Rescula gets FDA approval as concomitant therapy

WASHINGTON — Rescula (unoprostone isopropyl ophthalmic solution 0.15%; CIBA Vision) has received U.S. Food and Drug Administration (FDA) approval for the lowering of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are intolerant of other IOP lowering medications or insufficiently responsive to another IOP lowering medication.

"In terms of Rescula's IOP lowering effect, we've seen a 13% to 17.4% from baseline lowering of IOP," George Minno, PhD, director of medical marketing for CIBA Vision U.S. Ophthalmics told Ocular Surgery News. Clinical studies showed that in patients with mean baseline IOP of 23 mm Hg, Rescula lowers IOP by approximately 3 to 4 mm Hg throughout the day.

"And it has an excellent safety profile," Dr. Minno added. "We haven't seen any peak and trough effects that are associated with other glaucoma agents. There is no loss of efficacy over time and Rescula's maximum effect is established as soon as 24 hours after instillation."

Additionally, cardiovascular and pulmonary systems were not affected by Rescula use. No allergic reactions have been reported. The most common side effects of Rescula were stinging and burning upon instillation.

A low incidence of gradual iris color change has been reported with Rescula use. However, the 0.12% incidence of iris pigment change associated with Rescula is 100-fold less than that as seen with Xalatan (latanoprost, Pharmacia), according to Dr. Minno. Only one out of 813 patients experienced a change in eye color during the Rescula clinical trials.

Chemistry and function

Unoprostone was developed from a prostaglandin metabolite. The drug molecule is a docosanoid - essentially different in molecular structure from all other glaucoma compounds, according to Dr. Minno. Docosanoid compounds are based on a chain of 22 carbon atoms, as opposed to the 20 carbon atoms of primary prostaglandin known as eicosanoids.

"Although Rescula looks like a prostaglandin, it doesn't behave like one," Dr. Minno said. "It doesn't bind to any of the same receptors and it really doesn't have a lot of the properties that you would expect if you were comparing it with something like latanoprost."

The approved dosage for Rescula is one drop in the affected eye twice daily. It may be used concomitantly with other topical ophthalmic drugs to lower IOP. If two drugs are used, it is recommended that they be administered at least 5 minutes apart.

"When instilled in the eye, Rescula is believed to reduce elevated IOP by increasing the outflow of aqueous humor," Dr. Minno said, but the exact mechanism is unknown at this time. After application to the eye, unoprostone isopropyl is absorbed through the cornea and conjunctival epithelium where it is hydrolyzed by esterases to unoprostone-free acid. Rescula appears to lower IOP without affecting cardiovascular or pulmonary function, Dr. Minno said.

Side effects

Stinging and burning were the most common reported side effects reported with Rescula use. Unoprostone was not associated with increased IOP, bitter taste, bradycardia, tissue inflammation, miosis, changes in visual acuity or accommodation, damage to the blood-aqueous barrier or decreased blood pressure, according to Dr. Minno.

Iris pigment change

In clinical studies of Rescula, only one patient experienced a change in iris color. According to Thomas K. Mundorf, MD, that one incidence of iris color change in a patient receiving 0.15% unoprostone isopropyl was so gradual that it was not detected by the patient or the doctor, but by clinical investigators. "This one case was found, and it wasn't found by the doctor or the patient, in out of about 850 patients," Dr. Mundorf told Ocular Surgery News. "So it looks like it is a very uncommon effect."

The international version of Rescula, which is marketed under the same name in Japan and most of Central American and South American countries, but in a 0.12% concentration of unoprostone isopropyl, has been associated with a gradual change in eye color too. The change in iris color occurs slowly and may not be noticeable for months to several years. The long-term effects or the possibility of potential injury to the eye are currently unknown.

Iris color change, hypertrichosis and eyelid pigmentation were reported in less than 0.01% of patients treated with the 0.12% of unoprostone for 5 years. A 64-year-old Japanese male with normal tension glaucoma showed an iris color change in the 0.12% unoprostone-treated eye. The iris color before treatment was uniformly brown, but 20 months after treatment, the iris had darkened, slightly roughened and appeared somewhat atrophic compared with the fellow eye.

Dr. Mundorf investigated Rescula 0.15% preclinically, and he reports that during clinical investigations, the drug demonstrated a pressure-lowering capability within 1 to 1.5 mm of timolol.

Rescula was found in clinical trials to have no cardiopulmonary side effects, but may play a role in improving blood flow in the eye, Dr. Mundorf said, although this has not yet been determined.

For Your Information:

George Minno, PhD, can be reached at CIBA Vision Corp., 11460 Johns Creek Parkway, Duluth, GA 30097-1556; (678) 415-3875; fax: (678) 415-7474; e-mail: georgeminno@cibavision.novartis.com.

Thomas K. Mundorf, MD, can be reached at 1718 E. 4th St., Ste. 806, Charlotte, NC 28204; (704) 334-3222; fax: (704) 334-1532.