of OZURDEX® in pediatric patients have not been established.
Gender
There is no FDA guidance on the use of Dexamethasone implant with respect to specific gender populations.
Race
There is no FDA guidance on the use of Dexamethasone implant with respect to specific racial populations.
Renal Impairment
There is no FDA guidance on the use of Dexamethasone implant in patients with renal impairment.
Hepatic Impairment
There is no FDA guidance on the use of Dexamethasone implant in patients with hepatic impairment.
Females of Reproductive Potential and Males
There is no FDA guidance on the use of Dexamethasone implant in women of reproductive potentials and males.
Immunocompromised Patients
There is no FDA guidance one the use of Dexamethasone implant in patients who are immunocompromised.
Administration and Monitoring
Administration
Intravitreal
Monitoring
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.
IV Compatibility
There is limited information regarding IV Compatibility of Dexamethasone implant in the drug label.
Overdosage
There is limited information regarding Dexamethasone implant overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.
Pharmacology
There is limited information regarding Dexamethasone implant Pharmacology in the drug label.
Mechanism of Action
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.
Structure
OZURDEX® is an intravitreal implant containing 0.7 mg (700 mcg) dexamethasone in the NOVADUR® solid polymer sustained-release drug delivery system. OZURDEX® is preloaded into a single-use, DDS® applicator to facilitate injection of the rod-shaped implant directly into the vitreous. The NOVADUR® system contains poly (D,L-lactide-co-glycolide) PLGA intravitreal polymer matrix without a preservative. The chemical name for dexamethasone is Pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11β,16α)-. Its structural formula is:
There is limited information regarding Pharmacodynamics of Dexamethasone implant in the drug label.
Pharmacokinetics
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.
Nonclinical Toxicology
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
No adequate studies in animals have been conducted to determine whether OZURDEX® (dexamethasone intravitreal implant) has the potential for carcinogenesis.
Although no adequate studies have been conducted to determine the mutagenic potential of OZURDEX®, dexamethasone has been shown to have no mutagenic effects in bacterial and mammalian cells in vitro or in the in vivo mouse micronucleus test.
Adequate fertility studies have not been conducted in animals.
Clinical Studies
Retinal Vein Occlusion
The efficacy of OZURDEX® for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO) was assessed in two, multicenter, double-masked, randomized, parallel studies.
Following a single injection, OZURDEX® demonstrated the following clinical results for the percent of patients with ≥ 15 letters of improvement from baseline in best-corrected visual acuity (BCVA):
In each individual study and in a pooled analysis, time to achieve ≥ 15 letters (3-line) improvement in BCVA cumulative response rate curves were significantly faster with OZURDEX® compared to sham (p < 0.01), with OZURDEX® treated patients achieving a 3-line improvement in BCVA earlier than sham-treated patients.
The onset of a ≥ 15 letter (3-line) improvement in BCVA with OZURDEX® occurs within the first two months after implantation in approximately 20-30% of subjects. The duration of effect persists approximately one to three months after onset of this effect.
Posterior Segment Uveitis
The efficacy of OZURDEX® was assessed in a single, multicenter, masked, randomized study of 153 patients with non-infectious uveitis affecting the posterior segment of the eye.
After a single injection, the percent of patients reaching a vitreous haze score of 0 (where a score of 0 represents no inflammation) was statistically significantly greater for patients receiving OZURDEX® versus sham at week 8 (primary time point) (47% versus 12%). The percent of patients achieving a 3-line improvement from baseline BCVA was 43% for patients receiving OZURDEX® versus 7% for sham at week 8.
Diabetic Macular Edema
The efficacy of OZURDEX® for the treatment of diabetic macular edema was assessed in two, multicenter, masked, randomized, sham-controlled studies. Subjects were to be evaluated for retreatment eligibility every three months starting from Month 6 but could only receive successive treatments at least 6 months apart. Retreatment was based on physician's discretion after examination including Optical Coherence Tomography. Patients in the OZURDEX® arm received an average of 4 treatments during the 36 months.
The primary endpoint was the proportion of patients with 15 or more letters improvement in BCVA from baseline at Month 39 or final visit for subjects who exited the study at or prior to Month 36. The Month 39 extension was included to accommodate the evaluation of safety and efficacy outcomes for subjects who received re-treatment at Month 36. Only fourteen percent of the study patients completed the Month 39 visit (16.8% from OZURDEX® and 12.2% from Sham).
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.
Intravitreal Injection-related Effects
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
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
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.
Precautions with Alcohol
Alcohol-Dexamethasone implant interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
