Recommended Topic Related To:

Durezol

"In May, Healthy Vision Month, the National Eye Institute (NEI) calls on Americans to make their vision a priority by taking the necessary steps to protect vision, prevent vision loss, and make the most of the vision they may have remaining.

"...

Durezol

Durezol

CLINICAL PHARMACOLOGY

Mechanism of Action

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and 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 leukotrienes by inhibiting the release of their common precursor arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.

Difluprednate is structurally similar to other corticosteroids.

Pharmacokinetics

Difluprednate undergoes deacetylation in vivo to 6α,9-difluoroprednisolone 17-butyrate (DFB), an active metabolite of difluprednate.

Clinical pharmacokinetic studies of difluprednate after repeat ocular instillation of 2 drops of difluprednate (0.01% or 0.05%) four times per day for 7 days showed that DFB levels in blood were below the quantification limit (50 ng/mL) at all time points for all subjects, indicating the systemic absorption of difluprednate after ocular instillation of DUREZOL is limited.

Animal Toxicology and/or Pharmacology

In multiple studies performed in rodents and non-rodents, subchronic and chronic toxicity tests of difluprednate showed systemic effects such as suppression of body weight gain; a decrease in lymphocyte count; atrophy of the lymphatic glands and adrenal gland; and for local effects, thinning of the skin; all of which were due to the pharmacologic action of the molecule and are well known glucocorticosteroid effects. Most, if not all of these effects were reversible after drug withdrawal. The NOEL for the subchronic and chronic toxicity tests were consistent between species and ranged from 1–1.25 mcg/kg/day.

Clinical Studies

Ocular Surgery

Clinical efficacy was evaluated in 2 randomized, double-masked, placebo-controlled trials in which subjects with an anterior chamber cell grade ≥ “2” (a cell count of 11 or higher) after cataract surgery were assigned to DUREZOL or placebo (vehicle) following surgery. One drop of DUREZOL or vehicle was self instilled either 2 times per day or 4 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 4 times per day DUREZOL –treated group in ocular inflammation and reduction of pain when compared with placebo. The consolidated clinical trial results are provided below.

Ocular Inflammation and Pain Endpoints (Studies Pooled)

Day DUREZOL 4 times per day
N=107
Vehicle
N=220
8 15 8 15
Anterior Chamber cell clearing (% subjects) 24 (22%)* 44 (41%)* 17 (7%) 25 (11%)
Pain free (% subjects) 62 (58%)* 67 (63%)* 59 (27%) 76 (35%)
* Statistically significantly better than vehicle, P < 0.01

Endogenous Anterior Uveitis

Clinical efficacy was evaluated in two randomized, double masked active controlled trials in which patients who presented with endogenous anterior uveitis were treated with either DUREZOL 4 times daily or prednisolone acetate ophthalmic suspension, 1%, 8 times daily for 14 days. Both studies demonstrated that DUREZOL was equally effective as prednisolone acetate ophthalmic suspension, 1% in treating subjects with endogenous anterior uveitis.

Mean Change from Baseline in Anterior Chamber Cell Grade*

Study 1 time point DUREZOL
N=57
Prednisolone Acetate
N=53
Difference**
(95% CI)
Baseline 2.6 2.5 0.0 (-0.22, 0.28)
Day 3 -1.0 -1.0 -0.1 (-0.35, 0.25)
Day 7 -1.6 -1.5 -0.0 (-0.31, 0.25)
Day 14 -2.0 -1.8 -0.2 (-0.46, 0.10)
Day 21 -2.2 -1.9 -0.3 (-0.53, 0.01)
Day 28 -2.2 -2.1 -0.1 (-0.37, 0.18)
Day 35 -2.1 -2.0 -0.1 (-0.39, 0.20)
Day 42 -2.1 -2.1 0.0 (-0.27, 0.34)
Study 2 time point DUREZOL N=50 Prednisolone Acetate
N=40
Difference**
(95% CI)
Baseline 2.4 2.4 0.0 (-0.21, 0.29)
Day 3 -0.9 -0.9 -0.0 (-0.34, 0.25)
Day 7 -1.7 -1.6 -0.1 (-0.35, 0.21)
Day 14 -1.9 -1.8 -0.1 (-0.34, 0.20)
Day 21 -2.0 -2.0 0.0 (-0.25, 0.28)
Day 28 -2.0 -2.0 0.0 (-0.21, 0.26)
Day 35 -2.1 -2.0 -0.1 (-0.32, 0.16)
Day 42 -2.0 -1.9 -0.1 (-0.36, 0.24)
* with 5 grades: 0 = 0 cells; 1 = 1 to 10 cells; 2 = 11 to 20 cells; 3 = 21 to 50 cells; and 4 = > 50 cells.
** adjusted for baseline AC cell grade and study center and based on ITT dataset with LOCF for missing data.

Last reviewed on RxList: 4/4/2013
This monograph has been modified to include the generic and brand name in many instances.

A A A

Durezol - User Reviews

Durezol User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Durezol sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


WebMD Daily

Get breaking medical news.

advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations