DEXYCU- dexamethasone injection, suspension

Dexycu by

Drug Labeling and Warnings

Dexycu by is a Prescription medication manufactured, distributed, or labeled by EyePoint Pharmaceuticals US, Inc, Albany Molecular Research, Inc. (AMRI Burlington, Inc.), Albany Molecular Research Inc. (AMRI), Life Science Outsourcing, Inc. (LSO). Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

• HIGHLIGHTS OF PRESCRIBING INFORMATION

  These highlights do not include all the information needed to use DEXYCU™ safely and effectively. See full prescribing information for DEXYCU.
  
  DEXYCU (dexamethasone intraocular suspension) 9%, for intraocular administration
  Initial U.S. Approval: 1958

  INDICATIONS AND USAGE

  DEXYCU is a corticosteroid indicated for the treatment of postoperative inflammation (1).

  DOSAGE AND ADMINISTRATION

  • For intraocular administration (2).
  • Administer 0.005 mL of DEXYCU into the posterior chamber inferiorly behind the iris at the end of ocular surgery (2).

  DOSAGE FORMS AND STRENGTHS

  Intraocular suspension: 9% equivalent to dexamethasone 103.4 mg/mL in a single-dose vial provided in a kit (3).

  CONTRAINDICATIONS

  None (4).

  WARNINGS AND PRECAUTIONS

  • Increase in intraocular pressure (IOP): Monitor for increases in IOP (5.1).
  • Delayed Healing: Monitor for delayed healing (5.2).
  • Infection Exacerbation: Monitor and treat for any exacerbations of bacterial, viral or fungal infections (5.3).
  • Cataract Progression: Cataracts may develop or progress in phakic patients (5.4).

  ADVERSE REACTIONS

  In controlled studies, the most common adverse reactions reported by 5-15% of patients were intraocular pressure increased, corneal edema and iritis (6.1).

  
  

  To report SUSPECTED ADVERSE REACTIONS, contact EyePoint Pharmaceuticals US at 1-833-EYEPOINT (1-833-393-7646) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

  Revised: 12/2018

• Table of Contents

  FULL PRESCRIBING INFORMATION: CONTENTS*

  1 INDICATIONS AND USAGE

  2 DOSAGE AND ADMINISTRATION

  2.1 Dosing Information

  2.2 Preparation and Administration

  3 DOSAGE FORMS AND STRENGTHS

  4 CONTRAINDICATIONS

  5 WARNINGS AND PRECAUTIONS

  5.1 Increase in Intraocular Pressure

  5.2 Delayed Healing

  5.3 Exacerbation of Infection

  5.4 Cataract Progression

  6 ADVERSE REACTIONS

  6.1 Clinical Trials Experience

  8 USE IN SPECIFIC POPULATIONS

  8.1 Pregnancy

  8.2 Lactation

  8.4 Pediatric Use

  8.5 Geriatric Use

  11 DESCRIPTION

  12 CLINICAL PHARMACOLOGY

  12.1 Mechanism of Action

  12.3 Pharmacokinetics

  13 NONCLINICAL TOXICOLOGY

  13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

  14 CLINICAL STUDIES

  16 HOW SUPPLIED/STORAGE AND HANDLING

  * Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS AND USAGE

DEXYCU (dexamethasone intraocular suspension) 9% is indicated for the treatment of postoperative inflammation.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Information

DEXYCU should be administered as a single dose, intraocularly in the posterior chamber at the end of surgery. The dose is 0.005 mL of dexamethasone 9% (equivalent to 517 micrograms).

2.2 Preparation and Administration

Each kit of DEXYCU is for a single administration. After preparation, 0.005 mL will be administered.

