Loteprednol etabonate for inflammatory conditions of the anterior segment of the eye: twenty years of clinical experience with a retrometabolically designed corticosteroid

Abstract

Topical corticosteroids are an important pharmacotherapy for the management of various inflammatory conditions affecting the anterior segment of the eye. However, medications in this class are associated with well-known risks including increased intraocular pressure (IOP) and development of cataracts. The topical corticosteroid loteprednol etabonate (LE) was developed with the specific intention of minimizing these side effects. Areas covered: The focus of this review is to examine published efficacy and safety data for LE, a drug engineered to undergo rapid metabolism to inactive metabolites with the goal of improved safety. Two decades of clinical research focused on LE formulations are reviewed, including the use of LE in combination with tobramycin. The cumulative body of experience affirms the concept that the molecular design of LE confers certain safety benefits without compromising the desired anti-inflammatory efficacy of a topical corticosteroid. Expert opinion: Loteprednol etabonate is a mainstay for topical therapy of a wide variety of commonplace and niche conditions of the ocular surface and the anterior segment, including in the healing post-operative patient. Its versatility and safety allow eye care providers to recommend both acute induction as well as chronic maintenance therapy with appropriate follow-up.

Safety and efficacy of twice daily administration of KPI-121 1% for ocular inflammation and pain following cataract surgery

“…As demonstrated in these two studies, KPI-121 1% with MPP technology delivers a desirable combination of robust efficacy with twice daily dosing, a low overall incidence of AEs, and the favorable IOP-safety profile consistently demonstrated with LE 8–14. While the efficacy and safety of LE in treating postoperative inflammation and pain are well established,15–22 all currently available formulations require QID dosing. This is due at least in part to the eye’s innate ability to remove foreign material, including suspended drug particles, from the ocular surface.…”

Loteprednol Etabonate for the Treatment of Dry Eye Disease

“…However, suspension formulations may be less convenient and possibly less comfortable to instill than gel formulations, which do not require shaking, have a lower concentration of BAK, and have a more physiological pH. 33 , 36 , 38 In addition to preventing settling, the polycarbophil polymer in current LE gel formulations also prolongs ocular surface retention and contains demulcent/lubricants, which may improve comfort. 33 , 36 , 38 The reduction in BAK from 0.01% in the suspension formulation to 0.003% in the gel formulations 36 is important given concerns with use of this preservative in DED patients, especially for those who may be on multiple BAK-containing medications long-term.…”

“… 33 , 36 , 38 In addition to preventing settling, the polycarbophil polymer in current LE gel formulations also prolongs ocular surface retention and contains demulcent/lubricants, which may improve comfort. 33 , 36 , 38 The reduction in BAK from 0.01% in the suspension formulation to 0.003% in the gel formulations 36 is important given concerns with use of this preservative in DED patients, especially for those who may be on multiple BAK-containing medications long-term. 12 , 65 While LE is also available formulated in a BAK-free ointment, there are no studies to date which have evaluated the ointment for DED.…”

“…LE was initially formulated as an ophthalmic suspension at concentrations of 0.2% 31 and 0.5%. 32 , 33 LE ophthalmic suspension 0.5% is indicated for the treatment of steroid-responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the eye as well as for the treatment of postoperative inflammation following ocular surgery. 32 LE ophthalmic suspension 0.2% is indicated for the temporary relief of signs and symptoms of allergic conjunctivitis.…”

“…Of note, the vehicle of both LE gel 0.5% and LE (submicron) gel 0.38% contains mucoadhesive polymers, which may potentiate longer contact time with the ocular surface, 36 , 38 and a demulcent/lubricant, which may improve comfort. The LE gel formulations also contain lower concentrations of the preservative benzalkonium chloride (BAK) compared with LE ophthalmic suspension 0.5% and 1% and have a pH close to that of tears, 33 , 36 , 43 which may be beneficial when treating ocular surface disorders. Pharmacokinetic studies in rabbits demonstrated that LE was present at high concentrations in the cornea and conjunctiva through 24 h following topical administration of LE 0.5% suspension, 44 , 45 LE gel 0.5%, 46 and LE gel 0.38%.…”