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.

Prospective randomised clinical trial to evaluate the safety and efficacy of nepafenac 0.1% treatment for the prevention of macular oedema associated with cataract surgery in patients with diabetic retinopathy

“…Corneal erosion has been labelled as an NSAID class effect, and was therefore targeted as an AE of special interest in the study. As such, exclusion criteria were added to prevent enrolment of patients with compromised corneas 23 24. One case of corneal erosion in the nepafenac group was assessed by the investigator as related to study treatment (out of two reported).…”

Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies

“…Hydrophobic NSAIDs such as indomethacin, ibuprofen, and diclofenac, indicated for inflammatory disorders, are an excellent example to demonstrate the need for improved ocular delivery. Although, in-vitro studies have suggested their pharmacological effectiveness, studies involving animal models and patients generally fail to achieve sufficient therapeutic activity [5, 6]. Such failure is most likely due to insufficient retention and accumulation at the target site resulting in suboptimal therapeutic levels.…”

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“…Inflammatory process involves many mediators such as prostaglandin, leukotrienes, vascular endothelial growth factor and interleukins. Antiinflammatory effects of NSAIDs are mainly by inhibition of Cyclooxygenase (COX) activity which reduces prostaglandin production [14,15]. By blocking prostaglandin synthesis which is one of the inflammatory mediators, NSAIDS are shown to be effective in inhibiting the blood-retinal barrier breakdown thus reducing vascular hyperpermeability [11,13,16].…”