The DEXYCU administration kit contains the following items:

1. One glass vial: 0.5 mL of DEXYCU
2. One sterile 1-mL syringe
3. One sterile syringe guide
4. One sterile syringe ring
5. One sterile 18-gauge needle (1½ inches long), plastic cap attached
6. One sterile 25-gauge bent cannula (8 mm long), plastic cap attached

3 DOSAGE FORMS AND STRENGTHS

DEXYCU contains dexamethasone 9% w/w (103.4 mg/mL) as a sterile suspension for intraocular ophthalmic administration. DEXYCU is provided as a kit for administration of a single dose of 0.005 mL of 9% dexamethasone (equivalent to 517 micrograms of dexamethasone).

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Increase in Intraocular Pressure

Prolonged use of corticosteroids including DEXYCU 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.

5.2 Delayed Healing

The use of steroids after cataract surgery may delay healing and increase the incidence of bleb formation. In those diseases causing thinning of the cornea or sclera, perforations have been known to occur with the use of corticosteroids.

5.3 Exacerbation of Infection

The use of DEXYCU, as with other ophthalmic corticosteroids, is not recommended in the presence of most active viral diseases of the cornea and conjunctiva including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella, and also in mycobacterial infection of the eye and fungal disease of ocular structures.

Employment of a corticosteroid medication in the treatment of patients with a history of herpes simplex requires caution. Use of ocular steroids may prolong the course and may exacerbate the severity of many viral infections of the eye (including herpes simplex). Fungal infections of the cornea are particularly prone to develop coincidentally with long-term local steroid application. 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.

Prolonged use of corticosteroids may suppress the host response and thus increase the hazard of secondary ocular infections. In acute purulent conditions, steroids may mask infection or enhance existing infection.

5.4 Cataract Progression

The use of corticosteroids in phakic individuals may promote the development of posterior subcapsular cataracts.

6 ADVERSE REACTIONS

The following adverse reactions are described elsewhere in the labeling:

• Increase in Intraocular Pressure [see Warning and Precautions (5.1)]
• Delayed Healing [see Warnings and Precautions (5.2)]
• Infection Exacerbation [see Warnings and Precautions (5.3)]
• Cataract Progression [see Warnings and Precautions (5.4)]

6.1 Clinical Trials 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.

The following adverse events rates are derived from three clinical trials in which 339 patients received the 517 microgram dose of DEXYCU. The most commonly reported adverse reactions occurred in 5-15% of subjects and included increases in intraocular pressure, corneal edema and iritis. Other ocular adverse reactions occurring in 1-5% of subjects included, corneal endothelial cell loss, blepharitis, eye pain, cystoid macular edema, dry eye, ocular inflammation, posterior capsule opacification, blurred vision, reduced visual acuity, vitreous floaters, foreign body sensation, photophobia, and vitreous detachment.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

There are no adequate and well-controlled studies of DEXYCU (dexamethasone intraocular suspension) 9% 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 abdominal wall/intestines and kidneys in rabbits at doses 7 and 5 times higher than the injected recommended human ophthalmic dose (RHOD) of DEXYCU (517 micrograms dexamethasone), respectively [see Data].

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 7-times the injected RHOD of DEXYCU, 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 5-times the injected RHOD of DEXYCU, on a mg/m2 basis. A no-observed-adverse-effect-level (NOAEL) was not identified in the mouse or rabbit studies.

8.2 Lactation

Risk Summary

Systemically administered corticosteroids are present in human milk and can suppress growth, interfere with endogenous corticosteroid production, or cause other unwanted effects. There is no information regarding the presence of injected DEXYCU in human milk, the effects on breastfed infants, or the effects on milk production to inform risk of DEXYCU to an infant during lactation. The developmental and health benefits of breastfeeding should be considered, along with the mother's clinical need for DEXYCU and any potential adverse effects on the breastfed child from DEXYCU.

8.4 Pediatric Use

Safety and effectiveness of DEXYCU in pediatric patients have not been established.

8.5 Geriatric Use

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

11 DESCRIPTION

DEXYCU (dexamethasone intraocular suspension) 9% is a corticosteroid, sterile, white to off-white opaque suspension for intraocular administration. Each vial of DEXYCU contains 0.5 mL of 9% w/w dexamethasone suspension equivalent to 51.7 mg of dexamethasone. The inactive ingredient is acetyl triethyl citrate. DEXYCU does not contain an antimicrobial preservative.

