General Information

Durezol is a sterile, topical anti-inflammatory corticosteroid for ophthalmic use. Corticosteroids inhibit the inflammatory response to a variety of inciting agents that may delay or slow healing. They inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation.

Durezol is specifically indicated for the treatment of inflammation and pain associated with ocular surgery.

Durezol is supplied as a sterile, aqueous ophthalmic emulsion designed for topical administration. The recommended initial dose of the drug is one drop into the conjunctival sac of the affected eye(s) 4 times daily, beginning 24 hours after surgery and continuing throughout the first 2 weeks of the postoperative period. This should be followed by administration 2 times daily for a week and then a taper based on the response.

Clinical Results

FDA Approval
FDA approval of Durezol was based on the results of two clinical trials. These randomized, double-masked, placebo-controlled studies enrolled 327 subjects with an anterior chamber cell grade of less than or equal to 2 (a cell count of 10 or higher) after cataract surgery. The subjects received one drop of Durezol or placebo, self instilled either 2 (BID) or 4 (QID) times per day for 14 days, beginning the day after surgery. The presence of complete clearing (a cell count of 0) was assessed 8 and 15 days post-surgery using a slit lamp binocular microscope. In the intent-to-treat analyses of both studies, a significant benefit was seen in the QID Durezol-treated group in ocular inflammation and reduction of pain when compared with placebo. The results are as follows: Day Eight Anterior Chamber cell clearing was seen in 22% of the Durezol QID arm compared to 7% in the placebo group and reduction of pain was reported in 58% of the Durezol arm and 27% of the placebo arm (p<0.01 for both endpoints). Day Fifteen Anterior Chamber cell clearing was seen in 41% of the Durezol QID arm compared to 11% of the placebo arm and reduction of pain was reported in 63% of the Durezol arm and 35% of the placebo arm (p<0.01 for both endpoints).

Ongoing Study Commitments

• Sirion has agreed to a deferred pediatric study under PREA for the treatment of treatment of post-operative inflammation following cataract surgery in pediatric patients aged 0 to 3 years of age undergoing cataract surgery.
  Final Report Submission: June 26, 2011
• Sirion has agreed to Description of Commitment - post-marketing study of difluprednate in pediatric subjects.
  Protocol Submission: by 10/26/2008
  Study Start: by 01/26/2009
  Final Report Submission: by 06/26/2011

Side Effects

Adverse events associated with the use of Durezol may include, but are not limited to, the following:

• elevated intraocular pressure
• visual acuity and field defects
• posterior subcapsular cataract formation
• posterior subcapsular cataract formation
• secondary ocular infection from pathogens
• perforation of the globe
• corneal edema
• ciliary and conjunctival hyperemia
• eye pain
• photophobia
• posterior capsule opacification
• anterior chamber flare
• conjunctival edema
• blepharitis

Mechanism of Action

Durezol is a sterile, topical anti-inflammatory corticosteroid for ophthalmic use. Corticosteroids inhibit the inflammatory response to a variety of inciting agents that may delay or slow healing. They inhibit edema, fibrin deposition, capillary dilation, leukocyte migration, capillary proliferation, fibroblast proliferation, deposition of collagen, and scar formation associated with inflammation. There is no generally accepted explanation for the mechanism of action of ocular corticosteroids. However, corticosteroids are thought to act by the induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotreines by inhibiting the release of their common precursor arachidonic acid.

Literature References

Yamaguchi M, Yasueda S, Isowaki A, Yamamoto M, Kimura M, Inada K, Ohtori A Formulation of an ophthalmic lipid emulsion containing an anti-inflammatory steroidal drug, difluprednate. International journal of pharmaceutics 2005 Sep 14;301(1-2):121-8

Yasueda S, Kimura M, Ohtori A, Kakehi K Analysis of an anti-inflammatory steroidal drug, difluprednate, in aqueous humor by combination of semi-micro HPLC and column switching method. Journal of pharmaceutical and biomedical analysis 2003 Jan 15;30(6):1735-42

Additional Information

For additional information regarding Durezol or pain and inflammation associated with ocular surgery, please visit the Durezol web page.