Since its introduction more than a decade ago, the anti-inflammatory efficacy of ketorolac has been well documented.
The nonsteroidal anti-inflammatory drugs (NSAIDs) are a diverse class of medications that inhibit the synthesis of prostaglandins by interfering with the activity of cyclo-oxygenases (COX-1 and COX-2).1
Several ophthalmic preparations are available and several others have been recently introduced or are under FDA review.
The NSAID with the most available data is ketorolac tromethamine. Introduced more than 13 years ago, numerous studies have evaluated the efficacy and safety of ketorolac. The original ophthalmic formulation of ketorolac tromethamine is a 0.5% solution (Acular, Allergan). However, a new formulation of ketorolac tromethamine, 0.4% (Acular LS, Allergan), was introduced in the United States in 2003. This new formulation contains 20% less active ingredient than the original formulation and offers patients increased comfort. Specifically, the most common side effect of the original formulation has been reported to be burning and stinging. With the new 0.4% formulation, patients rarely report discomfort upon instillation.
Efficacy without adverse effects
A study by Sheri Rowen, MD, found that NSAIDs ketorolac tromethamine 0.5% and diclofenac sodium 0.1% (Voltaren, Novartis Pharmaceuticals) offer equivalent anti-inflammatory efficacy without the typical corticosteroid-associated adverse events.3 In addition, both medications control inflammation following cataract extraction.4 While diclofenac sodium 0.1% has been shown to inhibit intraoperative miosis and control postsurgical inflammation,5 topical ketorolac has been shown to be a more effective inhibitor of miosis than topical diclofenac during extracapsular cataract extraction and IOL implantation, and it provides a more stable mydriatic effect throughout surgery.6
The reformulation of ketorolac 0.5% to ketorolac 0.4% has not reduced its efficacy. Conversely, it may have improved the medication's anti-inflammatory properties. Helga P. Sandoval, MD, and associates compared the safety and efficacy of 0.4% ketorolac tromethamine ophthalmic solution versus 0.5% ketorolac tromethamine ophthalmic solution to prevent inflammation after cataract surgery in a prospective, randomized, double-masked, clinical trial of 40 patients undergoing phacoemulsification and IOL implantation. After 1 week, statistically significant between-group differences were found in anterior chamber cells and flare. Patients complained of less foreign body sensation with 0.4% ketorolac tromethamine than with the 0.5% formulation. The authors concluded that both medications were effective in preventing inflammation but the 0.4% ketorolac solution was associated with less anterior chamber cells, flare, and ocular symptoms.7
The efficacy of ketorolac 0.4% for relief of patient pain has also been recently evaluated by Dr. Solomon and associates in a pooled analysis of two multicenter, randomized, double-masked, vehicle-controlled, parallel-group studies of 313 patients who underwent unilateral photorefractive keratectomy (PRK).8
Throughout the 4 days of follow-up, patients in the ketorolac group reported significantly less pain intensity than patients in the vehicle group (p < 0.001). During the first 12 hours post-PRK, 50% fewer patients in the ketorolac group than in the vehicle group had severe to intolerable pain (41.6% [64/154] and 84.5% [131/155], respectively). The median time to no pain was 30 hours in the ketorolac group and 54 hours in the vehicle group (p < 0.001). Ketorolac-treated patients reported significantly greater pain relief than patients who received vehicle throughout the study (p < 0.001) and used significantly less escape medication than patients who received vehicle for 48 hours post-PRK (p < 0.008).