The chemical name of dexamethasone is pregna-1,4-diene-3,20-dione, 9-fluoro-11,17,21-trihydroxy-16-methyl-, (11β,16α)-. It has a molecular formula of C22H29FO5 and a molecular weight of 392.46 grams per mole. Its structural formula is:

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Dexamethasone is a corticosteroid. Corticosteroids have been shown to suppress inflammation by inhibiting multiple inflammatory cytokines resulting in decreased edema, fibrin deposition, capillary leakage and migration of inflammatory cells.

12.3 Pharmacokinetics

Systemic exposure to dexamethasone was evaluated in a subgroup of patients enrolled in two studies (n=25 for the first study and n=13 for the second study). The patients received a single intraocular injection of DEXYCU containing 342 mcg or 517 mcg of dexamethasone at the end of cataract surgery and blood samples were collected prior to surgery and at several time points post-surgery between Day 1 and up to Day 30. In the first study, the dexamethasone plasma concentrations on post-surgery Day 1 ranged from 0.09 to 0.86 ng/mL and from 0.07 to 1.16 ng/mL following administration of DEXYCU 342 mcg and 517 mcg, respectively. In the second study, dexamethasone plasma concentrations on post-surgery Day 1 ranged from 0.349 to 2.79 ng/mL following administration of DEXYCU 517 mcg. In both the studies, dexamethasone plasma concentrations declined over time and very few patients had quantifiable dexamethasone plasma concentrations at the final time point of sampling (Day 15 or Day 30).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies have not been conducted to determine whether DEXYCU has the potential for carcinogenesis or mutagenesis. Fertility studies have not been conducted in animals

14 CLINICAL STUDIES

Clinical efficacy was evaluated in a randomized, double-masked, placebo-controlled trial (NCT02006888) in which subjects received either DEXYCU or placebo (vehicle). A dose of 5 microliters of DEXYCU (equivalent to 517 micrograms of dexamethasone), a dose equivalent to 342 micrograms of dexamethasone or vehicle was administered by the physician at the end of the surgical procedure. The primary efficacy endpoint for the study was the proportion of patients with anterior chamber cell clearing (i.e., cell score=0) on postoperative day (POD) 8. The presence of anterior cells was assessed using a slit lamp binocular microscope up to 30 days post treatment. The percentage of patients with anterior chamber clearing at Day 8 was 20% in the placebo group, and 57%, and 60% in the 342 and 517 microgram treatment groups, respectively (Table 1). The percentage of subjects receiving rescue medication of ocular steroid or NSAID was significantly lower at Day 3, 8, 15 and 30 in the 342 and 517 microgram treatment groups compared to placebo (Table 2).

Table 1: Proportion of subjects with clearing of the anterior chamber cells by visit

	Treatments			Difference and 97.5% CI
Visits	Placebo N=80	DEX342 N=158	DEX517 N=156	DEX342 vs Placebo	DEX517 vs Placebo
Subjects who received rescue medication were treated as failure.
Day 1	7 (9%)	17 (11%)	24 (15%)	2% (-7%, 11%)	7% (-3%, 16%)
Day 3	13 (16%)	60 (38%)	44 (28%)	22% (9%, 34%)	12% (0%, 24%)
Day 8	16 (20%)	90 (57%)	94 (60%)	37% (24%, 50%)	40% (27%, 54%)
Day 15	21 (26%)	83 (52%)	91 (58%)	26% (12%, 40%)	32% (18%, 46%)
Day 30	28 (35%)	113 (72%)	103 (66%)	36% (22%, 51%)	31% (16%, 46%)

