Beyond Conventional NSAIDs: Transdermal Efficacy and Therapeutic Potential of Nepafenac in Comparison to Diclofenac Sodium

Oral non-steroidal anti-inflammatory drugs (NSAIDs) are associated with a multitude of treatment-limiting contraindications, conflicting comorbidities, drug-drug interactions, and bothersome systemic effects. Contrary to the widespread use and well-established efficacy of systemic NSAIDs, locally-acting NSAIDs are still an area of ongoing pharmacologic investigation. As of December 2024, diclofenac sodium 1% topical gel is the only FDA-approved cutaneous NSAID, despite the availability of other structurally similar NSAIDs with comparable potencies, physicochemical properties, and pharmacokinetics. Nepafenac, a relatively new ophthalmic NSAID, has certain unique attributes which make it a promising candidate for transdermal formulations. Having undergone an expansive review of the available literature, we identify pharmacodynamic, pharmacokinetic, and physicochemical similarities between diclofenac and nepafenac. Our results infer that transdermal nepafenac possesses superior therapeutic efficacy vs diclofenac in the management of localized pain and inflammation. Given its unique pharmacodynamic attributes and enhanced efficacy profile, transdermal nepafenac shows great promise as a viable option for localized pain and inflammation. Moving ahead, further formulary and clinical efficacy studies are needed to fully assess its potential in a transdermal application.