Difluprednate

Class: Corticosteroids
Chemical Name: 6α,9-difluoro-11β,17,21-trihydroxypregna-1,4-diene-3,20-dione 21-acetate 17-butyrate
Molecular Formula: C27H34F2O7
CAS Number: 23674-86-4
Brands: Durezol

Introduction

Difluorinated corticosteroid.1 2

Uses for Difluprednate

Postoperative Ocular Inflammation and Pain

Treatment of inflammation and pain associated with ocular surgery.1 2

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Difluprednate Dosage and Administration

Administration

Ophthalmic Administration

Apply topically to the eye as an ophthalmic emulsion.1

Not for intraocular administration.1

Avoid contamination of the preparation container.1

Do not wear contact lenses during therapy.1

If used with other topical ophthalmic drugs (e.g., β-adrenergic blocking agents, carbonic anhydrase inhibitors, α-agonists, cycloplegics, mydriatics) separate administration by 10 minutes.3

Dosage

Adults

Postoperative Ocular Inflammation and Pain
Ophthalmic

Initially, 1 drop into the conjunctival sac of the affected eye(s) 4 times daily beginning 24 hours after surgery and continuing for 2 weeks.1 Then decrease to 1 drop twice daily for 1 week.1 Thereafter, taper based on response.1

Special Populations

No special population dosage recommendations at this time.1 3

Cautions for Difluprednate

Contraindications

  • Active viral diseases of the cornea and conjunctiva (e.g., epithelial herpes simplex keratitis [dendritic keratitis], vaccinia, varicella).1 a

  • Mycobacterial infection of the eye.1 a

  • Fungal disease of ocular structures.1 a

  • Known hypersensitivity to difluprednate, other corticosteroids, or any ingredient in the formulation.3

Warnings/Precautions

Ocular Effects

Risk of glaucoma (with damage to optic nerve), defects in visual acuity and fields of vision, and posterior subcapsular cataract formation with prolonged use of corticosteroids.1 a Use with caution in glaucoma because IOP may increase.1

If used for ≥10 days, monitor IOP routinely, even though monitoring may be difficult in uncooperative patients.1 a

In conditions causing thinning of the cornea and sclera, perforations reported with use of topical corticosteroids.1 a

Use of high-dose corticosteroids may delay healing.1 a Use after cataract surgery may delay healing and increase incidence of bleb formation.1 a

Immunosuppressive Effects

Risk of secondary ocular infections (bacterial, fungal, or viral) with prolonged use of corticosteroids.1 a Consider possibility of fungal invasion if persistent corneal ulceration occurs.1 a Obtain fungal culture when appropriate.1

In acute purulent conditions, corticosteroids may mask infection or exacerbate existing infections.1 If no improvement after 2 days, reevaluate the patient.1 (See Contraindications under Cautions.)

Herpes Simplex

Use of corticosteroids in patients with a history of herpes simplex infections other than epithelial herpes simplex keratitis, in which corticosteroids are contraindicated, requires great caution;1 slit-lamp microscopy is essential.a

Evaluation of Ocular Condition

Initial prescription or renewal of medication order >28 days should be provided only after examination of the patient with the aid of magnification (e.g., slit-lamp biomicroscopy and fluorescein staining where appropriate).1 3

Specific Populations

Pregnancy

Category C.1

Lactation

Not known whether topical ophthalmic administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in milk.1 3 a

Caution if used in nursing women.1 3

Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.1

Pediatric Use

Safety and efficacy not established.1 3

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1

Common Adverse Effects

Corneal edema, ciliary and conjunctival hyperemia, eye pain, photophobia, posterior capsule opacification, anterior chamber cells, anterior chamber flare, conjunctival edema, blepharitis.1

Difluprednate Pharmacokinetics

Absorption

Bioavailability

Corticosteroids are absorbed through the aqueous humor; because only low doses are given, little if any systemic absorption occurs.1 a

Distribution

Extent

Systemically absorbed corticosteroids are distributed into milk; not known whether topical corticosteroids could produce detectable levels in human milk.1 a

Elimination

Metabolism

Deacetylated to active metabolite.1

Stability

Storage

Ophthalmic

Emulsion

15–25°C.1 Do not freeze; protect from light.1 Keep bottle in protective carton when not in use.1

Actions

  • Derivative of prednisolone;2 structurally similar to other corticosteroids.1

  • Corticosteroids suppress the inflammatory response to mechanical, chemical, or immunologic agents.1 a

  • Corticosteroids inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.1 a

  • Mechanism of ocular effects is unknown.1 Corticosteroids may induce phospholipase A2 inhibitory proteins; these proteins may inhibit release of arachidonic acid, thus controlling biosynthesis of potent mediators of inflammation (e.g., prostaglandins, leukotrienes).1

Advice to Patients

  • Importance of learning and adhering to proper administration techniques to avoid contamination of the tip of the container.1

  • Importance of not wearing contact lenses during therapy unless specifically directed by a clinician.1 3

  • Importance of administering other topical ophthalmic preparations 10 minutes apart from difluprednate administration.3

  • Risks of adverse ocular effects, wound healing complications, and ocular infections.1 3 Consult a clinician if pain develops or if redness, itching, or inflammation worsens.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

    Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Difluprednate

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Emulsion

0.05%

Durezol

Sirion

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Durezol 0.05% Emulsion (ALCON VISION): 5/$114.99 or 15/$323.98

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions August 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Sirion Therapeutics, Inc. Durezol (difluprednate) ophthalmic emulsion 0.05% prescribing information. Tampa, FL; 2008 Sep.

2. Stevens E. Sirion Therapeutics announces FDA approval of Durezol for treatment of postoperative ocular inflammation and pain. Reuters. 2008 Jun 24. From Reuters website ().

3. Sirion Therapeutics, Tampa, FL: Personal communication.

a. AHFS drug information 2009. McEvoy GK, ed. EENT corticosteroids general statement. Bethesda, MD: American Society of Health-Systems Pharmacists; 2009:2879-81.

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