Difluprednate

FDA Drug Information • Also known as: Difluprednate, Durezol

Brand Names: Difluprednate, Durezol
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION Difluprednate ophthalmic emulsion 0.05% is a sterile, white opaque to slightly translucent topical anti-inflammatory corticosteroid for topical ophthalmic use. The chemical name is 6α, 9-difluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate 17-butyrate (CAS number 23674-86-4). Difluprednate is represented by the following structural formula: Difluprednate has a molecular weight of 508.56 g/mol, and the empirical formula is C 27 H 34 F 2 O 7 . Each mL of difluprednate ophthalmic emulsion contains: ACTIVE: difluprednate 0.5 mg (0.05%); INACTIVE: boric acid, castor oil, glycerin, polysorbate 80, water for injection, sodium acetate, edetate disodium, sodium hydroxide (to adjust the pH to 5.2 to 5.8). The emulsion is essentially isotonic with a tonicity of 304 to 411 mOsm/kg. PRESERVATIVE: sorbic acid 0.1%. Difluprednate Structural Formula

What Is Difluprednate Used For?

1 INDICATIONS AND USAGE Difluprednate ophthalmic emulsion is a corticosteroid indicated for:

The treatment of inflammation and pain associated with ocular surgery ( 1.1 )

The treatment of endogenous anterior uveitis ( 1.2 ) 1.1 Ocular Surgery Difluprednate ophthalmic emulsion is indicated for the treatment of inflammation and pain associated with ocular surgery. 1.2 Endogenous Anterior Uveitis Difluprednate ophthalmic emulsion is indicated for the treatment of endogenous anterior uveitis.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION

For the treatment of inflammation and pain associated with ocular surgery instill one drop into the conjunctival sac of the affected eye 4 times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period, followed by 2 times daily for a week and then a taper based on the response. ( 2.1 )

For the treatment of endogenous anterior uveitis instill one drop into the conjunctival sac of the affected eye 4 times daily for 14 days followed by tapering as clinically indicated. ( 2.2 ) 2.1 Ocular Surgery Instill one drop into the conjunctival sac of the affected eye 4 times daily beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period, followed by 2 times daily for a week and then a taper based on the response. 2.2 Endogenous Anterior Uveitis Instill one drop into the conjunctival sac of the affected eye 4 times daily for 14 days followed by tapering as clinically indicated. 2.3 Prescribing Guidelines The initial prescription and renewal of the medication order beyond one bottle 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 two days, the patient should be reevaluated. Not more than one bottle should be prescribed initially, and the prescription should not be refilled without further evaluation.

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious reactions are found elsewhere in the labeling:

Intraocular Pressure (IOP) Increase [see Warnings and Precautions (5.1) ]

Cataracts [see Warnings and Precautions (5.2) ]

Delayed Healing [see Warnings and Precautions (5.3) ]

Corneal and Scleral Melting [see Warnings and Precautions (5.4) ]

Bacterial Infections [see Warnings and Precautions (5.5) ]

Viral Infections [see Warnings and Precautions (5.6) ]

Fungal Infections [see Warnings and Precautions (5.7) ] For treatment of inflammation and pain associated with ocular surgery, most common adverse reactions (incidence 5% to 15%) are corneal edema, ciliary and conjunctival hyperemia, eye pain, photophobia, posterior capsule opacification, anterior chamber cells, anterior chamber flare, conjunctival edema, and blepharitis. For treatment of endogenous anterior uveitis, most common adverse reactions (incidence 5% to 10%) are blurred vision, eye irritation, eye pain, headache, increased IOP, iritis, limbal and conjunctival hyperemia, punctate keratitis, and uveitis. To report SUSPECTED ADVERSE REACTIONS, contact Mylan at 1-877-446-3679 (1-877-4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Ocular Surgery Ocular adverse reactions occurring in 5% to 15% of subjects in clinical studies with difluprednate ophthalmic emulsion included corneal edema, ciliary and conjunctival hyperemia, eye pain, photophobia, posterior capsule opacification, anterior chamber cells, anterior chamber flare, conjunctival edema, and blepharitis. Other ocular adverse reactions occurring in 1% to 5% of subjects included reduced visual acuity, punctate keratitis, eye inflammation, and iritis. Ocular adverse reactions occurring in less than 1% of subjects included application site discomfort or irritation, corneal pigmentation and striae, episcleritis, eye pruritis, eyelid irritation and crusting, foreign body sensation, increased lacrimation, macular edema, sclera hyperemia, and uveitis. Most of these reactions may have been the consequence of the surgical procedure. 6.2 Endogenous Anterior Uveitis A total of 200 subjects participated in the clinical trials for endogenous anterior uveitis, of which 106 were exposed to difluprednate ophthalmic emulsion. The most common adverse reactions of those exposed to difluprednate ophthalmic emulsion occurring in 5% to 10% of subjects included blurred vision, eye irritation, eye pain, headache, increased IOP, iritis, limbal and conjunctival hyperemia, punctate keratitis, and uveitis. Adverse reactions occurring in 2% to 5% of subjects included anterior chamber flare, corneal edema, dry eye, iridocyclitis, photophobia, and reduced visual acuity.

Contraindications

4 CONTRAINDICATIONS Difluprednate ophthalmic emulsion, as with other ophthalmic corticosteroids, is contraindicated in 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. Difluprednate ophthalmic emulsion is contraindicated in 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 diseases of ocular structures. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no available data on difluprednate ophthalmic emulsion use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes. Systemic exposure to difluprednate ophthalmic emulsion following ocular administration is low [see Clinical Pharmacology (12.3) ] . Consequently, the systemic exposure of a pregnant woman to difluprednate is expected to be minimal following topical ocular administration. In animal reproductive studies, subcutaneous administration of difluprednate to pregnant rabbits and rats throughout organogenesis produced maternal toxicity, embryo-fetal toxicity and teratogenicity in rabbits and fetotoxicity in rats. Administration of difluprednate to rats during late gestation through lactation did not produce adverse maternal, fetal or neonatal effects at clinically relevant doses. 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. In the U.S. 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 In embryofetal development studies, subcutaneous administration of difluprednate to pregnant rats during the period of organogenesis decreased the placental weight, at doses greater than or equal to 10 mcg/kg/day (approximately 0.48-fold higher than the maximum recommended human ophthalmic dose [MRHOD] of 0.2 mg/day, on a mg/m 2 basis and assuming 100% absorption of the dose). Decreased weight gain and delayed ossification of the fetus were observed at a dose of 100 mcg/kg/day (approximately 4.8-fold higher than the MRHOD). The no-observed-effect level (NOEL) for teratogenic effects was 10 mcg/kg/day. In rabbits, subcutaneous administration of difluprednate during the period of...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Difluprednate Ophthalmic Emulsion 0.05%, is a sterile, aqueous topical ophthalmic emulsion supplied in an opaque plastic bottle with a controlled drop tip and a pink cap in the following size: NDC 0378-7518-35 5 mL in a 5 mL bottle Storage and Handling Store at 15° to 25°C (59° to 77°F). Do not freeze. Protect from light. When not in use, keep the bottles in the protective carton.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.