Table 2: Proportion of subjects receiving rescue medications

Visits	Number (Percent) of Patients Receiving Rescue Medication, and 95% CI
	Placebo N=80	DEX342 N=158	DEX517 N=156
Subjects who received an ocular corticosteroid or NSAID in study eye.
Day 1	10 (13%); 6%, 22%	9 (6%); 3%, 10%	10 (6%); 3%, 12%
Day 3	30 (38%); 27%, 49%	9 (6%); 3%, 10%	16 (10%); 6%,16%
Day 8	40 (50%); 39%, 61%	12 (8%); 4%, 13%	16 (10%); 6%,16%
Day 15	43 (54%); 42%, 65%	22 (14%); 9%, 20%	26 (17%); 11%, 24%
Day 30	43 (54%); 42%, 65%	25 (16%); 10%, 22%	31 (20%); 14%, 27%

16 HOW SUPPLIED/STORAGE AND HANDLING

Each kit of DEXYCU contains a single dose for a single patient. The 2-mL glass vial is filled with 0.5 mL of 9% dexamethasone intraocular suspension and has a blue cap (NDC # 71879-001-01).

Each kit also contains one sterile 18-gauge, 1.5-inch needle with a plastic cap attached, one sterile plastic 1-mL syringe for withdrawal of the vial contents, one sterile 25-gauge 8-mm cannula with a plastic cap attached for the intraocular administration, and one syringe assembly pouch containing a sterile ring and a sterile syringe guide used for measuring and injection of the 0.005 mL dose.

Store at 20°C to 25°C (68°F to 77°F).

SPL UNCLASSIFIED SECTION

Manufactured for: EyePoint Pharmaceuticals US, Inc. Watertown, MA 02472

PRINCIPAL DISPLAY PANEL - 0.005 mL Vial Carton

DEXYCU™
(dexamethasone intraocular suspension) 9%
0.005 mL dose in single dose vial
for intraocular administration

Please see enclosed full Prescribing Information for Instructions

Rx Only
NDC: 71879-001-01

EYEPOINT™
PHARMACEUTICALS

For Intraocular Injection
Store at 20°C to 25°C (68°F to 77°F)

INGREDIENTS AND APPEARANCE

DEXYCU 
dexamethasone injection, suspension

Product Information
Product Type	HUMAN PRESCRIPTION DRUG	Item Code (Source)	NDC: 71879-001
Route of Administration	INTRAOCULAR

Active Ingredient/Active Moiety
Ingredient Name	Basis of Strength	Strength
DEXAMETHASONE (UNII: 7S5I7G3JQL) (DEXAMETHASONE - UNII:7S5I7G3JQL)	DEXAMETHASONE	517 ug  in 0.005 mL

Inactive Ingredients
Ingredient Name	Strength
ACETYLTRIETHYL CITRATE (UNII: 5WBR36T90E)	5233 ug  in 0.005 mL
Nitrogen (UNII: N762921K75)

Packaging
#	Item Code	Package Description	Marketing Start Date	Marketing End Date
1	NDC: 71879-001-01	1 in 1 CARTON	03/11/2019
1		0.5 mL in 1 VIAL, GLASS; Type 0: Not a Combination Product

Marketing Information
Marketing Category	Application Number or Monograph Citation	Marketing Start Date	Marketing End Date
NDA	NDA208912	03/11/2019

Labeler - EyePoint Pharmaceuticals US, Inc (968003785)

Establishment
Name	Address	ID/FEI	Business Operations
EyePoint Pharmaceuticals US, Inc		968003785	MANUFACTURE(71879-001)

Establishment
Name	Address	ID/FEI	Business Operations
Albany Molecular Research, Inc. (AMRI Burlington, Inc.)		556991748	ANALYSIS(71879-001) , MANUFACTURE(71879-001)

Establishment
Name	Address	ID/FEI	Business Operations
Albany Molecular Research Inc. (AMRI)		080046430	ANALYSIS(71879-001)

Establishment
Name	Address	ID/FEI	Business Operations
Life Science Outsourcing, Inc. (LSO)		017149456	MANUFACTURE(71879-001) , STERILIZE(71879-001)