Loteprednol Etabonate

Abstract

Loteprednol etabonate is a corticosteroid which is the product of ‘soft drug’ design (synthesis of a compound that undergoes predictable metabolism to inactive metabolites after its therapeutic effects have been expressed at or near the site of application). It has been developed as a topical treatment for ocular inflammation.

Loteprednol etabonate is designed to be rapidly converted to inactive and nontoxic metabolites, thus minimising systemic adverse effects. The concentration of the drug in plasma from 10 healthy volunteers who received ocular loteprednol etabonate at therapeutic or supratherapeutic dosages was below the limit of detection.

In 2 double-masked, placebo-controlled studies, loteprednol etabonate 0.5% 4 times daily (1 drop/eye) for 2 weeks was more effective than placebo in relieving moderate to severe postoperative ocular inflammation after cataract surgery. The same regimen was also effective when administered for up to 6 weeks in 3 double-masked placebo-controlled studies in patients with moderate or severe contact lens-associated giant papillary conjunctivitis. Data from 2 double-masked placebo-controlled studies indicate that loteprednol etabonate 0.2% (1 drop/eye 4 times daily for 2 weeks) is effective in patients with moderate to severe seasonal allergic conjunctivitis. Furthermore, a single placebo-controlled trial has shown that loteprednol etabonate 0.5% has prophylactic efficacy in patients with a history of seasonal allergic conjunctivitis.

Ocular loteprednol etabonate was well tolerated, both locally and systemically, in clinical trials reported to date. Elevated intraocular pressure (IOP) is possible after ocular administration of the drug but is infrequent overall: only 1.7% of 901 patients or volunteers who received loteprednol 0.2 or 0.5% for ≥ 28 days had a clinically significant increase (≥ 10mm Hg) in IOP. Unlike prednisolone acetate, loteprednol etabonate did not significantly increase IOP from baseline in a small randomised crossover study in known steroid responders. There were no serious or unexpected treatment-related ocular adverse events in patients receiving loteprednol etabonate in clinical trials. The potential for cataract formation or glaucoma after long term treatment is unknown.

Thus, loteprednol etabonate can reduce ocular inflammation caused by cataract surgery, seasonal allergic conjunctivitis or contact lens wear. The benign tolerability profile of loteprednol etabonate, in particular its low propensity to cause elevated IOP (when used in the short term) is an attractive characteristic. However, the place of loteprednol etabonate in clinical practice cannot be properly assessed until direct efficacy comparisons with other active treatments are available.