Rx Perspectives

A Drop a Day Takes the Pain Away

By Jack Persico, Executive Editor

Ophthalmologists have made great strides in improving cataract outcomes by using minimally invasive surgical techniques, premium IOLs and LRIs. With these successes well in hand, extending the premium-quality experience to the postop drug regimen is becoming a higher priority. Surgeons are finding that a regimen offering easier dosing, negligible side effects and rapid pain relief can help change the patient's impression of their surgery from “ow!” to “wow!”

Given that the typical postoperative course of therapy runs six to eight weeks, greater dosing convenience boosts compliance; by contrast, TID or QID dosing encourages missed doses. “Four times a day for at least six weeks is tough,” says Uday Devgan, MD, of Beverly Hills. “You have to take the bottle with you throughout the day.” That's why Dr. Devgan recently embraced the once-daily dosing now available in the new NSAID Bromday (bromfenac 0.09%) from Ista Pharmaceuticals, the first and only QD option on the market. “Patients can instill one drop in the morning and be done with their NSAID for the day,” he says.

Bromday uses the same formulation (bromfenac 0.09%) as its predecessor Xibrom, which was dosed BID. A trial conducted by Ista comparing the 0.09% concentration to a double-strength 0.18% formulation showed that efficacy results were essentially identical, according to Dr. Devgan. “The bromfenac molecule has a half-life that is greater than 24 hours,” he says. “If you put one drop in the eye now, 24 hours later you'll still have therapeutic levels of drug present.”

Bromday benefits from its use of bromine, a halogen. “Halogenation polarizes the molecule, like a magnet, which allows better penetration of the cornea and binding to the COX enzyme receptor with greater affinity.” Bromday is the only halogenated NSAID on the market. With the high efficacy achieved by the 0.09% dose and its long duration of action, increasing the dosing or concentration didn't yield measurable improvement.

“Bromday is same drug you're used to, with the same efficacy, but now you can use it once a day and achieve the same results,” says Dr. Devgan. “Before, we were giving too much of it. Now, we're giving a very appropriate amount.” Some surgeons successfully used QD dosing with Xibrom; now there's clinical data and a label indication to support such a regimen.

Rapid Results

The positive outcomes in the bromfenac 0.09% vs. 0.18% trial prompted Ista to conduct three prospective, placebo-controlled trials of the QD 0.09% formulation in postop cataract patients. Bromday was used one day preoperatively, the day of surgery and daily for two weeks postoperatively.

The primary endpoint of the trials was clearing of ocular inflammation, as measured by summed ocular inflammation score (SOIS), by Day 15. Bromday's SOIS improvement over placebo was statistically significant at Day 3. In two of the three studies, Bromday had a statistically significant higher incidence of clearing inflammation completely (46-47% vs. 25-29%). Integrating the data from the FDA trials found that 58.9% were completely cleared or had only trace inflammation at Day 15 (vs. 19.8% for placebo).

Significantly, the FDA trials did not include concomitant steroid use, so some surgeons may opt to reserve steroid use only for high-risk patients, managing many patients with just Bromday and an antibiotic. The integrated data found that only 2.9% discontinued use due to lack of efficacy and had to be switched to another anti-inflammatory agent.

Another efficacy endpoint was the number of patients pain-free on Day 1 after cataract surgery, which was achieved in 83-89% for Bromday vs. 51-71% for placebo. The integrated data puts the number of pain-free patients at 84% on Day 1, increasing to 96% at Day 15.

Clinically, it's very well tolerated, says Dr. Devgan, because it's a drop that doesn't sting at all. “In the FDA clinical trials, the incidence of burning, stinging and irritation was less in Bromday patients than in placebo, because of the drug's anti-inflammatory effects.”

Although Bromday contains the preservative BAK, Dr. Devgan says patient exposure and medication levels are negligible, for two reasons. First, Bromday's concentration is the lowest of all NSAIDs on the market, and secondly, the QD dosing minimizes exposure even more. “Bromfenac 0.09% has one-fifth the medication concentration of ketorolac 0.45% (Acuvail),” he notes. “And when you consider the dosing—twice a day for Acuvail compared with once-daily for Bromday—it's actually one-tenth the amount of drug exposure to have the same effect.” Similar disparities exist with the other NSAIDs vis-à-vis Bromday, Dr. Devgan says.

Ista will discontinue Xibrom this year. From the looks of it, Bromday is a worthy successor. OM