Retisert (Fluocinolone Acetonide Intravitreal Implant) Drug Information: Clinical Pharmacology

Pill Identifier Search

May 27, 2012

Retisert

Uveitis »

Introduction

Uveitis (pronounced you-vee-EYE-tis) is basically an inflammation of the eye. The condition involves all inflammatory processes of the middle layers of the eye, also called the uveal tract or uvea. The uvea includes the iris (colored part of the eye), choroid (a thin membrane containing many blood vessels) and ciliary body (the part of the eye that joins these together).

The uvea is very important because its many veins and arteries transport blood to the parts of the eye that are critical for vision.

Learn more about the structures that make up the eye in the article titled " The Amazing Human Eye ."

What Are the Symptoms of Uveitis?

Symptoms of uveitis may include:

Eye redness and irritation
Blurred vision
Eye pain
Increased sensitivity to light ...

Read the Uveitis article »

« Previous
1
2
3
4
5
6
7
8
9
10
Next »

Retisert

Eye Diseases and Conditions Slideshow Pictures

Pink Eye Slideshow Pictures

Cataracts Slideshow Pictures

font size

CLINICAL PHARMACOLOGY

Mechanism Of Action

Corticosteroids inhibit the inflammatory response to a variety of inciting agents and probably delay or slow healing. They inhibit the 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. Corticosteroids are capable of producing a rise in intraocular pressure.

Pharmacokinetics

In a subset of patients who received the intravitreal implant, and had blood samples taken at various times (weeks 1, 4 and 34) after implantation, plasma levels of fluocinolone acetonide were below the limit of detection (0.2 ng/mL) at all times. Aqueous and vitreous humor samples were assayed for fluocinolone acetonide in a further subset of patients. While detectable concentrations of fluocinolone acetonide were seen throughout the observation interval (up to 34 months), the concentrations were highly variable, ranging from below the limit of detection (0.2 ng/mL) to 589 ng/mL.

Clinical Studies

In two randomized, double-masked, multicenter controlled clinical trials, 224 patients with chronic (a one year or greater history) non-infectious uveitis affecting the posterior segment of one or both eyes were randomized to receive a 0.59 mg RETISERT. The primary efficacy endpoint in both trials was the rate of recurrence of uveitis affecting the posterior segment of the study eye in the 34 week pre-implantation period compared to the rate of recurrence in the 34 week post-implantation period. Uveitis recurrence rates at 1, 2, and 3 year post-implantation were also compared to the 34 week preimplantation period.

Detailed results are shown in table 1 below:

Table 1: Uveitis Recurrence Rates

Time Point	Study 1 N=108	Study 2 N=116
Time Point	UVEITIS RECURRENCE RATES^1,2 N (%)
34 Weeks Pre-implantation	58 (53.7)	46 (39.7)
34 Weeks Post-implantation	2 (1.8)	15 (12.9)
1 Year Post-implantation	4 (3.7)	15 (12.9)
2 Years Post-implantation	11 (10.2)	16 (13.8)
3 Years Post-implantation	22 (20.4)	20 (17.2)
3 Years³ Post-implantation	33 (30.6)	28 (24.1)
¹ Recurrence of uveitis for all post-implantation time points was compared to the 34 weeks pre-implantation time point. ² p-value < 0.01 from McNemar's χ2 test. ³ Results presented include imputed recurrences. Recurrences were imputed when a subject was not seen within 10 weeks of their final scheduled visit.