Topical ophthalmic NSAIDs: a discussion with focus on nepafenac ophthalmic suspension

Abstract

The removal of diclofenac sodium ophthalmic solution as a viable pharmaceutical entity in September 1999 from the US market spurred considerable interest in the general safety and effectiveness of topical ophthalmic NSAIDs for treatment of anterior segment inflammation. In late 1999 the use of topical ocular NSAIDs declined in the US as a result of incidents involving corneal melts and toxicity surrounding use of generic diclofenac. However, since the removal of diclofenac sodium ophthalmic solution from the marketplace, ophthalmic NSAIDs have regained use as viable pharmacotherapeutic entities. Moreover, several new ophthalmic NSAID products have recently been introduced for commercial use in the US including the novel chemical entity nepafenac. The purpose of this report is to revisit the use of topical ophthalmic NSAIDs for the treatment of surgically induced anterior segment inflammation with a particular focus on nepafenac. Nepafenac is unique among ophthalmic NSAIDs in that it is a prodrug deaminated to amfenac, a highly effective non-selective cyclooxygenase inhibitor. In the case of topical ophthalmic NSAIDs, practitioners should carefully weigh the cost-benefit of implementing "highly potent" new drug products because perturbations in pharmacodynamic response due to the inherent novelty in terms of chemical designs may outweigh the demonstrated replicative pharmacologic action of all topical ophthalmic NSAIDs.

Keywords: nepafenac; ocular inflammatory disease; ophthalmic NSAIDs.

Figure 1

General pathways of arachidonic acid metabolism.

Figure 2

Pathways of arachadonate metabolism in the cornea. Reproduced with permission from Mieyal PA, Bonazzi A, Jiang H, et al 2000. The effect of hypoxia on endogenous corneal epithelial eicosanoids. Invest Ophthalmol Vis Sci, 41:2170–6. Copyright © 2000. Association for Research in Vision and Ophthalmology. Abbreviations: CYP450, cytochrome P450; 12-HETE, 12(R)-hydroxy-5, 8, 11, 14-eicosatetraenoic acid; 12(R)-HETrE, 12(R)-hydroxy-5, 8, 14-eicosatrienoic acid; PG, prostaglandin.

Figure 3

Chemical structures and names of topical ophthalmic NSAID products approved for use in the US.

Figure 4

Deamination of nepafenac to the active compound amfenac.