After a priority 6-month review, the FDA approved nepafenac ophthalmic suspension 0.1% (Nevanac, Alcon Laboratories), a novel nonsteroidal anti-inflammatory prodrug, for the treatment of pain and inflammation associated with cataract surgery.
Ophthalmologists who participated as investigators in the premarketing clinical trials are enthused about the availability of this new compound because they consider it an important advance with potential safety and efficacy advantages compared with existing topical nonsteroidal anti-inflammatory drugs (NSAIDs).
Nepafenac is the amide analog and a prodrug of the potent NSAID amfenac. When instilled in the eye, nepafenac rapidly penetrates through the cornea and is distributed uniformly within intraocular target tissues (retina/choroid, iris/ciliary body) where it is bioactivated to amfenac by hydrolase enzymes.
In various animal models, topically applied nepafenac was also demonstrated to be effective for inhibiting prostaglandin synthesis in the retina/choroid and for suppressing inflammation-mediated retinal edema, whereas ketorolac tromethamine (Acular, Allergan) and diclofenac had minimal to no activity.
In two identically designed multicenter, randomized, vehicle-controlled clinical trials that included nearly 700 patients undergoing cataract surgery, nepafenac showed efficacy for controlling postoperative pain and inflammation. In addition, it was associated with a favorable safety profile with rates and types of adverse events in nepafenac-treated patients being comparable with those seen in vehicle-treated controls.
"The clinical trial results along with other studies show unequivocally that nepafenac is a potent NSAID able to decrease postoperative inflammation in cataract surgery patients more effectively than any other topical NSAID available," said Stephen S. Lane, MD, clinical professor of ophthalmology, University of Minnesota, Minneapolis.
"Because of its novel prodrug formulation, nepafenac targets the ciliary body, choroid, and retina and presents to those tissues in high concentrations while causing minimal to no surface toxicity or discomfort on instillation," Dr. Lane explained. "This combination of safety and effectiveness will create a paradigm shift in how ophthalmologists will use NSAIDs in clinical practice."
"As ophthalmologists increasingly embrace the value of topical NSAIDs and use them more routinely to increase patient comfort after ocular surgery as well as to reduce the incidence of cystoid macular edema, which is the most common sight-threatening complication after cataract surgery, I expect nepafenac will become the most popular topical NSAID in the market," added Dr. Lindstrom, founder of Minnesota Eye Consultants, where he is also the attending surgeon.
Dr. Lindstrom advocated routine use of a topical NSAID combined with a topical steroid in cataract surgery patients to reduce pain, photophobia, intraoperative miosis, and postoperative inflammation along with the risk of cystoid macular edema. NSAIDs are also useful in reducing postoperative discomfort and photophobia in refractive surgery, especially after surface ablation, he said.
Pivotal trial results
The pivotal premarketing clinical trials evaluating nepafenac to treat pain and inflammation after cataract surgery randomly assigned patients 1:1 to treatment with vehicle or nepafenac. The assigned study agent was administered three times a day beginning 1 day preoperatively and then continuing on the day of surgery and for 14 days after surgery. All patients also received an additional dose of nepafenac or vehicle just prior to the procedure.
Assessments were performed before treatment initiation and at days 1, 3, 7, and 14, and included various measures to evaluate and control pain and inflammation. The results showed that patients using nepafenac had significantly less ocular pain and inflammation beginning at the earliest postoperative visit and continuing throughout the study period.