Durezol®

Difluprednate 0.05% · ophthalmic emulsion

Steroid

Approved uses

Inflammation and pain after ocular surgery

1 drop QID beginning 24 hours after surgery through the first 2 postoperative weeks, then BID for 1 week, then taper based on response

Anterior chamber cells and pain clear by day 8, with a clinically significant IOP rise in 3%.

Endogenous anterior uveitis

1 drop QID for 14 days, then taper as clinically indicated

QID matches prednisolone acetate 1% eight times daily on day-14 cell clearing.

OFF-LABELNot in the FDA label for this product

Non-infectious anterior scleritis

4 or more drops per day initially as the single treatment agent, tapered on response

Retrospective series · n=25

Retrospective interventional case series of 25 patients (35 eyes) treated with difluprednate as the single agent. 83% of eyes reached clinical resolution, at a median of 6 weeks. Eyes started at 4 or more times daily were more likely to resolve (hazard ratio 3.43, 95% CI 1.19 to 9.88, P=0.02). 9 eyes developed IOP elevation (defined as 24 mmHg or higher), 4 eyes lost 2 or more lines of BCVA with 1 of those from cataract progression, and 1 eye needed cataract surgery. Uncontrolled and retrospective; the authors conclude only that it may effectively treat non-infectious anterior scleritis with a tolerable side effect profile.

Liberman P, Burkholder BM, Thorne JE, Berkenstock MK. Effectiveness of difluprednate for the treatment of anterior scleritis. Am J Ophthalmol. Volume 235, pages 172-177; PubMed publication date 2021 Sep 20. Retrospective interventional case series.

Contraindications

Most active viral diseases of the cornea and conjunctiva, including epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, and varicella.
Mycobacterial infection of the eye.
Fungal disease of ocular structures.

Available Forms

0.05% emulsion (difluprednate 0.5 mg/mL), 5 mL in an 8 mL bottle

Mechanism of Action

Potent topical corticosteroid: induces phospholipase A2 inhibitory proteins (lipocortins), which cut release of arachidonic acid and the prostaglandins and leukotrienes downstream of it, suppressing edema, fibrin deposition, capillary dilation, leukocyte migration, fibroblast and capillary proliferation, collagen deposition, and scar formation, at the cost of delayed healing. Deacetylated in vivo to the active metabolite 6-alpha,9-difluoroprednisolone 17-butyrate; after 2 drops QID for 7 days blood levels of that metabolite stayed below the 50 ng/mL quantification limit in all subjects, so systemic absorption is limited.

Warnings & Precautions

IOP elevation and glaucoma: Prolonged corticosteroid use may produce glaucoma with optic nerve damage and defects in visual acuity and visual fields; use with caution in the presence of glaucoma and monitor IOP if the product is used 10 days or longer.
Posterior subcapsular cataract: Corticosteroid use may produce it.
Delayed healing after cataract surgery: Steroids may delay healing and increase the incidence of bleb formation.
Corneal or scleral perforation: In diseases causing thinning of the cornea or sclera, perforations have occurred with topical steroids.
Prescription renewal beyond 28 days: Initial prescription and renewal past 28 days only after examination with magnification such as slit lamp biomicroscopy and, where appropriate, fluorescein staining.
Secondary ocular infection: Prolonged use may suppress host response and increase the hazard of secondary ocular infection; in acute purulent conditions steroids may mask infection or enhance existing infection, and the patient should be reevaluated if signs and symptoms fail to improve after 2 days.
Viral infection exacerbation: Ocular steroids may prolong the course and worsen the severity of many ocular viral infections including herpes simplex; a history of herpes simplex requires great caution.
Fungal keratitis: Fungal corneal infection is particularly prone to develop coincidentally with long-term local steroid use; consider fungal invasion in any persistent corneal ulceration where a steroid has been used or is in use, and culture when appropriate.
Route restriction: Topical ophthalmic use only, not indicated for intraocular administration.
Soft contact lenses: Do not instill while lenses are worn, and remove lenses first; the sorbic acid 0.1% preservative may be absorbed by soft lenses, which may be reinserted 10 minutes after administration.

Common Side Effects

Ocular surgery, 5% to 15%: Corneal edema, ciliary and conjunctival hyperemia, eye pain, photophobia, posterior capsule opacification, anterior chamber cells, anterior chamber flare, conjunctival edema, blepharitis.
Ocular surgery, 1% to 5%: Reduced visual acuity, punctate keratitis, eye inflammation, iritis.
Ocular surgery, under 1%: Application site discomfort or irritation, corneal pigmentation and striae, episcleritis, eye pruritus, eyelid irritation and crusting, foreign body sensation, increased lacrimation, macular edema, scleral hyperemia, uveitis.
Endogenous anterior uveitis, 5% to 10%: Blurred vision, eye irritation, eye pain, headache, increased IOP, iritis, limbal and conjunctival hyperemia, punctate keratitis, uveitis.
Endogenous anterior uveitis, 2% to 5%: Anterior chamber flare, corneal edema, dry eye, iridocyclitis, photophobia, reduced visual acuity.
Serious reactions: Elevated IOP, posterior subcapsular cataract formation, secondary ocular infection, perforation of the globe.
Attribution caveat: The label notes most of the ocular surgery reactions may have been consequences of the surgical procedure itself.

Pregnancy & Lactation

Pregnancy: Category C. Embryotoxic (reduced embryonic body weight, delayed embryonic ossification) and teratogenic (cleft palate, skeletal anomalies) in rabbits dosed subcutaneously during organogenesis at 1 to 10 mcg/kg/day, with a no-observed-effect level of 1 mcg/kg/day and 10 mcg/kg/day also in the toxic range for fetuses and pregnant females; rats showed no reproductive toxicity at 10 mcg/kg/day but reduced fetal weight and delayed ossification at 100 mcg/kg/day. Human pregnancy use has not been evaluated and harm cannot be ruled out, so use only if the potential benefit justifies the potential risk to the embryo or fetus.

Lactation: Whether topical ophthalmic corticosteroid dosing produces detectable quantities in breast milk is unknown; systemically administered corticosteroids do appear in human milk and could suppress growth or interfere with endogenous corticosteroid production, so use with caution in a nursing woman.

Pediatric Use

Safety profile similar to prednisolone acetate 1% in patients aged 0 to 3 years.