Bromfenac approval brings lower-concentration formulation

Take-home

The recent FDA approval of bromfenac 0.07% ophthalmic solution (Prolensa, Bausch + Lomb) brings cataract surgeons an innovative once-daily nonsteroidal anti-inflammatory drug option for treating inflammation and reducing pain after cataract surgery.

By Cheryl Guttman Krader; Reviewed by Mitchell Jackson, MD

Lake Villa, IL-The evolution of bromfenac solution continues with a newly approved lower-concentration formulation.

Bromfenac 0.07% ophthalmic solution (Prolensa, Bausch + Lomb) brings cataract surgeons an innovative once-daily nonsteroidal anti-inflammatory drug (NSAID) option for treating inflammation and reducing pain after cataract surgery, according to Mitchell Jackson, MD.

“This is an advanced formulation of bromfenac with potent therapeutic activity and the potential for improved safety and tolerability,” said Dr. Jackson, who was a clinical investigator in the pivotal trial and founder and director, Jacksoneye, Lake Villa, IL. “By manipulating the pH of the vehicle, formulation engineers have created a novel delivery system that facilitates bromfenac corneal penetration while maintaining good comfort.

“With more than 20 million uses over the past 10-plus years, bromfenac has a strong track record of efficacy and safety,” he said. “Clinical trial results show this new formulation delivers the expected benefits of bromfenac, and with its lower concentration of the active ingredient, it may minimize risks of delayed healing and adverse corneal effects intrinsic to all NSAIDs.”

Patient-friendly

Dr. Jackson added that in addition to good comfort, bromfenac 0.07% has other patient-friendly features. Since it is a solution, patients need not shake the bottle prior to use and are assured of getting a uniform dose from the first drop to the last.

Furthermore, it is being marketed in two fill sizes, 1.6 and 3 ml, at an equal price. The larger volume will enable patients to complete their course of therapy with a single bottle.

“Patients may run out of their medications early after cataract surgery as a result of wastage from missing the eye or squeezing out an excessively large drop,” Dr. Jackson said. “I applaud the FDA for taking this issue into account and approving the 3-ml product size that should limit any need to dispense two bottles initially or for patients to refill the prescription.”

Formulation features

Compared with the existing bromfenac 0.09% ophthalmic solution (Bromday, Bausch + Lomb), bromfenac 0.07% is formulated at a closer to physiologic pH, 7.8 versus 8.3. The lower pH enhances bromfenac bioavailability by increasing the amount of drug that is in the nonionized, lipophilic state and able to penetrate through the hydrophobic corneal surface.

However, because the product pH remains slightly closer to physiologic rather than acidic, the drop is well tolerated on instillation.

Pivotal trial results 

The efficacy and safety of bromfenac 0.07% was investigated in two double-masked, vehicle-controlled studies that included 440 patients in the intent-to-treat analysis. Patients were randomly assigned 1:1 to bromfenac or vehicle and instilled their assigned study medication once daily, beginning the day before surgery and continuing on the day of surgery and 14 days thereafter. All patients received an antibiotic, but there was no routine topical corticosteroid treatment in either arm of the study. Follow-up visits were conducted on postoperative days 1, 3, 8, and 15, and also on day 22 for final safety analysis.

The proportion of patients with a Summed Ocular Inflammation Score (SOIS) of 0 (no cells or flare) on day 15 was analyzed as the primary efficacy endpoint, and the results showed a statistically significant difference favoring bromfenac 0.07% over vehicle, 46% versus 20%. Data from earlier follow-up visits showed bromfenac acted rapidly to control inflammation as by postoperative day 8, there was already a significant difference favoring bromfenac in the analysis of proportions of patients with total clearance of inflammation.

A secondary efficacy analysis considered the proportion of patients with absence of flare and no more than trace cells (0 to 5) at day 15, and the results also showed a significant difference favoring the bromfenac group with 80% of bromfenac-treated eyes meeting this criterion compared with only 47% of controls.

Ocular comfort

Patients enrolled in the study also used a diary to record the severity of seven ocular symptoms (ocular pain, tearing, itching, foreign body sensation, photophobia, eye discharge, haziness) comprising the Ocular Comfort Grading Assessment (OCGA). Analyses of the pain ratings demonstrated that bromfenac 0.07% provided potent and rapid pain control. The proportion of patients who were pain-free was already significantly greater in the bromfenac group compared with controls by postoperative day 1 (79% versus 50%). The percentage of pain-free patients rose progressively in both study groups through day 8, but the difference in favor of bromfenac continued to increase. At day 8, 92% of bromfenac patients versus 61% of controls reported being pain-free.

“Pain after cataract surgery has a major impact on patient satisfaction and word-of-mouth referrals,” Dr. Jackson said. “No matter what the visual outcome, patients may not recommend their surgeon if they were uncomfortable after the procedure.”

Patient ratings for tearing and photophobia also consistently favored the bromfenac group through day 8, and between-group comparisons for the other four components of the OCGA showed that the bromfenac-treated patients either fared better or similar to the controls.

“Anterior chamber inflammation, foreign body sensation, eye pain, photophobia, and blurred vision were the most commonly recorded adverse events in bromfenac-treated patients, although they occurred at rates of only 3% to 8% and are generally sequelae of the surgery rather than being medication-related,” Dr. Jackson said.

Mitchell Jackson, MD

E: mjlaserdoc@msn.com

Dr. Jackson is a consultant to Bausch + Lomb and on the speakers' bureau for other companies that market ophthalmic nonsteroidal anti-inflammatory drugs.